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PMC6989633 | 31996712 | Introduction
The composition of Australia’s theropod fauna is poorly understood in comparison to those of contemporaneous assemblages around the world, due primarily to the isolated and fragmentary mode of preservation in fossiliferous deposits. To date, the majority of documented theropod remains from Australia are fr... | Methods and Materials
LRF 3050.AR and NMV P221202 were inserted into a recently published ceratosaurian phylogenetic matrix 39 (see Supplementary Dataset S1 ) and analysed with equal weights parsimony in TNT 1.5 93 . A driven search strategy was implemented to calculate optimal trees, with each search using 100 repli... | Discussion
Comparisons of LRF 3050.AR
Opisthocoelous vertebral centra characterise the cervical series of many neotheropods. The posterior surfaces are typically moderately to strongly concave and the anterior surface may be generally flattened 49 , 50 or slightly convex as in ceratosaurians 51 – 54 and basal tetanur... | The diversity of Australia’s theropod fauna from the ‘mid’-Cretaceous (Albian–Cenomanian) is distinctly biased towards the medium-sized megaraptorids, despite the preponderance of abelisauroids in the younger but latitudinally equivalent Patagonian theropod fauna. Here, we present new evidence for the presence of cerat... | Taxonomic Framework
There are presently two hypotheses regarding the content of Noasauridae and the phylogeny of non-abelisaurid, non-ceratosaurid ceratosaurians. Abelisauroidea was originally considered to include Abelisauridae and Noasauridae, and all ceratosaurs more closely related to them than to Ceratosaurus nas... | Supplementary information
is available for this paper at 10.1038/s41598-020-57667-7.
Acknowledgements
We are indebted to Robert Foster who discovered the ‘Sheepyard’ specimens and Joanne Foster and Gregory Robert Foster who generously donated the specimens under the Australian Government’s Cultural Gifts program. We th... | CC BY | no | 2024-01-16 23:34:59 | Sci Rep. 2020 Jan 29; 10:1428 | oa_package/16/47/PMC6989633.tar.gz | ||
PMC7168315 | 32059467 | 1. Introduction
Biofilms—aggregations of densely packed microbial cells embedded inside exopolysaccharide (EPS) matrix—are a major challenge in public health management. The EPS matrix provides a protective barrier to the biofilm, making them recalcitrant to antimicrobial agents and host defenses [ 1 ]. Staphylococcus... | 2. Materials and Methods
2.1. Materials
Chitosan (75–85% deacetylated), sodium tripolyphosphate (TPP) and Chrysin were procured from Sigma-Aldrich. The test stain, S. aureus (MCC 2408) was purchased from Microbial Culture Collection (MCC), Pune, India.
2.2. Synthesis of Chrysin-Loaded Chitosan Nanoparticles
Medium mo... | 3. Results
3.1. Synthesis and Characterization of Chrysin-Loaded Chitosan NPs
The CCNPs were synthesized using the ionotropic gelation method, using TPP molecules as a linker. The ratio of chitosan and TPP used is one of the factors that influence the aggregation of nanoparticles. Chitosan/TPP in the ratio of 5:1 was f... | 4. Discussion
The formation of biofilm is one of the major obstacles in the modern antibacterial therapy. The biofilm-forming ability of bacteria provides the pathogen with advantages by blocking the entry of antimicrobial agents, thus causing hindrance in the clearance of these pathogens by the host immune system. Dru... | 5. Conclusions
This study displayed an enhanced antibiofilm activity of chrysin against S. aureus when loaded on to chitosan-TPP nanoparticles, with a profound loading capacity. Chrysin-loaded chitosan nanoparticles were characterized to confirm the effective loading of the flavone on chitosan nanoparticles. Anti-bio... | The application of nanotechnology in medicine is gaining popularity due to its ability to increase the bioavailability and biosorption of numerous drugs. Chrysin, a flavone constituent of Orocylumineicum vent is well-reported for its biological properties. However, its therapeutic potential has not been fully exploit... | Acknowledgments
We are grateful to the Central Instrumentation Facility (CIF), Pondicherry University for the DLS and FTIR analysis. We would like to thank the Sophisticated Test and Instrumentation Centre (STIC), Cochin for the TEM analysis. We are also thankful to Bharathidasan University, Tiruchirappalli for support... | CC BY | no | 2024-01-16 23:36:45 | Pathogens. 2020 Feb 12; 9(2):115 | oa_package/ba/c7/PMC7168315.tar.gz | |
PMC7408465 | 32610539 | 1. Introduction
Flibanserin (FLB) is a recently FDA-approved nonhormonal drug for the treatment of women with hypoactive sexual appetite disorder. FLB acts via decreasing the level of serotonin and increasing the levels of dopamine and norepinephrine for maintaining healthy sexual response [ 1 ]. FLB-treated women have... | 2. Materials and Methods
2.1. Materials
Flibanserin (FLB) was purchased from Qingdao Sigma Chemical Co., Ltd. (Qingdao, China); Phospholipon 90G (phosphatidyl choline from soy, at least 90% purity) was purchased from Lipoid GmbH (Frigenstr, Ludwigshafen, Germany); Span 65, Span 80, methanol, and chloroform were purchas... | 3. Results
3.1. Polynomial Model Selection and Diagnostic Analysis
The observed vesicle size of the prepared TRFs best fitted to the quadratic model based on its highest correlation coefficient (R 2 ) is shown Table 2 . There was a satisfactory agreement between the predicted and adjusted R 2 , indicating that the sel... | 4. Discussion
The nanoscale size observed could contribute to enhancing the drug permeation via the nasal mucosa and facilitating passing through the blood–brain barrier. Analysis of variance (ANOVA) for the vesicle size affirmed that the quadratic model was significant ( p < 0.0001). The positive sign of the coeffici... | 5. Conclusions
TRF-loaded hydrogel has been investigated as a possible intranasal delivery system of FLB. Box–Behnken design was successfully applied for optimization of FLB TRFs with minimized vesicular size. The optimized FLB TRFs (1:1.12 drug:PL molar ratio, surfactant HLB of 2.3, and hydration medium pH of 7.2) wer... | Flibanserin (FLB) is a nonhormonal medicine approved by the Food and Drug Administration (FDA) to treat the hypoactive sexual appetite disorder in females. However, the peroral administration of the medicine is greatly affected by its poor bioavailability as a result of its extensive first-pass effect and poor solubili... | Author Contributions
Conceptualization, O.A.A.A. and U.A.F.; methodology, S.M.B.-E.; software, H.M.A.; validation, Z.A.A., H.Z.A., and A.K.K.; formal analysis, G.C.; investigation, F.C.; resources, A.A.; data curation, R.A.A.-G. (Raniyah A. Al-Ghamdi); writing—original draft preparation, U.A.F.; writing—review and edit... | CC BY | no | 2024-01-16 23:35:06 | Nanomaterials (Basel). 2020 Jun 29; 10(7):1270 | oa_package/82/4e/PMC7408465.tar.gz | |
PMC7615524 | 37727079 | Introduction
Randomized controlled trials (RCTs) are considered the gold standard for assessing the causal effect of an exposure on an outcome, but are vulnerable to bias due to missingness in the outcome—or “dropout.” The impact of dropout depends on the missingness mechanism and the analysis model ( Dziura et al., 20... | Methods for Testing Differences in Variances
Various methods are available for testing and estimating the difference in variance between two groups, including Bartlett’s test ( Bartlett & Fowler, 1937 ), Levene’s test ( Levene at al., 1960 ), the Brown–Forsythe test ( Brown & Forsythe, 1974 ), the Breusch–Pagan test ( ... | Results
The simulation results are shown in Table 2 . We first consider the seven scenarios when there is no effect modification and the treatment effects are homogeneous (A–G). When dropout is MCAR (A), and when dropout is MAR conditional on treatment (B), some measured covariate (C), or both (D), the treatment effec... | Discussion
In this paper, we show that, in RCTs, the outcome variance difference across trial arms at baseline, in the set of study participants who did not drop out, is an indicator of outcome-dependent MNAR dropout, and consequently, a biased CCA treatment effect estimate. In contrast, when outcomes are MAR or MCAR, ... | Randomized controlled trials (RCTs) are vulnerable to bias from missing data. When outcomes are missing not at random (MNAR), estimates from complete case analysis (CCA) and multiple imputation (MI) may be biased. There is no statistical test for distinguishing between outcomes missing at random (MAR) and MNAR. Current... | Notation
Let U be some unmeasured covariate, and C some measured covariate. Let X = j denote the randomized trial arms, with j = {0, 1}, and X = 0 denoting the comparator arm and X = 1 the intervention arm. We define the continuous outcome variable, Y , as a linear function of X, U , and C so that w... | Acknowledgments
We would like to thank Dr Andrew Vickers and the acupuncture trial team for making the data from “Acupuncture for chronic headache in primary care: large, pragmatic, randomized trial” publicly available. AH, TP and KT were supported by the Integrative Epidemiology Unit, which receives funding from the U... | CC BY | no | 2024-01-16 23:47:20 | Biom J. 2023 Dec 1; 65(8):e2200116 | oa_package/98/16/PMC7615524.tar.gz | |
PMC7615526 | 38160938 | Introduction
Lysosomal acid lipase (LAL) hydrolyzes cholesteryl esters (CE) and triacylglycerols (TG) at acidic pH [ 1 , 2 ]. Congenital mutations of the LAL-encoding LIPA gene cause a substantial reduction in enzyme activity, resulting in a massive accumulation of neutral lipids in lysosomes [ 3 , 4 ], ultimately le... | Materials and Methods
Animals
Male young (8–12 or 12–17 weeks of age) and mature (40–55 weeks of age), as well as female young (19–21 weeks of age) and mature (33–44 weeks of age) Lal−/− mice and their corresponding Wt littermates on a C57BL/6J background were used for the experiments. We analyzed quadriceps (QU), gast... | Results
Reduced cross-sectional area and SM mass in Lal −/− mice
To study the consequences of LAL loss in SM, we isolated gastrocnemius (GA), quadriceps (QU), tibialis anterior (TA), and soleus (SO) and compared the mass between male Wt and Lal−/− mice in the fed (15–16 weeks of age, designated young) and fasted (40–55... | Discussion
The impact of LAL-D on the pathophysiology of SM is still unclear, although decreased muscle size and muscle weakness were reported as characteristic features of LAL-D patients [ 23 – 26 , 28 ]. Compromised lipid homeostasis in Lal−/− mice, arising from impaired hepatic and intestinal lipid metabolism as wel... | Conclusion
Taken together, our data provide conclusive evidence that whole-body loss of LAL affects the phenotype and, most probably, functions of SM, due to insufficient ATP production associated with dysfunctional mitochondria and impaired energy metabolism. The described alterations result in SM fiber switch, and La... | Objective
Lysosomal acid lipase (LAL) is the only enzyme known to hydrolyze cholesteryl esters (CE) and triacylglycerols in lysosomes at an acidic pH. Despite the importance of lysosomal hydrolysis in skeletal muscle (SM), research in this area is limited. We hypothesized that LAL may play an important role in SM devel... | Supplementary Material | Acknowledgments
This work was supported by the Austrian Science Fund FWF (SFB 10.55776/F73, DK-MCD 10.55776/W1226, 10.55776/P32400, 10.55776/P30882, 10.55776/P28854, 10.55776/I3792, 10.55776/DOC-130, 10.55776/FG12), Austrian Research Promotion Agency grants 864690 and 870454, Integrative Metabolism Research Center Graz... | CC BY | no | 2024-01-16 23:47:21 | Mol Metab. 2023 Dec 30;:101869 | oa_package/db/ce/PMC7615526.tar.gz |
PMC8550499 | 34723203 | Introduction
As a consequence of large-scale phenomena such as globalization, social integration, migrations, and progress in information and communication technology, the world has become a much more complex place than it used to be. Today, social systems, which I shall define as collections of interacting components... | Conclusions
Throughout this paper I tried to show that computational methods can play an important role in the field of language policy. This role has been largely overlooked until recently. This does not only concern simulation-based methods, but computational methods in general, such as natural language processing an... | In this paper I argue in favour of the adoption of an interdisciplinary approach based on computational methods for the development of language policies. As a consequence of large-scale phenomena such as globalization, economic and political integration and the progress in information and communication technologies, so... | Language policy and complexity
Public policy can be defined as “ an intentional course of action followed by a government institution or official for resolving an issue of public concern . Such a course of action must be manifested in laws, public statements, official regulations, or widely accepted and publicly visibl... | Funding
Open access funding provided by University of Geneva.
Data availability
The manuscript has no associated data.
Declarations
Conflict of interest
The corresponding author states that there is no conflict of interest. | CC BY | no | 2024-01-16 23:35:01 | SN Soc Sci. 2021 Aug 2; 1(8):197 | oa_package/eb/8e/PMC8550499.tar.gz | |||
PMC9002620 | 35406088 | 1. Introduction
Homocysteine (Hcy) is a sulfhydryl-containing amino acid that is produced when methionine is demethylated. Hcy can be converted to cysteine via the sulphuration pathway, or remethylated utilizing methyltetrahydrofolate or betaine [ 1 ].
The clinical definition of hyperhomocysteinemia (HHcy) is a total ... | 2. Materials and Methods
2.1. Animals
Male Sprague Dawley rats (250 g, Envigo, Milan, Italy) were housed in a well-organized environment (room 22.1 °C, 12 h dark–light cycles) and fed normal rodent food and water. For one week, the animals were acclimatized to these conditions. The research was approved by the Animal W... | 3. Results
3.1. Effect of Cashew Nuts on Serum Hcy Levels after Methionine Administration
In the present study, to see whether the oral administration of methionine effectively caused the condition HHcy, we measured the levels of Hcy in the serum. Methionine administration (1 g/kg oral) for 30 days caused an increased ... | 4. Discussion
HHcy is a methionine metabolism abnormality that can cause a variety of disorders in humans, including cardiovascular and neurological conditions like atherosclerosis and stroke; inflammatory syndromes, including osteoporosis and rheumatism; and Alzheimer’s and Parkinson’s diseases. Meth’s biochemistry is... | These authors contributed equally to this work.
These authors contributed equally to this work.
Hyperhomocysteinemia (HHcy) is a methionine metabolism problem that causes a variety of inflammatory illnesses. Oxidative stress is among the processes thought to be involved in the pathophysiology of the damage produced by ... | Acknowledgments
We would like to acknowledge Salma Seetaroo from Ivorienne de Noix de Cajou S.A. of Cote d’Ivoire for providing the cashew kernel samples from the Ivory Coast. In addition, we would like to thank Valentina Malvagni for editorial support with the manuscript.
Author Contributions
Conceptualization, R.D.P.... | CC BY | no | 2024-01-16 23:35:07 | Nutrients. 2022 Apr 1; 14(7):1474 | oa_package/5c/7a/PMC9002620.tar.gz | ||
PMC9094045 | 35573302 | Introduction
Acetylcholine is an important neurotransmitter for both the maintenance of internal homeostasis and the interaction of individuals with the external environment ( Picciotto et al., 2012 ). Several physiological functions depend on cholinergic transmission, including immunological, endocrine, and neural res... | Conclusion
In conclusion, experimental models such as the Chrna9 KO mouse have allowed the development of multiple lines of auditory research, facilitating substantial advances in the knowledge about AES functioning, providing therapeutic possibilities for the treatment of auditory pathologies. Notwithstanding all the ... | Edited by: Victoria M. Bajo Lorenzana, University of Oxford, United Kingdom
Reviewed by: Adrian Rodriguez-Contreras, City College of New York (CUNY), United States
This article was submitted to Auditory Cognitive Neuroscience, a section of the journal Frontiers in Neuroscience
Cholinergic transmission is essential for ... | Auditory Efferent System
The auditory efferent system is a neural network that originates in the auditory cortex and projects to multiple subcortical nuclei of the central auditory pathways. These corticofugal pathways generate several feedback loops, including: the (i) collicular-thalamic-cortico-collicular- loop; (ii... | CC BY | no | 2024-01-16 23:36:46 | Front Neurosci. 2022 Apr 27; 16:866161 | oa_package/d6/a7/PMC9094045.tar.gz | ||||
PMC9117295 | 35115661 | Introduction
Genetic variations at the DLG2 gene locus are linked to multiple psychiatric disorders including schizophrenia [ 1 , 2 ], bipolar [ 3 , 4 ], autism spectrum [ 5 – 7 ], attention deficit hyperactivity [ 8 ], intellectual disability [ 9 , 10 ], and Parkinson’s disease [ 11 , 12 ]. This clinical evidenc... | Materials and methods
Animals and husbandry
All procedures were carried out under local institutional guidelines, approved by the University of Bristol Animal Welfare and Ethical Review Board, and in accordance with the UK Animals (Scientific procedures) Act 1986. The experiments employed a novel Dlg2 + /− heterozygo... | Results
Dlg2 + /− heterozygous knockout rats were generated by CRISPR-Cas9 targeting of the Dlg2 gene (Supplementary information). In this model, DLG2 protein expression levels were reduced by ~50% in hippocampus without effects on expression of other components of the postsynaptic density, including the closely rel... | Discussion
NMDAR currents are increased in the Dlg2 + /− heterozygous rat model. Additionally, dendritic arborisation is reduced. These observations would be expected to combine to enhance neuronal excitability, dendritic integration and synaptic plasticity. Instead, the effects are entirely offset, and indeed revers... | Copy number variants indicating loss of function in the DLG2 gene have been associated with markedly increased risk for schizophrenia, autism spectrum disorder, and intellectual disability. DLG2 encodes the postsynaptic scaffolding protein DLG2 (PSD93) that interacts with NMDA receptors, potassium channels, and cyt... | Supplementary information
| Supplementary information
The online version contains supplementary material available at 10.1038/s41386-022-01277-6.
Acknowledgements
We thank Jenny Carter for coordinating the initial generation and breeding of the Dlg2+/− rat line, Rachel Humphries for computational modelling discussions and Aleks Domanski and all m... | CC BY | no | 2024-01-16 23:35:01 | Neuropsychopharmacology. 2022 Jun 3; 47(7):1367-1378 | oa_package/84/a0/PMC9117295.tar.gz | |
PMC9363242 | 35944931 | Background
Description of the condition
High blood pressure is the leading cause of preventable deaths worldwide, contributing to more than 10 million deaths and 211 million disability‐adjusted life years annually, mainly due to acute coronary syndrome (formerly called ischaemic heart disease) and stroke ( Forouzanfar ... | Methods
Criteria for considering studies for this review
Types of studies
The Populations, Intervention, Comparison, and Outcomes (PICO) were agreed by the WHO NUGAG Subgroup on Diet and Health, who ranked the outcomes and also agreed on subgroups and study designs to be included. As per these agreements and our prospe... | Results
Description of studies
For detailed information, see Characteristics of included studies ; Characteristics of excluded studies ; Characteristics of ongoing studies ; Characteristics of studies awaiting classification .
Results of the search
The study selection flowchart is available in Figure 1 . We screen... | Discussion
Summary of main results
This review examined the effects and safety of LSSS compared to regular salt or no active intervention on blood pressure and cardiovascular health in adults, children and pregnant women. We included 16 RCTs and ten cluster‐RCTs (n = 26) conducted in adults from a range of different se... | Authors' conclusions
| Abstract
Background
Elevated blood pressure, or hypertension, is the leading cause of preventable deaths globally. Diets high in sodium (predominantly sodium chloride) and low in potassium contribute to elevated blood pressure. The WHO recommends decreasing mean population sodium intake through effective and safe strat... | Summary of findings
Objectives
To assess the effects and safety of replacing salt with LSSS to reduce sodium intake on cardiovascular health in adults, pregnant women and children. | Acknowledgements
The World Health Organization (WHO) provided funding to Stellenbosch University towards the cost of carrying out this systematic review. AB, MV, AS and CN are partly supported by the Research, Evidence and Development Initiative (READ‐It). READ‐It (project number 300342‐104) is funded by UK aid from th... | CC BY | no | 2024-01-16 23:36:46 | Cochrane Database Syst Rev. 2022 Aug 10; 2022(8):CD015207 | oa_package/97/5a/PMC9363242.tar.gz |
PMC9680264 | 36412589 | CC BY | no | 2024-01-16 23:35:05 | Diseases. 2022 Nov 1; 10(4):95 | oa_package/4f/7f/PMC9680264.tar.gz | ||||||||
PMC10067837 | 37005419 | Introduction
Archaea are a prokaryotic domain of life that structurally resemble, but are evolutionarily distinct, from bacteria. Apart from the sharp separation in the phylogenetic trees of universal genes (mostly encoding translation system components), archaea differ from bacteria in many major features including pa... | Methods
Isolation, identification, morphological observation
The sediment samples were collected from Qijiaojing Salt Lake in Xinjiang Uygur Autonomous Region, China. Isolation was done using the standard dilution-plating technique on Modified Gause (MG) medium 11 containing (g/L): soluble starch, 5; lotus root starch... | Results and discussion
A new haloarchaeal lineage with complex morphological differentiation
During the investigation of actinobacterial diversity from hypersaline environments, an unexpected hyper-halophilic archaeon with a distinct growth pattern was discovered serendipitously from the Qijiaojing Salt Lake in the Xin... | Results and discussion
A new haloarchaeal lineage with complex morphological differentiation
During the investigation of actinobacterial diversity from hypersaline environments, an unexpected hyper-halophilic archaeon with a distinct growth pattern was discovered serendipitously from the Qijiaojing Salt Lake in the Xin... | Several groups of bacteria have complex life cycles involving cellular differentiation and multicellular structures. For example, actinobacteria of the genus Streptomyces form multicellular vegetative hyphae, aerial hyphae, and spores. However, similar life cycles have not yet been described for archaea. Here, we sho... | Supplementary information
| Supplementary information
The online version contains supplementary material available at 10.1038/s41467-023-37389-w.
Acknowledgements
We are indebted to Dr. Wen-Jun Li for support in the early stage of this project. The authors thank Dr. Xiu-Zhu Dong, Yong-Jun Liu, Lei Song and Man Cai for strains, reagents, and discu... | CC BY | no | 2024-01-16 23:34:59 | Nat Commun. 2023 Apr 1; 14:1827 | oa_package/58/4d/PMC10067837.tar.gz | |
PMC10091483 | 37039501 | Background
Description of the condition
The ductus arteriosus is a blood vessel that connects the main pulmonary artery to the proximal descending aorta. It plays an important role in maintaining foetal circulation by allowing a significant proportion of right ventricular output to bypass the pulmonary circulation ( Go... | Methods
Criteria for considering reviews for inclusion
Types of studies
In this overview of systematic reviews, we included only published Cochrane Systematic Reviews on the management of patent ductus arteriosus (PDA) in a preterm infant.
Types of participants
For objective 1 (prevention of PDA)
Preterm (gestational a... | Results
Our search (October 2022) identified 17 relevant Cochrane Reviews and two Cochrane Review protocols under review ( Figure 1 ). Out of these 19 reviews, we included 16 reviews in this overview. The review by Mitra 2022 was identified to be a Bayesian network meta‐analysis of data obtained from studies, most of... | Discussion
Summary of main results
We included 16 Cochrane Reviews (138 randomised controlled trials (RCTs), 11,856 preterm infants) on the management of patent ductus arteriosis (PDA) in preterm infants. The number of trials included in each review ranged from none to 39. Six reviews (N = 4976) reported on prophylacti... | Authors' conclusions
| Abstract
Background
Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Several non‐pharmacological, pharmacological, and surgical approaches have been explored to prevent or treat a PDA.
Objectives
To summarise Cochrane Neonatal evidence on interventions (pharmacol... | Objectives
To summarise Cochrane Neonatal evidence on:
interventions (pharmacological or surgical) for prevention of patent ductus arteriosus and related complications in preterm infants; and interventions (pharmacological or surgical) for management of patent ductus arteriosus in preterm infants, including: interventi... | Acknowledgements
We would like to thank Ms Abbey MacLellan , MD candidate, Dalhousie University, Halifax, Canada, and Mr Austin Cameron, Neonatal Research Coordinator, IWK Health, Halifax, Canada , for their help with data extraction.
The methods section of this review is based on a standard template used by Cochrane... | CC BY | no | 2024-01-16 23:35:05 | Cochrane Database Syst Rev. 2023 Apr 11; 2023(4):CD013588 | oa_package/65/67/PMC10091483.tar.gz |
PMC10185832 | 37205182 | Introduction
Lipids, one of four broad classes of macromolecules in living organisms, are hydrophobic organic molecules with a diverse variety of important functions in many cellular processes. Some notable functions related to cancer progression include the involvement of lipids in cellular signaling, energy storage, ... | Edited by: Roger Chammas, University of São Paulo, Brazil
Reviewed by: Avigdor Leftin, GE Healthcare, United States
Ana Patricia Cardoso, University of Porto, Portugal
Alyssa Joy Cozzo, University of North Carolina at Chapel Hill, United States
Lipids are a diverse class of biomolecules that have been implicated in ca... | Lipids and lipid oxidation in immune cells
T cells
T lymphocytes are an indispensable component of the adaptive immune system, as they mount cell-mediated responses to fight pathogens as well as tumor cells. T cells are of three broad types: helper T cells (CD4 + ), cytotoxic T cells (CD8 + ), and suppressor T cells (e... | Acknowledgments
The authors thank Christine F. Wogan, MS, ELS, for providing editing support during the preparation of this manuscript. Figures created with BioRender.com.
Conflict of interest
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could b... | CC BY | no | 2024-01-16 23:36:46 | Front Oncol. 2023 May 2; 13:1187279 | oa_package/78/35/PMC10185832.tar.gz | ||||
PMC10318005 | 37258583 | Introduction
The prevalence of diabetes mellitus (DM) is increasing rapidly worldwide. The number of people with DM worldwide is over 425 million and is expected to reach 700 million by 2045 1 . DM is strongly associated with cardiovascular disease (CVD). Among CV complications, heart failure (HF) increases significant... | Materials and methods
Zebrafish maintenance
Adult zebrafish ( Danio rerio ) were maintained at 28 °C on a 14:10 h light-dark cycle in an automatic circulating tank system and fed Artemia 2 times a day. Embryos were raised at 28 °C in egg water (60 μg/ml ocean salts, Sigma‒Aldrich, St. Louis, MO, USA), and experiments... | Results
Treatment with empagliflozin or sotagliflozin improved survival and locomotion in DM-HFrEF zebrafish
We first investigated the viability of DM-HFrEF zebrafish after treatment with various concentrations of EMPA or SOTA to determine whether these drugs increased the survival rate. The DM-HFrEF model had signific... | Discussion
This study provides new insights into the protective effects of EMPA, a highly selective SGLT2 inhibitor, and SOTA, a dual SGLT1/2 inhibitor, against DM-HFrEF. First, at the same molarity, EMPA and SOTA exerted similar contraction regularity-improving, locomotion-preserving, and survival-promoting effects; E... | The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin (EMPA) and dual SGLT1/2 inhibitor sotagliflozin (SOTA) are emerging as heart failure (HF) medications in addition to having glucose-lowering effects in diabetes mellitus (DM). However, the precise mechanism underlying this cardioprotective effect has no... | Supplementary information
| Supplementary information
The online version contains supplementary material available at 10.1038/s12276-023-01002-3.
Acknowledgements
The Zebrafish Center for Disease Modeling (ZCDM), Korea, provided the transgenic ( myl7:EGFP ) zebrafish strain. This work was supported by a grant from the New Faculty Startup Fund fro... | CC BY | no | 2024-01-16 23:35:00 | Exp Mol Med. 2023 Jun 1; 55(6):1174-1181 | oa_package/f3/69/PMC10318005.tar.gz | |
PMC10364560 | 37477590 | Background
Young people in Malawi face multiple health challenges, most of them related to their sexual and reproductive health and rights (SRHR). Malawi faces one of the highest HIV prevalence rates, estimated at 8.9% for the general population, with one in three new HIV infections occurring among adolescents and yout... | Methods and analysis
Study design
This formative study was carried out between June 2020 and April 2022 to inform the design for the delivery of CSE to out-of-school YPLHIV and YPWD. We used a desk review and a mapping exercise of programmes delivering CSE in Malawi to understand the context of YPLHIV and YPWD. The des... | Results
The situation of YPWD in Malawi
In Malawi, it is estimated that 10.4% of the population over 5 years old have at least one type of disability. 11 The most common types of impairment are limited sight, mobility and hearing. Evidence shows that rural and poor residents are more likely to have impairments leading... | Discussion
Our study set out to provide a situation analysis of YPLHIV and YPWD, map CSE programmes and explore how CSE delivery channels reach the target populations. CSE in Malawi is delivered through three main channels: in school through the life skills education curriculum; through traditional or religious initiat... | Conclusions
The study describes the challenges that YPLHIV and YPWD face: stigma, discrimination and isolation, as well as being vulnerable to abuse, all of which highlight their need for CSE. The study also highlights the different programmes that are being implemented to provide CSE to young people and the various mo... | Abstract
This formative study was undertaken between June 2020 and April 2021 to provide evidence to inform the design and delivery of comprehensive sexuality education (CSE) in Malawi for young people living with HIV (YPLHIV) and young people with disabilities (YPWD). The study included a desk review of the situation ... | Disclosure statement
No potential conflict of interest was reported by the author(s). | CC BY | no | 2024-01-16 23:36:47 | Sex Reprod Health Matters.; 31(2):2226345 | oa_package/26/43/PMC10364560.tar.gz | |
PMC10378336 | 37508647 | Pediatric endocrinology will undergo an extraordinary revolution this century. It has also become increasingly apparent that experiences and exposure throughout fetal life and childhood can have important effects on many diseases that develop much later during adult life. Alterations to the endocrine system mediate man... | Conflicts of Interest
The author declares no conflict of interest. | CC BY | no | 2024-01-16 23:35:05 | Children (Basel). 2023 Jun 30; 10(7):1151 | oa_package/0b/3d/PMC10378336.tar.gz | ||||||
PMC10427713 | 37582804 | Introduction
Ultra-thin ferromagnetic insulators (FMI) with perpendicular magnetic anisotropy (PMA) and low damping provide new opportunities for inducing emergent magnetic and topological phenomena at interfaces and efficiently sourcing, controlling and detecting pure spin currents, thereby changing the landscape of s... | Methods
Sample fabrication
Films of LAFO were synthesized via pulsed laser deposition (PLD) with a KrF laser ( λ = 248 nm) on (001)-oriented single crystal MGO substrates. The MGO substrates of size 5 × 5 × 0.5 mm 3 were prepared from high quality bulk single crystals grown by the Czochralski method at the Leibniz-In... | Results
Structural characterization
LAFO films were grown by pulsed laser deposition on (001)-oriented MgGa 2 O 4 (MGO) substrates (see Methods). Structural characterization of LAFO films indicates excellent epitaxy and crystallinity. Figure 1 a shows an atomic resolution high-angle annular dark-field scanning transm... | Discussion
A recent study on a different Pt/FMI spinel system using Mg(Al,Fe) 2 O 4 (MAFO) found an above average damping-like SOT efficiency of θ DL ≈ 0.15 40 . However, the damping-like SOT efficiency in Pt/MAFO is still lower than that observed in Pt/LAFO, indicating that Pt epitaxy alone is insufficient to expla... | Ultra-thin films of low damping ferromagnetic insulators with perpendicular magnetic anisotropy have been identified as critical to advancing spin-based electronics by significantly reducing the threshold for current-induced magnetization switching while enabling new types of hybrid structures or devices. Here, we have... | Supplementary information
| Supplementary information
The online version contains supplementary material available at 10.1038/s41467-023-40733-9.
Acknowledgements
We thank Satoru Emori for helpful discussions and Jutta Schwarzkopf for a critical reading of the paper. This work was supported by the U.S. Department of Energy, Director, Office of Sc... | CC BY | no | 2024-01-16 23:35:00 | Nat Commun. 2023 Aug 15; 14:4918 | oa_package/22/91/PMC10427713.tar.gz | |
PMC10474874 | 37662555 | Introduction
Mental illnesses are among the most debilitating medical conditions due to their prevalence ( Lewinsohn et al., 1998 ) and the vast toll they take on individuals ( Monkul et al., 2007 ) and society ( Leon et al., 1998 ). Yet the brain and the malfunctioning neural dynamics responsible for mental illness re... | Conclusions
We have developed an approach for finding a single stimulatable brain network that correlates with a condition or behaviour. Our strategy is based on supervised autoencoders, which are more conducive to finding a single network predictive of an outcome of interest than joint factor models. We are able to fi... | Conflict of interest All authors declare that they have no conflicts of interest.
Abstract
Targeted brain stimulation has the potential to treat mental illnesses. We develop an approach to help design protocols by identifying relevant multi-region electrical dynamics. Our approach models these dynamics as a superpos... | Data and model
In this section, we introduce the electrophysiological data analysed in this paper and the scientific motivation for a latent variable model. We highlight the need for a single latent variable to predict the experimental outcomes; here, these outcomes relate to an animal model of stress and a genotype as... | Acknowledgments
We would like to thank Michael Hunter Klein and Neil Gallagher for providing helpful feedback and testing the code for the NMF and PCA models.
Funding
Research reported in this publication was supported by the National Institute of Biomedical Imaging and Bioengineering and the National Institute of Ment... | CC BY | no | 2024-01-16 23:36:47 | J R Stat Soc Ser C Appl Stat. 2023 May 22; 72(4):912-936 | oa_package/f8/5b/PMC10474874.tar.gz | |||
PMC10477232 | 37666925 | Introduction
In men, physical and psychological stresses caused by different factors, including resistance and endurance exercises, increase the secretion of cortisol and testosterone, which in turn affect the hypothalamic pituitary axis 1 . These hormones have their own circadian rhythms: the circulating cortisol conc... | Methods
Ethical approval and consent to participate
Written informed consent was obtained from all participants. This study was approved by Gunma University ethics review board for medical research involving human subjects, and registered with University Hospital Medical Information Network Clinical Trials Registry (UM... | Results
Correlations between the salivary and serum testosterone and cortisol concentrations and the T/C ratio
Table 1 presents the characteristics of the participants. Table 2 shows the Spearman’s correlation analyses of the salivary and serum testosterone and cortisol concentrations obtained from ECLIA. The saliv... | Discussion
In this study, we investigated whether the automated measurement of the salivary testosterone and cortisol concentrations and the salivary T/C ratio can be used to assess the stress induced by exercise at different intensities among male long-distance runners accurately and effectively while considering circ... | In this study, our aim was to validate whether the automated measurement of salivary testosterone and cortisol concentrations and the testosterone-to-cortisol (T/C) ratio, considering their individual circadian rhythms can be used to assess the stress response of male athletes to different exercise intensities accurate... | Acknowledgements
We are grateful to Hidekazu Shimazu, Koji Hase, Mai Murata, Larasati Martha, and Mayumi Nishiyama for providing technical assistance and helpful discussion. This work was supported by the Ministry of Education, Culture, Sports, Science, and Technology of Japan [grant numbers 18K07406 and 23K10581 (K. T... | CC BY | no | 2024-01-16 23:35:00 | Sci Rep. 2023 Sep 4; 13:14532 | oa_package/9d/31/PMC10477232.tar.gz | ||
PMC10477254 | 37666894 | Introduction
Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of hepatic disorders, defined by the presence of steatosis in ≥ 5% of hepatocytes in the absence of excessive alcohol consumption or other known liver diseases 1 , 2 . NAFLD represents a spectrum of chronic liver diseases, starting ... | Methods and materials
Subjects and study design
From 2019 to 2021, 452 Fibroscan-proven NAFLD patients were enrolled in the present study and their clinical data were collected prospectively. The inclusion criteria for this cross-sectional study were as follows: (1) adults 18–65-year-old; (2) Fibroscan findings confirm... | Results
Clinical and biochemical characteristics according to BMI classification
The clinical and biochemical characteristics of participants stratified by BMI are listed in Table 1 . Among the 452 NAFLD patients (mean age 45 ± 11.88 years; women 47%), 82 were classified as normal weight, 121 as overweight and 249 as ... | Discussion
This cross-sectional study was performed to elucidate the differences in metabolic features of obese and non-obese NAFLD patients. Our results disclosed that both obese and non-obese NAFLD patients shared several clinical and laboratory characteristics, although MetS was more prevalent among obese participan... | Conclusion
We performed this cross-sectional study to elucidate the metabolic differences of obese and non-obese NAFLD patients. Based on the results of the present study, it can be concluded non-obese NAFLD patients discloses a similar degree of NAFLD histological severity and metabolic abnormalities compared to their... | Nonalcoholic fatty liver disease (NAFLD) is closely associated with cardiometabolic abnormalities. This association could be partly influenced by weight, but not entirely. This study aimed to compare the cardiometabolic risk factors between obese and non-obese NAFLD patients, and explored the relationship between adipo... | Author contributions
Conceptualization, Z.Y. & D.F.; Formal analysis, Z.Y.; Methodology, D.F. & A.H.; Writing—review & editing, Z.Y. and A.H. All authors read and approved.
Data availability
All data generated or analyzed during this study are included in this published article.
Competing interests
The authors declare ... | CC BY | no | 2024-01-16 23:35:00 | Sci Rep. 2023 Sep 4; 13:14531 | oa_package/65/4f/PMC10477254.tar.gz | |
PMC10491610 | 37684257 | Introduction
Patients with schizophrenia (SCZ) are usually associated with multiple domains of cognitive deficits, which are the core symptoms of SCZ 1 . There is clear evidence that cognitive impairments are present at different stages of SCZ, from prodrome to multi-episode stage, and more severe in chronic patients 2... | Methods
Patients
The study protocol was approved by the Institutional Review Board of Hebei Rongjun Hospital. Each patient provided written, informed consent to participate in this clinical trial.
One hundred and thirty-one SCZ inpatients were recruited in the hospital. Recruited patients should meet the following recr... | Results
Baseline demographic and neurocognitive functioning
RM-ANCOVA analysis revealed a significant interaction effect of time and stimulation group on immediate memory ( p < 0.05). Of the initial 131 recruited patients, the patients without COX-2 rs5275 genotype data were removed, and a total of 76 patients were in... | Discussion
We found that rs5275 polymorphism in the COX-2 gene was correlated with cognitive improvements following HF-rTMS treatment for 4 weeks in SCZ, after adjusting for the confounding factors. In addition, Rs5275 C allele carriers showed greater improvements in cognitive functions.
We found that SCZ patients with... | High frequency (HF)-rTMS has been shown to improve cognitive functions in patients with schizophrenia (SCZ). This study aimed to investigate whether COX-2 rs5275 variants were associated with cognitive improvements following rTMS treatment in patients with SCZ. Forty-eight hospitalized patients with SCZ were assigned t... | Acknowledgements
This study was supported by grants from the Science and Technology Program of Guangzhou (202206060005, 202201010093, SL2022A03J01489), Guangdong Basic and Applied Basic Research Foundation Outstanding Youth Project (2021B1515020064), Medical Science and Technology Research Foundation of Guangdong (A202... | CC BY | no | 2024-01-16 23:35:00 | Schizophrenia (Heidelb). 2023 Sep 8; 9(1):56 | oa_package/22/9e/PMC10491610.tar.gz | ||
PMC10500770 | 37705082 | Introduction
Grapevine Pinot gris virus (GPGV) is a species in the genus Trichovirus , in the family Betaflexiviridae . The GPGV genome is a linear, positive-sense, single-stranded RNA of approximately 7259 nucleotides (nt), excluding the poly (A) tail at the 3′ end [ 1 ]. It has a typical Trichovirus genome with ... | Methods
Sampling of the grapevine samples
During 2017–2021, Agriculture Victoria’s Crop Health Services (CHS) plant diagnostic laboratory received a total of 2171 samples for GPGV testing from different grape-growing regions of Australia, including 1531 samples from South-eastern Australia in the states of VIC, NSW, an... | Results
RT-PCR results
GPGV was detected in 473/2171 (21.8%) of the samples tested, including 23/133 samples from NSW, 26/706 samples from SA and 424/1176 samples from VIC. GPGV was not detected in 23 samples from Tasmania or 133 samples from Western Australia. The samples from VIC and NSW were analyzed by region (Fig.... | Discussion
This study provides a snapshot of the prevalence of GPGV in wine, table grape and rootstock varieties in Australia between the years 2017 and 2021. GPGV was detected in grapevines with GLMD-like symptoms as well as in grapevines with other symptoms such as delayed budburst, increased berry acidity, stunted s... | Conclusions
In this study, a combination of the documented history of importation of some infected grapevine varieties into Australia, together with data obtained from surveillance and phylogenetic, MJ network, sequence identity and recombination analyses contributes to an improved understanding of GPGV introduction an... | Grapevine Pinot gris virus (GPGV; genus Trichovirus in the family Betaflexiviridae ) was detected in Australia in 2016, but its impact on the production of nursery material and fruit in Australia is still currently unknown. This study investigated the prevalence and genetic diversity of GPGV in Australia. GPGV was d... | Supplementary Information
| Acknowledgements
We thank the growers and Crop Health Services (CHS) for supplying samples and colleagues, including Dr. Ian Dry and Libby Tassie (Tassie Viticulture Consulting), who assisted in sending samples for the present study. Thanks to Chris Bottcher (Agriculture Victoria Research) and Ruvinda N Aluthgama Kanka... | CC BY | no | 2024-01-16 23:35:05 | Virol J. 2023 Sep 13; 20:211 | oa_package/2e/c5/PMC10500770.tar.gz |
PMC10539721 | 37781318 | Introduction
Other Effective area-based Conservation Measures (OECMs) were introduced in 2010 by the Convention on Biological Diversity (CBD) as areas that achieve long-term and effective in-situ biodiversity conservation outside of protected areas ( CBD, 2010 ). Consequently, OECMs represent a novel conservation ap... | Methodology
The proposed ScR will follow the methodology outlined by Arksey and O'Malley (2005) , as further developed by Levac et al. (2010) and the Joanna Briggs Institute (JBI) methodology ( Peters et al., 2020 ). The ScR encompass the following nine stages, as recommended by the JBI methodology: 1. Defining... | No competing interests were disclosed.
This scoping review (ScR) protocol aims to establish the methodological approach for identifying and mapping the evidence regarding the actual contribution of Other Effective area-based Conservation Measures (OECMs) to spatial conservation targets. Emphasis will be placed on exami... | Review question
The overall research question that will guide the ScR is: What is the current knowledge regarding the contribution of OECMs to biodiversity conservation targets? The ScR will aim to address the following sub-questions:
What is the geographical distribution of studies that have assessed potential OECMs a... | Data availability
Underlying data
No data is associated with this article.
Extended data
Open Science Framework (OSF): Assessing the potential of other effective area-based conservation measures for contributing to conservation targets: a global scoping review protocol – PRISMA-ScR Checklist and Data Extraction Tool. ... | CC BY | no | 2024-01-16 23:35:05 | Open Res Eur. 2024 Jan 10; 3:118 | oa_package/86/63/PMC10539721.tar.gz | |||
PMC10587034 | 37733148 | Introduction
Diabetes mellitus is a chronic illness often accompanied by peripheral vascular disease affecting many individuals worldwide. By 2040, it is projected that 642 million people on the planet will have diabetes, about 10% of the world’s population [ 1 •]. The risk of patients with diabetes developing diabetic... | Conclusions
While there continues to be improvement in the management of diabetic foot, there is a dire need to address the racial and ethnic disparities that exist. Future efforts must be made to improve the diversity in patient participation when investigating novel approaches to treat diabetic foot ulcers and other ... | Purpose of Review
Diabetes mellitus is a chronic medical condition affecting many individuals worldwide and leads to billions of dollars spent within the healthcare system for its treatment and complications. Complications from diabetes include diabetic foot conditions that can have a devasting impact on quality of lif... | Race, Ethnicity, and Disparity
In discussing racial and ethnic disparities in managing diabetic feet, the concepts of race and health disparities must be explored. Race is a social construct and does not have a scientific foundation [ 6 ]. It groups individuals based on physical characteristics like skin color through ... | Declarations
Conflict of Interest
Elizabeth O. Clayton, Confidence Njoku-Austin, Devon M. Scott, Jarrett D. Cain, and MaCalus V. Hogan declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of ... | CC BY | no | 2024-01-16 23:34:58 | Curr Rev Musculoskelet Med. 2023 Sep 21; 16(11):550-556 | oa_package/dc/77/PMC10587034.tar.gz | |||
PMC10626779 | 37932771 | Background
The importance of gene-environment interactions in lung disease is well recognized [ 1 ], and given that the lung is a major port of entry for xenobiotics and pathogens into the systemic circulation, its barrier function at the alveolar septa is of critical importance. As with other organs, the lung ages wit... | Methods
Depicted in Fig. 2 is the workflow and data analysis for the mouse and human pulmonary genomes and single cell RNAseq.
Mouse lung genomic data
We retrieved data from the Gene Expression Omnibus (GEO) database ( https://www.ncbi.nlm.nih.gov/geo/ ). A total of 89 individual data sets from 15 studies (see supple... | Results
Figure 2 depicts the workflow of the data analysis. The process is divided into data retrieval, normalization, statistical testing for DEGs, gene enrichment analysis and single cell RNAseq. Meanwhile, we divided the mouse and human lung genomic data into a test and validation set and performed independent com... | Discussion
This study aimed to investigate age-related changes in the pulmonary genomes of mice and humans, and the gene set enrichment analysis of DEGs informed on various biological pathways which changed over time. We focused on four major biological processes, namely extracellular matrix remodeling, cellular senesc... | Background
The aging lung is a complex process and influenced by various stressors, especially airborne pathogens and xenobiotics. Additionally, a lifetime exposure to antigens results in structural and functional changes of the lung; yet an understanding of the cell type specific responses remains elusive. To gain ins... | Supplementary Information
| Abbreviations
ATP binding cassette subfamily A member 3
ADAM metallopeptidase with thrombospondin type 1 motif 1
Adipocyte enhancer-binding protein 1
5'-Aminolevulinate synthase 2)
Activated leukocyte cell-adhesion molecule
Annexin
Type 1 pneumocytes
Type 2 pneumocytes
Benjamini-Hochberg
Coiled-coil domain containing 8... | CC BY | no | 2024-01-16 23:36:45 | Immun Ageing. 2023 Nov 6; 20:58 | oa_package/48/6a/PMC10626779.tar.gz | |
PMC10632145 | 37914938 | Methods
Worm maintenance
C. elegans were stored in the dark, and only minimal light was used when transferring worms or mounting worms for experiments. Strains generated in this study (Extended Data Fig. 1a ) have been deposited in the Caenorhabditis Genetics Center (CGC), University of Minnesota, for public distribu... | Discussion
Signal propagation in C. elegans measured by neural activation differs from model predictions based on anatomy, in part because anatomy does not account for wireless connections such as the extrasynaptic release of neuropeptides 49 .
By directly evoking calcium activity on a timescale of seconds, extrasyna... | Establishing how neural function emerges from network properties is a fundamental problem in neuroscience 1 . Here, to better understand the relationship between the structure and the function of a nervous system, we systematically measure signal propagation in 23,433 pairs of neurons across the head of the nematode C... | Main
Brain connectivity mapping is motivated by the claim that “nothing defines the function of a neuron more faithfully than the nature of its inputs and outputs” 2 . This approach to revealing neural function drives large-scale efforts to generate connectomes—anatomical maps of the synaptic contacts of the brain—in a... | Extended data figures and tables
Extended data
is available for this paper at 10.1038/s41586-023-06683-4.
Supplementary information
The online version contains supplementary material available at 10.1038/s41586-023-06683-4.
Acknowledgements
We thank J. Bien, A. Falkner, F. Graf L... | CC BY | no | 2024-01-16 23:34:57 | Nature. 2023 Nov 1; 623(7986):406-414 | oa_package/70/2d/PMC10632145.tar.gz | |||
PMC10655799 | 38024459 | Introduction
Social, economic, environmental and structural disparities contribute to health inequities between and within communities. 1 , 2 Those who are socially disadvantaged have less access to health services, suffer from more illnesses and die at a younger age. 3 Due to unjust social structures and institu... | Methods
Study design
This was a qualitative study that used focus groups and one-on-one interviews. This dual approach was used due to availability of participants during a substantial wave of COVID-19 in our jurisdiction. Interviews and focus group sessions took place virtually on Zoom for Healthcare, which has additi... | Results
Two focus groups, each with 5 participants and 6 one-on-one interviews ( n = 16), were conducted between May and June 2021. The majority of participants were female and between the ages of 18 and 35, and most had resided in Nova Scotia since birth. All participants had completed formal education at the college... | Discussion
Three major themes were identified in this research: 1) Difficulties navigating a pharmacy as a Black person, 2) Lack of inclusivity and cultural competence in the pharmacy and 3) Transactional relationships with pharmacists. These 3 themes refer to the inadequate care provided by pharmacists to Black patien... | Conclusion
This research describes the lived experiences of Black patients with community pharmacists. It also highlights the fact that in the current pharmacy setting, many pharmacists do not provide culturally safe care to Black patients. Unless effort is made to understand systemic racism, perceived discrimination a... | Although previous research has shown that systemic racism and discrimination is a significant contributor to the poorer health outcomes experienced by Black patients, there is little research within North America evaluating the impact on Black patients accessing pharmacy services specifically. We were interested in pur... | Transactional relationships with pharmacists
This theme included the categories Lack of relationships with pharmacists, Lack of privacy in the pharmacy and Loyalty.
Lack of relationships with pharmacists
The transactional relationship between participants and their pharmacist was a major discussion item. Most participa... | We thank the participants who volunteered to take part in this research and all organizations and individuals who advertised this research. | CC BY | no | 2024-01-16 23:36:46 | Can Pharm J (Ott). 2023 Oct 12; 156(6):316-323 | oa_package/9e/76/PMC10655799.tar.gz |
PMC10686531 | 38034939 | Introduction
Modern dual-chamber pacemakers (DCPPM) typically operate in atrial-based timing when programmed DDD, where the atrial–atrial (A–A) interval is fixed and the ventriculo-atrial interval (VAI, also known as the atrial escape interval) varies. 1 However, when certain devices are set to DDI or automatic mode s... | Discussion
Jafri et al. 2 reported a unique case of rapid atrial pacing at 150 b.p.m. in an Abbott device set DDI with lower rate of 90 b.p.m., which started with a series of PACs that fell just outside PVAB of the preceding AP event; and with prolonged AV time, led to pacing ‘crossover’ with delayed VS event occurri... | Conclusion
With ventricular-based pacing modes, atrial pacing at rates surpassing the lower set rate is a known phenomenon when intrinsic AV conduction is shorter than programmed paced AV delay. 1 While Jafri et al. previously reported a case of elevated atrial pacing in the setting of prolonged AV conduction, we re... | Conflict of interest: None declared.
Abstract
Background
While ventricular-based timing modes are known to cause elevated atrial pacing above the lower rate when intrinsic atrioventricular (AV) conduction is shorter than programmed AV delay, there is one case report in 2015 by Jafri et al. where rapid atrial pacin... | Summary figure
Case report
A 74-year-old man with sick sinus syndrome and a St. Jude Abbott DCPPM, placed 8 months prior, presented for routine device check. Presenting rhythm was atrial paced (AP) ventricular sensed (VS) at 70 b.p.m. Atrial and ventricular impedance, sensing, and thresholds were appropriate and consis... | Lead author biography
After completing medical school at Dartmouth in 2016, I completed internal medicine residency at Vanderbilt in 2019 and general cardiology residency at Wake Forest in 2022. I am currently a rising second year electrocardiology fellow at Wake Forest University School of Medicine.
Consent: Info... | CC BY | no | 2024-01-16 23:35:07 | Eur Heart J Case Rep. 2023 Nov 21; 7(11):ytad586 | oa_package/4e/64/PMC10686531.tar.gz | ||
PMC10694898 | 38044421 | Introduction
As one of the most aggressive and deadly malignancies, pancreatic ductal adenocarcinoma (PDAC) has become the fourth leading cause of cancer-related death and is expected to advance to the second leading cause of cancer-related death within decades [ 1 , 2 ]. Despite the advances in the understanding of t... | Materials and methods
Clinical tissue samples
A total of 95 pairs of PDAC tissues and adjacent tumor tissues were collected from Xuzhou Medical University Affiliated Hospital. Among them, 50 patients had not received radiotherapy or chemotherapy while 45 patients received GEM neoadjuvant therapy. This study was approve... | Results
hsa_circ_0007919 is upregulated in GEM-resistant PDAC and predicts poor prognosis
We performed next-generation sequencing to identify circRNAs that contribute to GEM resistance in three GEM-resistant PDAC tissues and three GEM-sensitive PDAC tissues. A total of 62 circRNAs were differentially expressed (FC<-1 o... | Discussion
PDAC is one of the most aggressive and deadly malignancies and is expected to become the second leading cause of cancer-related death within a decade [ 2 ]. Although molecular mechanistic research and treatment methods for PDAC have progressed in recent decades, the 5-year survival rate of PDAC is still the ... | Background
Circular RNAs (circRNAs) play important roles in the occurrence and development of cancer and chemoresistance. DNA damage repair contributes to the proliferation of cancer cells and resistance to chemotherapy-induced apoptosis. However, the role of circRNAs in the regulation of DNA damage repair needs clarif... | Electronic supplementary material
Below is the link to the electronic supplementary material.
| Abbreviations
Circular RNA
Gemcitabine
Pancreatic ductal adenocarcinoma
Overall survival
Disease-free survival
DNA damage response
5-fluorouracil
Breast cancer
Fetal Bovine Serum
Immunofluorescence
Bovine Serum Albumin
Immunohistochemical
Gene set enrichment analysis
Fluorescence in situ hybridization
Chromatin Isolati... | CC BY | no | 2024-01-16 23:36:45 | Mol Cancer. 2023 Dec 4; 22:195 | oa_package/60/59/PMC10694898.tar.gz | |
PMC10696062 | 38049453 | Introduction
As of September 23rd, 2023, over 70 million SARS-CoV-2 diagnostic tests have been performed in the United States 1 . Deploying individual testing programs at this scale is extraordinarily expensive and resource-intensive, and has become increasingly unsustainable in most jurisdictions. New strategies are n... | Methods
Ethics statement
Our study does not evaluate the effectiveness of air samplers for diagnosing individuals for COVID-19 or other illnesses, nor does it collect samples directly from individuals. Therefore, it does not constitute human subjects research.
Air sample collection and processing
AerosolSense instrumen... | Results
Study design
From July 2021 to December 2022, we deployed active air samplers in several community settings in the Upper Midwestern states of Wisconsin and Minnesota for routine pathogen monitoring. Thermo Fisher AerosolSense Samplers were used to collect air samples from high-traffic areas in several different... | Discussion
In this study, we used air samples and metagenomic sequencing to detect human RNA viruses in a variety of congregate settings. Specifically, our results show that active air sampling, SISPA library preparation, long-read Oxford Nanopore sequencing, and metagenomic bioinformatics can be used to detect both co... | Innovative methods for evaluating virus risk and spread, independent of test-seeking behavior, are needed to improve routine public health surveillance, outbreak response, and pandemic preparedness. Throughout the COVID-19 pandemic, environmental surveillance strategies, including wastewater and air sampling, have been... | Supplementary Information
| Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-48352-6.
Acknowledgements
This work was made possible by financial support through the National Institutes of Health grant (AAL4371). M.D.R. is supported by the National Institute of Allergy and Infectious Disea... | CC BY | no | 2024-01-16 23:35:01 | Sci Rep. 2023 Dec 4; 13:21398 | oa_package/f3/2d/PMC10696062.tar.gz | |
PMC10703939 | 38062134 | Introduction
Chronic kidney disease (CKD) is an age-related, dangerous, and progressive pathological condition that affects the reduction in kidney function 1 – 3 . It occurs when the kidneys are damaged and unable to effectively filter waste products from the blood. Over time, the condition may progress to end-stage r... | Materials and methods
Dataset collection and subject information
The present investigation employed a dataset obtained from 7 , which included health records of 544 patients collected from Tawam Hospital located in Al-Ain city, Abu Dhabi, United Arab Emirates (UAE) between January 1, 2008, and December 31, 2008. Figure... | Results and discussion
In this study, a total of 467 participants with eGFR greater than or equal to 60 mL/min/1.73 was considered during every 3-month follow-up period from baseline visit to June, 30 2017. After a period of follow-up, a total of 54 new cases (male: 34; female: 20) of CKD stages 3–5 were identified. ... | Results and discussion
In this study, a total of 467 participants with eGFR greater than or equal to 60 mL/min/1.73 was considered during every 3-month follow-up period from baseline visit to June, 30 2017. After a period of follow-up, a total of 54 new cases (male: 34; female: 20) of CKD stages 3–5 were identified. ... | Conclusion
This study presents a novel machine learning-driven nomogram for predicting CKD stages 3–5. The proposed approach offers an accurate and personalized risk assessment tool with the potential to improve early detection and preventive strategies. The integration of advanced machine learning algorithms and compr... | Chronic kidney disease (CKD) remains one of the most prominent global causes of mortality worldwide, necessitating accurate prediction models for early detection and prevention. In recent years, machine learning (ML) techniques have exhibited promising outcomes across various medical applications. This study introduces... | Supplementary Information
| Supplementary Information
The online version contains supplementary material available at 10.1038/s41598-023-48815-w.
Acknowledgements
The authors would like to acknowledge Saif Al-Shamsi from UAE University provided additional information about the dataset.
Author contributions
Research idea and study design: S.K.G, A... | CC BY | no | 2024-01-16 23:35:02 | Sci Rep. 2023 Dec 7; 13:21613 | oa_package/7b/50/PMC10703939.tar.gz |
PMC10704617 | 38062447 | Background
The national toll-free phone number for emergency medical assistance in Norway is 113. The 16 emergency medical communication centers (EMCC) are organised as public services within the specialized hospital healthcare system and consist of a network of control rooms. When contacting 113, the call is received ... | Material and methods
Setting
The study was conducted in Bergen, the second-largest city in Norway. The Bergen EMCC covers an area of approximately 460,000 inhabitants and handles nearly 60,000 calls annually. To get in contact with past callers to the emergency medical number, a SMS message was sent to all mobile phone... | Results
A total of 4807 SMS messages were sent to recent callers, of which 1680 (35%) responded. The vast majority (88%, rating 5 or 6) were very satisfied with the 113-call (Fig. 1 ).
Based on the solid responses to the SMS survey, it was evident that people needed or wanted to provide feedback on their experiences w... | Discussion
The SMS survey results showed that most callers were very satisfied with their conversations with the 113 operators. In addition, based solely on responses to the SMS survey, it is clear that people want to provide feedback on their experiences with this part of the healthcare service.
The interviews reveale... | Conclusion
Most callers seemed to be satisfied with the services provided from the EMCC. This study’s findings conclude that the result of the conversations, the most applicable for a 113 call being ‘getting an ambulance or not’ is not the main criterion determining whether a caller is satisfied with the EMCC service. ... | Background
The Emergency Medical Communications Center (EMCC) is essential in emergencies and often represents the public’s first encounter with the healthcare system. Previous research has mainly focused on the dispatcher’s perspective. Therefore, there is a lack of insight into the callers’ perspectives, the attainme... | Limitations
The response rate was 35%, but relative to other SMS surveys, it is rather high. Other callers may have expressed opinions that were not reflected in the 31 interviews. The data from the satisfied callers proved to be surprisingly consistent, but due to available resources, it was impossible to contact all ... | Abbreviations
Emergency medical communication centre
Emergency medical dispatcher
Acknowledgements
We would like to express our deepest gratitude to Bergen EMCC for facilitating the identification of informants, The police Crisis and Hostage Negotiator Service (KGF), and the former dispatcher expert for significant kno... | CC BY | no | 2024-01-16 23:36:45 | Scand J Trauma Resusc Emerg Med. 2023 Dec 7; 31:94 | oa_package/82/ca/PMC10704617.tar.gz |
PMC10710729 | 38072936 | Introduction
Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has garnered considerable scientific interest due to its advantageous features such as high throughput, rapid analysis, and robustness against high salt concentrations. However, the effective utilization of MALDI-MS for the analysis o... | Materials & methods
Chemicals
All starting materials, unless mentioned otherwise, were obtained from commercial suppliers and used directly. Ammonium metavanadate (NH 4 VO 3 , 99.95%), hexadecylpyridinium bromide (CDPB, 96%), lauric acid (LA, analytical standard), myristic acid (MA, analytical standard), palmitoleic ac... | Results and discussion
Characterization and LDI-MS performance of IVONS:Sm
As depicted in Fig. 1 a, the preparation of IVONSs:Sm was carried out using the microemulsion-mediated solvothermal method. Transmission electron microscopy (TEM) analysis revealed that the as-synthesized IVONSs:Sm were of translucence and corr... | Results and discussion
Characterization and LDI-MS performance of IVONS:Sm
As depicted in Fig. 1 a, the preparation of IVONSs:Sm was carried out using the microemulsion-mediated solvothermal method. Transmission electron microscopy (TEM) analysis revealed that the as-synthesized IVONSs:Sm were of translucence and corr... | Conclusion
In brief, the initial synthesis of IVONSs:Sm nanosheets was accomplished, and subsequently, these nanosheets were incorporated into a negative-ion SALDI-MS system as an appropriate nano-matrix for the detection of LMW compounds. The IVONSs:Sm exhibited distinct advantages in the interpretation and reproducib... | This study presents the first-ever synthesis of samarium-doped indium vanadate nanosheets (IVONSs:Sm) via microemulsion-mediated solvothermal method. The nanosheets were subsequently utilized as a nano-matrix in laser desorption/ionization mass spectrometry (LDI-MS). It was discovered that the as-synthesized IVONSs:Sm ... | Electronic supplementary material
Below is the link to the electronic supplementary material.
| Author Contributions
J.W. conceived and designed the research. Y.Z., P.Z., Y.S., and H.L. performed experiments. J.W. and Y.Z. analyzed the data and wrote the manuscript. C.F., S.L., and P.A. provided suggestions and technical support. All authors reviewed and approved the manuscript.
Funding
This work is financially s... | CC BY | no | 2024-01-16 23:36:45 | J Nanobiotechnology. 2023 Dec 10; 21:475 | oa_package/74/a7/PMC10710729.tar.gz |
PMC10713752 | 38090265 | Introduction
Occipital neuralgia (ON) is a disabling headache disorder that involves lancinating pain in the distribution of the greater occipital nerves (GON), lesser occipital nerves (LON), and/or third occipital nerves (TON). The GON is most frequently involved and presents with pain that originates in the neck or s... | Methods
Institutional review board approval was obtained at the Massachusetts General Hospital in Boston, Massachusetts, with all patients providing informed consent. This prospective case series includes 15 consecutive patients who were managed and referred by a single-board certified, fellowship-trained headache spec... | Results
All 15 patients were included in the final analysis. Patients were predominantly female (80%). The average age of ON onset was 20 (±8) years. The time between the onset of ON headache and surgical decompression averaged at 19.9 (±13.6) years. Prior to nerve decompression surgery, median headache days per month ... | Discussion
This case series (1) described the clinical features of patients with refractory ON amenable to surgical treatment, (2) demonstrated that all patients benefited from occipital nerve decompression surgery to varying degrees, and (3) suggests that the collaborative selection criteria employed by neurologist an... | Conclusion
In conclusion, ON can cause disabling headaches and may be highly underdiagnosed.
The frequent coexistence of ON with other headache disorders likely contributes to its underdiagnosis. Therefore, screening for ON should be considered among other headache patients to improve ON diagnosis and treatment.
Furthe... | Edited by: Sabina Cevoli, IRCCS Institute of Neurological Sciences of Bologna (ISNB), Italy
Reviewed by: Raffaele Ornello, University of L'Aquila, Italy; Umberto Pensato, Humanitas Research Hospital, Italy
Background
The management of refractory occipital neuralgia (ON) can be challenging. Selection criteria for occipi... | Data availability statement
The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.
Ethics statement
The studies involving humans were approved by Massachusetts General Hospital, Boston. The studies were conducted in accordance with the local legislation... | Conflict of interest
PM was employed by Harvard Vanguard Medical Associates. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note
All claims expressed in this article are so... | CC BY | no | 2024-01-16 23:36:46 | Front Neurol. 2023 Nov 28; 14:1284101 | oa_package/50/b3/PMC10713752.tar.gz |
PMC10720392 | 38095857 | INTRODUCTION
Statistical mechanics describes the behavior of large numbers of physically identical systems [ 1 ]. Molecular dynamics (MD) is the computational application of statistical mechanics to molecular systems such as proteins, nucleic acids and lipid membranes [ 2–5 ]. The fundamental postulate of statistical m... | METHODS
Theoretical considerations for Gaussian versus non-Gaussian inputs to Boltzmann generators
One major theoretical limitation of traditional MD that carries over to BGs is difficulty in sampling disconnected local energy minima (i.e. metastable states). Fundamentally, the neural networks used in BGs are different... | RESULTS
We begin with an overview of the changes we made to the BG framework to address the five issues enumerated in the introduction. We first address the theoretical concerns (i) and (ii), then we discuss aspects of our implementations addressing practical concerns (iii)–(v), and finally we discuss the results and b... | DISCUSSION
In this work, we addressed five categories of fundamental deficiencies in the BG framework. In deficiencies (i) and (ii), we addressed sources of neural network bias by using continuous sampling of rotameric states. Since we have addressed these theoretical issues in the Results and Methods, we will focus on... | CONCLUSION
In conclusion, we present a comprehensive toolkit of differentiable methods for molecular science. Our contributions include ad hoc propagation of forces from an arbitrary force field for cases in which rewriting the force field is infeasible, differentiable and parallel rotamer sampling/protein fragment a... | Abstract
Molecular dynamics (MD) is the primary computational method by which modern structural biology explores macromolecule structure and function. Boltzmann generators have been proposed as an alternative to MD, by replacing the integration of molecular systems over time with the training of generative neural netwo... | Supplementary Material | FUNDING
National Institutes of Health (1R35 GM134864, 1RF1 AG071675, 1R01 AT012053); the National Science Foundation (2210963); the Passan Foundation.
AUTHOR CONTRIBUTIONS
C.M.S: conceptualization, data curation, formal analysis, investigation, methodology, software, validation, visualization, writing—original draft, w... | CC BY | no | 2024-01-16 23:49:21 | Brief Bioinform. 2023 Dec 12; 25(1):bbad456 | oa_package/5c/42/PMC10720392.tar.gz |
PMC10721706 | 38097904 | Introduction
Radiotherapy is an important treatment modality offered to approximately 50% of patients with cancer in either the curative or palliative setting [ 1 ]. Radiotherapy-induced nausea and vomiting (RINV) are common and often undertreated symptoms among patients receiving radiotherapy, and the risk varies with... | Literature review and methods
A medical librarian searched Ovid Medline, the Cochrane Central Register of Controlled Trials, Embase Classic, and Embase for references pertaining to RINV and C-RINV without restrictions on the type of study. An initial search was conducted on 8 July 2022 for references published from 1 M... | Results
The combined searches yielded 343 references (321 from the first search and 22 from the second); 114 duplicates were removed (113 + 1), leaving 229 total references for screening (208 + 21). Of the 229, 169 were excluded during screening leaving 60 references for which the full articles were reviewed. Of the 60... | Discussion
The systematic literature review provided the basis for an evidence-based update of the recommendations for RINV and C-RINV management. However, the evidence for management of, especially, low and minimal emetogenic radiotherapy remains very limited. For high and moderate emetic level, the evidence for the r... | Conclusion
In summary, none of the published data on RINV since 2015 has influenced the current update of the RINV antiemetics recommendations. However, in concomitant chemoradiotherapy, a single study was identified to impact the guidelines update for C-RINV [ 10 ], providing specific recommendations for prophylaxis d... | Purpose
Radiotherapy and chemoradiotherapy-induced nausea and vomiting (RINV and C-RINV) are common and distressing, and there is a need for guidance for clinicians to provide up to date optimal antiemetic prophylaxis and treatment. Through a comprehensive review of the literature concerning RINV and C-RINV, this manus... | Guideline recommendations: update 2023
Recommendation 1; High emetic risk: Patients receiving radiotherapy at a high emetic risk level should receive prophylaxis with a 5-HT 3 -RA plus dexamethasone. Level of Evidence: II; Grade of Recommendation: B (for the addition of dexamethasone: III/C). Recommendation 2; Modera... | Acknowledgements
The authors thank Risa Shorr, medical librarian, The Ottawa Hospital, Ottawa, Canada, for the extensive literature search support.
Funding
Open access funding provided by University Library of Southern Denmark Meeting and production costs have been covered by MASCC and ESMO from central funds.
Declarat... | CC BY | no | 2024-01-16 23:34:58 | Support Care Cancer. 2024 Dec 15; 32(1):26 | oa_package/e3/fd/PMC10721706.tar.gz |
PMC10722787 | 38098072 | Introduction
Annually, approximately 10% of patients receiving chronic anticoagulation therapy undergo diagnostic or therapeutic procedures that are associated with bleeding risks and require therapy interruption [ 1 ]. In particular, patients scheduled for major surgery have a high risk of bleeding. With the growing u... | Methods
Study design
The design and overall results of the Global EMIT-AF/VTE programme (NCT02950168, NCT02951039) are published [ 11 , 13 ]. EMIT-AF/VTE is a multicentre, prospective, observational programme conducted in Europe and Asia in accordance with the Declaration of Helsinki and with local Institutional Revie... | Results
Patient demographics and baseline characteristics
Overall, 1830 patients who underwent 2436 procedures were enrolled in the Global EMIT-AF/VTE programme, of which 250 (35.2%) patients underwent major surgeries and 461 (64.8%) patients underwent nonmajor surgeries; 788 surgeries were analysed, as some patients u... | Discussion
This subanalysis of the Global EMIT-AF/VTE programme assessed the periprocedural management of edoxaban and the occurrence of bleeding and thromboembolic events in edoxaban-treated patients who underwent major or nonmajor surgeries. To the authors’ knowledge, this analysis is the first to report treatment in... | Conclusion
In this subanalysis of the EMIT-AF/VTE programme, patients’ edoxaban regimens were interrupted more frequently and for longer periods of time for major vs. nonmajor surgeries. Periprocedural management of edoxaban driven by decisions from the attending clinicians was associated with low rates of all bleeding... | Background
Optimising periprocedural management of direct oral anticoagulation in patients with atrial fibrillation on chronic treatment undergoing major surgeries is an important aspect of balancing the risk of surgery-related bleeding with the risk of thromboembolic events, which may vary by surgery type.
Methods
Thi... | Observations and outcomes
Observations, including edoxaban interruption and clinical event data, were recorded from 5 days before the procedure until 30 days after the procedure. To enhance data capture, patients received a memory aid booklet at study enrolment, which was reviewed at the end of the study. Edoxaban ther... | Abbreviations
Acute coronary syndrome
Atrial fibrillation
Congestive heart failure, Hypertension, Age ≥75 (doubled), Diabetes, Stroke (doubled), Vascular disease, Age 65–74 years, and Sex category (female)
Creatinine clearance
Clinically relevant nonmajor bleeding
Cardiovascular
Direct oral anticoagulants
European Hear... | CC BY | no | 2024-01-16 23:36:45 | Thromb J. 2023 Dec 14; 21:124 | oa_package/72/e9/PMC10722787.tar.gz |
PMC10724087 | 38102530 | Introduction
Lymphedema is a chronic debilitating disease marked by deficits in lymph drainage and accumulation of protein-rich fluid, leading to limb edema that can progress to cellulitis and fibrosis over time. People with lymphedema are susceptible to extremity impairment, recurrent soft tissue inflammation and infe... | Materials and methods
Study design and population
The study was an on-label, prospective, randomized, 2-group feasibility study conducted at 2 centers. Ethics approval was received through Western IRB (Puyallup, WA) and University of Louisville Human Subjects Protection Program Office (Louisville, KY). The study is reg... | Results
Sixty-one participants were screened for the study with 29 ultimately enrolled and randomized between August 2020 and September 2021. Four participants withdrew, resulting in 60-day follow-up available for 25 participants (14 test, 11 control).
Demographic and other baseline data are presented Table 1 . Partic... | Discussion
Our study findings indicate that the text reminders did not improve treatment compliance because the BCRL patients were already highly treatment compliant. Overall, there were significant improvements in mean weight and BMI at the 30-day visit and in arm girth at the 60-day visit. There were significant impr... | Conclusion
Automated text reminders did not improve compliance in patients with BCRL as compliance rates were already high in this patient population across racial and ethnic variables. Improvements in weight, BMI, arm girth, disease-specific quality of life, and symptom severity measures were observed regardless of th... | Purpose
Do cell phone text reminders impact the rate of compliance with pneumatic compression device (PCD) therapy among women with breast cancer-related lymphedema (BCRL)?
Methods
A prospective, randomized, 2-group feasibility study conducted at 2 centers. Participants were adult females (≥18 years old) with unilatera... | Acknowledgements
We thank Marc Schwartz for the statistical analysis and the other investigators: Sarah Pesek, MD, St. Peters’ Health Partners, Troy, NY and Nicolas Ajkay, MD, University of Louisville, Louisville, KY. We also thank the patient participants and research team at St. Peter’s Health System.
Author contribu... | CC BY | no | 2024-01-16 23:34:58 | Support Care Cancer. 2024 Dec 16; 32(1):33 | oa_package/bd/86/PMC10724087.tar.gz | |
PMC10724324 | 38100037 | Introduction
Lymphocyte-specific protein tyrosine kinase (LCK) is critical for T-cell development and activation. LCK is recruited to the T-cell antigen receptor (TCR) after ligation of the TCR by peptide:MHC complexes on the surface of antigen-presenting cells [ 3 , 4 ]. LCK-dependent phosphorylation of immunorecepto... | Methods
Human Samples
Blood samples were taken from the patient, relatives, and healthy volunteers who were treated at Mustafa Eraslan-Fevzi Mercan Children’s Hospital at Erciyes University and analyzed there and at the Dr. von Hauner Children’ Hospital at Ludwig-Maximilians-Universität München. Informed consent was ... | Results
Case Description of a Girl with Profound T-Cell Immune Deficiency
The female patient was born at term to consanguineous parents of Syrian descent (Fig. 1 A). There were 4 healthy siblings and one sister, who had died of respiratory failure due to a fulminant respiratory infection at the age of 7 months. The pa... | Discussion
In the current study, we identified a novel biallelic missense LCK c.1393T>C, p.C465R variant in a patient from a consanguineous Syrian family with profound T-cell immune deficiency characterized by complete LCK protein expression deficiency and ensuing proximal TCR signaling- and CD4 and CD8-co-receptor-m... | Lymphocyte-specific protein tyrosine kinase (LCK) is an SRC-family kinase critical for initiation and propagation of T-cell antigen receptor (TCR) signaling through phosphorylation of TCR-associated CD3 chains and recruited downstream molecules. Until now, only one case of profound T-cell immune deficiency with complet... | Supplementary Information
| Acknowledgements
We thank the patient and her family for their personal contribution. We thank Gabriele Heilig for technical assistance with sequencing and the flow cytometry facility at the Dr. von Hauner Children’s Hospital for excellent technical support with immunophenotyping.
Author Contribution
Anna-Lisa Lanz, Se... | CC BY | no | 2024-01-16 23:35:01 | J Clin Immunol. 2024 Dec 15; 44(1):1 | oa_package/72/40/PMC10724324.tar.gz | |
PMC10728221 | 38110598 | Palliative care, with its focus on comprehensive patient assessment encompassing physical, social, emotional, and spiritual pain, plays a crucial role in modern medicine. Despite its significance, integration with oncology and other healthcare specialties often occurs late in the disease trajectory. Strategies to bridg... | Palliative care holds a unique place among medical specialties where it has gained recognition by virtue of its approach to the cancer: treating a patient with a tumor versus the tumor of the patient [ 1 ]. Palliative care goes beyond Quality-of-Life issues common to other specialties to focus on regular assessment of ... | Author contribution
C.C. projected the manuscript and drafted the paper. C.I.R. overviewed the project and reviewed the manuscript.
Data availability
Not applicable.
Declarations
Ethical approval
Not applicable.
Competing interests
The authors declare no competing interests. | CC BY | no | 2024-01-16 23:34:57 | Support Care Cancer. 2024 Dec 19; 32(1):41 | oa_package/0c/87/PMC10728221.tar.gz | |||||
PMC10728275 | 38110572 | Introduction
Head and neck cancer (HNC) represents the seventh most common cancer worldwide [ 1 ]. They account for different histologies (mainly squamous cell carcinoma but also salivary glands tumors, undifferentiated carcinoma, melanoma, lymphomas...) located in different head and neck subsites (oral cavity, pharyng... | Materials and methods
On 11 May 2022, an online survey composed of a total of 53 questions, including both multiple-choice and open-ended ones, was administered through a personnel contact to radiation oncologists working in 25 different RT centers across Italy.
The survey was composed of 40 questions divided into thre... | Results
All the 25 contacted RT centers responded to the survey and all sections have been completed. Dividing according to geographical location, seven centers are located in northern Italy, five in central Italy, and the remaining in southern Italy. | Discussion
Results of the present survey confirmed that a great variety exists among Italian centers in the management (prevention and treatment) of RIOM in the setting of HNC. Of note, the majority of participating centers are provided with different supportive care services and follow internal guidelines and/or liter... | Conclusions
To the best of our knowledge, this is the first study reporting an accurate snapshot of the Italian attitude on which agents and drugs are currently used in daily clinical practice to prevent and treat RIOM in Italian RT facilities. Results showed that a great variety still exist despite the availability of... | Aim
Radiation-induced oral mucositis (RIOM) is the most frequent side effect in head and neck cancer (HNC) patients treated with curative radiotherapy (RT). A standardized strategy for preventing and treating RIOM has not been defined. Aim of this study was to perform a real-life survey on RIOM management among Italian... | Section 1: questionnaire
Retrospective analysis
In 2021, a total of 1554 patients with HNC were treated in the 25 centers participating (median 54, IQR: 20–70). The majority (median 91%) of the treatments had a curative intent (36% of them postoperative), while the others were administered for palliative intent. In mos... | Abbreviations
area under curve
head and neck cancer
intensity-modulated radiotherapy
non-steroidal anti-inflammatory drug
low-energy laser
radiation-induced oral mucositis
radiotherapy
quality of life
Acknowledgements
IEO, the European Institute of Oncology, is partially supported by the Italian Ministry of Health (“Ri... | CC BY | no | 2024-01-16 23:35:02 | Support Care Cancer. 2024 Dec 19; 32(1):38 | oa_package/78/81/PMC10728275.tar.gz |
PMC10731717 | 38124066 | Introduction
Osteoarthritis (OA), the most prevalent joint disease, stands as a primary cause of joint pain and disability [ 1 ]. Featured by comprehensive joint lesions including cartilage degradation, synovial inflammation, osteophyte formation and subchondral bone sclerosis, OA significantly impacts life quality, la... | Materials and methods
Human synovial tissue
Human synovial tissue was obtained from 13 patients in the Department of Orthopaedic Surgery, at Sun Yat-sen Memorial Hospital, Sun Yat-sen University. The patients underwent arthroscopic surgery or joint replacement of the knee, with ten diagnosed with osteoarthritis. Ethica... | Results
NOD2 is upregulated in synovial macrophages of osteoarthritis patients and HMGB1-stimulated macrophages
To investigate potential molecules orchestrating macrophage activation, we subjected RAW264.7 macrophages to HMGB1 stimulation for 4 h, to capture mRNA profiles through RNA sequencing. DEGs were identified (|... | Discussion
This study focused on the pivotal role of NOD2 in the pathogenesis of OA. NOD2 as a differentially expressed gene in activated macrophages, as suggested by RNA sequencing, was further corroborated by IHC staining of synovial tissue sections. Elevated in response to HMGB1 stimulation, NOD2 demonstrates a nega... | Conclusions
In this study, NOD2 emerged as a critical inhibitor of macrophage activation and M1 polarization, particularly in response to HMGB1 stimulation, by acting as a reciprocal modulator of the HMGB1/TLR4 signaling pathway in macrophages. This, in turn, reshapes the paracrine effect of activated macrophages on FL... | Objective
Synovial inflammation, which precedes other pathological changes in osteoarthritis (OA), is primarily initiated by activation and M1 polarization of macrophages. While macrophages play a pivotal role in the inflammatory process of OA, the mechanisms underlying their activation and polarization remain incomple... | Supplementary Information
| Abbreviations
Osteoarthritis
Fibroblast-like synoviocyte
Magnetic resonance imaging
Damage-associated molecular pattern
High-mobility group box-1
Pattern recognition receptor
Toll-like receptor
Tumor necrosis factor α
Nucleotide-binding oligomerization domain containing 2
Collagenase-induced osteoarthritis
Specific pat... | CC BY | no | 2024-01-16 23:35:05 | Arthritis Res Ther. 2023 Dec 20; 25:249 | oa_package/07/6b/PMC10731717.tar.gz |
PMC10739567 | 38129578 | Introduction
Malnutrition is an important problem among oncology patients, with estimated rates ranging from 30.9% to 83%, depending on cancer location and patient age [ 1 – 4 ]. The muscle wasting disorders cachexia and sarcopenia are commonly associated with malnutrition in cancer patients; an estimated 50–80% of can... | Methods
The SLR was performed in accordance with Cochrane Collaboration [ 30 ], Centre for Reviews and Dissemination (CRD) [ 31 ], and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines [ 32 ].
Literature sources and searches
Electronic database searches were performed on October 5 t... | Results
The electronic database searches identified 3,333 citations. After removal of 877 duplicates, 2,133 publications at the title/abstract screening stage, and 305 publications at the full-text screening stage, 18 publications from the electronic database searches were deemed eligible for inclusion in the SLR. Hand... | Discussion
To the best of our knowledge, this was the first SLR with the aim of comparing outcomes between malnourished oncology patients receiving low- (< 1 g/kg/day), standard- (1–1.5 g/kg/day), or high-protein HPN doses (> 1.5 g/kg/day). However, no studies were identified reporting on high-protein HPN in this popu... | Conclusions
Despite the biological plausibility and emerging evidence from critically ill patients, at the time of writing there is a lack of evidence investigating and supporting the use of high-protein HPN in malnourished oncology patients. A minimum of 1.5 g/kg/day or > 20% of total caloric intake from protein appea... | Introduction
Up to 83% of oncology patients are affected by cancer-related malnutrition, depending on tumour location and patient age. Parenteral nutrition can be used to manage malnutrition, but there is no clear consensus as to the optimal protein dosage. The objective of this systematic literature review (SLR) was t... | Author contributions
Pilar Garcia Lorda and Julian Shepelev contributed to the conception of the research; Paolo Cotogni, Clare Shaw, Paula Jimenez-Fonseca, Dom Partridge, David Pritchett, and Neil Webb contributed to the conception and design of the research; all authors contributed to acquisition, analysis, or interp... | CC BY | no | 2024-01-16 23:35:02 | Support Care Cancer. 2024 Dec 22; 32(1):52 | oa_package/05/bf/PMC10739567.tar.gz | |
PMC10748576 | 38057149 | Materials and Methods
Reagents
Six linear oligopeptides (>95% pure) acetylated and amidated at the N- and C-termini, respectively ( Table 1 ), the linear (Vi45-51), and the cyclic-retro-inverse-vasoinhibin-(45-51)-peptide (CRIVi45–51) were synthesized by GenScript (Piscataway, NJ). Recombinant vasoinhibin isoforms of 1... | Results
Antiangiogenic HGR-Containing Vasoinhibin Analogues Are Not Apoptotic, Inflammatory, or Fibrinolytic
The linear– (Vi45-51) and cyclic retro-inverse– (CRIVi45-51) HGR-containing vasoinhibin analogues, like vasoinhibin standards of 123 residues (Vi1-123) and 48-residues (Vi1-48) ( Fig. 1A ), inhibited the VEGF- a... | Discussion
Vasoinhibin represents a family of proteins comprising the first 48 to 159 amino acids of PRL, depending on the cleavage site of several proteases, including matrix metalloproteases ( 26 ), cathepsin D ( 27 ), bone morphogenetic protein 1 ( 28 ), thrombin ( 15 ), and plasmin ( 29 ). The cleavage of PRL occur... | Juan Pablo Robles and Magdalena Zamora equal contribution
Abstract
Vasoinhibin, a proteolytic fragment of the hormone prolactin, inhibits blood vessel growth (angiogenesis) and permeability, stimulates the apoptosis and inflammation of endothelial cells, and promotes fibrinolysis. The antiangiogenic and antivasopermeab... | The formation of new blood vessels (angiogenesis) underlies the growth and repair of tissues and, when exacerbated, contributes to multiple diseases, including cancer, vasoproliferative retinopathies, and rheumatoid arthritis ( 1 ). Antiangiogenic therapies based on tyrosine kinase inhibitors ( 2 , 3 ) and monoclonal ... | Acknowledgments
We thank Xarubet Ruíz Herrera, Fernando López Barrera, Adriana González Gallardo, Alejandra Castilla León, José Martín García Servín, and María A. Carbajo Mata for their excellent technical assistance.
Funding
The work was supported by grant A1-S-9620B from Consejo Nacional de Humanidades, Cien... | CC BY | no | 2024-01-16 23:35:07 | Endocrinology. 2023 Dec 6; 165(2):bqad185 | oa_package/0c/fb/PMC10748576.tar.gz | ||
PMC10754748 | 38006481 | Introduction
Green Chemistry is mainly about how to protect the environment and ourselves from the adverse effects of our own chemicals and how to convert harmful materials to more benign ones. Slurry is once thought to be an inherently safe and benign source of nutrients. Due to the intensifying technologies of modern... | Materials and methods
Description of the cattle farm
The farm studied is situated near Budapest, Hungary. The livestock consists of 2500 animals on average, out of which 1600 are active dairy cows, while the rest are dry cows, heifers and calves. There are 1500 calvings/ annum on average. Manure is collected as slurry... | Results
Validation of the UHPLC method
Linearity, precision (repeatability), accuracy (recovery) and limits of detection (LOD) and quantification (LOQ) were evaluated to verify the performance of the method. Validation was performed according to International Conference on Harmonisation (ICH) guideline Q2 (R1). The lin... | Discussion
The present field-based, longitudinal study investigates the fate of 5 different oestrus -inducer drugs from the use phase to their appearance in the slurry at a dairy cow farm in Europe, Hungary. We examined the use of these OIVPs from 2017 to 2020 and determined the estrogenic effects of the generated hig... | Conclusions
The first principle of Green Chemistry warns us that preventing the formation of wastes is much better, cheaper and more sustainable than treating or cleaning an already polluted material or a site in the environment. Our study reveals that intensifying breeding practices in dairy cow farms generate the hid... | Responsible Editor: Ester Heath
The main objective of the research was to study the environmental “price” of the large-scale, milk production from a rarely known perspective, from the mapping of the estrogenic footprint (the amount of oestrus- inducer hormonal products, and the generated endoestrogens) in the resultin... | Supplementary Information
Below is the link to the electronic supplementary material. | Author contribution
E. G.: conceptualisation, formal analysis, funding acquisition, investigation, methodology, supervision, writing—original draft. J. P.: conceptualisation, formal analysis, funding acquisition, investigation, methodology, supervision, review and editing. T. M.: writing—original draft, review and edit... | CC BY | no | 2024-01-16 23:35:01 | Environ Sci Pollut Res Int. 2023 Nov 25; 30(60):125596-125608 | oa_package/6c/88/PMC10754748.tar.gz |
PMC10756890 | 38157081 | Introduction
Pain is a common symptom in cancer patients; some studies suggested that almost half of patients experience pain at least 3 months after completing curative treatment, and nearly a third experience moderate to severe pain [ 1 , 2 ]. Cancer pain may be caused by the cancer itself or metastases, or may be r... | Methods
The study was registered on the Japan Pharmaceutical Information Center clinical trial information (JapicCTI-184143) and Japan Registry of Clinical Trials (jRCT2080224082) (date registered: October 5, 2018).
Patients
Patients were eligible for this study if they had been diagnosed with cancer, had an estimated ... | Results
Patients
A total of 281 patients initially provided consent, of which 251 were randomized (126 to the bilayer tablet group and 125 to the IR capsule group) (Fig. 2 ). Of these, 105 completed the study in the bilayer tablet group and 91 in the IR capsule group (Fig. 2 ).
The baseline characteristics of patient... | Discussion
Our aim was to investigate the non-inferiority of a bilayer tablet formulation of tramadol, comprising IR and SR layers, versus an IR capsule formulation in terms of managing cancer pain. The two treatments achieved similar improvements in the VAS for pain at rest, satisfying the criterion for non-inferiorit... | Conclusions
Twice-daily administration of bilayer tramadol tablets comprising 35% immediate-release and 65% sustained-release tramadol was as effective as four-times-daily IR capsules regarding the improvement in the VAS for pain at rest. We also observed strong similarity in the other effectiveness outcomes, including... | Purpose
We investigated whether twice-daily administration of a bilayer tablet formulation of tramadol (35% immediate-release [IR] and 65% sustained-release) is as effective as four-times-daily IR tramadol capsules for managing cancer pain.
Methods
This randomized, double-blind, double-dummy, active-comparator, non-inf... | Supplementary Information
Below is the link to the electronic supplementary material. | Acknowledgements
The authors express their gratitude to the patients, investigators, and research staff who were involved in this study. The study sponsor acknowledges Nippon Shinyaku Co., Ltd. for manufacturing and supplying the IR capsules. The authors thank Nicholas D. Smith (EMC K.K.) for medical writing support, w... | CC BY | no | 2024-01-16 23:35:01 | Support Care Cancer. 2024 Dec 29; 32(1):69 | oa_package/9e/d0/PMC10756890.tar.gz |
PMC10759284 | 0 | Editor-in-Chief
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Editor-in-Chief | Over 200 health journals call on the United Nations, political leaders, and health professionals to recognise that climate change and biodiversity loss are one indivisible crisis and must be tackled together to preserve health and avoid catastrophe. This overall environmental crisis is now so severe as to be a global h... | CC BY | no | 2024-01-16 23:35:07 | Int Health. 2023 Oct 25; 16(1):1-3 | oa_package/d9/fc/PMC10759284.tar.gz | ||||||
PMC10761990 | 38168108 | Introduction
Organelles in eukaryotic cells are considered the results of early bacterial endosymbiotic events 1 . Chloroplasts, the apparatus for photosynthesis, retain a genome of about 100–200 kb in size that comprises two inverted repeats (IR) separated by a small single-copy (SSC) region and a large single-copy (L... | Methods
Plant growth and materials
All Arabidopsis thaliana materials used in this study are in the ecotype Columbia-0 (Col) background. The T-DNA insertion mutants atrnh1c , rhon1 , and SALK_152246 were obtained from Nottingham Arabidopsis Stock Centre, UK. Surface-sterilized seeds were sown on 1/2 MS medium and i... | Results
A point mutation in ATH rescues the developmental defects of atrnh1c
The chloroplast-localized ribonuclease AtRNH1C plays a key role in maintaining plastid genome stability in Arabidopsis, and atrnh1c displays pale yellow leaves, which is caused by aberrant R-loop accumulation and genome degradation 20 . T... | Discussion
Transcription and replication are the most essential events of living organisms to sustain life, and they rely on the same genome as the template. According to the coding strand of gene transcription relative to the movement of the replisome, the transcription and replication machinery either move head-on or... | Transcription-replication conflicts (TRCs), especially Head-On TRCs (HO-TRCs) can introduce R-loops and DNA damage, however, the underlying mechanisms are still largely unclear. We previously identified a chloroplast-localized RNase H1 protein AtRNH1C that can remove R-loops and relax HO-TRCs for genome integrity. Thro... | Supplementary information
Source data
| Supplementary information
The online version contains supplementary material available at 10.1038/s41467-023-44443-0.
Acknowledgements
The authors thank all the members of The Sun Lab and Professor Jie Ren (from Beijing Institute of Genomics, Chinese Academy of Sciences) for their helpful discussions and constructive s... | CC BY | no | 2024-01-16 23:35:02 | Nat Commun. 2024 Jan 2; 15:73 | oa_package/68/8f/PMC10761990.tar.gz | |
PMC10762076 | 38167300 | Introduction
Much like classical anions, electrons can behave as solutes in solution. In water, such hydrated electrons (e – (aq) ) have attracted much attention as fundamental quantum solutes and because of their role in radiation chemistry 1 , 2 . The structure and dynamics of e – (aq) has been a topic of much debat... | Methods
Experimental
The time-resolved sum-frequency generation spectroscopy arrangement has been detailed in Ref. 64 . The output of an Yb:KWG laser (Light Conversion, Carbide 5, producing 230 fs pulses at 1026 nm with 83 μJ pulse –1 energy at 12 kHz) was split into three parts. One part was used to generate pump pu... | Results
Figure 2a shows the square-root of the SFG signal, I SFG 1/2 (proportional to interfacial concentration), as a function of time and over a range of ω 1 . Signal before t = 0 has been subtracted, residual fluorescence contributions removed, and traces offset for clarity. At all ω 1 , the SFG signal rises... | Discussion
The optical spectrum of e – (aq/air) is similar to that of e – (aq) , demonstrating that most of the electron density resides within the aqueous phase rather than the vapor phase as suggested in certain previous studies. The implication is that the electron by itself is no more reactive at the interface tha... | The hydrated electron, e – (aq) , has attracted much attention as a central species in radiation chemistry. However, much less is known about e – (aq) at the water/air surface, despite its fundamental role in electron transfer processes at interfaces. Using time-resolved electronic sum-frequency generation spectroscop... | Supplementary information
| Supplementary information
The online version contains supplementary material available at 10.1038/s41467-023-44441-2.
Acknowledgements
We thank Faith Prichard for her support with parts of the experimental work. This work was supported by the Engineering and Physical Sciences Research Council [grant number EP/R513039/1... | CC BY | no | 2024-01-16 23:35:00 | Nat Commun. 2024 Jan 2; 15:182 | oa_package/04/e9/PMC10762076.tar.gz | |
PMC10763720 | 0 | Conclusions
I hope that my perspective as a scientist who is deeply engaged in discovering and developing medicines, framed in the context of atherosclerosis, highlights the importance of staying grounded in human biology when pursuing disease-related research. While signals emanating from human diversity data will not... | Developing new and effective medicines is perhaps one of the most important, yet difficult endeavors that we pursue as a society. As a drug developer, I am part of a team wrestling with a daunting task — picking the most promising drug targets from the myriad biological pathways in the human body, designing drug molecu... | I thank Kári Stefánsson, Narimon Honarpour, Raymond Deshaies, and Simon Jackson for engaging in thoughtful discussion and providing constructive input.
01/16/2024
Electronic publication | CC BY | no | 2024-01-16 23:40:16 | J Clin Invest.; 134(2):e178332 | oa_package/27/b1/PMC10763720.tar.gz | |||||
PMC10763722 | 37962957 | Introduction
The giant myofilament titin is the third most abundant sarcomeric protein besides actin and myosin ( 1 ). A single titin molecule spans half of the sarcomere from the Z-disk to the M-line ( 2 ). Titin’s main function is to provide passive stiffness to striated muscle ( 3 ), but it also plays a prominent ro... | Methods
Sample collection and handling.
Human myocardial tissue samples were obtained from the Transplantation Biobank of the Heart and Vascular Center at Semmelweis University in Budapest, Hungary. Myocardial septum samples were collected from 127 patients with clinically identified end-stage DCM, who were undergoing ... | Results
Patient data and gene sequencing: identification of a TTNtv DCM cohort.
We screened 127 myocardial samples from explanted hearts of patients who were clinically identified as having DCM ( Table 1 , Supplemental Table 1 , and Supplemental Table 2 ); supplemental material available online with this article; ht... | Discussion
Heterozygous TTNtvs are the most common genetic cause of familial DCM, accounting for 15%–25% of the cases ( 6 , 9 , 10 ). The pathomechanism by which titin mutations induce the cardiac phenotype are under extensive research ( 32 ). Although haploinsufficiency and a dominant negative effect have recently b... | Authorship note: DK and HT are co–first authors and contributed equally to this work.
Heterozygous (HET) truncating variant mutations in the TTN gene (TTNtvs), encoding the giant titin protein, are the most common genetic cause of dilated cardiomyopathy (DCM). However, the molecular mechanisms by which TTNtv mutations... | Author contributions
DK and HT designed research studies, conducted experiments, acquired data, analyzed data, and wrote the manuscript. The order of the co–first authors’ names was determined on the basis of the amount of experiments and analyses conducted. BK conducted STED experiments, acquired and analyzed STED dat... | We gratefully acknowledge the assistance of Krisztina Lór with experimental preparations (Department of Biophysics and Radiation Biology, Semmelweis University, Budapest, Hungary). We thank András Csillag and Gergely Zachar (Department of Anatomy, Histology, and Embryology of Semmelweis University) for providing acce... | CC BY | no | 2024-01-16 23:40:16 | J Clin Invest.; 134(2):e169753 | oa_package/dc/49/PMC10763722.tar.gz | |
PMC10766496 | 38176709 | INTRODUCTION
Peripheral nerve regeneration is a complex time and space‐dependent cellular programming (Jessen & Mirsky, 2019 ). Identifying the mechanisms of nerve regeneration requires an examination of all cellular molecules and signaling pathways at different times and neural tissue locations (Li et al., 2020 ). T... | CONCLUSION
After PNI, the expression of all proteins involved in iron homeostasis is increased in SCs and axons, which shows a high demand for iron during this period. Based on previous studies, iron homeostasis proteins play a role in SC differentiation, myelination, and axonal outgrowth. However, the intracellular si... | Abstract
Iron accumulates in the neural tissue during peripheral nerve degeneration. Some studies have already been suggested that iron facilitates Wallerian degeneration (WD) events such as Schwann cell de‐differentiation. On the other hand, intracellular iron levels remain elevated during nerve regeneration and gradu... | INTRACELLULAR IRON SIGNALING PATHWAYS IN SCHWANN CELLS (SCS)
Iron, either as free form (ferric ammonium citrate [FAC] only at concentrations of 0.5 and 0.65 mM) or holo‐Tf (iron‐bound Tf) induces an increase in cyclic adenosine monophosphate (cAMP), phosphorylated (p)‐ cAMP‐response element binding protein (CREB), reac... | ACKNOWLEDGMENTS
Declared none.
DATA AVAILABILITY STATEMENT
Not applicable. | CC BY | no | 2024-01-16 23:35:06 | Physiol Rep. 2024 Jan 4; 12(1):e15908 | oa_package/eb/c5/PMC10766496.tar.gz | |||
PMC10766658 | 38175303 | Introduction
Childhood is a sensitive period in life, with rapid bodily, neurological, cognitive, emotional, and social development. Experiencing multiple adverse events during childhood such as losing a parent, physical abuse, or having a parent with a mental illness are known risk factors for physical and mental heal... | Method
Data sources and search strategy
A systematic review of the literature up to August 27th, 2023 was conducted in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of four databases (PubMed, PsychINFO, Web of Science, and Cochrane) were searched for relevant ... | Results
In Fig. 1 , a flow chart is depicted of the inclusion and exclusion of articles derived from the database searches. In total, 1413 references were found, and after the removal of 295 duplicates, 1118 unique articles were retrieved. These articles were assessed for eligibility and 79 full-text articles were ass... | Discussion
The aim of this systematic literature review was to investigate the association between ACEs and psychological problems in cancer survivors. Although variations were found, and not all studies reported an association between ACEs and mental health problems in cancer survivors, the majority did. On the basis ... | Conclusion
Childhood adversities are prevalent and a risk factor for psychological problems in patients diagnosed with cancer. Recognizing the prevalence of ACE and its impact on mental health in cancer survivors and responding in a way that prevents re-traumatization and promotes resilience should become a focus of at... | Purpose
The purpose of this study was to systematically review the literature on the association between adverse childhood events (ACEs) and mental health problems in cancer survivors.
Methods
This review was conducted in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. ... | Author contribution
CH had the idea for the article, EH and FT performed the literature search, CH, EH, FT, performed data analysis, CH and FM drafted and critically revised the work.
Declarations
Ethics approval and consent to participate
Given the nature of the article, no approval by a certified Medical Ethics Commi... | CC BY | no | 2024-01-16 23:35:01 | Support Care Cancer. 2024 Jan 4; 32(1):80 | oa_package/b3/68/PMC10766658.tar.gz | |
PMC10768880 | 38188453 | Methods
Study Design and Participants
This cross-sectional study used the baseline data from the Bunkyo Health Study [ 11 ]. Briefly, we recruited 1629 individuals aged 65 to 84 years living in Bunkyo-ku, an urban area in Tokyo, Japan from October 15, 2015, to October 1, 2018. Among the Bunkyo Health Study participants... | Results
The characteristics and metabolic parameters of the study participants are shown in Table 1 . There were no differences in the proportion of men and women across groups. The proportion of participants with normal glucose tolerance was significantly lower in the older group, while the proportion of participants... | Discussion
The purpose of this study was to investigate whether insulin sensitivity and β-cell function deteriorate after the age of 65 years and the factors contributing to the exacerbation of glucose tolerance with aging among older adults with no history of diabetes. The present study showed that the prevalence of n... | Abstract
Context
Older adults have a high prevalence of new-onset diabetes, often attributed to age-related decreases in insulin sensitivity and secretion. It remains unclear whether both insulin sensitivity and secretion continue to deteriorate after age 65.
Objective
To investigate the effects of aging on glucose met... | The high incidence of new-onset diabetes in older adults is a well-known and pressing issue, especially in countries like Japan, which has the highest population aging rate in the world [ 1 ]. Older adults have reduced β-cell function and increased insulin resistance, leading to a higher prevalence of diabetes [ 2-7 ].... | Acknowledgments
The authors would like to thank Liu L., Aoki T., Nakagata T., Hui H., and all staff members who contributed to data collection at the Sportology Center.
Funding
This study was supported by Strategic Research Foundation at Private Universities (S1411006) and KAKENHI (18H03184) grants from the Ministry of... | CC BY | no | 2024-01-16 23:36:47 | J Endocr Soc. 2023 Dec 20; 8(2):bvad164 | oa_package/32/ed/PMC10768880.tar.gz | ||
PMC10769316 | 38187745 | INTRODUCTION
In the visual cortex of mammals, the precise wiring of geniculocortical afferents and intrinsic connections that forms the organizational basis for the systems of ocular dominance (OD) and orientation selectivity develops from, and is maintained by, a fine balance of activity-based neuronal interactions ( ... | MATERIAL AND METHODS
Experiments were performed on 5 kittens (K349, K352, K359, K362 and K396) born and housed with their mother in the University of California, San Francisco cat colony. All procedures were approved by the Committee on Animal Research (University of California, San Francisco) in accordance with Nation... | RESULTS
The Results are presented in three sections. In the first section, the experimental paradigm will be presented in detail. The second section describes the NT-4/5-mediated structural changes in visual cortical neurons. Finally, we analyze the pattern of immunostaining of a presynaptic marker, synaptophysin, in N... | DISCUSSION
The present study demonstrates that excess NT-4/5 administered in vivo into the visual cortex induces a remarkable sprouting of processes from both proximal dendrites and somata of cortical neurons. The morphology of these newly formed processes closely resembles spines, although at times they appear unusual... | Conclusions for the role of neurotrophins in the formation of cortical circuits
The present findings provide anatomical confirmation of the suggestion made from physiological studies ( Gillespie et al., 2000 ) that NT-4/5 infusion into critical period visual cortex stimulates the formation of promiscuous neuronal conne... | Current hypotheses on the mechanisms underlying the development and plasticity of the ocular dominance system through competitive interactions between pathways serving the two eyes strongly suggest the involvement of neurotrophins and their high affinity receptors. In the cat, infusion of the tyrosine kinase B ligand (... | ACKNOWLEDGEMENTS
Supported by NIH R37 EY02874. We thank Genentech for providing the NT-4/5 used in this study, Drs. J. Grutzendler and R. Wong for introducing us to the DiOlistics technique, and Karen MacLeod for invaluable help during the surgical procedures. | CC BY | no | 2024-01-16 23:49:20 | bioRxiv. 2023 Dec 22;:2023.12.20.572693 | oa_package/14/a0/PMC10769316.tar.gz | |
PMC10769358 | 38187569 | INTRODUCTION
Bacterial replication requires available nutrients and transcription of anabolic genes. When nutrients become limiting, cells adapt to their environment by activating the broadly conserved bacterial stress response pathway known as the stringent response (SR) ( 1 ). During the SR, stressors such as nutrien... | METHODS
Caulobacter crescentus and Escherichia coli growth media and conditions
C. crescentus NA1000 cells were grown at 30°C in peptone-yeast extract (PYE) medium or minimal media described below. E. coli NEB Turbo (NEB Catalog #C2986K) and Rosetta(DE3)/pLysS cells were grown at 37°C and 30°C, respectively, in L... | RESULTS
CdnL is cleared during the stringent response in a SpoT-dependent manner
Our prior work indicated that many anabolic genes are regulated in a CdnL-dependent manner, apparently echoing transcriptional changes that occur during the SR. This prompted us to review transcriptomic data from our lab and others to expl... | DISCUSSION
Adapting to environmental challenges such as nutrient deprivation requires efficient changes in transcription in order to downregulate biosynthetic genes and upregulate those that promote survival. While the direct binding of the SR alarmone (p)ppGpp to RNAP is a major way in which cells alter the transcript... | In response to nutrient deprivation, bacteria activate a conserved stress response pathway called the stringent response (SR). During SR activation in Caulobacter crescentus , SpoT synthesizes the secondary messengers (p)ppGpp, which affect transcription by binding RNA polymerase to downregulate anabolic genes. (p)ppG... | Supplementary Material | ACKNOWLEDGEMENTS
We thank Allison Daitch and Marie Stoltzfus for the construction of some Caulobacter strains and plasmids. We thank Allen Buskirk and Annie Campbell for helpful discussions about ribosomes. This project was supported by funds from the NIH (NIH-NIGMS Grant R35GM136221 to E.D.G. and Grant R35GM130320 t... | CC BY | no | 2024-01-16 23:49:20 | bioRxiv. 2023 Dec 21;:2023.12.20.572625 | oa_package/7f/8e/PMC10769358.tar.gz | |
PMC10769382 | 38187625 | Introduction
Genome scans, where genetic variants across the genome are tested for association with traits of interest, are an important tool to discover insights into the etiology of a trait or disease. Recent advancements in high-throughput technologies make it possible to collect large number of traits in a single i... | Computational methods
In this section, we detail the computational strategies we used to speed up the computation.
Heritability estimation precision.
The computational complexity of the LMM fitting scheme mainly comes from the estimation of the heritability , which requires solving a one-parameter optimization problem... | Results
In order to provide the future users of BulkLMM a comprehensive view of its performances under various scenarios, depending on the sizes of the input data, as well as the options for model evaluation requested by the user, we used BulkLMM to perform two analyses - one on the BXD mice liver proteome traits and t... | Discussion
Our BulkLMM package is able to perform genome scans for thousands of traits in moderately-sized populations in a few seconds (5 seconds for the BXD data, 14 seconds for the HS data). These represent speedups of 94 times and 16,000 times respectively compared to running GEMMA one trait at a time. Running GEMM... | Genetic studies often collect data using high-throughput phenotyping. That has led to the need for fast genomewide scans for large number of traits using linear mixed models (LMMs). Computing the scans one by one on each trait is time consuming. We have developed new algorithms for performing genome scans on a large nu... | Acknowledgments
Funding
This work was supported by NIH grants R01GM070683 (KWB,SS), P30DA044223 (RWW,SS), R01GM123489 (RWW,KWB,SS,ZY,GF).
Data availability
For the two datasets used during our experimentation, the BXD individual liver proteome and the HS rats mRNA data, both are open to public access and are accessible... | CC BY | no | 2024-01-16 23:49:20 | bioRxiv. 2023 Dec 21;:2023.12.20.572698 | oa_package/19/af/PMC10769382.tar.gz | ||
PMC10769392 | 38187742 | Introduction
Genomic sequence-to-activity models predict molecular phenotypes, such as DNA accessibility, transcription factor (TF) binding, histone modifications, and gene expression, directly from DNA sequence. Numerous deep learning models have been trained for these tasks using experimental assay data from a divers... | Methods
Ensemble model training.
We train five replicate models using the Basenji2 model architecture, training procedure, and human training data [ 4 ]. We use the Basenji Github repository for model training [ 34 ].
Reference sequence predictions.
To make predictions for held out reference sequences, we average predi... | Results
Uncertainty quantification
In a supervised learning setup, with inputs and outputs related through the joint distribution , we can train a model on a finite dataset with training examples. Adopting a Bayesian framework, we can decompose the predictive uncertainty into data (aleatoric) and model (epis... | Conclusion
We analyze uncertainty in the predictions of genomic sequence-to-activity models by measuring prediction consistency across five replicate Basenji2 models, when applied to reference genome sequences, reference genome sequences perturbed with TF motifs, eQTLs, and personal genome sequences. For held out refer... | Authors contributed equally to paper. Co-authorship order was randomly chosen and happens to correspond to love for carrot
Genomic sequence-to-activity models are increasingly utilized to understand gene regulatory syntax and probe the functional consequences of regulatory variation. Current models make accurate predic... | Supplementary Material | Acknowledgements
We thank Gabriel Loeb and Ioannidis lab members for helpful discussions. This work was partially supported by the U.S. National Institutes of Health grant R00HG009677, an Okawa Foundation Research Grant, and a grant from the UC Noyce Initiative for Computational Transformation. N.M.I. is a Chan Zuckerb... | CC BY | no | 2024-01-16 23:49:19 | bioRxiv. 2023 Dec 23;:2023.12.21.572730 | oa_package/e4/2d/PMC10769392.tar.gz | |
PMC10771998 | 38185712 | Introduction
The benefits of physical activity for the prevention, management and survival of many adult cancers are well established, as highlighted by multiple systematic reviews [ 1 – 3 ]. Physical activity during and after treatment is safe and acceptable to patients and is endorsed by the World Health Organisation... | Methods
Design
A qualitative, semi-structured interview study was conducted with breast cancer patients and HCPs. The study is reported in line with the COREQ guidelines (see supplementary document ). Ethical approval was granted by the Loughborough University Research Ethics Committee (Ref: 2022–5729-10266). Data col... | Results
Participant characteristics
Fifty-four patients and twenty-one HCPs expressed an interest in participating in this study and 26 consented: 11 HCPs (Table 1 ) and 15 patients (Table 2 ). All patients were female and had received a diagnosis of breast cancer in the UK within 6 months to 10 years of the date of ... | Discussion
Summary of findings
This study provides useful insight and practical guidance to support the integration of physical activity into the pathway for all patients with breast cancer. Findings confirm that physical activity is not routinely discussed with all patients who receive treatment for breast cancer in t... | Conclusion
Many HCPs who offer cancer care are reluctant to raise the topic of participation in physical activity, yet patients would welcome discussions. Providing HCPs with education regarding the benefits of physical activity along with evidence-based, low-cost, remote interventions would allow them to integrate con... | Objective
The benefits of physical activity across the cancer continuum for many adult cancers are well established. However, physical activity is yet to be routinely implemented into health services throughout the world. This study aims to explore patients’ and healthcare professionals’ views about integrating convers... | Supplementary Information
Below is the link to the electronic supplementary material. | Author contributions
KG developed the original idea for the study with support from AJD. KG led the study and conducted data collection. KG conducted data analysis with substantial input from CDM and AJD. KG wrote the manuscript with input from CDM and AJD. All authors read and approved the final manuscript.
Funding
AJ... | CC BY | no | 2024-01-16 23:34:58 | Support Care Cancer. 2024 Jan 8; 32(1):87 | oa_package/e6/47/PMC10771998.tar.gz |
PMC10772494 | 38193025 | Commentary
Invasive lobular carcinoma of the breast (ILC) presents distinct difficulties in diagnosis and clinical management. Detection is a particular challenge because ILC typically does not form a palpable mass and is often difficult to image, including by mammography and positron emission tomography/computed tomog... | Funding
This work was supported by the Office of the Assistant Secretary of Defense for Health Affairs through the Breast Cancer Research Program under Awards W81XWH-22-1-0715 (M.J.S.) and W81XWH-22-1-0716 (J.H.O.). Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessar... | CC BY | no | 2024-01-16 23:36:46 | J Endocr Soc. 2023 Dec 26; 8(2):bvad171 | oa_package/b3/d9/PMC10772494.tar.gz | ||||||
PMC10775316 | 38196637 | Methods (Online)
Subjects
We used male and female Fos-mRFP +/− transgenic rats on Wistar background (NIDA transgenic breeding facility, n = 54), weighing 250–450 g in all experiments. We group-housed rats (two to three per cage) in the animal facility and single-housed them before the experiments. For all experiments... | Author contributions
K.E.S., R.M. and B.T.H. designed the experiments. K.E.S., and R.M. conceptualized the XPoSE-seq approach. J.C.M. generated XPoSE-tag reagent. K.E.S. and R.G.P. validated the XPoSE-tag reagent. R.M., R.G.P., and O.R.D., and M.B.B., ran behavioral experiments and collected samples for XPoSE-seq. K.E.... | Single cell and nucleus RNA-sequencing (sc/sn-RNAseq) approaches disentangle the heterogeneity of complex tissues and aid in the identification of rare populations otherwise masked by conventional bulk-tissue procedures. While current pipelines effectively characterize common populations, there are multiple challenges ... | Acknowledgements
We thank members of Hope lab for their support and insight during all stages of this study. We thank Ueta lab (University of Occupational and Environmental Health, Kitakysushu, Japan) for providing the Fos-mRFP transgenic line. We thank Dr. Francois Vautier and the NIDA IRP Transgenic Breeding staff ... | CC BY | no | 2024-01-16 23:49:19 | bioRxiv. 2023 Sep 29;:2023.09.27.559834 | oa_package/06/98/PMC10775316.tar.gz | ||||
PMC10775317 | 38196583 | INTRODUCTION
Prion disease features striking biomarker signatures 1 – 4 , but limited data exist on pre-symptomatic changes 5 – 7 . Mirroring disease duration 8 , prodomal change in genetic prion disease appears brief, preceding symptoms by at most 1–4 years 6 , 7 . Prion “seeds” in CSF have been detected by real-time ... | METHODS
Study participants.
This previously described 5 cohort study includes asymptomatic individuals with pathogenic PRNP mutations; individuals at risk for same; and controls ( Table 1 ; Figure S1 ). Individuals with contraindication to lumbar puncture were excluded. Each visit included CSF and plasma collection... | RESULTS
Of 41 carriers ( Table 1 ), four converted to active disease (N=3 E200K, N=1 P102L). 6 RT-QuIC positives ( Figure 1A ) belonged to 3 E200K individuals who converted and died of prion disease. 2 PRNP codon 129 heterozygotes (M/V) were RT-QuIC positive at first sample (2.5 and 3.1 years before onset); prion tit... | DISCUSSION
Here we describe fluid biomarker profiles in a longitudinal cohort of genetic prion disease mutation carriers, including 4 individuals who converted to active disease. As before 5 – 7 , at any given time, cross-sectionally, most carriers of genetic prion disease mutations do not have any detectable molecular... | CONCLUSIONS
In E200K carriers, RT-QuIC seeding activity in CSF can precede symptom onset by 1–3 years, perhaps depending on PRNP codon 129 genotype. CSF and plasma markers of neurodegeneration and neuroinflammation do not unambiguously identify imminent converters. CSF PrP levels are longitudinally stable over time i... | AUTHOR CONTRIBUTIONS
Dr. Vallabh had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: SMV, SEA, EVM. Patient visits and sample accrual: SEA, AJM, SWA, ACK, AMF, AB, KDM, GD. Sample analysis: MAM, SWA, PKW, BLH, ... | Supplementary Material | FUNDING
This study was supported by the Broad Institute (BroadIgnite Accelerator), Ionis Pharmaceuticals, Prion Alliance, CJD Foundation, and the National Institutes of Health (R21 TR003040, R01 NS125255).
Role of the Funder/Sponsor:
The funders had no role in the design and conduct of the study; collection, management... | CC BY | no | 2024-01-16 23:49:21 | medRxiv. 2023 Dec 18;:2023.12.18.23300042 | oa_package/b9/e9/PMC10775317.tar.gz |
PMC10775320 | 38196653 | Introduction
Understanding the relationship between human mobility and the spread of pathogens is crucial for mitigating outbreak events. This has been demonstrated for acute respiratory infections, such as influenza and daily commuter patterns [ 1 ] , for measles and large-scale seasonal movements [ 2 ] , and for HI... | Methods
Data sources
We scanned and digitized printed versions of Michelin Road maps of Central and South Africa that were published in 1963, 1969, 1974, 1981, 1989, 2003, 2007, and 2019 and West Africa from 1975, 1989, 1991, 2003, and 2019 ( Table 1 ) [ 13 , 14 ] . We used shapefiles of administrative areas from DIV... | Results
We mapped each EBOV spillover event ( Fig. 1a ). Between 1976 and 2020, 10 EBOV spillover events occurred in the DRC, 3 in the ROC, 4 in Gabon, and 1 in Guinea. The total number of cases for each outbreak ranged from 1 to 28,652 ( Table 1 ) [ 5 , 7 ] . The Guinea outbreak of 2013 reported 28,652 cases and a du... | Discussion
This study provides a novel data resource and novel analyses of transportation infrastructure surrounding all documented EBOV spillover events through 2020. All 18 of these events occurred within Central and West Africa. We examined the relationship between transportation infrastructure, which we used as a p... | Contributions
NB and VM were responsible for the concept of the study. NB, AG, and BN completed the analyses. VM, MJM, and SNS provided relevant insight, data, and feedback. HDR provided support for map discovery, archiving, and digitization. NB and AG prepared the first draft of the manuscript. All authors reviewed an... | Supplementary Material | Acknowledgments
We thank Kelsee Baranowski, Christina Faust, and Ephraim Hanks for their valuable feedback and insight in the development of this manuscript.
Funding
This study was supported by the joint National Institutes of Health (NIH) - National Science Foundation (NSF) - National Institute of Food and Agriculture... | CC BY | no | 2024-01-16 23:49:21 | medRxiv. 2023 Dec 19;:2023.12.18.23300175 | oa_package/2e/97/PMC10775320.tar.gz | |
PMC10775321 | 38196589 | Methods
Over 20,000 primary cancer and matched normal samples from 33 different cancer types are molecularly described by The Cancer Genome Atlas (TCGA). The National Human Genome Research Institute and National Cancer Institute started working together on this project in 2006. Over 2.5 petabytes of genomic, epigenomic... | Results
Table 1 contains demographics and clinical characteristics of lower grade glioma and colorectal cancers studied.
Figure 1 shows age at diagnosis of lower grade glioma and colorectal cancers studied.
Figure 2 shows overall survival and disease-free survival of lower grade glioma and colorectal cancers studied... | Discussion
Enteric neurons and enteric glial cells are a part of the enteric nervous system, which is sometimes referred to as the “second brain” of the body. This complex network of neurons controls various functions of the gastrointestinal tract, including motility, secretion, and blood flow. Research has shown that ... | Dr. Lehrer and Dr. Rheinstein contributed equally to the conception, writing, and data analysis of this study.
Background:
Enteric neurons and enteric glial cells are a part of the enteric nervous system, which is sometimes referred to as the “second brain” of the body. This complex network of neurons controls various ... | Eighty percent of malignant primary brain tumors are gliomas. They arise from mutations affecting neural stem cells or glial cells. One well documented pair of mutations is the chromosome 1p 19q codeletion in lower grade gliomas, a favorable prognostic marker ( 1 ).
Glial cells are present in the brain, central nervous... | This work was supported in part through the computational and data resources and staff expertise provided by Scientific Computing and Data at the Icahn School of Medicine at Mount Sinai and supported by the Clinical and Translational Science Awards (CTSA) grant UL1TR004419 from the National Center for Advancing Transla... | CC BY | no | 2024-01-16 23:49:21 | medRxiv. 2023 Dec 22;:2023.11.07.23298214 | oa_package/c1/44/PMC10775321.tar.gz | ||
PMC10775324 | 38196612 | Introduction
Non-diabetic chronic kidney disease (CKD) is associated with metabolic dysregulation including disrupted insulin and glucose homeostasis 1 – 3 . Factors contributing to CKD-associated glucometabolic complications include increased inflammation 4 and hyperglucagonemia 5 . Prior studies in CKD using hyperin... | Methods
Study population and study design:
The Study of Glucose and Insulin in Renal Disease (SUGAR) was a cross-sectional study of moderate-severe non-diabetic CKD. A total of 98 participants were recruited for this study among which 59 had CKD (eGFR < 60 ml/min per 1.73 m 2 ) and 39 were controls (eGFR > 60 ml/min pe... | Results
Characteristics of the study participants.
The study included a total of 98 total participants, of whom 59 had CKD (eGFR <60 ml/min per 1.73 m 2 ) and 39 were healthy controls (eGFR ≥60 ml/min per 1.73 m 2 ). The mean (± SD) age among CKD participants was 63.6 ± 13.9 years, 51% were female, and 22% self-identif... | Discussion
Our findings demonstrate that the presence and severity of non-diabetic moderate-severe CKD is associated with greater plasma levels of incretins during fasting and in response to an OGTT. The elevated circulating GLP-1 and GIP levels in the fasting state and postprandial conditions were observed in the abse... | AA and JG contributed equally to this work.
BPC and BR contributed equally to this work.
Author Contributions
The conceptualization was contributed by AA, BR, BPC, and IHDB. The methodology was contributed by AA, BR, BPC, BC, SF and IHDB. The formal analysis was conducted by AA and SF. The investigation was performed b... | Supplementary Material | Acknowledgments
We thank Anthony Dematteo at Vanderbilt University who measured plasma DPP-4 antigen and activity levels. We would like to express our sincere gratitude to Steven Kahn for his valuable feedback and insightful comments on this manuscript. We thank all the participants in the SUGAR cohort for their contri... | CC BY-ND | no | 2024-01-16 23:49:21 | medRxiv. 2023 Dec 18;:2023.12.15.23300050 | oa_package/fc/85/PMC10775324.tar.gz | |
PMC10775342 | 38196593 | Summary
The R644C variant of lamin A is controversial, as it has been linked to multiple phenotypes in familial studies, but has also been identified in apparently healthy volunteers. Here we present data from a large midwestern US cohort showing that this variant associates genetically with hepatic steatosis, and with... | Metabolic dysfunction-associated steatotic liver disease (MASLD) and, when associated with lipotoxicity and inflammation, metabolic dysfunction-associated steatohepatitis (MASH) together represent a genetically and phenotypically diverse entity that is now the most common liver disease in the United States and for whic... | Grant Support:
This work was supported by K08DK120948 (G.F.B.) and the University of Michigan Department of Internal Medicine. X.D., Y.C., and E.K.S. are supported in part by R01DK106621 (E.K.S.), R01DK107904 (E.K.S.), R01DK128871 (E.K.S.), R01DK131787 (E.K.S.), the University of Michigan Department of Internal Medicin... | CC BY | no | 2024-01-16 23:49:21 | medRxiv. 2023 Dec 22;:2023.12.20.23300290 | oa_package/56/2f/PMC10775342.tar.gz | |||||
PMC10775343 | 38196747 | Introduction
The overarching goal of drug discovery is to generate chemicals with specific functionality through the design of chemical structure ( Li & Kang, 2020 ). Functionality, often in the context of drug discovery, refers to the specific effects a chemical exhibits on biological systems (i.e., vasodilator, analg... | Methods
Database creation.
The SureChEMBL database was shuffled and converted to chiral RDKit-canonicalized SMILES strings, removing malformed strings ( Weininger, 1988 ; Papadatos et al., 2016 ; Landrum et al., 2013 ). SMILES strings were converted to InChI keys and used to obtain PubChem CIDs ( Kim et al., 2023 ). ... | Results
Patents are an abundant source of highly specific chemical knowledge. It is plausible that a large dataset of patent-derived molecular function would capture most known functional relationships and could approximate the chemical function landscape. High-fidelity approximation of the chemical function landscape ... | Discussion
While in silico drug discovery often proceeds through structural and empirical methods such as protein-ligand docking, receptor binding affinity prediction, and pharmacophore design, we set out to investigate the practicality of orthogonal methods that leverage the extensive corpus of chemical literature. ... | The fundamental goal of small molecule discovery is to generate chemicals with target functionality. While this often proceeds through structure-based methods, we set out to investigate the practicality of orthogonal methods that leverage the extensive corpus of chemical literature. We hypothesize that a sufficiently l... | Related Work
Labeled chemical datasets.
Chemicals are complex interacting entities, and there are many labels that can be associated with a given chemical. One class is specific protein binding, commonly used to train chemical representation models ( Mysinger et al., 2012 ; Wu et al., 2018 ). Datasets linking chemical... | Acknowledgments
The authors acknowledge the Biomedical Research Computing Facility at The University of Texas at Austin for providing high-performance computing resources. We would also like to thank AMD for the donation of critical hardware and support resources from its HPC Fund. This work was supported by the Welch ... | CC BY | no | 2024-01-16 23:35:06 | ArXiv. 2023 Dec 18;:arXiv:2309.08765v2 | oa_package/81/1d/PMC10775343.tar.gz | |
PMC10775347 | 38196746 | Introduction
Myelination is increasingly recognized as an important dynamic biomarker of brain development, aging, and various neurological conditions, including but not limited to multiple sclerosis, leukodystrophies, and neurodegenerative disorders ( 1 – 3 ). These conditions can lead to alterations in the biophysica... | Methods
ViSTa-MRF sequence
Figure 1(A) shows the sequence diagram of the ViSTa-MRF acquisition, where each acquisition group consists of multiple ViSTa-preparation blocks and one MRF-block. A water-exciting rectangular (WE-Rect) hard pulse ( 49 ) was employed for signal excitation, where the RF duration was set to 2.3... | Results
Figure 3(B) shows reconstructed 1mm-iso T 2 and MWF maps acquired from a healthy adult using the original FAs and the CRLB-optimized FAs. The red arrows indicate the CRLB-optimized results achieve higher SNR in MWF maps. The zoom-in figures demonstrate that the CRLB-optimized ViSTa images exhibit higher SNR a... | Discussion
In this work, we developed a 3D ViSTa-MRF sequence with a CRLB-optimized FAs and a memory-efficient subspace reconstruction to achieve high-resolution MWF, T 1 , T 2 , and PD mapping in a single scan. Compared to the accurate yet time-consuming standard ViSTa sequence, the proposed fast ViSTa-MRF approach pr... | Conclusion
In this work, we have developed a 3D ViSTa-MRF technique that combines the accurate but time-consuming ViSTa technique with MR fingerprinting for whole-brain multi-parametric MRI. This approach enables us to obtain whole-brain 1mm and 660μm isotropic myelin-water fraction, quantitative T 1 , T 2 and PD maps... | Purpose:
This study aims to develop a high-resolution whole-brain multi-parametric quantitative MRI approach for simultaneous mapping of myelin-water fraction (MWF), T 1 , T 2 , and proton-density (PD), all within a clinically feasible scan time.
Methods:
We developed 3D ViSTa-MRF, which combined Vi sualization of S ... | Supplementary Material | Acknowledgement
The authors would like to thank Dr. Vaidehi Subhash Natu, Sarah Shi Tung, Clara Maria Bacmeister and Bella Fascendini from Stanford University for their invaluable assistance in preparing the experiments. In the preparation of this manuscript, the OpenAI’s Large Language Model (LLM), specifically the GP... | CC BY | no | 2024-01-16 23:35:07 | ArXiv. 2023 Dec 21;:arXiv:2312.13523v1 | oa_package/f0/f8/PMC10775347.tar.gz |
PMC10775349 | 38196750 | Introduction
Moderate and high doses of ionising radiation are well established causes of most types of cancer 1 , 2 . There is emerging evidence, particularly for leukaemia and thyroid cancer, of risk at low dose (<0.1 Gy) radiation 3 – 6 (roughly 50 times the dose from background radiation in a year). For most other... | Methods
Synthetic data used for assessing corrections for dose error
The methods and data used closely parallel those of the previous paper 32 . We used the publicly available version of the leukaemia and lymphoma data of Hsu et al 36 to guide construction of a synthetic dataset. We assumed a composite Berkson-classi... | Results
As shown in Table 1 , the coverage probabilities of the ERC method for the linear coefficient are near the desired 95% level, irrespective of the magnitudes of assumed Berkson error, whether shared or unshared. However, the ERC method yields coverage probabilities that are somewhat too low when shared and un... | Discussion
We have demonstrated that the quasi-2DMC with BMA method performs poorly, with coverage probabilities both for the linear and quadratic dose coefficients that are under 5% when the magnitude of shared Berkson errors is large (50%) ( Table 1 ). This method also produces substantially biased (by a factor of 10... | Conclusions
We have demonstrated that the quasi-2DMC with BMA method performs poorly, with coverage probabilities both for the linear and quadratic dose coefficients that are under 5% when the magnitude of shared Berkson error is moderate to large ( Table 1 ). This method also produces substantially biased (by a factor... | Contributorship
M.P.L. formulated the analysis, wrote and ran the analysis code and wrote the first draft of the paper. L.B.Z. and N.H. contributed to extensive rewrites of the subsequent drafts of the paper. All authors reviewed the manuscript and approved its submission.
For many cancer sites low-dose risks are not k... | Acknowledgements
The authors are grateful for the detailed and helpful comments of Dr Jay Lubin. The Intramural Research Program of the National Institutes of Health, the National Cancer Institute, Division of Cancer Epidemiology and Genetics supported the work of MPL. The work of LBZ was supported by National Cancer I... | CC BY | no | 2024-01-16 23:35:06 | ArXiv. 2023 Dec 22;:arXiv:2312.02215v2 | oa_package/0b/d6/PMC10775349.tar.gz | |
PMC10775354 | 38196749 | INTRODUCTION: FMRI BRAIN DATA AND EFFECTIVE CONNECTIVITY
Functional Magnetic Resonance Imaging (fMRI) offers the highest-currently-available spatial resolution for three-dimensional images of real-time functional activity across the entire human brain [ Glasser et al., 2016 ]. For this reason, enormous resources have b... | CDA AND EFFECTIVE CONNECTIVITY METHODS FOR FMRI
When selecting a CDA method for fMRI analysis, the large number of algorithms developed over the last thirty years can be intimidating. However, the majority of CDA methods do not meet the minimum requirements for analyzing parcellated fMRI data. For example, many CDA met... | RESULTS FROM THE HCP CASE STUDY
Here we briefly review the findings from the HCP case study by Rawls et al. [2022 ]. This study developed the GANGO causal connectivity method, which was applied to n=442 resting-state fMRI data sets. The connectomes produced were extremely sparse (2.25% edge density) compared to Pearso... | CONCLUSION
Here we have outlined nine challenges that will be faced by researchers attempting to use CDA for fMRI effective connectivity analysis, and presented a recent case study that attempted to resolve at least some of these challenges. We have also discussed challenges that remain following this case study, such ... | Author Contributions
All authors contributed to the ideas in this paper and contributed to its drafting. All authors have reviewed and edited the paper’s content for correctness.
Designing studies that apply causal discovery requires navigating many researcher degrees of freedom. This complexity is exacerbated when the... | PRACTICAL CHALLENGES OF APPLYING CDA TO FMRI DATA
Any research study where CDA is applied to fMRI data will have to confront numerous study design challenges. Here we enumerate 9 challenges that apply to all CDA fMRI studies.
C1: Preprocessing.
Raw fMRI data contains numerous artifacts due to a wide variety of physical... | Acknowledgements
ER was supported by the National Institutes of Health’s National Center for Advancing Translational Sciences, grants TL1R002493 and UL1TR002494. BA was supported by the Comorbidity: Substance Use Disorders and Other Psychiatric Conditions Training Program T32DA037183. EK was supported by grants P50 MH1... | CC BY | no | 2024-01-16 23:35:06 | ArXiv. 2023 Dec 20;:arXiv:2312.12678v1 | oa_package/c9/35/PMC10775354.tar.gz | |
PMC10775355 | 38196754 | Materials and Methods
Flies were maintained using standard methods, and embryos were collected and prepared for imaging and laser surgery as previously described ( 35 , 66 – 68 ). Cell junctions were labeled via ubiquitous expression of DE-cadherin-GFP ( 69 ). Images were captured using Micro-Manager 2.0 software (Ope... | Results
We tracked the following quantities during dorsal closure, in model and experiments: mean cell shape index , mean aspect ratio (see SI section D ), orientational order parameter ( 44 ) (see SI section E ) characterizing the degree of cellular alignment (where is the angle between the major axis of each... | Discussion
We find experimentally that the AS remains in a solid phase ( i.e . with no cell neighbor exchanges) during dorsal closure. One might not be surprised since cells adhere to each other. It is important to realize, though, that cadherins have rapid on-off kinetics and the actin cortex has rapid turnover on the... | All authors conceived and designed the research project. IT and DH performed the vertex model simulations and analyzed and visualized the data from model and experiments. JC and DPK contributed experimental data. All authors contributed to data interpretation and collaborated on writing the manuscript.
Authors contribu... | The developmental stage of dorsal closure in Drosophila melangaster occurs roughly midway through embryogenesis and provides a model for cell sheet morphogenesis ( 1 – 4 ). The amnioserosa (AS) consists of a single sheet of cells that fills a gap on the dorsal side of the embryo separating two lateral epidermal cell ... | ACKNOWLEDGMENTS.
We thank M. L. Manning and S. R. Nagel for instructive discussions. This project was supported by NIH through Awards R35GM127059 (DPK) and 1-U01-CA-254886-01 (IT), NSF-DMR-MT-2005749 (IT, AJL) and by the Simons Foundation through Investigator Award #327939 (AJL). AJL thanks CCB at the Flatiron Institut... | CC BY | no | 2024-01-16 23:35:07 | ArXiv. 2023 Dec 20;:arXiv:2312.12926v1 | oa_package/a1/0b/PMC10775355.tar.gz | ||
PMC10775356 | 38196743 | Introduction
Cochlear implants are a successful neuroprosthetic that can restore hearing to people with severe sensorineural hearing loss. While partially implanted, they rely on an external hearing aid microphone that is positioned on the side of the head. The external nature of this microphone imposes many lifestyle ... | Results
A hearing device should ideally have a flat frequency response from 100 Hz to 4 kHz, as this is the frequency range of human speech [ 20 ]. The UmboMic apparatus performs well between 100 Hz to 7 kHz, with the frequency response determined mostly by the middle ear impedance; Figure 10 shows the frequency resp... | Conclusion
A totally-implantable cochlear implant would significantly improve the lives of users. The microphone component is one of the largest roadblocks to internalizing the entire system. Here, we present the UmboMic, a proof-of-concept prototype of a PVDF-based microphone that senses the motion of the umbo. We dem... | Objective:
We present the “UmboMic,” a prototype piezoelectric cantilever microphone designed for future use with totally-implantable cochlear implants.
Methods:
The UmboMic sensor is made from polyvinylidene difluoride (PVDF) because of its low Young’s modulus and biocompatibility. The sensor is designed to fit in the... | Cantilever design and fabrication
The UmboMic sensor is a triangular bimorph cantilever approximately 3 mm wide at the base, 3 mm long, and 200 μm thick. The free end of the triangular tip interfaces with the umbo to sense its motion. We design the UmboMic sensor to have a relatively uniform stress distribution in the ... | Acknowledgements
Kurt Broderick’s (MIT.nano) and Dave Terry’s (MIT.nano) expertise were instrumental in designing the UmboMic’s fabrication process. Many thanks to Yew Song Cheng (MEE, UCSF) for helping carry out temporal bone experiments at Mass. Eye and Ear.
Submitted December 2023. This paper is partially supported ... | CC BY | no | 2024-01-16 23:35:07 | ArXiv. 2023 Dec 22;:arXiv:2312.14339v1 | oa_package/63/f5/PMC10775356.tar.gz | ||
PMC10775357 | 38196649 | Background
Structural and systemic factors are central to ongoing racial and socioeconomic inequities in the United States 1 – 3 . Residential location is one such structural factor that influences a range of social, economic, and health-related outcomes. Increasing attention is being given to understanding the influen... | Methods
Block Groups
Our study area was the contiguous United States. We selected the U.S. Census block group as our areal unit of analysis for defining a neighborhood for several reasons. Block groups have relatively small geographic areas with a population range of approximately 600–3000 and it is the unit used by th... | Results
There were 241,764 block groups of which 44,330 (18%) overlapped at least partially with a HOLC neighborhood and 32,646 (14%) overlapped at least 50% and therefore met our inclusion criteria. An ADI decile was not assigned to 502 of these block groups due to low population counts and/or high populations residin... | Discussion
Structural inequity and racism remain major driving forces behind health inequities yet our ability to capture or measure structural inequity has been challenging. Here we describe one method that captures the dynamic legacy of housing policy. The Neighborhood Trajectories evaluate the influence of the histo... | The role of historic residential redlining on health disparities is intertwined with policy changes made before and after the 1930s that influence current neighborhood characteristics and shape ongoing structural racism in the United States. We developed Neighborhood Trajectories which combine historic redlining data a... | Financial Support
HC provided support through the GeoSpatial Resource, a section of the Biostatistical and Bioinformatics Shared Resource at the Dartmouth Cancer Center with NCI Cancer Center Support Grant 5P30CA023108. AL and JW were supported by the National Cancer Institute of the National Institutes of Health under... | CC BY | no | 2024-01-16 23:35:07 | Res Sq. 2023 Dec 22;:rs.3.rs-3783331 | oa_package/1f/57/PMC10775357.tar.gz | ||
PMC10775359 | 38196752 | INTRODUCTION
The human brain undergoes notable changes during development, particularly in white matter tracts that modulate cognitive and motor functions [ 1 ]. Accurately estimating these fibers is crucial for understanding developmental patterns and detecting abnormalities. Advances in diffusion magnetic resonance i... | METHODOLOGY
Data Processing
We used dMRI data from the 3 rd release of the Developing Human Connectome Project (dHCP) [ 16 ] and the Baby Connectome Project (BCP) [ 17 ]. The dHCP dataset includes 783 subjects from 20–44 post-menstrual weeks, acquired using a 3T Philips scanner and a multi-shell sequence ( b ∈ {0, 40... | RESULTS
Intra-Site Experiments
The DL metrics are first compared to the GT consistency (GS in Table 1 ) for dHCP and BCP. As previously reported in [ 23 ], single-fiber predictions show good agreement, but performance decreases with multiple fibers for both datasets. This is more pronounced in three-fiber cases, which... | CONCLUSION
This work has demonstrated that even a small number of target data samples can be instrumental in overcoming domain shifts encountered in white matter fiber estimation with deep learning. Through the application of fine-tuning and to a lesser extent the MoM harmonization strategies, models have shown improve... | H. Kebiri and M. Bach Cuadra — Equal contribution.
Deep learning models have shown great promise in estimating tissue microstructure from limited diffusion magnetic resonance imaging data. However, these models face domain shift challenges when test and train data are from different scanners and protocols, or when the ... | ACKNOWLEDGMENTS
We acknowledge the CIBM Center for Biomedical Imaging, a Swiss research center of excellence founded and supported by CHUV, UNIL, EPFL, UNIGE, HUG, and the Leenaards and Jeantet Foundations. This research was partly funded by the Swiss National Science Foundation (grants 182602, 215641); also by the Nat... | CC BY | no | 2024-01-16 23:35:06 | ArXiv. 2023 Dec 22;:arXiv:2312.14773v1 | oa_package/58/f7/PMC10775359.tar.gz | ||
PMC10775360 | 38196607 | BACKGROUND
Kidney cancer is one of the ten most prevalent cancers in the United States, ranking as the sixth and ninth most common cancer in men and women, respectively ( 1 ). In 2023, it is anticipated that around 81,800 new cases of kidney cancer will be diagnosed in the United States, resulting in 14,890 deaths ( 1 ... | METHODS
Reagents
DOPC and DSPE-(PEG)2000-OMe were purchased from Avanti Polar Lipids and Nanosoft Polymers, respectively. Cholesterol was purchased from Sigma. TTP-conjugated lipopeptide was synthesized as described previously. Everolimus and YM155 were obtained from LC laboratories and MedChemExpress, respectively. An... | RESULTS
EY-L is a homogeneous, positively charged nanoformulation
The amount of lipid and drug components of the drug-loaded liposomes (E-L, Y-L, and EY-L) are reported in Supplementary Table S1 along with drug loading efficiency (DLE) and encapsulation efficiency (EE) values. The initial amounts of Everolimus and YM... | DISCUSSION
The primary objective of RT in radiation oncology is to hinder the proliferation of cancer cells and ultimately eliminate them. RT employs various mechanisms to achieve this, including, apoptosis, autophagy, mitotic death (or mitotic catastrophe), necrosis, and senescence ( 45 ). However, given that radiatio... | CONCLUSION
In summary, our study utilized a rational combination of an mTOR inhibitor and a survivin inhibitor in a tumor-targeted liposomal formulation to augment radiation therapy in renal cancer by inhibiting DNA damage repair and enhancing mitotic catastrophe. The combination itself showed excellent tumor growth in... | Authors’ contributions
HKR developed and characterized the liposomal formulations, performed in vitro and in vivo experiments, and acquired the data. VSM optimized the liposomal formulation. RSA performed the confocal imaging studies and related analysis. NMN helped with the characterization of the liposomal formulatio... | Acknowledgements
The authors would like to thank Brandy Edenfield and Laura Lewis-Tuffin for immunohistochemistry and assistance with the digitization of the slides respectively.
Funding
This work was supported by the Academy of Kidney Cancer Investigators Early Career Investigator award W81XWH-21-1-0678 (KP) and NIH g... | CC BY | no | 2024-01-16 23:35:07 | Res Sq. 2023 Dec 23;:rs.3.rs-3770403 | oa_package/32/0b/PMC10775360.tar.gz | |
PMC10775365 | 38196659 | Introduction
Antiretroviral therapy (ART) has demonstrated remarkable efficacy in mitigating HIV/AIDS-related morbidity and mortality, particularly in resource-limited settings [ 1 , 2 ]. However, the full realization of its benefits has been impeded by the high loss to follow-up (LTFU) [ 3 ], especially within the fi... | Methods
Objective
This comprehensive cost study aimed to improve the understanding of the financial and economic implications of routine proactive and reactive retention interventions for ART clients at the MPC clinic in Lilongwe, Malawi.
Setting: Lighthouse Trust (LT) Martin Preuss Center (MPC)
MPC is the largest publ... | Results
MPC ART clients
In 2021, there were 3,280 new ARTs initiated. Among these clients on ART, 7,588 had tracing events. All new ART clients are expected to have an initial encounter with a promoter to receive support during their first year of treatment, ensuring their continued care. Additionally, the B2C approach... | Discussion
In this study, we provide a comprehensive breakdown of the routine costs associated with proactive and reactive ART retention interventions at the large, public ART clinic in Lilongwe, Malawi. This cost analysis provides valuable insights into the financial aspects of an ART retention intervention conducted ... | Conclusion
These findings significantly contribute to our understanding of the financial landscape surrounding ART retention interventions. To ensure the long-term sustainability and efficiency of the ART retention care program at the MPC, it is imperative to explore resource optimization strategies for both proactive ... | Introduction
Antiretroviral therapy (ART) improves the health of people living with HIV (PLHIV). However, a high loss to follow-up, particularly in the first year after ART initiation, is problematic. The financial expenses related to client retention in low- and middle-income countries (LMICs) in sub-Saharan Africa ar... | Funding:
The research reported in this publication was supported by the Fogarty International Center of the National Institutes of Health (NIH) under Award Number R21TW011658/R33TW011658 (CF). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National I... | CC BY | no | 2024-01-16 23:35:07 | Res Sq. 2023 Dec 22;:rs.3.rs-3773952 | oa_package/21/d2/PMC10775365.tar.gz | |
PMC10775376 | 38196608 | Introduction
Hidradenitis Suppurativa (HS) is a chronic skin condition characterized by inflammatory nodules and abscesses that progress to draining sinus tracts, punctuated by periods of disease exacerbation and flaring. In addition to a decreased quality of life 1 , HS is often co-morbid with other high-risk conditio... | Methods
Study design
The qualitative approach used in this study was grounded theory. Individual semistructured, virtual interviews were performed with adults diagnosed with HS. The virtual interviews were conducted over a video conference platform. The interview questions explored patients’ perspectives on how their p... | Results
A total of 23 study participants with hidradenitis suppurativa were interviewed in this study in which 21 participants (91%) were female and 2 participants (9%) were male. The mean age of participants was 31.2 (SD: 6.9, range: 19–43) ( Table 1 ).
Impact of HS on Personal Health
Most participants described HS as... | Discussion
The patient perspectives explored in this qualitative study revealed that HS has a significant impact on multiple aspects of a patient’s perceived personal health which influences their decisions around their medical care. HS patients describe considering their skin condition when deciding which medications ... | Conclusion
In conclusion, this qualitative study found that HS has a significant impact a patient’s perception of their personal health and how this affects their medical decision making as well as their decisions around vaccines. These findings are important because they provide more detailed insight about the individ... | Background:
Hidradenitis suppurativa (HS) is a chronic skin disease that causes significant burden for patients in multiple aspects of their life. However, the details regarding the impact on factors aside from skin are limited.
Objective:
We explored patient perspectives around the impact of HS on personal health and ... | Acknowledgements:
There are no acknowledgements.
Funding sources:
This study was funded by a K23 Career Development Award (K23-AR073932) from the National Institute of Arthritis, Musculoskeletal and Skin Diseases (MHN). | CC BY | no | 2024-01-16 23:35:06 | Res Sq. 2023 Dec 22;:rs.3.rs-3778510 | oa_package/a2/80/PMC10775376.tar.gz | |
PMC10775378 | 38196646 | Introduction
The mosquito-transmitted protozoan parasite Plasmodium falciparum is the major etiological agent of human malaria, causing more than 200 million clinical cases and 500,000 deaths per year, especially in young children in sub-Saharan Africa ( 1 ).Vector control strategies such as insecticide-treated nets ... | Materials and methods
Antigen production, immunization, and monoclonal antibody production
The Pfs230 D1M domain (SVLQSGALPSVGVDELDKIDLSYETTESGDTAVSEDSYDKYASQNTNKEYVCDFTDQLKPTESGPKVKKCEVKVNEPLIKVKIICPLKGSVEKLYDNIEYVPKKSPYVVLTKEETKLKEKLLSKLIYGLLISPTVNEKENNFKEGVIEFTLPPVVHKATVFYFICDNSKTEDDNKKGNRGIVEVYVEPYGNKING) was codon... | Results
Mouse-antisera generated after immunization with recombinant Pfs230 D1M domain show high reactivity in vitro
Pfs230 is a 230 kDa cysteine-rich protein, originally present as a 360 kDa precursor on the gametocyte surface( 24 ). It includes 14 cysteine-rich domains (CM) and a natural protease cleavage site at po... | Discussion
Targeting the malaria parasite in the mosquito vector using transmission-blocking vaccines is a disease control strategy that has been gaining increasing interest over the past decades due to the difficulties in eliminating malaria for the lack of an effective vaccine ( 30 ). Transmission-blocking vaccine’s ... | Authors contribution
Conceived and designed the experiments: E.C.C., G.D., and E.B.; performed the experiments: E.C.C., Y.D., and M.L.S.; analyzed the data: all authors; First draft: E.C.C. All authors have read and agreed to the published version of the manuscript.
Vector control is a crucial strategy for malaria elim... | Acknowledgments
We thank all members of the Bier laboratory and Dimopoulos laboratory for constructive ideas and discussions. We thank the Johns Hopkins Malaria Research Institute Insectary and Parasitology core facilities and Bloomberg Philanthropies for their support. We also thank Dr. Sabyasachi Pradhan for providin... | CC BY | no | 2024-01-16 23:35:07 | Res Sq. 2023 Dec 19;:rs.3.rs-3757253 | oa_package/b6/3d/PMC10775378.tar.gz | ||
PMC10775397 | 38196580 | Introduction
The International Space Station (ISS) is a modular spacecraft replete with stressors that challenge the bounds of human physiology. Astronauts aboard the ISS live in a tight-quarter, enclosed, near-weightless environment in low Earth orbit. Astronauts face superterrestrial levels of ionizing radiation, dis... | Methods
Cell culture
Deidentified human cortical kidney samples were collected through the Northwest Biotrust at the University of Washington Medical Center with local IRB approval (UW IRB Study 1297). Primary human proximal tubule epithelial cells were isolated by mechanical and enzymatic dissociation and cultured as ... | Results
PT-MPS platform and perfusion system
Nortis microfluidic chips are molded from polydimethylsiloxane, a semi-transparent, flexible, generally bio-compatible, and gas-permeable silicone polymer ( Fig. 1 ). While the footprint of the Nortis Triplex chip is relatively small, the equipment required for perfusion inc... | Discussion
Plasma levels of 1α,25(OH) 2 D 3 have been shown to decrease over time in astronauts on flight. This phenomenon could be due to several known factors including 1) changes in hydrostatic pressure that drive the movement of water and protein from the intravascular space to intracellular and interstitial compa... | Author contributions
KAL, KJI, CKY, EJK, and JH developed and designed the experiments, KAL, KJI, JY, JB conducted the experiments. KAL, KJI, CKY, JH, LW, TKB, JWM and EJK conducted data analysis. JC and KET conducted the vitamin D analyses. SC and PK led the development of hardware. All authors contributed to writing ... | Acknowledgements
This work was supported by the National Center for Advancing Translational Sciences (UH3TR000504, UG3TR002158 and UH3TR002178), jointly by the National Center for Advancing Translational Sciences and the Center for the Advancement of Science in Space (UG3TR002178), the National Institute of Environment... | CC BY | no | 2024-01-16 23:35:07 | Res Sq. 2023 Dec 21;:rs.3.rs-3778779 | oa_package/4c/3a/PMC10775397.tar.gz | ||
PMC10775398 | 38196640 | Introduction
According to National Alliance on Mental Illness (NAMI), in 2021 22.8 percent (57.8 million) of United States (US) adults experienced a mental illness; the annual prevalence is 21.4% in African Americans. 47.2 percent of adults with mental illness received treatment, with treatment rates of 39.4 percent in... | Methods
A peer-reviewed literature search was done using Google Scholar and PubMed databases between 2001 and 2019. Keywords like “African American” “Mental Health” “Underutilization” and “Barriers” were used to narrow the search. A total of twelve articles were reviewed and determined to be in the scope of this litera... | Results
159 participants were included in this study. 68 of the students were under 21 years of age, while 91 of the students were 21 years of age or older. 85.53% (136) of the participants were female and 13.84% (22) were male. 1 participant responded as non-binary. 60.24% (100) of the students were Black or African A... | Discussion
Students were predominately African American (60.24%) and female (85.53%). These statistics are consistent with the demographics of the University at study being mostly African American female students. Of the 159 surveys completed, 13 responded they have used mental health resources on campus. Approximately... | Conclusions
This study shows that there are multiple barriers that have been attributed to the underutilization of mental health resources both on and off campus. According to the results of this survey, the majority of students lack time to utilize or denied the need for any mental health resources. Further research s... | Author Contribution
Ahlam Ayyad contributed to the conception of the study, study design, data analysis, and first manuscript draft preparation. Thomas Maestri was a research mentor that assisted in every step of the process. Savannah Harris, Nina Casanova, and Hanan Ibrahim contributed to the literature review, survey... | Acknowledgment:
This work was supported by NIH RCMI program at Xavier University of Louisiana through Gran U54MD00795. Additionally, we would like to acknowledge Dr.Carroll J. Diaz, Jr., Ph.D. for assisting in statistical analysis of data. | CC BY | no | 2024-01-16 23:35:07 | Res Sq. 2023 Dec 19;:rs.3.rs-3760662 | oa_package/15/6f/PMC10775398.tar.gz | |
PMC10775400 | 38196619 | Introduction
Uveal melanoma (UM) is the most common intraocular malignancy in adults, with a high rate of metastasis and a poor prognosis. 1 The accurate diagnosis of small UM is challenging due to similar clinical characteristics to benign choroidal nevi. Tumors diagnosed as choroidal nevi that subsequently grow duri... | Methods
This retrospective study included analysis of 223 eyes from 221 patients with melanocytic choroidal lesions seen at the eye clinic at the University of Illinois at Chicago between 01/2010 and 07/2022 ( Table 1 ). The study was approved by the institutional review board (IRB) and patient records were collected f... | Results
Patient demographics
A total of 115 patients with choroidal nevi and 108 patients with UM were included in this study. The mean age of patients with choroidal nevi was 64.9 years (range: 27–95), while patients with UM had a mean age of 66.1 years (range: 30–97) ( Table 1 ). The majority of patients were female ... | Discussion
The accurate diagnosis of small melanocytic choroidal tumors is challenging due to similar clinical characteristics between benign choroidal nevi and small malignant UM. These patients benefit from the careful evaluation by an ocular oncologist experienced in managing intraocular tumors. Current practice use... | Objective
This study aims to assess a machine learning (ML) algorithm using multimodal imaging to accurately identify risk factors for uveal melanoma (UM) and aid in the diagnosis of melanocytic choroidal tumors.
Subjects and Methods
This study included 223 eyes from 221 patients with melanocytic choroidal lesions seen... | Acknowledgments
We acknowledge the editorial assistance of the University of Illinois Chicago Center for Clinical and Translational Science (CCTS), which is supported by the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health, through Grant Award Number UL1TR002003.
Financial Sup... | CC BY | no | 2024-01-16 23:35:07 | Res Sq. 2023 Dec 21;:rs.3.rs-3778562 | oa_package/d5/ab/PMC10775400.tar.gz | ||
PMC10775408 | 38196633 | Introduction
Genome-wide associations studies (GWAS) in Alzheimer’s disease (AD) 1 and Parkinson’s disease (PD) 2 continue to identify an increasing number of genetic variants associated with the risk for developing these neurodegenerative disorders. However, the functional mechanisms underlying these associations re... | Methods
Methylation quantitate trait locus (meQTL) genome-wide association study (GWAS) and independent replication analyses.
Human samples
In this study, we analyzed a total of 2,592 samples from three independent datasets (“Berlin Aging Study II” [BASE-II] recruited in Berlin, Germany, “Barcelona Brain Health Initiat... | Results
Methylation quantitative trait locus (meQTL) genome-wide association studies (GWAS) and independent replication analyses
For each of the three available tissues, blood (n=1,058), buccals (n=1,527) and saliva (n=837), we performed meQTL GWAS analyses testing approximately 5.5 million common (minor allele frequen... | Discussion
In this work, we performed extensive genome-wide mapping of meQTLs in three peripheral human tissues of which two (buccal and saliva) were not sufficiently covered in comparable previous efforts. After performing more than 12 trillion statistical tests, we identified between 11 and 15 million genome-wide sig... | Author contributions Conception and design of study: O.O., Y.S., C.M.L., L.B. Sample recruitment and handling: D.B.F., G.C., S.D., A.M.F., U.L., A.P.L., C.S.P., J.M.T., V.M.V., K.B.W., I.D. Generation of molecular data: Y.S. V.D., S.S.S., T.W., M.W., A.F. Statistical analysis and interpretation: O.O., Y.S., J.H., L.D.... | Data availability
All results of this study have been made available on Zenodo (URL: https://doi.org/10.5281/zenodo.10410506 ). Together with the AD/PD summary statistics from Bellenguez et al. (ref. 1 ) and Nalls et al. (ref. 2 ) these allow a full reproduction of all MR (incl. SMR) and colocalization analyses pres... | Acknowledgements
The authors are grateful to all participants for their time, commitment, and willingness to participate the in BASE-II, BBHI, and LCBC studies. Part of this research was funded by the EU Horizon 2020 Grant: ‘Healthy minds 0–100 years: Optimising the use of European brain imaging cohorts (“Lifebrain”; g... | CC BY-ND | no | 2024-01-16 23:49:21 | medRxiv. 2023 Dec 24;:2023.12.22.23300365 | oa_package/2a/74/PMC10775408.tar.gz | |
PMC10775420 | 38196643 | Background
In regulated clinical trials, investigators must rely on research data acquired to (1) ensure the safety and efficacy of medical treatments (to protect research participants and the general population at large), and (2) ensure the reliability and reproducibility of study results. High quality data provide th... | Methods
Literature Review
A PubMed search on the Medical Subject Heading (MeSH) terms “data quality” AND (registry OR “clinical research” OR “clinical trial”) through 2008 was conducted to identify relevant citations (see Additional File 1, Appendix A, Item A1 for the full PubMed Search Strategy and Table A2 for the PR... | Results
Manuscripts Included for Analysis
An initial search of the literature identified 350 citations. After excluding duplicates and performing the initial screen of abstracts, 54 manuscripts remained. A search using PubMed related links and secondary and tertiary references identified an additional 70 manuscripts, y... | Discussion
This study calculated and compared error rates across the various data processing methods described in the literature. The results indicated that the accuracy associated with data processing methods varied widely. Error rates ranged from 2 to 2,784 errors per 10,000 fields within the 4 most common data proce... | Conclusion
Based on the pooled analysis of error rates from the published literature, we conclude that data processing and cleaning methods used in clinical trials research may explain a significant amount of the variability in data accuracy. For example, MRA error rates were associated with the highest and most variab... | This work was conducted while Dr. Simon was at the ECHO Program at the NIH. He is now at the National Center for Health Statistics (NCHS), Centers for Disease Control and Prevention (CDC).
Authors’ Contributions
MYG and MNZ conceived and designed the study. ACW, AES, LAD, LWY, JL, JS, and SO contributed significantly t... | Acknowledgments
We thank Phyllis Nader, BSE for her assistance with this project.
Funding
Research reported in this publication was supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under award numbers UL1TR003107 and KL2TR003108, and by the IDeA States Pediatric... | CC BY | no | 2024-01-16 23:35:07 | Res Sq. 2023 Dec 21;:rs.3.rs-2386986 | oa_package/99/d1/PMC10775420.tar.gz | |
PMC10775493 | 38196590 | Background
For patients with metastatic colorectal cancer (mCRC), surgical resection, when possible, has been associated with long-term progression-free survival (PFS) and overall survival (OS). Several large retrospective series have demonstrated 5-year OS rates of 40–70% in patients with isolated liver metastasis fol... | Methods/Design
Study Objectives
The primary objective of ERASur is to compare the outcome of using TAT in addition to SOC systemic therapy versus SOC systemic therapy alone in terms of OS, measured from the time of randomization, in patients with newly diagnosed limited mCRC. The secondary objectives include evaluating... | Discussion
ERASur is a multicenter randomized phase III clinical trial currently accruing through the U.S. NCI NCTN, which is designed to evaluate the benefit of adding metastatic-directed therapy to SOC systemic therapy in patients with limited mCRC. As imaging and treatment technology and techniques improve, the abil... | Authors’ contributions: All authors contributed to both the original protocol and the manuscript. All have read and approved the final manuscript.
Background:
For patients with liver-confined metastatic colorectal cancer (mCRC), local therapy of isolated metastases has been associated with long-term progression-free a... | Acknowledgements:
We acknowledge Jennifer Huber for editorial assistance.
Funding:
Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Numbers U10CA180821 and U10CA180882 (to the Alliance for Clinical Trials in Oncology), U10CA180820 (ECO... | CC BY | no | 2024-01-16 23:35:07 | Res Sq. 2023 Dec 23;:rs.3.rs-3773522 | oa_package/6d/59/PMC10775493.tar.gz | |||
PMC10775679 | 38196638 | Introduction
Rare diseases, also known as orphan diseases, are defined by the European Union as those affecting fewer than one in 2,000 people, and in the United States as those affecting fewer than 200,000 people nationwide 1 , 2 . Rare diseases are collectively very common, and it is estimated that as many as 1 in 16... | Methods
Data collection and preprocessing
The primary training data were derived from the UK Biobank 73 . For each participant, we retrieved age at recruitment (field 21022), sex (field 31), and a list of all ICD-10 diagnosis codes recorded across all inpatient hospital records (field 41270). We also retrieved self-rep... | Results
Model training and cross-validation
We implemented a transformer model with a self-attention mechanism similar to AI language models such as BERT and GPT, along with a “masked diagnosis modeling” training objective by analogy to the “masked language modeling” objective used by some of these language models 19 .... | Discussion
Here we present RarePT, a transformer-based phenotype prediction method designed to predict rare disease diagnoses based on diagnosis codes present in a patient’s electronic health records (EHR). We apply this method to predicting rare disease in the UK Biobank, and find that a very large fraction of rare di... | Author Contributions: Dr. Jordan and Dr. Do had full access to all of the data in the study and take responsibility for the integrity of the data and accuracy of the data analysis.
It is estimated that as many as 1 in 16 people worldwide suffer from rare diseases. Rare disease patients face difficulty finding diagnosi... | Supplementary Material | Funding/Support:
Dr. Do is supported by the National Institute of General Medical Sciences of the NIH (R35-GM124836). This research has been conducted using the UK Biobank Resource under Application Number 16218. This work was supported in part through the Mount Sinai Data Warehouse (MSDW) resources and staff expertise... | CC BY | no | 2024-01-16 23:49:21 | medRxiv. 2023 Dec 24;:2023.12.21.23300393 | oa_package/f0/75/PMC10775679.tar.gz | |
PMC10775685 | 38196663 | Materials and Methods
Research Subjects
Blood samples and clinical, biological, and questionnaire data were collected after obtaining written informed consent. Genetic data for this project originated from 3 independent cohorts: (1) the Malta Next Generation Sequencing (NGS) Project (ethics approval: 031/2014) that use... | Results
Analysis of HTS data of 146 research subjects from the Malta NGS project identified 8 heterozygotes harboring the GNRHR p.Q106R variant. Four of these (2 of whom were parent and offspring) formed part of the IHH cohort (n = 17), while the other 4 did not have any IHH characteristics, nor a family history of I... | Discussion
Based on available fertility data ( Table 1 ) and hormone profile analyses ( Table 2 ) of GNRHR p.Q106R heterozygote and wild-type individuals, we report no differences between the 2 genotypes. In fact, there were no differences in median levels of the reproductive hormones (LH, FSH, estradiol, free testos... | Abstract
Context
The gonadotropin-releasing hormone receptor variant GNRHR p.Q106R (rs104893836) in homozygosity, compound heterozygosity, or single heterozygosity is often reported as the causative variant in idiopathic hypogonadotropic hypogonadism (IHH) patients with GnRH deficiency. Genotyping of a Maltese newbor... | Idiopathic hypogonadotropic hypogonadism (IHH) is a rare genetic disorder that is characterized by partial or complete absence of pubertal development. Dysfunction of the hypothalamic-pituitary-gonadal axis leads to disorders of development, sexual maturation, and reproduction. Disruption in migration, differentiation ... | Acknowledgments
Ms. Anna Lisa Sciortino is acknowledged for overseeing biochemical assays carried out on the IMMULITE 2000 and Ms. Simona Maria Pagano and Ms. Dorianne Cassar for assisting with LH and FSH assays.
Funding
This work was funded by the MAMI study (R&I-2008-006, a collaboration between the University of Mal... | CC BY | no | 2024-01-16 23:36:47 | J Endocr Soc. 2023 Dec 29; 8(2):bvad172 | oa_package/49/a4/PMC10775685.tar.gz | ||
PMC10776312 | 38205163 | Methods
Cell Cultures, Sample Preparations, and Reagents
The detailed steps for cell culture were in accordance with those described in our previous studies. Briefly, keratinocytes (HEK, Cat # 2110, ScienCell) were cultured in normal (6mM) and high (30mM) glucose media for 24 hours respectively, to simulate diabetic co... | Results
Increased KRT17 Expression in HEK and HaCaT Cultures Under High Glucose
Although KRT17 mRNA expression was increased in our previous study using RNA sequencing–based transcriptome analysis, measuring gene expression in normal and high glucose–stimulated skin cells, the activity of KRT17 was indeterminate. We fu... | Discussion
To investigate the gene expression changes and interactions of skin cells under high conditions, we established 3 major skin cell models (HEK, HDF, and HDMEC) stimulated by high glucose in the preliminary stage and we performed RNA-seq analysis on the cell samples. In this study, we first verified the upregu... | Peng Zhou, Yiqing Li and Chao Yang contributed equally to this work.
Abstract
Objective
To investigate the effects of overexpressed keratin 17 (KRT17) on the biology of human dermal fibroblasts (HDFs) and to explore the mechanism of KRT17 in diabetic wound healing.
Methods
KRT17 expression was tested in diabetic kerati... | Diabetes mellitus is one of the most common systemic chronic metabolic diseases, mainly manifested by symptoms of hyperglycemia caused by defective insulin secretion and/or insulin function, and it is a serious threat to human health worldwide [ 1 , 2 ]. Diabetes mellitus and its associated complications have a seriou... | Funding
This project was supported by Grant No. 82270520 of the National Natural Science Foundation of China.
Author Contributions
L.Q. and Y.C. contributed substantially to the design of the study. Z.P. and L.Y.Q. contributed substantially to study completion. C.D.X., G.R.K., and Z.S. collected the data. Z.P. and L.Y.... | CC BY | no | 2024-01-16 23:36:47 | J Endocr Soc. 2024 Jan 2; 8(2):bvad176 | oa_package/77/b4/PMC10776312.tar.gz | ||
PMC10777671 | 38205164 | Patients and Methods
A retrospective review was conducted on the clinical records of all boys with BUDT who had undergone evaluation over a 14-year period from January 1, 2008, to December 31, 2021, by the endocrine service at the Royal Hospital for Children, Glasgow. Boys were selected by searching the hospital's oper... | Results
Characteristics of the Study Population
A total of 243 bilateral orchidopexies were performed at RHCG between 2008 and 2021. Of these, 130 (53%) boys were seen by the endocrine team ( Table 1 ). There was no statistically significant difference in those who were referred to the endocrine team compared to those ... | Discussion
This study considers the evaluation of boys with BUDT from a large tertiary pediatric center within the United Kingdom over a 13-year period. We demonstrate variation in the extent to which these children are investigated even within a single center, without any clear clinical predictors regarding this varia... | Abstract
Background
Bilateral undescended testes (BUDT) may be a marker of an underlying condition that affects sex development or maturation.
Aims
To describe the extent of gonadal dysfunction in cases of BUDT who had systematic endocrine and genetic evaluation at a single tertiary pediatric center.
Methods
A retrospe... | Undescended testis is a common congenital anomaly with a birth prevalence of between 1.5% and 8% of newborns [ 1 ]. The majority will have a unilateral undescended testis, and only 1/10 of these newborns will present with bilateral undescended testes (BUDT) [ 2 ]. Undescended testes, especially when they are bilateral ... | Acknowledgments
A.K.L.H. is funded by an NHS Education for Scotland/Chief Scientist Office Clinical Lectureship PCL/21/05.
Disclosures
The authors have nothing to disclose.
Data Availability
Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from ... | CC BY | no | 2024-01-16 23:36:47 | J Endocr Soc. 2023 Dec 12; 8(2):bvad153 | oa_package/b9/75/PMC10777671.tar.gz | ||
PMC10781692 | 38199983 | Introduction
Suicide risk in patients with major depressive disorder (MDD) is 20 times more than that of the general population [ 1 , 2 ], and suicidal behavior exists at all times during major depressive episodes [ 3 ]. The lifetime prevalence of suicide attempts in patients with MDD is 31% [ 4 ]. and more than half ... | Methods
Participants
The study was approved by the Ethics Committee of the First Affiliated Hospital, Fourth Military Medical University, and was conducted in accordance with the Declaration of Helsinki (clinicaltrial.gov identifier: NCT04653337). Written informed consents were obtained from all the participants.
All p... | Results
For all 26 patients, the MNI coordinates of the stimulation targets, the corresponding superficial depths, resting motor thresholds (RMT) and relevant clinical outcomes were displayed in Table 2 . No severe adverse events occurred during the whole trial and the most common side effect was headache (supplementa... | Discussion
In the current study, we examined the feasibility and clinical efficacy of SAINT in the relief of suicidal ideation in patients with MDD. Our results showed that SAINT rapidly reduced the severity of suicidal ideation with a high response rate of up to 65.63% with only 5 days of treatment. Moreover, stimulat... | High suicide risk represents a serious problem in patients with major depressive disorder (MDD), yet treatment options that could safely and rapidly ameliorate suicidal ideation remain elusive. Here, we tested the feasibility and preliminary efficacy of the Stanford Accelerated Intelligent Neuromodulation Therapy (SAIN... | Supplementary information
| Supplementary information
The online version contains supplementary material available at 10.1038/s41398-023-02707-9.
Acknowledgements
This work was supported by the National Natural Science Foundation of China (61976248, 81974215), Clinical Research Project of Fourth Military Medical University (2021XB023), and Shenzh... | CC BY | no | 2024-01-16 23:34:59 | Transl Psychiatry. 2024 Jan 10; 14:21 | oa_package/c6/b6/PMC10781692.tar.gz | |
PMC10782803 | 38205965 | INTRODUCTION
Accurate pathological diagnosis is crucial for managing cancer patients, and many efforts have been made for it. In virtue of artificial intelligence (AI) techniques, various diagnostic classifiers emerge, such as the ones trained from hematoxylin and eosin images [ 1–3 ], stimulated Raman histology data [... | METHODS AND RESULTS
Package overview
The package has three modules ( Figure 1 ). The first is a machine learning module. It constructs classifiers from DNAm data, including the methods of RF, SVM, XGBoost, ELNET (elastic net classification), eSVM, eNeural and MOGONET . The second module is a multi-omics module. It con... | METHODS AND RESULTS
Package overview
The package has three modules ( Figure 1 ). The first is a machine learning module. It constructs classifiers from DNAm data, including the methods of RF, SVM, XGBoost, ELNET (elastic net classification), eSVM, eNeural and MOGONET . The second module is a multi-omics module. It con... | DISCUSSION
DNAm profiling is a useful tool for tumor diagnosis [ 5–8 ], and large margin classifiers, such as SVM, have better accuracy than other methods to classify DNAm data. However, SVM has a time-consuming problem because its sequential minimal optimization (SMO) solving algorithm will largely slow down when many... | Abstract
DNA methylation profiling is a useful tool to increase the accuracy of a cancer diagnosis. However, a comprehensive R package specially for it is lacking. Hence, we developed the R package methylClass for methylation-based classification. Within it, we provide the eSVM (ensemble-based support vector machine)... | Supplementary Material | Yu Liu PhD, is a Research Fellow (VP) at Laboratory of Pathology, Center for Cancer Research, National Cancer Institute. | CC BY | no | 2024-01-16 23:36:46 | Brief Bioinform. 2024 Jan 9; 25(1):bbad485 | oa_package/0a/8b/PMC10782803.tar.gz | |
PMC10782991 | 38222060 | Introduction
In the last two decades, economists have developed a growing interest in multidimensional measures of complex social phenomena, such as poverty and well-being ( Stiglitz et al., 2010 ), as a tool to evaluate the outcomes of public policies and the Welfare State ( Atkinson 2005 ; Pestieau & Lefebvre 2018 )... | Methods
The Choquet integral as aggregation operator
Hereafter, we assume that Social Inclusion can be described with a bounded cardinal indicator, generated by a function W , having a vector of attributes as its arguments. The function W needs to be expressive enough to approximate its target sufficiently well, and... | Results
Decision-makers’ preferences
Twelve Experts were interviewed to gather preferences on the criteria considered in the composite index. In this section, the results of the decision process are shown, with a focus on the main behavioural indices listed in section 3.1 ; full results are available in online supple... | Discussion
While Social Inclusion has become central to the policy debate within the European Union, there is limited comparative evidence on how countries have performed in reducing Social Inclusion in the last decades. While some recent studies have provided multidimensional indices of Social Inclusion for Europe, th... | Conflicts of interest : the authors declare no conflicts of interests.
Abstract
This paper introduces a normative, expert-informed, time-dependent index of Social Inclusion for European administrative regions in five countries, using longitudinal data from Eurostat. Our contribution is twofold: first, our indicator i... | Social inclusion: conceptual framework and data
Promoting Social Inclusion is a priority target in the European Commission’s strategic vision, as exemplified by large policy initiatives such as the Lisbon Strategy, Europe 2020 and Europe 2030. For example, in 2010 the EU countries committed to reduce by at least 20 mil... | Acknowledgments
The authors thank Michele Bernasconi, Giovanni Bertin, Danilo Cavapozzi, Martina Celidoni, Koen Decancq, Marco Fattore, and Filomena Maggino for their valuable comments to previous versions of this paper. The authors are most grateful to the public servants who took part to the study. Ludovico Carrino i... | CC BY | no | 2024-01-16 23:36:47 | J R Stat Soc Ser A Stat Soc. 2023 Sep 5; 187(1):229-257 | oa_package/17/08/PMC10782991.tar.gz | |
PMC10785227 | 38223528 | Pseudo-CT Results:
The total RMSE for the pseudo-CT compared to gold-standard CT across all volumes were 98 HU (−13 ± 97 HU) for ZeDD-CT and 95 HU (−6.5 ± 94 HU) for BpCT. The BpCT is the same pseudo-CT image used in UpCT-MLAA. | DISCUSSION
This article presents the use of a Bayesian deep convolutional neural network to enhance MLAA by providing an accurate pseudo-CT prior alongside predictive uncertainty estimates that automatically modulate the strength of the priors (UpCT-MLAA). The method was evaluated in patients without and with implants ... | A major remaining challenge for magnetic resonance-based attenuation correction methods (MRAC) is their susceptibility to sources of magnetic resonance imaging (MRI) artifacts (e.g., implants and motion) and uncertainties due to the limitations of MRI contrast (e.g., accurate bone delineation and density, and separatio... | I ntroduction
The Quantitative accuracy of simultaneous positron emission tomography and magnetic resonance imaging (PET/MRI) depends on accurate attenuation correction. Simultaneous imaging with positron emission tomography and computed tomography (PET/CT) is the current clinical gold standard for PET attenuation corr... | ACKNOWLEDGMENT
The Titan X Pascal used was donated by the NVIDIA Corporation.
This work was supported in part by NIH/NCI under Grant R01CA212148; in part by NIH/NIAMS under Grant R01AR074492; in part by the UCSF Graduate Research Mentorship Fellowship award; and in part by GE Healthcare.
This work involved human subjec... | CC BY | no | 2024-01-16 23:35:03 | IEEE Trans Radiat Plasma Med Sci. 2022 Jul 6; 6(6):678-689 | oa_package/62/b1/PMC10785227.tar.gz | |||
PMC10785288 | 38222874 | Introduction to collagen receptors
As the most abundant class of ECM proteins, collagens provide structural support for connective tissues, skin and, most importantly, bones and teeth, and can convey information about the extracellular mechanical environment via their interaction with cells using specific collagen rece... | Author contributions
RF wrote and edited the article. SH wrote portions of the article and edited the entire article CG wrote portions of the article and edited the entire article. All authors contributed to the article and approved the submitted version.
The extracellular matrix (ECM) niche plays a critical role in de... | DDR structure and function
Unlike integrins, which lack intrinsic kinase activity, the DDRs are collagen-activated receptor tyrosine kinases (RTKs) that share homology in their kinase domain with growth factor receptors such as the neurotrophin receptor, TrkA ( 25 , 27 , 28 ). DDRs are named for their homology to the... | Funding
Research from the authors laboratory described in this article was supported by NIH/NIDCR grants DE11723, DE029012, DE029465, DE030675, Department of Defense grant PR190899, research funds from the Department of Periodontics and Oral Medicine, University of Michigan School of Dentistry and the Michigan Musculos... | CC BY | no | 2024-01-16 23:35:04 | Front Dent Med. 2023 May 11; 4:1181817 | oa_package/e0/95/PMC10785288.tar.gz | ||||
PMC10785745 | 38223904 | Introduction
Glaucoma, the second-most-common cause of blindness worldwide, is a neurodegenerative disease that culminates in the irreversible loss of retinal ganglion cells (RGCs) ( 1 ). Elevated levels of intraocular pressure (IOP) is one of the major risk factors for glaucoma disease progression and associated visio... | Methods
Human trabecular meshwork cell culture
De-identified whole globes or corneal rims from human donors were obtained from Miracles in Sight (Winston-Salem, NC, USA) in accordance with the Declaration of Helsinki on research involving human tissue and with the approval of the Duke University Health System Instituti... | Results
Characteristics of small extracellular vesicles released from TM cells
The EVs were isolated from conditioned media from glaucomatous TM (GTM) cells and non-glaucomatous or “normal” TM (NTM) cells. The gradient fractions with densities of approximately 1.05 g/mL–1.10 g/mL (fractions 5–8) and approximately 1.11 ... | Discussion
The current study rigorously profiled the proteome of sEVs from GTM and NTM cells. Although we observed some similarities, the overall proteomic profiles of the sEV cargo from the NTM and GTM cells were very different. Specifically, there were decreased numbers of ECM proteins in the GTM sEVs. The two major ... | Author contributions
FM: Conceptualization, Data curation, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing – original draft, Writing – review & editing. BR: Data curation, Formal analysis, Investigation, Writing – review & editing. HR: Data curation, Invest... | Supplementary Material | Funding
The authors declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by National Institutes of Health Grant EY031737 (FSM), EY022359 (WDS) and National Institutes of Health Core Grant EY014800 (Moran Eye Center) and EY005722 (Duke Eye Cente... | CC BY | no | 2024-01-16 23:35:03 | Front Ophthalmol (Lausanne). 2023 Oct 6; 3:1257737 | oa_package/f4/6c/PMC10785745.tar.gz | |
PMC10785782 | 38222943 | Introduction
Building computational and mathematical models to simulate complex non-linear biological processes requires many key steps in defining both the model as well as identifying ranges of values for many corresponding parameters. Complex models often require concurrent estimation of dozens of parameters using r... | Method
Here we outline how we perform both the CaliPro and ABC calculations. In our previously published work, CaliPro was only used to tune uniform distributions; to compare CaliPro more directly to ABC, here we extend CaliPro’s uniform distribution boundaries to non-uniform distributions. We do this by fitting non-un... | Results
Our goal is to apply both CaliPro and ABC approaches to calibrate two different examples and compare them: a non-complex and complex model. The following models of ordinary differential equations (ODEs), will be evaluated: the classic predator–prey model [ 39 , 40 ], and a viral–host response model of HIV-1/AI... | Discussion
Calibration of complex models often needs to be performed when building complex models or when adding equations or reparametrizing. Both CaliPro and ABC rely on pseudo-likelihood to tune model parameters so that they capture full ranges of biological and clinical outcomes. As we detail in Table 3 , CaliPro’... | Author contributions
PN: Methodology, Software, Visualization, Writing—original draft, Writing—reviewing and editing. DK: Conceptualization, Funding acquisition, Supervision, Writing—review and editing.
Mathematical and computational models of biological systems are increasingly complex, typically comprised of hybrid m... | Acknowledgments
We thank Dr. Linus Schumacher for helpful discussions on this manuscript and ABC-SMC. We thank Paul Wolberg for computational assistance and support.
Funding
The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported... | CC BY | no | 2024-01-16 23:35:04 | Front Appl Math Stat. 2023 Oct 18; 9:1256443 | oa_package/1b/30/PMC10785782.tar.gz | ||
PMC10785826 | 38223701 | Introduction
Abiotic factors such as salt, heat, and drought stresses, and nutrient deficiency are responsible for extensive crop loss and soil degradation, resulting in an estimated $27B annual loss ( Pitman and Lauchli, 2002 ; Hoang et al., 2016 ; Zorb et al., 2019 ). For example, salt stress is a primary abiotic s... | Materials and methods
Plant material, growth conditions, salt treatment, and bacterial inoculation
The plant preparation and growth conditions in this study were similar to previous studies ( Hiltenbrand et al., 2016 ; Thomas et al., 2019 ; Wiggins et al., 2022 ). First, the wild-type rice ( Oryza sativa cv. Nipponb... | Results
Azospirillum brasilense inoculation improves rice growth when grown under high salt concentrations
We investigated if A. brasilense Sp245 could improve growth in rice plants when grown under high-salt concentrations (100 mM and 200 mM NaCl). At seven days post-treatment (dpt), our results show that the total... | Discussion
Soil salinity is considered one of the most limiting factors for agricultural productivity and food security ( FAO, 2015 ; FAO et al., 2022 ). In fact, rice is one of the most susceptible crops to high salt concentrations and experiences a significant yield reduction due to salinity stress ( Eynard et al., ... | Conclusion
Our findings indicate that the plant growth-promoting bacterium A. brasilense improves growth in salt-stressed rice. This opens the possibility of using this PGPB to mitigate salt stress in salt-sensitive crops. Our transcriptomic data suggest that A. brasilense improves rice growth under salt stress by ... | Author contributions
Conceived, designed, and contributed reagents/materials/analysis tools: AM. Performed the experiments: ZD, SD, MG, SG, HP, and JC. Analyzed the data: ZD, SD, YR, GG, and AM. Wrote the paper: ZD, AM, YR, and GG. All authors contributed to the article and approved the submitted version.
Major food cr... | Supplementary Material | Acknowledgments
The authors wish to thank the USDA Dale Bumpers National Rice Research Center, Stuttgart, Arkansas, for providing rice seeds Oryza sativa (cv. Nipponbare). The authors also thank the reviewers for their comments and helpful suggestions.
Funding
The authors declare financial support was received for th... | CC BY | no | 2024-01-16 23:35:04 | Front Agron. 2023 Oct 4; 5:1216503 | oa_package/9a/fe/PMC10785826.tar.gz |
PMC10785958 | 38222464 | INTRODUCTION
TRANSCRANIAL focused ultrasound (tFUS) is a therapeutic modality successfully demonstrated for drug delivery via blood-brain barrier opening, studying the brain through neuromodulation, and liquefying clots through histotripsy [ 1 ]. tFUS is suitable for targeting cortical and deep regions in the brain whi... | METHODS
PHANTOM CREATION
Agar-graphite phantoms were used for all phantom and ex vivo skull cap phantom experiments. Two custom 3D-printed transducer coupling cones designed in-house were used for each setup that better conformed with either the phantom mold or the skull cap, shown in Figure 1 . For the phantom setu... | RESULTS
PHANTOM RESULTS
For all phantom data sets (N=8), the target registration error of the optical tracking system, or TRE Opti,ARFI , was 3.4 ± 1.0 mm. TRE Opti,ARFI and the separated axial and lateral error components are plotted in Figure 3a for each data set and the average for all data sets. The mean axial... | DISCUSSION
Neuronavigation using optical tracking provides a noninvasive approach to position a transducer about a subject’s head during tFUS procedures independent of the MR scanner for guidance. For transcranial applications, the aberrating skull displaces the focus from the intended target but because of subject sku... | CONCLUSION
In our study, we described a workflow to integrate acoustic simulations with optically tracked tFUS setups. Simulations from our pipeline were validated with MR measurements and found comparable results with the predicted focus from optical tracking. However, this pipeline is limited by the targeting accurac... | Optical tracking is a real-time transducer positioning method for transcranial focused ultrasound (tFUS) procedures, but the predicted focus from optical tracking typically does not incorporate subject-specific skull information. Acoustic simulations can estimate the pressure field when propagating through the cranium ... | ACKNOWLEDGMENT
The funders had no role in study design, data collection and analysis, the decision to publish, or the preparation of this manuscript. All acoustic simulations were run on a Quadro P6000 GPU donated by NVIDIA Corporation. Code, example data sets, and tutorials are available at: https://github.com/mksigo... | CC BY | no | 2024-01-16 23:35:04 | IEEE Open J Ultrason Ferroelectr Freq Control. 2023 Sep 25; 3:146-156 | oa_package/c5/38/PMC10785958.tar.gz | |
PMC10786321 | 38222444 | INTRODUCTION
Midportion Achilles tendinopathy (AT) is an overuse injury of insidious onset resulting in pain and stiffness in the midportion of the Achilles tendon. Although commonly attributed to deficient plantar flexor muscle function ( 1 , 2 ), there is limited empirical evidence that supports this assumption, part... | METHODS
Participants
Twenty-eight volunteers participated in the study: 14 with AT and 14 controls ( Table 1 ). AT inclusion criteria were history of gradual, insidious onset of pain and/or stiffness at the midportion of the Achilles tendon, which had become chronic (i.e., persisted for at least 3 months); pain reprodu... | RESULTS
Of the AT participants, half had bilateral AT. Thus, for within-group analyses, limbs were divided into more and less affected limbs and referred to, for simplicity, as “AT” and “AT–Control.” AT symptom duration ranged from 3 to 240 months. Limbs were matched for dominance when comparing AT and controls. Despit... | DISCUSSION
This study is unique in that it evaluates neural and muscular contributions to maximal strength in AT. Despite similar plantar flexor strength, the contributions differed between AT and controls. In AT, maximal isometric torque was associated with RT, indicating contractile function predicted strength. In co... | Conclusions
Plantar flexor strength and power differences cannot be assumed in AT, whether evaluated isometrically, concentrically, or eccentrically. Pain sensitivity quantified using algometry also cannot be assumed in AT. Despite similar magnitudes of RT and VA, their relationships to MVC differed between AT and cont... | Introduction/Purpose:
The purpose of this study was to determine the following in persons with midportion Achilles tendinopathy (AT): 1) maximal strength and power; 2) neural drive during maximal contractions and contractile function during electrically evoked resting contractions; and 3) whether pain, neural drive, an... | Supplementary Material | ACKNOWLEDGMENTS
We are incredibly grateful to the following people who contributed to data collection and processing for the study: Karis, Meggie, Monica, Michael, and Elizabeth.
These contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of... | CC BY | no | 2024-01-16 23:35:04 | Exerc Sport Mov. 2023 Oct 26 Fall; 1(4):1-7 | oa_package/f3/61/PMC10786321.tar.gz |
PMC10786409 | 38222460 | Introduction
Community-Based Participatory Research (CBPR) is an effective approach for addressing health disparities by bridging the gap between research and action ( N. B. Wallerstein & Duran, 2006 ). In CBPR, knowledge is collaboratively produced and owned by a diverse group of stakeholders, including local communit... | Methods
The ASCEND Small Grants Program
The ASCEND Center, a multi-disciplinary program, was created under the Morgan State University (MSU)’s Division for Research and Economic Development. This housed the ASCEND Small CBPR Grants Program, funded by the National Institutes of Health BUILD initiative, aimed to create c... | Results
Overview of the Applications and Funded Projects
Figure 3 summarizes the program’s outcomes. Our program consisted of three rounds, with a total of 105 individuals (51 academic and 54 community) forming 48 partnerships and submitting 58 letters of intent. Out of these, 33 full proposals were submitted and revi... | Discussion
Seed funding is a critical element for initiating CBPR projects. Some studies have emphasized the value of seed funding alone ( Main et al., 2012 ; Thompson et al., 2010 ), while others have suggested that it should be complemented by additional support ( Coombe et al., 2023 ; Jenkins et al., 2020 ; Kegle... | Conclusion
Our CBPR Small Grants Program led to the development of the CARES model, a novel approach to guide community-academic collaborative projects to address health disparities. The model is flexible and adaptable to the changing needs and challenges of community-academic partnerships. It combines existing CBPR in... | Community-based participatory research (CBPR) is an effective approach for addressing health disparities by integrating diverse knowledge and expertise from both academic and community partners throughout the research process. However, more is needed to invest in the foundational infrastructure and resources that are n... | Qualitative Evidence
Stages of Partnership Readiness
As shown by Table 3 , a few stages of partnership readiness were identified through qualitative assessments. Partners with similar levels of readiness reported comparable assets, perceived needs, and recommended services. This table summarizes these stages based on ... | Acknowledgment
The authors would like to express their sincere gratitude to Dr. Nina Wallerstein and the University of New Mexico Center for participator Research, as well as the Detroit Urban Research Center, Dr. Amy Shultz and her team for their invaluable support and guidance throughout this project. The authors wou... | CC BY | no | 2024-01-16 23:35:02 | Metrop Univ. 2023 Nov 1; 34(5):7-19 | oa_package/c5/dd/PMC10786409.tar.gz |
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