bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential risk of falls associated with pain medication among community-dwelling older adults by cognitive status
Authors: Yoshikawa Aya , Smith Matthew Lee , Ory Marcia G 
Published: February 2021

AbstractBackgroundPersons living with dementia have an elevated risk of falling and chronic pain. This study investigates the relationship of pain medication use with falls among community-dwelling adults based on their cognitive status.MethodsWe analysed a nationally representative sample of community-dwelling Medicare beneficiaries (n = 7,491) who completed cognitive assessments used for dementia classification in the 2015 US National Health and Aging Trends Study. We performed survey-weighted logistic regression to investigate differential associations between pain medication use and a recent fall by cognitive status: no dementia, possible dementia and probable dementia, controlling for sociodemographic and health characteristics.ResultsAbout 16.5% of the analytic sample was classified as possible dementia (8.3%) and probable dementia (8.2%). Pain medication use was associated with a recent fall among those with probable dementia [odds ratio (OR) = 1.86, 95% confidence interval (CI): 1.14, 3.03], controlling for sociodemographic and health characteristics. Taking medication for pain 2 days a week or more (OR = 2.14, 95% CI: 1.20, 3.81) was associated with falls among those with probable dementia. Bothersome pain and worry about falling down were also associated with falls among participants with no dementia and possible dementia, respectively.ConclusionDifferential risk factors for falls by cognitive status imply the need for tailored pain management and fall prevention strategies. The provision of fall prevention programmes stressing balance training and medication use is important regardless of cognitive status in community-dwelling older adults. Future research should explore other modifiable factors associated with the risk of falls among community-dwelling adults.
Transient Receptor Potential Melastatin 2 Enhances Vascular Reactivity During Development of Atherosclerosis in Mice
Authors: Dai Yi-quan , Yan Xiao-xiao , Lin Yi-chen , Chen Hong-yu , Liu Xiao-ru 
Published: February 2021

Abstract

Background
To investigate the function of transient receptor potential melastatin 2 (TRPM2) in vascular reactivity induced by 5-hydroxytryptamine (5-HT) in the aorta during development of atherosclerosis in mice.

Methods
Forty mice were randomly divided into 4 groups: C57BL/6J on normal diet (C57 + ND), C57BL/6J on high-fat diet (C57 + HFD), apolipoprotein E gene knockout mice (ApoE−/−) on ND (ApoE−/− + ND), and ApoE−/− on HFD (ApoE−/− + HFD). They were fed with a ND or HFD for 16 weeks. Aortic TRPM2 expression and isometric contractions were analyzed.

Results
In the ApoE−/− + HFD group, body weight, blood glucose, and blood lipid concentrations were increased, and aortic plaques were developed. Compared with the other 3 groups, aortic TRPM2 mRNA and protein levels were significantly increased in the ApoE−/− + HFD group (P &lt; 0.01). Aortic reactivity to 5-HT was enhanced in ApoE−/− + HFD mice with lower EC50 values. The enhanced reactivity to 5-HT was significantly inhibited by TRPM2 inhibitors, N-p-amylcinnamoyl anthranilic acid (1 µmol/l) and 2-aminoethyl diphenylborinate (10 µmol/l).

Conclusions
Aortic TRPM2 expression is upregulated in ApoE knockout mice fed with a HFD. Upregulation of TRPM2 enhances 5-HT vascular reactivity during development of atherosclerosis.
Expression of adenylate kinase fused mouse ubiquitin active enzyme in Escherichia coli and its application in ubiquitination
Authors: Liu Xiaoliang , Hu Ling , Zhang Yuan , Li Hongtao 
Published: February 2021

ABSTRACT
Ubiquitination is involved in the regulation of numerous cellular functions. Research works in the ubiquitin realm rely heavily on ubiquitination assays in vitro and require large amounts of ubiquitin-activating enzyme (UBA1) and keep ATP supplies. However, UBA1 is hard to be obtained with large quantities using reported methods. We fused Escherichia coli adenylate kinase (adk) and mouse UBA1 and obtained fusion protein adk-mUBA1. The expression level of adk-mUBA1 increased about 8-fold compared with mUBA1 in an E. coli expression system, and adk-mUBA1 was easily purified to 90% purity via 2 purification steps. The purified adk-mUBA1 protein was functional for ubiquitination and could use ATP in addition to ADP as energy supply and had a higher catalytic activity than mUBA1 in cell lysis. adk-mUBA1 can be applied to preparing ubiquitin-modified substrates and kinds of ubiquitin chains in a chemical synthesis process and is a preferable application than mUBA1 in vitro ubiquitination.
A variable selection approach for highly correlated predictors in high-dimensional genomic data
Authors: Zhu Wencan , Lévy-Leduc Céline , Ternès Nils 
Published: February 2021

AbstractMotivationIn genomic studies, identifying biomarkers associated with a variable of interest is a major concern in biomedical research. Regularized approaches are classically used to perform variable selection in high-dimensional linear models. However, these methods can fail in highly correlated settings.ResultsWe propose a novel variable selection approach called WLasso, taking these correlations into account. It consists in rewriting the initial high-dimensional linear model to remove the correlation between the biomarkers (predictors) and in applying the generalized Lasso criterion. The performance of WLasso is assessed using synthetic data in several scenarios and compared with recent alternative approaches. The results show that when the biomarkers are highly correlated, WLasso outperforms the other approaches in sparse high-dimensional frameworks. The method is also illustrated on publicly available gene expression data in breast cancer.Availabilityand implementationOur method is implemented in the WLasso R package which is available from the Comprehensive R Archive Network (CRAN).Supplementary informationSupplementary data are available at Bioinformatics online.
METTL3-mediated m6A methylation negatively modulates autophagy to support porcine blastocyst development‡
Authors: Cao Zubing , Zhang Ling , Hong Renyun , Li Yunsheng , Wang Yiqing , Qi Xin , Ning Wei , Gao Di , Xu Tengteng , Ma Yangyang , Yu Tong , Knott Jason G , Sathanawongs Anucha , Zhang Yunhai 
Published: February 2021

Abstract
N6-methyladenosine (m6A) catalyzed by METTL3 regulates the maternal-to-zygotic transition in zebrafish and mice. However, the role and mechanism of METTL3-mediated m6A methylation in blastocyst development remains unclear. Here, we show that METTL3-mediated m6A methylation sustains porcine blastocyst development via negatively modulating autophagy. We found that reduced m6A levels triggered by METTL3 knockdown caused embryonic arrest during morula-blastocyst transition and developmental defects in trophectoderm cells. Intriguingly, overexpression of METTL3 in early embryos resulted in increased m6A levels and these embryos phenocopied METTL3 knockdown embryos. Mechanistically, METTL3 knockdown or overexpression resulted in a significant increase or decrease in expression of ATG5 (a key regulator of autophagy) and LC3 (an autophagy marker) in blastocysts, respectively. m6A modification of ATG5 mRNA mainly occurs at 3’UTR, and METTL3 knockdown enhanced ATG5 mRNA stability, suggesting that METTL3 negatively regulated autophagy in an m6A dependent manner. Furthermore, single-cell qPCR revealed that METTL3 knockdown only increased expression of LC3 and ATG5 in trophectoderm cells, indicating preferential inhibitory effects of METTL3 on autophagy activity in the trophectoderm lineage. Importantly, autophagy restoration by 3MA (an autophagy inhibitor) treatment partially rescued developmental defects of METTL3 knockdown blastocysts. Taken together, these results demonstrate that METTL3-mediated m6A methylation negatively modulates autophagy to support blastocyst development.
Ageing promotes pathological alpha-synuclein propagation and autonomic dysfunction in wild-type rats
Authors: Van Den Berge Nathalie , Ferreira Nelson , Mikkelsen Trine Werenberg , Alstrup Aage Kristian Olsen , Tamgüney Gültekin , Karlsson Páll , Terkelsen Astrid Juhl , Nyengaard Jens Randel , Jensen Poul Henning , Borghammer Per 
Published: February 2021

Abstract
Neuronal aggregates of misfolded alpha-synuclein protein are found in the brain and periphery of patients with Parkinson’s disease. Braak and colleagues have hypothesized that the initial formation of misfolded alpha-synuclein may start in the gut, and then spread to the brain via peripheral autonomic nerves hereby affecting several organs, including the heart and intestine. Age is considered the greatest risk factor for Parkinson’s disease, but the effect of age on the formation of pathology and its propagation has not been studied in detail. We aimed to investigate whether propagation of alpha-synuclein pathology from the gut to the brain is more efficient in old versus young wild-type rats, upon gastrointestinal injection of aggregated alpha-synuclein. Our results demonstrate a robust age-dependent gut-to-brain and brain-to-gut spread of alpha-synuclein pathology along the sympathetic and parasympathetic nerves, resulting in age-dependent dysfunction of the heart and stomach, as observed in patients with Parkinson’s disease. Moreover, alpha-synuclein pathology is more densely packed and resistant to enzymatic digestion in old rats, indicating an age-dependent maturation of alpha-synuclein aggregates. Our study is the first to provide a detailed investigation of alpha-synuclein pathology in several organs within one animal model, including the brain, skin, heart, intestine, spinal cord and autonomic ganglia. Taken together, our findings suggest that age is a crucial factor for alpha-synuclein aggregation and complete propagation to heart, stomach and skin, similar to patients. Given that age is the greatest risk factor for human Parkinson’s disease, it seems likely that older experimental animals will yield the most relevant and reliable findings. These results have important implications for future research to optimize diagnostics and therapeutics in Parkinson’s disease and other age-associated synucleinopathies. Increased emphasis should be placed on using aged animals in preclinical studies and to elucidate the nature of age-dependent interactions.
Accelerated Brain Aging and Cerebral Blood Flow Reduction in Persons With Human Immunodeficiency Virus
Authors: Petersen Kalen J , Metcalf Nicholas , Cooley Sarah , Tomov Dimitre , Vaida Florin , Paul Robert , Ances Beau M 
Published: February 2021

Abstract

Background
Persons with human immunodeficiency virus (PWH) are characterized by altered brain structure and function. As they attain normal lifespans, it has become crucial to understand potential interactions between human immunodeficiency virus (HIV) and aging. However, it remains unclear how brain aging varies with viral load (VL).

Methods
In this study, we compare magnetic resonance imaging (MRI) biomarkers among PWH with undetectable VL (UVL; ≤50 genomic copies/mL; n = 230), PWH with detectable VL (DVL; &gt;50 copies/mL; n = 93), and HIV-uninfected (HIV–) controls (n = 206). To quantify gray matter cerebral blood flow (CBF), we utilized arterial spin labeling. To measure structural aging, we used a publicly available deep learning algorithm to estimate brain age from T1-weighted MRI. Cognitive performance was measured using a neuropsychological battery covering 5 domains.

Results
Associations between age and CBF varied with VL. Older PWH with DVL had reduced CBF vs PWH with UVL (P = .02). Structurally predicted brain aging was accelerated in PWH vs HIV– controls regardless of VL (P &lt; .001). Overall, PWH had impaired learning, executive function, psychomotor speed, and language compared to HIV– controls. Structural brain aging was associated with reduced psychomotor speed (P &lt; .001).

Conclusions
Brain aging in HIV is multifaceted. CBF depends on age and current VL and is improved by medication adherence. By contrast, structural aging is an indicator of cognitive function and reflects serostatus rather than current VL.
Physician-related predictors of referral for multidisciplinary paediatric obesity management: a population-based study
Authors: Gehring Nicole D , Kebbe Maryam , Rathwell Sarah , Perez Arnaldo , Peng Chenhui , Zendher Emily , Ho Josephine , Ball Geoff D C 
Published: February 2021

AbstractBackgroundIt is recommended that primary care-based physicians refer children with overweight and obesity to multidisciplinary paediatric obesity management, which can help to improve weight and health.ObjectiveTo determine predictors of referral to multidisciplinary paediatric obesity management.MethodsThis retrospective, population-level study included physicians who could refer 2–17 years old with a body mass index ≥85th percentile to one of three multidisciplinary paediatric obesity management clinics in Alberta, Canada. Physician demographic and procedural data were obtained from Practitioner Claims and Provider Registry maintained by Alberta Health from January 2014 to December 2017. Physician characteristics were compared based on whether they did or did not refer children for obesity management. Univariable and multivariable logistic regression models analysed associations between physician characteristics and referral making.ResultsOf the 3863 physicians (3468 family physicians, 395 paediatricians; 56% male; 49.3 ± 12.2 years old; 22.3 ± 12.6 years since graduation) practicing during the study period, 1358 (35.2%) referred at least one child for multidisciplinary paediatric obesity management. Multivariable regression revealed that female physicians (versus males) [odds ratio (OR): 1.68, 95% confidence interval (CI): 1.46–1.93; P &lt; 0.0001], paediatricians (versus family physicians) (OR: 4.89, 95% CI: 3.85–6.21; P &lt; 0.0001) and urban-based physicians (versus non-urban-based physicians) (OR: 2.17, 95% CI: 1.79–2.65; P &lt; 0.0001) were more likely to refer children for multidisciplinary paediatric obesity management.ConclusionsApproximately one-third of family physicians and paediatricians referred children for multidisciplinary paediatric obesity management. Strategies are needed to improve referral practices for managing paediatric obesity, especially among male physicians, family physicians and non-urban-based physicians as they were less likely to refer children.
Robust deep learning seismic inversion witha prioriinitial model constraint
Authors: Zhang Jian , Li Jingye , Chen Xiaohong , Li Yuanqiang , Huang Guangtan , Chen Yangkang 
Published: February 2021

SUMMARYSeismic inversion is one of the most commonly used methods in the oil and gas industry for reservoir characterization from observed seismic data. Deep learning (DL) is emerging as a data-driven approach that can effectively solve the inverse problem. However, existing DL-based methods for seismic inversion utilize only seismic data as input, which often leads to poor stability of the inversion results. Besides, it has always been challenging to train a robust network since the real survey has limited labelled data pairs. To partially overcome these issues, we develop a neural network framework with a priori initial model constraint to perform seismic inversion. Our network uses two parts as one input for training. One is the seismic data, and the other is the subsurface background model. The labels for each input are the actual model. The proposed method is performed by log-to-log strategy. The training data set is first generated based on forward modelling. The network is then pre-trained using the synthetic training data set, which is further validated using synthetic data that have not been used in the training step. After obtaining the pre-trained network, we introduce the transfer learning strategy to fine-tune the pre-trained network using labelled data pairs from a real survey to acquire better inversion results in the real survey. The validity of the proposed framework is demonstrated using synthetic 2-D data including both post-stack and pre-stack examples, as well as a real 3-D post-stack seismic data set from the western Canadian sedimentary basin.
Noradrenergic Enhancement of Motor Learning, Attention, and Working Memory in Humans
Authors: Kuo Hsiao-I , Qi Feng-Xue , Paulus Walter , Kuo Min-Fang , Nitsche Michael A 
Published: February 2021

Abstract

Background
Noradrenaline has an important role as a neuromodulator of the central nervous system. Noradrenergic enhancement was recently shown to enhance glutamate-dependent cortical facilitation and long term potentiation-like plasticity. As cortical excitability and plasticity are closely linked to various cognitive processes, here we aimed to explore whether these alterations are associated with respective cognitive performance changes. Specifically, we assessed the impact of noradrenergic enhancement on motor learning (serial reaction time task), attentional processes (Stroop interference task), and working memory performance (n-back letter task).

Methods
The study was conducted in a cross-over design. Twenty-five healthy humans performed the respective cognitive tasks after a single dose of the noradrenaline reuptake inhibitor reboxetine or placebo administration.

Results
The results show that motor learning, attentional processes, and working memory performance in healthy participants were improved by reboxetine application compared with placebo.

Conclusions
The results of the present study thus suggest that noradrenergic enhancement can improve memory formation and executive functions in healthy humans. The respective changes are in line with related effects of noradrenaline on cortical excitability and plasticity.
Persistent SARS-CoV-2 RNA Shedding Without Evidence of Infectiousness: A Cohort Study of Individuals With COVID-19
Authors: Owusu Daniel , Pomeroy Mary A , Lewis Nathaniel M , Wadhwa Ashutosh , Yousaf Anna R , Whitaker Brett , Dietrich Elizabeth , Hall Aron J , Chu Victoria , Thornburg Natalie , Christensen Kimberly , Kiphibane Tair , Willardson Sarah , Westergaard Ryan , Dasu Trivikram , Pray Ian W , Bhattacharyya Sanjib , Dunn Angela , Tate Jacqueline E , Kirking Hannah L , Matanock Almea ,   Household Transmission Study Team, Duca Lindsey M , Rabold Elizabeth , Gharpure Radhika , Njuguna Henry , Dawson Patrick , Conners Erin E , Fields Victoria , Salvatore Phillip , Marcenac Perrine , Reses Hannah E , Fajans Mark , Laws Rebecca L , Yin Sherry , Ye Dongni , Pevzner Eric , Battey Katherine , Tran Cuc , O’Hegarty Michelle , Vuong Jeni , Chancey Rebecca J , Gregory Christopher J , Banks Michelle , Rispens Jared , Lester Sandra , Mills Lisa , Fry Alicia , Nabity Scott , Freeman Brandi , Buono Sean 
Published: February 2021

Abstract

Background
To better understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) shedding and infectivity, we estimated SARS-CoV-2 RNA shedding duration, described participant characteristics associated with the first negative rRT-PCR test (resolution), and determined if replication-competent viruses was recoverable ≥10 days after symptom onset.

Methods
We collected serial nasopharyngeal specimens from 109 individuals with rRT-PCR–confirmed COVID-19 in Utah and Wisconsin. We calculated viral RNA shedding resolution probability using the Kaplan-Meier estimator and evaluated characteristics associated with shedding resolution using Cox proportional hazards regression. We attempted viral culture for 35 rRT-PCR–positive nasopharyngeal specimens collected ≥10 days after symptom onset.

Results
The likelihood of viral RNA shedding resolution at 10 days after symptom onset was approximately 3%. Time to shedding resolution was shorter among participants aged &lt;18 years (adjusted hazards ratio [aHR], 3.01; 95% confidence interval [CI], 1.6–5.6) and longer among those aged ≥50 years (aHR, 0.50; 95% CI, .3–.9) compared to participants aged 18–49 years. No replication-competent viruses were recovered.

Conclusions
Although most patients were positive for SARS-CoV-2 for ≥10 days after symptom onset, our findings suggest that individuals with mild to moderate COVID-19 are unlikely to be infectious ≥10 days after symptom onset.
The Activin/Follistatin Axis Is Severely Deregulated in COVID-19 and Independently Associated With In-Hospital Mortality
Authors: Synolaki Evgenia , Papadopoulos Vasileios , Divolis Georgios , Tsahouridou Olga , Gavriilidis Efstratios , Loli Georgia , Gavriil Ariana , Tsigalou Christina , Tziolos Nikolaos R , Sertaridou Eleni , Kalra Bhanu , Kumar Ajay , Rafailidis Petros , Pasternack Arja , Boumpas Dimitrios T , Germanidis Georgios , Ritvos Olli , Metallidis Simeon , Skendros Panagiotis , Sideras Paschalis 
Published: February 2021

Abstract

Background
Activins are members of the transforming growth factor-β superfamily implicated in the pathogenesis of several immunoinflammatory disorders. Based on our previous studies demonstrating that overexpression of activin-A in murine lung causes pathology sharing key features of coronavirus disease 2019 (COVID-19), we hypothesized that activins and their natural inhibitor follistatin might be particularly relevant to COVID-19 pathophysiology.

Methods
Activin-A, activin-B, and follistatin were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in 3 independent centers, and compared with demographic, clinical, and laboratory parameters. Optimal scaling with ridge regression was used to screen variables and establish a prediction model.

Result
The activin/follistatin axis was significantly deregulated during the course of COVID-19, correlated with severity and independently associated with mortality. FACT-CLINYCoD, a scoring system incorporating follistatin, activin-A, activin-B, C-reactive protein, lactate dehydrogenase, intensive care unit admission, neutrophil/lymphocyte ratio, age, comorbidities, and D-dimers, efficiently predicted fatal outcome (area under the curve [AUC], 0.951; 95% confidence interval, .919−.983; P &lt;10−6). Two validation cohorts indicated similar AUC values.

Conclusions
This study demonstrates a link between activin/follistatin axis and COVID-19 mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based tool that allows dynamic prediction of disease outcome, supporting clinical decision making.
Allele-based analysis revealed the critical functions of region 277–297 in the NorA efflux pump of Staphylococcus aureus
Authors: Shang Yan , Lv Peiwen , Li Shannan , Wang Wenkai , Liu Yuanxiang , Yang Chunyu 
Published: February 2021

Abstract

Objectives
The NorA efflux pump in Staphylococcus aureus mediates resistance to many fluoroquinolone (FQ) antibiotics. Three norA alleles with high sequence similarity are found in various S. aureus strains exhibiting different FQ resistance profiles. This study aimed to elucidate the underlying molecular basis for the varying efflux activity of these three allelic variations.

Methods
The norA genotypes of 20 S. aureus isolates were analysed. Multiple alignments and conservative analyses were conducted to explore the evolutionary variations. After heterologous expression in Escherichia coli, seven mutants were constructed for MIC tests, efflux activity and conformational change measurements.

Results
Three NorA alleles were identified that displayed different FQ MICs and varying efflux activity for ethidium bromide, with the NorAII protein showing the strongest activity. A total of 29 single amino acid polymorphisms were identified by conservative analysis within three allelic peptides, with seven sites densely distributed in the 277–297 region. Mutations of these seven residues in NorAII all significantly impaired drug resistance and efflux activity, and three key mutants showed conformational changes in fluorescence resonance energy transfer (FRET) analysis.

Conclusions
Evolutionary variations of the 277–297 region could be a major explanation for the functional difference of three norA alleles and serve as a potential target for the development of novel NorA inhibitors.