bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methods for comparing uncertainty quantifications for material property predictions
Authors: Tran Kevin , Neiswanger Willie , Yoon Junwoong , Zhang Qingyang , Xing Eric , Ulissi Zachary W 
Published: March 2020

Abstract
Data science and informatics tools have been proliferating recently within the computational materials science and catalysis fields. This proliferation has spurned the creation of various frameworks for automated materials screening, discovery, and design. Underpinning these frameworks are surrogate models with uncertainty estimates on their predictions. These uncertainty estimates are instrumental for determining which materials to screen next, but the computational catalysis field does not yet have a standard procedure for judging the quality of such uncertainty estimates. Here we present a suite of figures and performance metrics derived from the machine learning community that can be used to judge the quality of such uncertainty estimates. This suite probes the accuracy, calibration, and sharpness of a model quantitatively. We then show a case study where we judge various methods for predicting density-functional-theory-calculated adsorption energies. Of the methods studied here, we find that the best performer is a model where a convolutional neural network is used to supply features to a Gaussian process regressor, which then makes predictions of adsorption energies along with corresponding uncertainty estimates.
Computational recognition of lncRNA signature of tumor-infiltrating B lymphocytes with potential implications in prognosis and immunotherapy of bladder cancer
Authors: Zhou Meng , Zhang Zicheng , Bao Siqi , Hou Ping , Yan Congcong , Su Jianzhong , Sun Jie 
Published: March 2020

AbstractLong noncoding RNAs (lncRNAs) have been associated with cancer immunity regulation and the tumor microenvironment (TME). However, functions of lncRNAs of tumor-infiltrating B lymphocytes (TIL-Bs) and their clinical significance have not yet been fully elucidated. In the present study, a machine learning-based computational framework is presented for the identification of lncRNA signature of TIL-Bs (named ‘TILBlncSig’) through integrative analysis of immune, lncRNA and clinical profiles. The TILBlncSig comprising eight lncRNAs (TNRC6C-AS1, WASIR2, GUSBP11, OGFRP1, AC090515.2, PART1, MAFG-DT and LINC01184) was identified from the list of 141 B-cell-specific lncRNAs. The TILBlncSig was capable of distinguishing worse compared with improved survival outcomes across different independent patient datasets and was also independent of other clinical covariates. Functional characterization of TILBlncSig revealed it to be an indicator of infiltration of mononuclear immune cells (i.e. natural killer cells, B-cells and mast cells), and it was associated with hallmarks of cancer, as well as immunosuppressive phenotype. Furthermore, the TILBlncSig revealed predictive value for the survival outcome and immunotherapy response of patients with anti-programmed death-1 (PD-1) therapy and added significant predictive power to current immune checkpoint gene markers. The present study has highlighted the value of the TILBlncSig as an indicator of immune cell infiltration in the TME from a noncoding RNA perspective and strengthened the potential application of lncRNAs as predictive biomarkers of immunotherapy response, which warrants further investigation.
The Glycine Receptor Allosteric Ligands Library (GRALL)
Authors: Cerdan Adrien H , Sisquellas Marion , Pereira Gilberto , Barreto Gomes Diego E , Changeux Jean-Pierre , Cecchini Marco 
Published: March 2020

Abstract

Motivation
Glycine receptors (GlyRs) mediate fast inhibitory neurotransmission in the brain and have been recognized as key pharmacological targets for pain. A large number of chemically diverse compounds that are able to modulate GlyR function both positively and negatively have been reported, which provides useful information for the development of pharmacological strategies and models for the allosteric modulation of these ion channels.

Results
Based on existing literature, we have collected 218 unique chemical entities with documented modulatory activities at homomeric GlyR-α1 and -α3 and built a database named GRALL. This collection includes agonists, antagonists, positive and negative allosteric modulators and a number of experimentally inactive compounds. Most importantly, for a large fraction of them a structural annotation based on their putative binding site on the receptor is provided. This type of annotation, which is currently missing in other drug banks, along with the availability of cooperativity factors from radioligand displacement experiments are expected to improve the predictivity of in silico methodologies for allosteric drug discovery and boost the development of conformation-based pharmacological approaches.

Availability and implementation
The GRALL library is distributed as a web-accessible database at the following link: https://ifm.chimie.unistra.fr/grall. For each molecular entry, it provides information on the chemical structure, the ligand-binding site, the direction of modulation, the potency, the 3D molecular structure and quantum-mechanical charges as determined by our in-house pipeline.

Contact
mcecchini@unistra.fr

Supplementary information
Supplementary data are available at Bioinformatics online.
Prospects for improved glomerular filtration rate estimation based on creatinine—results from a transnational multicentre study
Authors: Björk Jonas , Nyman Ulf , Courbebaisse Marie , Couzi Lionel , Dalton R Neil , Dubourg Laurence , Ebert Natalie , Eriksen Björn O , Gaillard Francois , Garrouste Cyril , Grubb Anders , Hansson Magnus , Jacquemont Lola , Jones Ian , Kamar Nassim , Lamb Edmund J , Legendre Christophe , Littmann Karin , Mariat Christophe , Melsom Toralf , Rostaing Lionel , Rule Andrew D , Schaeffner Elke , Sundin Per-Ola , Turner Stephen , Åkesson Anna , Delanaye Pierre , Pottel Hans 
Published: March 2020

Abstract

Background
The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation is routinely used to assess renal function but exhibits varying accuracy depending on patient characteristics and clinical presentation. The overall aim of the present study was to assess if and to what extent glomerular filtration rate (GFR) estimation based on creatinine can be improved.

Methods
In a cross-sectional analysis covering the years 2003–17, CKD-EPI was validated against measured GFR (mGFR; using various tracer methods) in patients with high likelihood of chronic kidney disease (CKD; five CKD cohorts, n = 8365) and in patients with low likelihood of CKD (six community cohorts, n = 6759). Comparisons were made with the Lund–Malmö revised equation (LMR) and the Full Age Spectrum equation.

Results
7In patients aged 18–39 years old, CKD-EPI overestimated GFR with 5.0–16 mL/min/1.73 m2 in median in both cohort types at mGFR levels &lt;120 mL/min/1.73 m2. LMR had greater accuracy than CKD-EPI in the CKD cohorts (P30, the percentage of estimated GFR within 30% of mGFR, 83.5% versus 76.6%). CKD-EPI was generally the most accurate equation in the community cohorts, but all three equations reached P30 above the Kidney Disease Outcomes Quality Initiative benchmark of 90%.

Conclusions
None of the evaluated equations made optimal use of available data. Prospects for improved GFR estimation procedures based on creatinine exist, particularly in young adults and in settings where patients with suspected or manifest CKD are investigated.
Longer or shorter dual antiplatelet therapy in dialysis patients receiving a coronary drug-eluting stent? A rope game still ongoing
Authors: Burlacu Alexandru , Covic Adrian 
Published: March 2020

Abstract
In this issue of Clinical Kidney Journal, Park et al. presents the results of a nationwide population-based trial that included &gt;5000 dialysis patients receiving a drug-eluting stent (DES). The main objective was to evaluate the effectiveness and the safety of prolonged dual antiplatelet therapy (DAPT). The primary outcome was a composite of mortality, non-fatal myocardial infarction, coronary revascularization and stroke, significantly lowered by a longer DAPT regimen at 12, 15 and 18 months, respectively. Longer DAPT tended to be correlated with higher bleeding events at all landmarks, with no statistical significance. An important element was that almost 75% of the index events were acute coronary syndromes. This study presents the first solid evidence for a significant benefit of prolonged DAPT in dialysis patients receiving a DES. We believe that end-stage renal disease is still in the middle of a rope game, being pulled to one side or another by other features, inclining towards a higher bleeding risk or towards higher ischaemic risk. The acute versus elective presentation seems to weigh in choosing the antiplatelet regimen. The ‘one-size-fits-all strategy’ is not suitable for this particular group. Probably in the future, practitioners will be provided with decision pathways generated by artificial intelligence algorithms yielding ‘truly individualized’ DAPT protocols for every single patient.
25-Hydroxyvitamin D and Risk of Osteoporotic Fractures: Mendelian Randomization Analysis in 2 Large Population-Based Cohorts
Authors: Çolak Yunus , Afzal Shoaib , Nordestgaard Børge G 
Published: March 2020

Abstract

Background
Whether low plasma 25-hydroxyvitamin D concentrations cause osteoporotic fractures is unclear. We tested the hypothesis that low plasma 25-hydroxyvitamin D concentrations are associated with increased risk of osteoporotic fractures using a Mendelian randomization analysis.

Methods
We genotyped 116 335 randomly chosen white Danish persons aged 20–100 years in 2 population-based cohort studies for plasma 25-hydroxyvitamin D decreasing genotypes in CYP2R1 (rs117913124 and rs12794714), DHCR7 (rs7944926 and rs11234027), GEMIN2 (rs2277458), and HAL (rs3819817); 35 833 had information on plasma 25-hydroxyvitamin D. We assessed risk of total, osteoporotic, and anatomically localized fractures from 1981 through 2017. Information on fractures and vital status was obtained from nationwide registries.

Results
During up to 36 years of follow-up, we observed 17 820 total fractures, 10 861 osteoporotic fractures, and 3472 fractures of hip or femur. Compared with individuals with 25-hydroxyvitamin D ≥ 50nmol/L, multivariable adjusted hazard ratios (95% CIs) for total fractures were 1.03 (0.97–1.09) for individuals with 25–49.9 nmol/L, 1.19 (1.10–1.28) for individuals with 12.5–24.9 nmol/L, and 1.39 (1.21–1.60) for individuals with 25-hydroxyvitamin D &lt; 12.5 nmol/L. Corresponding hazard ratios were 1.07 (1.00–1.15), 1.25 (1.13–1.37), and 1.49 (1.25–1.77) for osteoporotic fractures and 1.09 (0.98–1.22), 1.37 (1.18–1.57), and 1.41 (1.09–1.81) for fractures of hip or femur, respectively. Hazard ratios per 1 increase in vitamin D allele score, corresponding to 3.0% (approximately 1.6 nmol/L) lower 25-hydroxyvitamin D concentrations, were 0.99 (0.98–1.00) for total fractures, 0.99 (0.97–1.00) for osteoporotic fractures, and 0.98 (0.95–1.00) for fractures of hip or femur.

Conclusions
Low plasma 25-hydroxyvitamin D concentrations were associated with osteoporotic fractures; however, Mendelian randomization analysis provided no evidence supporting a causal role for vitamin D in the risk for osteoporotic fractures.
ASFVdb: an integrative resource for genomic and proteomic analyses of African swine fever virus
Authors: Zhu Zhenglin , Meng Geng 
Published: March 2020

AbstractThe recent outbreaks of African swine fever (ASF) in China and Europe have threatened the swine industry globally. To control the transmission of ASF virus (ASFV), we developed the African swine fever virus database (ASFVdb), an online data visualization and analysis platform for comparative genomics and proteomics. On the basis of known ASFV genes, ASFVdb reannotates the genomes of every strain and newly annotates 5352 possible open reading frames (ORFs) of 45 strains. Moreover, ASFVdb performs a thorough analysis of the population genetics of all the published genomes of ASFV strains and performs functional and structural predictions for all genes. Users can obtain not only basic information for each gene but also its distribution in strains and conserved or high mutation regions, possible subcellular location and topology. In the genome browser, ASFVdb provides a sliding window for results of population genetic analysis, which facilitates genetic and evolutionary analyses at the genomic level. The web interface was constructed based on SWAV 1.0. ASFVdb is freely accessible at http://asfvdb.popgenetics.net.
Non-obstructive high-risk plaques increase the risk of future culprit lesions comparable to obstructive plaques without high-risk features: the ICONIC study
Authors: Ferraro Richard A , van Rosendael Alexander R , Lu Yao , Andreini Daniele , Al-Mallah Mouaz H , Cademartiri Filippo , Chinnaiyan Kavitha , Chow Benjamin J W , Conte Edoardo , Cury Ricardo C , Feuchtner Gudrun , de Araújo Gonçalves Pedro , Hadamitzky Martin , Kim Yong-Jin , Leipsic Jonathon , Maffei Erica , Marques Hugo , Plank Fabian , Pontone Gianluca , Raff Gilbert L , Villines Todd C , Lee Sang-Eun , Al’Aref Subhi J , Baskaran Lohendran , Cho Iksung , Danad Ibrahim , Gransar Heidi , Budoff Matthew J , Samady Habib , Stone Peter H , Virmani Renu , Narula Jagat , Berman Daniel S , Chang Hyuk-Jae , Bax Jeroen J , Min James K , Shaw Leslee J , Lin Fay Y 
Published: March 2020

Abstract

Aims
High-risk plaque (HRP) and non-obstructive coronary artery disease independently predict adverse events, but their importance to future culprit lesions has not been resolved. We sought to determine in patients prior to confirmed acute coronary syndrome (ACS) the association between lesion percent diameter stenosis (%DS), and the absolute number and prevalence of HRP. The secondary objective was to examine the relative importance of non-obstructive HRP in future culprit lesions.

Methods and results
Within the ICONIC study, a nested case–control study of patients undergoing coronary computed tomographic angiography (coronary CT), we included ACS cases with culprit lesions confirmed by invasive coronary angiography and coregistered to baseline coronary CT. Quantitative CT was used to evaluate obstructive (≥50%) and non-obstructive (&lt;50%) diameter stenosis, with HRP defined as ≥2 features of spotty calcification, positive remodelling, or low-attenuation plaque at baseline. A total of 234 patients with downstream ACS over 54 (interquartile range 5–525.5) days exhibited 198/898 plaques with HRP on coronary CT. While HRP was less prevalent in non-obstructive (19.7%, 161/819) than obstructive lesions (46.8%, 37/79, P &lt; 0.001), non-obstructive plaque comprised 81.3% (161/198) of HRP lesions overall. Among the 128 patients with identifiable culprit lesion precursors, the adjusted hazard ratio (HR) was 1.85 [95% confidence interval (CI) 1.26–2.72] for HRP, with no interaction between %DS and HRP (P = 0.82). Compared to non-obstructive HRP lesions, obstructive lesions without HRP exhibited a non-significant HR of 1.41 (95% CI 0.61–3.25, P = 0.42).

Conclusions
While HRP is more prevalent among obstructive lesions, non-obstructive HRP lesions outnumber those that are obstructive and confer risk clinically approaching that of obstructive lesions without HRP.
The Tribulations of Trials: Lessons Learnt Recruiting 777 Older Adults Into REtirement in ACTion (REACT), a Trial of a Community, Group-Based Active Aging Intervention Targeting Mobility Disability
Authors: Withall Janet , Greaves Colin J , Thompson Janice L , de Koning Jolanthe L , Bollen Jessica C , Moorlock Sarah J , Fox Kenneth R , Western Max J , Snowsill Tristan , Medina-Lara Antonieta , Cross Rosina , Ladlow Peter , Taylor Gordon , Zisi Vasiliki , Clynes James , Gray Selena , Agyapong-Badu Sandra , Guralnik Jack M , Rejeski W Jack , Stathi Afroditi 
Published: March 2020

Abstract

Background
Challenges of recruitment to randomized controlled trials (RCTs) and successful strategies to overcome them should be clearly reported to improve recruitment into future trials. REtirement in ACTion (REACT) is a United Kingdom-based multicenter RCT recruiting older adults at high risk of mobility disability to a 12-month group-based exercise and behavior maintenance program or to a minimal Healthy Aging control intervention.

Methods
The recruitment target was 768 adults, aged 65 years and older scoring 4–9 on the Short Physical Performance Battery (SPPB). Recruitment methods include the following: (a) invitations mailed by general practitioners (GPs); (b) invitations distributed via third-sector organizations; and (c) public relations (PR) campaign. Yields, efficiency, and costs were calculated.

Results
The study recruited 777 (33.9% men) community-dwelling, older adults (mean age 77.55 years (SD 6.79), mean SPPB score 7.37 (SD 1.56)), 95.11% white (n = 739) and broadly representative of UK quintiles of deprivation. Over a 20-month recruitment period, 25,559 invitations were issued. Eighty-eight percent of the participants were recruited via GP invitations, 5.4% via the PR campaign, 3% via word-of-mouth, and 2.5% via third-sector organizations. Mean recruitment cost per participant was £78.47, with an extra £26.54 per recruit paid to GPs to cover research costs.

Conclusions
REACT successfully recruited to target. Response rates were lower than initially predicted and recruitment timescales required adjustment. Written invitations from GPs were the most efficient method for recruiting older adults at risk of mobility disability. Targeted efforts could achieve more ethnically diverse cohorts. All trials should be required to provide recruitment data to enable evidence-based planning of future trials.
Blood DNA Methylation and Aging: A Cross-Sectional Analysis and Longitudinal Validation in the InCHIANTI Study
Authors: Tharakan Ravi , Ubaida-Mohien Ceereena , Moore Ann Zenobia , Hernandez Dena , Tanaka Toshiko , Ferrucci Luigi 
Published: March 2020

Abstract
Changes in DNA methylation have been found to be highly correlated with aging in humans, but causes or consequences of these changes are not understood. We characterized the DNA methylomes of several hundred people in the Invecchiare in Chianti study to identify DNA sites in which percent methylation was systematically different with age. Then, we tested the hypothesis that changes of percent methylation in the same DNA sites occur longitudinally for the same DNA sites in the same subjects. We identified six differentially methylated regions in which percent methylation showed robust longitudinal changes in the same direction. We then describe functions of the genes near these differentially methylated regions and their potential relationship with aging, noting that the genes appear to regulate metabolism or cell type specificity. The nature of transcription factor binding sites in the vicinity of these differentially methylated regions suggest that these age-associated methylation changes reflect modulation of two biological mechanisms: the polycomb repressive complex 2, a protein complex that trimethylates histone H3 on lysine 27, and the transcriptional repressor CCCTC-binding factor or CTCF, both of which are regulators of chromatin architecture. These findings are consistent with the idea that changes in methylation with aging are of adaptive nature.
Chronic Polypharmacy with Increasing Drug Burden Index Exacerbates Frailty and Impairs Physical Function, with Effects Attenuated by Deprescribing, in Aged Mice
Authors: Mach John , Gemikonakli Gizem , Logan Caitlin , Vander Wyk Brent , Allore Heather , Ekambareshwar Swathi , Kane Alice E , Howlett Susan E , de Cabo Rafael , Le Couteur David G , Hilmer Sarah N 
Published: March 2020

AbstractPolypharmacy (use of ≥5 medications) and increasing Drug Burden Index (DBI) score (measure of person’s total exposure to anticholinergic/sedative medications) are associated with impaired physical function in observational studies of older adults. Deprescribing, the supervised withdrawal of medications for which harms outweigh benefits for an individual, may be a useful intervention. Current knowledge is limited to clinical observational studies that are unable to determine causality. Here, we establish a preclinical model that investigates the effects of chronic polypharmacy, increasing DBI, and deprescribing on global health outcomes in aging. In a longitudinal study, middle-aged (12 months) male C57BL/6J (B6) mice were administered control feed or feed and/or water containing polypharmacy or monotherapy with different DBI scores. At 21 months, each treatment group was subdivided (stratified by frailty at 21 months) to either continue on treatment for life or to have treatment withdrawn (deprescribed). Frailty and physical function were evaluated at 12, 15, 18, and 24 months, and were analyzed using a mixed modeling approach. Polypharmacy with increasing DBI and monotherapy with citalopram caused mice to become frailer, less mobile, and impaired their strength and functional activities. Critically, deprescribing in old age reversed a number of these outcomes. This is the first preclinical study to demonstrate that chronic polypharmacy with increasing DBI augments frailty and impairs function in old age, and that drug withdrawal in old age reversed these outcomes. It was not the number of drugs (polypharmacy) but the type and dose of drugs (DBI) that caused adverse geriatric outcomes.
Dissecting the Racial/Ethnic Disparity in Frailty in a Nationally Representative Cohort Study with Respect to Health, Income, and Measurement
Authors: Usher Therri , Buta Brian , Thorpe Roland J , Huang Jin , Samuel Laura J , Kasper Judith D , Bandeen-Roche Karen 
Published: March 2020

Abstract

Background
Racial/ethnic frailty prevalence disparities have been documented. Better elucidating how these operate may inform interventions to eliminate them. We aimed to determine whether physical frailty phenotype (PFP) prevalence disparities (i) are explained by health aspects, (ii) vary by income, or (iii) differ in degree across individual PFP criteria.

Methods
Data came from the 2011 National Health and Aging Trends Study baseline evaluation. The study sample (n = 7,439) included persons in all residential settings except nursing homes. Logistic regression was used to achieve aims (i)–(iii) listed above. In (i), health aspects considered were body mass index (BMI) status and number of chronic diseases. Analyses incorporated sampling weights and adjusted for sociodemographic factors.

Results
Comparisons are versus non-Hispanic whites: Non-Hispanic blacks (odds ratio [OR] = 1.46, 95% confidence interval [CI]: 1.21–1.76) and Hispanics (1.56, 1.20–2.03) continued to have higher odds of frailty after accounting for BMI status and number of chronic diseases. Non-Hispanic blacks had elevated odds of frailty in all income quartiles, including the highest (OR = 2.19, 1.24–3.397). Racial/ethnic disparities differed considerably across frailty criteria, ranging from a twofold increase in odds of slowness to a 25%–30% decrease in odds of self-reported exhaustion.

Conclusions
BMI and disease burden do not explain racial/ethnic frailty disparities. Black–white disparities are not restricted to low-income groups. Racial/ethnic differences vary considerably by NHATS PFP criteria. Our findings support the need to better understand mechanisms underlying elevated frailty burden in older non-Hispanic black and Hispanic Americans, how phenotypic measures capture frailty in racial/ethnic subgroups and, potentially, how to create assessments more comparable by race/ethnicity.