bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combining artificial intelligence: deep learning with Hi-C data to predict the functional effects of non-coding variants
Authors: Meng Xiang-He , Xiao Hong-Mei , Deng Hong-Wen 
Published: November 2020

Abstract

Motivation
Although genome-wide association studies (GWASs) have identified thousands of variants for various traits, the causal variants and the mechanisms underlying the significant loci are largely unknown. In this study, we aim to predict non-coding variants that may functionally affect translation initiation through long-range chromatin interaction.

Results
By incorporating the Hi-C data, we propose a novel and powerful deep learning model of artificial intelligence to classify interacting and non-interacting fragment pairs and predict the functional effects of sequence alteration of single nucleotide on chromatin interaction and thus on gene expression. The changes in chromatin interaction probability between the reference sequence and the altered sequence reflect the degree of functional impact for the variant. The model was effective and efficient with the classification of interacting and non-interacting fragment pairs. The predicted causal SNPs that had a larger impact on chromatin interaction were more likely to be identified by GWAS and eQTL analyses. We demonstrate that an integrative approach combining artificial intelligence—deep learning with high throughput experimental evidence of chromatin interaction leads to prioritizing the functional variants in disease- and phenotype-related loci and thus will greatly expedite uncover of the biological mechanism underlying the association identified in genomic studies.

Availability and implementation
Source code used in data preparing and model training is available at the GitHub website (https://github.com/biocai/DeepHiC).

Supplementary information
Supplementary data are available at Bioinformatics online.
Event history and topological data analysis
Authors: Garside K , Gjoka A , Henderson R , Johnson H , Makarenko I 
Published: November 2020

Summary
Persistent homology is used to track the appearance and disappearance of features as we move through a nested sequence of topological spaces. Equating the nested sequence to a filtration and the appearance and disappearance of features to events, we show that simple event history methods can be used for the analysis of topological data. We propose a version of the well-known Nelson–Aalen cumulative hazard estimator for the comparison of topological features of random fields and for testing parametric assumptions. We suggest a Cox proportional hazards approach for the analysis of embedded metric trees. The Nelson–Aalen method is illustrated on globally distributed climate data and on neutral hydrogen distribution in the Milky Way. The Cox method is used to compare vascular patterns in fundus images of the eyes of healthy and diabetic retinopathy patients.
The anatomy of spatial neglect after posterior cerebral artery stroke
Authors: Sperber Christoph , Clausen Jacob , Benke Thomas , Karnath Hans-Otto 
Published: November 2020

AbstractSpatial neglect is a common consequence of stroke in the territory of the right middle cerebral artery. Damage to a perisylvian fronto-temporo-parietal network has been demonstrated to underlie this disorder. Less common, stroke to the posterior cerebral artery territory may also lead to spatial neglect. This study aimed to uncover the anatomical underpinnings of spatial neglect after posterior cerebral artery infarction. A sample of 50 posterior cerebral artery infarct patients was screened for spatial neglect. Neural correlates of neglect were investigated both with voxel-based lesion behaviour mapping and with region-of-interest analyses. Brain damage neither to the splenium, nor to the parahippocampal gyrus, nor to the thalamus was predictive of spatial neglect. Only damage to the perisylvian fronto-temporo-parietal network of spatial neglect was significantly associated with neglect severity. We conclude that both posterior and middle cerebral artery stroke induce spatial neglect after damage to the same perisylvian brain network. The findings contradict previous theories that postulated neural correlates of spatial neglect specifically supplied by the posterior cerebral artery. In posterior cerebral artery stroke patients, affected parts of this network are located at the border zone between the posterior and middle cerebral artery territories. Inter-individual variability in the localization of the border between both artery territories appears to mediate the occurrence of spatial neglect after posterior cerebral artery stroke.
Features of Duration Mismatch Negativity Around the Onset of Overt Psychotic Disorders: A Longitudinal Study
Authors: Tateno Takahiro , Higuchi Yuko , Nakajima Suguru , Sasabayashi Daiki , Nakamura Mihoko , Ueno Maya , Mizukami Yuko , Nishiyama Shimako , Takahashi Tsutomu , Sumiyoshi Tomiki , Suzuki Michio 
Published: November 2020

Abstract
Reduced amplitude of duration mismatch negativity (dMMN) has been reported in psychotic disorders and at-risk mental state (ARMS); however, few longitudinal MMN studies have examined the amplitude changes during the course of psychosis. We compared dMMN amplitude between ARMS individuals with later psychosis onset and those without, and we longitudinally examined potential dMMN changes around psychosis onset. Thirty-nine ARMS subjects and 22 healthy controls participated in this study. Of the 39 ARMS subjects, 11 transitioned to psychosis (at-risk mental state with later psychosis onset [ARMS-P]) during follow-up and 28 did not (at-risk mental state without later psychosis onset [ARMS-NP]). dMMN was measured twice using an auditory oddball paradigm with a mean interval of 2 years. Follow-up dMMN data were available for all but four ARMS-P subjects. dMMN amplitude at baseline was smaller in ARMS-P subjects compared with control and ARMS-NP subjects. Additionally, ARMS-P subjects displayed a longitudinal decline in dMMN amplitude, which was not present in control and ARMS-P subjects. We also observed a progressive decline in dMMN amplitude during the transition period, suggesting dynamic brain changes associated with the psychosis onset. Our findings implicate dMMN amplitude as a biological predictor of future psychosis onset in high-risk individuals, which may be used for early detection and intervention of psychosis.
A Ventilator-associated Pneumonia Prediction Model in Patients With Acute Respiratory Distress Syndrome
Authors: Wu Zongsheng , Liu Yao , Xu Jingyuan , Xie Jianfeng , Zhang Shi , Huang Lili , Huang Yingzi , Yang Yi , Qiu Haibo 
Published: November 2020

Abstract

Background
Mechanical ventilation is crucial for acute respiratory distress syndrome (ARDS) patients and diagnosis of ventilator-associated pneumonia (VAP) in ARDS patients is challenging. Hence, an effective model to predict VAP in ARDS is urgently needed.

Methods
We performed a secondary analysis of patient-level data from the Early versus Delayed Enteral Nutrition (EDEN) of ARDSNet randomized controlled trials. Multivariate binary logistic regression analysis established a predictive model, incorporating characteristics selected by systematic review and univariate analyses. The model’s discrimination, calibration, and clinical usefulness were assessed using the C-index, calibration plot, and decision curve analysis (DCA).

Results
Of the 1000 unique patients enrolled in the EDEN trials, 70 (7%) had ARDS complicated with VAP. Mechanical ventilation duration and intensive care unit (ICU) stay were significantly longer in the VAP group than non-VAP group (P &lt; .001 for both) but the 60-day mortality was comparable. Use of neuromuscular blocking agents, severe ARDS, admission for unscheduled surgery, and trauma as primary ARDS causes were independent risk factors for VAP. The area under the curve of the model was .744, and model fit was acceptable (Hosmer-Lemeshow P = .185). The calibration curve indicated that the model had proper discrimination and good calibration. DCA showed that the VAP prediction nomogram was clinically useful when an intervention was decided at a VAP probability threshold between 1% and 61%.

Conclusions
The prediction nomogram for VAP development in ARDS patients can be applied after ICU admission, using available variables. Potential clinical benefits of using this model deserve further assessment.
Epidemiological Impact and Cost-Effectiveness of Varicella Vaccination Strategies in the United Kingdom
Authors: Akpo Esse Ifebi Herve , Cristeau Olivier , Hunjan Manjit , Casabona Giacomo 
Published: November 2020

Abstract

Background
Despite the burden of varicella, there is no universal varicella vaccination (UVV) program in the United Kingdom (UK) due to concerns that it could increase herpes zoster (HZ) incidence. We assessed the cost-utility of a first-dose monovalent (varicella [V]) or quadrivalent (measles-mumps-rubella-varicella [MMRV]) followed by a second-dose MMRV UVV program. GSK and MSD varicella-containing vaccines (VCVs) were considered.

Methods
Dynamic transmission and cost-effectiveness models were adapted to the UK. Outcomes measured included varicella and HZ incidences and the incremental cost-utility ratio (ICURs) over a lifetime horizon. Payer and societal perspectives were evaluated.

Results
The impact of V-MMRV and MMRV-MMRV UVV programs on varicella incidence was comparable between both VCVs at equilibrium. HZ incidence increased by 1.6%–1.7% over 7 years after UVV start, regardless of the strategies, then decreased by &gt;95% at equilibrium. ICURs ranged from £5665 (100 years) to £18 513 (20 years) per quality-adjusted life-year (QALY) gained with V-MMRV and from £9220 to £27 101 per QALY gained with MMRV-MMRV (payer perspective). MMRV-MMRV was cost-effective in the medium- and long-terms with GSK VCV and only cost-effective in the long term with MSD VCV at a £20 000 per QALY gained threshold. Without the exogenous boosting hypothesis, HZ incidence decreased through UVV implementation. ICURs were most sensitive to discount rates and MMRV price.

Conclusions
A 2-dose UVV was demonstrated to be a cost-effective alternative to no vaccination. With comparable effectiveness as MSD VCV at lower costs, GSK VCV may offer higher value for the money.
Trends in Hospital-Acquired and Ventilator-Associated Bacterial Pneumonia Trials
Authors: Bart Stephen M , Rubin Daniel , Kim Peter , Farley John J , Nambiar Sumathi 
Published: November 2020

Abstract

Background
New drug development for hospital-acquired bacterial pneumonia (HABP) and ventilator-associated bacterial pneumonia (VABP) is critical. Challenges remain in the conduct of HABP/VABP trials, especially in the contexts of enrollment, endpoints, nonstudy antibacterial drug therapy, and antimicrobial resistance.

Methods
Four Phase 3 noninferiority trials (n = 2433 participants) submitted to the Food and Drug Administration after 2015 were analyzed for enrollment statistics, participant characteristics associated with 28-day all-cause mortality (ACM), microbiology, and receipt of nonstudy antibacterial drugs. All trials primarily enrolled patients with gram-negative bacterial infections.

Results
The mean trial length was 2.7 years and the mean recruitment rate was 0.17 participants/site/month. ACM at 28 days was 17.1% and was higher among participants diagnosed with ventilated HABP (31.9%) or VABP (19.0%) than nonventilated HABP (9.9%). VABP participants tended to be younger, less likely to have chronic obstructive pulmonary disease, and more likely to have previously sustained an injury. Age, South American residence, diagnosis of ventilated HABP or VABP, and Acinetobacter baumannii infection were all associated with 28-day ACM in a multivariate logistic regression model. Infection by A. baumannii was most common in Eastern European and Asia/Pacific participants, and Eastern European isolates exhibited the highest levels of meropenem resistance. Concomitant nonstudy antibacterial drug therapy most commonly included beta-lactams and was initiated earliest in Western Europe.

Conclusion
This analysis of recent trials may assist in trial considerations for HABP/VABP development programs and promote needed antibacterial drug development for patients with serious infections.
Inflammation in Atherosclerosis—No Longer a Theory
Authors: Libby Peter 
Published: November 2020

AbstractBackgroundInflammation links to atherosclerosis and its complications in various experimental investigations. Animal studies have implicated numerous inflammatory mediators in the initiation and complication of atherosclerosis. Numerous studies in humans have shown associations of biomarkers of inflammation with cardiovascular events provoked by atheromata. Inflammatory status, determined by the biomarker C-reactive protein, can guide the allocation of statin therapy to individuals without elevated low-density lipoprotein (LDL) concentrations to prevent first ever adverse cardiovascular events.ContentUntil recently, no direct evidence has shown that an intervention that selectively limits inflammation can improve outcomes in patients with atherosclerosis. A recent study, based on decades of preclinical investigation, treated patients who had sustained a myocardial infarction and whose LDL was well-controlled on statin treatment with an antibody that neutralizes interleukin-1 beta. This trial, conducted in over 10 000 individuals, showed a reduction in major adverse cardiac events, establishing for the first time the clinical efficacy of an anti-inflammatory intervention in atherosclerosis. Two large subsequent studies have shown that colchicine treatment can also prevent recurrent events in patients recovering from an acute coronary syndrome or in the stable phase of coronary artery disease. These clinical trials have transformed inflammation in atherosclerosis from theory to practice.SummaryMuch work remains to optimize further anti-inflammatory interventions, minimize unwanted actions, and refine patient selection. This long road from discovery in the laboratory to successful clinical trials represents a victory for medical science, and opens a new avenue to reducing the risk that remains despite current treatments for atherosclerosis.
Diverging landscape impacts on macronutrient status despite overlapping diets in managed (Apis mellifera) and native (Melissodes desponsa) bees
Authors: Mogren Christina L , Benítez María-Soledad , McCarter Kevin , Boyer Frédéric , Lundgren Jonathan G 
Published: November 2020

Abstract
Declining pollinator populations worldwide are attributed to multiple stressors, including the loss of quality forage. Habitat management in agricultural areas often targets honey bees (Apis mellifera L.) specifically, with the assumption that native bees will benefit from an ‘umbrella species’ strategy. We tested this theory using a conservation physiology approach to compare the effects of landscape composition and floral dietary composition on the physiological status of honey bees and Melissodes desponsa in eastern South Dakota, USA. The total glycogen, lipid and protein concentrations were quantified from field collected bees. Next-generation sequencing of the trnL chloroplast gene from bee guts was used to evaluate dietary composition. The effects of landscape and dietary composition on macronutrient concentrations were compared between bee species. As the mean land-use patch area increased, honey bee glycogen levels increased, though M. desponsa experienced a decrease in glycogen. Protein levels decreased in honey bees as the largest patch index, a measure of single patch dominance, increased versus M. desponsa. Lipids in both species were unaffected by the measured landscape variables. Dietary analysis revealed that honey bees foraged preferentially on weedy non-native plant species, while M. desponsa sought out native and rarer species, in addition to utilizing non-native plants. Both species foraged on Asteraceae, Oleaceae and Fabaceae, specifically Melilotus sp. and Medicago sp. Dietary composition was not predictive of the macronutrients measured for either species. Together, these data highlight the management importance of including patch area in conservation recommendations, as bee species may have divergent physiological responses to landscape characteristics. While solitary bees may forage on weedy introduced plants in agricultural areas, robust strategies should also reincorporate native plant species, though they may not be preferred by honey bees, to maximize overall health and diversity of pollinator communities.
Respice, Adspice, Prospice: The ‘Marathon Stone’, Lewisohn Stadium, and the changing reception of the classics at City College in the twentieth century
Authors: Macaulay-Lewis Elizabeth , Reilly Matthew C 
Published: November 2020

AbstractThroughout its history, New York has received several archaeological objects as gifts, including a mid-fourth-century BCE Greek funerary stele. Dr John Huston Finley, the third president of City College, saw a stele when he was in Greece and asked the Greek Government to gift the stele to the college. The stele, dubbed the ‘Marathon Stone’ by Finley, was dedicated and proudly displayed at City College, now of the City University of New York. This article explores the gift’s context by drawing on contemporary newspaper reports, Finley’s tenuous association of the stele with the battle of Marathon, and the gifting of an archaeological object as a means for promoting ties between City College and Greece. The article then examines the context for the stele’s display, the Neo-Antique Lewisohn Stadium, and argues that the display of the stele and erection of Lewisohn Stadium both embodied Finley’s aspirations for City College to rival Columbia and New York Universities. The demise of the stadium in 1973 and the removal of the stele to a basement signaled a major shift in the significance of the classics, classical art, and Neo-Antique architecture at City College, as well as the changing priorities of the institution.
Effect of empagliflozin on exercise ability and symptoms in heart failure patients with reduced and preserved ejection fraction, with and without type 2 diabetes
Authors: Abraham William T , Lindenfeld JoAnn , Ponikowski Piotr , Agostoni Piergiuseppe , Butler Javed , Desai Akshay S , Filippatos Gerasimos , Gniot Jacek , Fu Michael , Gullestad Lars , Howlett Jonathan G , Nicholls Stephen J , Redon Josep , Schenkenberger Isabelle , Silva-Cardoso José , Störk Stefan , Krzysztof Wranicz Jerzy , Savarese Gianluigi , Brueckmann Martina , Jamal Waheed , Nordaby Matias , Peil Barbara , Ritter Ivana , Ustyugova Anastasia , Zeller Cordula , Salsali Afshin , Anker Stefan D 
Published: November 2020

Abstract

Aims
The EMPERIAL (Effect of EMPagliflozin on ExeRcise ability and HF symptoms In patients with chronic heArt faiLure) trials evaluated the effects of empagliflozin on exercise ability and patient-reported outcomes in heart failure (HF) with reduced and preserved ejection fraction (EF), with and without type 2 diabetes (T2D), reporting, for the first time, the effects of sodium-glucose co-transporter-2 inhibition in HF with preserved EF (HFpEF).

Methods and results
HF patients with reduced EF (HFrEF) (≤40%, N = 312, EMPERIAL-Reduced) or preserved EF (&gt;40%, N = 315, EMPERIAL-Preserved), with and without T2D, were randomized to empagliflozin 10 mg or placebo for 12 weeks. The primary endpoint was 6-minute walk test distance (6MWTD) change to Week 12. Key secondary endpoints included Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS) and Chronic Heart Failure Questionnaire Self-Administered Standardized format (CHQ-SAS) dyspnoea score. 6MWTD median (95% confidence interval) differences, empagliflozin vs. placebo, at Week 12 were −4.0 m (−16.0, 6.0; P = 0.42) and 4.0 m (−5.0, 13.0; P = 0.37) in EMPERIAL-Reduced and EMPERIAL-Preserved, respectively. As the primary endpoint was non-significant, all secondary endpoints were considered exploratory. Changes in KCCQ-TSS and CHQ-SAS dyspnoea score were non-significant. Improvements with empagliflozin in exploratory pre-specified analyses of KCCQ-TSS responder rates, congestion score, and diuretic use in EMPERIAL-Reduced are hypothesis generating. Empagliflozin adverse events were consistent with those previously reported.

Conclusion
The primary outcome for both trials was neutral. Empagliflozin was well tolerated in HF patients, with and without T2D, with a safety profile consistent with that previously reported in T2D. Hypothesis-generating improvements in exploratory analyses of secondary endpoints with empagliflozin in HFrEF were observed.
Quantifying the Predictive Performance of Objectively Measured Physical Activity on Mortality in the UK Biobank
Authors: Leroux Andrew , Xu Shiyao , Kundu Prosenjit , Muschelli John , Smirnova Ekaterina , Chatterjee Nilanjan , Crainiceanu Ciprian 
Published: November 2020

AbstractBackgroundObjective measures of physical activity (PA) derived from wrist-worn accelerometers are compared with traditional risk factors in terms of mortality prediction performance in the UK Biobank.MethodA subset of participants in the UK Biobank study wore a tri-axial wrist-worn accelerometer in a free-living environment for up to 7 days. A total of 82 304 individuals over the age of 50 (439 707 person-years of follow-up, 1959 deaths) had both accelerometry data that met specified quality criteria and complete data on a set of traditional mortality risk factors. Predictive performance was assessed using cross-validated Concordance (C) for Cox regression models. Forward selection was used to obtain a set of best predictors of mortality.ResultsIn univariate Cox regression, age was the best predictor of all-cause mortality (C = 0.681) followed by 12 PA predictors, led by minutes of moderate-to-vigorous PA (C = 0.661) and total acceleration (C = 0.661). Overall, 16 of the top 20 predictors were objective PA measures (C = 0.578–0.661). Using a threshold of 0.001 improvement in Concordance, the Concordance for the best model that did not include PA measures was 0.735 (9 covariates) compared with 0.748 (12 covariates) for the best model with PA variables (p-value &lt; .001).ConclusionsObjective measures of PA derived from accelerometry outperform traditional predictors of all-cause mortality in the UK Biobank except age and substantially improve the prediction performance of mortality models based on traditional risk factors. Results confirm and complement previous findings in the National Health and Nutrition Examination Survey (NHANES).