bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the treatment effect heterogeneity of antidepressants in major depression. A Bayesian meta-analysis
Authors: Volkmann Constantin , Volkmann Alexander , Müller Christian A. 
Published: February 2020

AbstractBackgroundThe average treatment effect of antidepressants in major depression was found to be about 2 points on the 17-item Hamilton Depression Rating Scale, which lies below clinical relevance. Here, we searched for evidence of a relevant treatment effect heterogeneity that could justify the usage of antidepressants despite their low average treatment effect.MethodsBayesian meta-analysis of 169 randomized, controlled trials including 58,687 patients. We considered the effect sizes log variability ratio (lnVR) and log coefficient of variation ratio (lnCVR) to analyze the difference in variability of active and placebo response. We used Bayesian random-effects meta-analyses (REMA) for lnVR and lnCVR and fitted a random-effects meta-regression (REMR) model to estimate the treatment effect variability between antidepressants and placebo.ResultsThe variability ratio was found to be very close to 1 in the best fitting models (REMR: 95% HPD [0.98, 1.02], REMA: 95% HPD [1.00, 1.02]). The between-study variance τ2 under the REMA was found to be low (95% HPD [0.00, 0.00]). Simulations showed that a large treatment effect heterogeneity is only compatible with the data if a strong correlation between placebo response and individual treatment effect is assumed.ConclusionsThe published data from RCTs on antidepressants for the treatment of major depression is compatible with a near-constant treatment effect. Although it is impossible to rule out a substantial treatment effect heterogeneity, its existence seems rather unlikely. Since the average treatment effect of antidepressants falls short of clinical relevance, the current prescribing practice should be re-evaluated.
ACP risk grade: a simple mortality index for patients with confirmed or suspected severe acute respiratory syndrome coronavirus 2 disease (COVID-19) during the early stage of outbreak in Wuhan, China
Authors: Lu Jiatao , Hu Shufang , Fan Rong , Liu Zhihong , Yin Xueru , Wang Qiongya , Lv Qingquan , Cai Zhifang , Li Haijun , Hu Yuhai , Han Ying , Hu Hongping , Gao Wenyong , Feng Shibo , Liu Qiongfang , Li Hui , Sun Jian , Peng Jie , Yi Xuefeng , Zhou Zixiao , Guo Yabing , Hou Jinlin 
Published: February 2020

AbstractBackgroundSince the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) outbreaks in Wuhan, China, healthcare systems capacities in highly endemic areas have been overwhelmed. Approaches to efficient management are urgently needed and key to a quicker control of the outbreaks and casualties. We aimed to characterize the clinical features of hospitalized patients with confirmed or suspected COVID-19, and develop a mortality risk index for COVID-19 patients.MethodsIn this retrospective one-centre cohort study, we included all the confirmed or suspected COVID-19 patients hospitalized in a COVID-19-designated hospital from January 21 to February 5, 2020. Demographic, clinical, laboratory, radiological and clinical outcome data were collected from the hospital information system, nursing records and laboratory reports.ResultsOf 577 patients with at least one post-admission evaluation, the median age was 55 years (interquartile range [IQR], 39 - 66); 254 (44.0%) were men; 22.8% (100/438) were severe pneumonia on admission, and 37.7% (75/199) patients were SARS-CoV-2 positive. The clinical, laboratory and radiological data were comparable between positive and negative SARS-CoV-2 patients. During a median follow-up of 8.4 days (IQR, 5.8 - 12.0), 39 patients died with a 12-day cumulative mortality of 8.7% (95% CI, 5.9% to 11.5%). A simple mortality risk index (called ACP index), composed of Age and C-reactive Protein, was developed. By applying the ACP index, patients were categorized into three grades. The 12-day cumulative mortality in grade three (age ≥ 60 years and CRP ≥ 34 mg/L) was 33.2% (95% CI, 19.8% to 44.3%), which was significantly higher than those of grade two (age ≥ 60 years and CRP < 34 mg/L; age < 60 years and CRP ≥ 34 mg/L; 5.6% [95% CI, 0 to 11.3%]) and grade one (age < 60 years and CRP < 34 mg/L, 0%) (P <0.001), respectively.ConclusionThe ACP index can predict COVID-19 related short-term mortality, which may be a useful and convenient tool for quickly establishing a COVID-19 hierarchical management system that can greatly reduce the medical burden and therefore mortality in highly endemic areas.
Evaluating the impact of international airline suspensions on the early global spread of COVID-19
Authors: Adiga Aniruddha , Venkatramanan Srinivasan , Schlitt James , Peddireddy Akhil , Dickerman Allan , Bura Andrei , Warren Andrew , Klahn Brian D , Mao Chunhong , Xie Dawen , Machi Dustin , Raymond Erin , Meng Fanchao , Barrow Golda , Mortveit Henning , Chen Jiangzhuo , Walke Jim , Goldstein Joshua , Wilson Mandy L , Orr Mark , Porebski Przemyslaw , Telionis Pyrros A , Beckman Richard , Hoops Stefan , Eubank Stephen , Baek Young Yun , Lewis Bryan , Marathe Madhav , Barrett Chris 
Published: February 2020

ABSTRACTGlobal airline networks play a key role in the global importation of emerging infectious diseases. Detailed information on air traffic between international airports has been demonstrated to be useful in retrospectively validating and prospectively predicting case emergence in other countries. In this paper, we use a well-established metric known as effective distance on the global air traffic data from IATA to quantify risk of emergence for different countries as a consequence of direct importation from China, and compare it against arrival times for the first 24 countries. Using this model trained on official first reports from WHO, we estimate time of arrival (ToA) for all other countries. We then incorporate data on airline suspensions to recompute the effective distance and assess the effect of such cancellations in delaying the estimated arrival time for all other countries. Finally we use the infectious disease vulnerability indices to explain some of the estimated reporting delays.
Modulation of the Cardiac Sodium Channel NaV1.5 Peak and Late Currents by NAD+Precursors
Authors: Matasic Daniel S. , Yoon Jin-Young , McLendon Jared M. , Mehdi Haider , Schmidt Mark S. , Greiner Alexander M. , Quinones Pravda , Morgan Gina M. , Boudreau Ryan L. , Irani Kaikobad , Brenner Charles , London Barry 
Published: February 2020

ABSTRACTRationaleThe cardiac sodium channel NaV1.5, encoded bySCN5A, produces the rapidly inactivating depolarizing current INathat is responsible for the initiation and propagation of the cardiac action potential. Acquired and inherited dysfunction of NaV1.5 results in either decreased peak INaor increased residual late INa(INa,L), leading to tachy/bradyarrhythmias and sudden cardiac death. Previous studies have shown that increased cellular NAD+and NAD+/NADH ratio increase INathrough suppression of mitochondrial reactive oxygen species and PKC-mediated NaV1.5 phosphorylation. In addition, NAD+-dependent deacetylation of NaV1.5 at K1479 by Sirtuin 1 increases NaV1.5 membrane trafficking and INa. The role of NAD+precursors in modulating INaremains unknown.ObjectiveTo determine whether and by which mechanisms the NAD+precursors nicotinamide riboside (NR) and nicotinamide (NAM) affect peak INaand INa,Lin vitroand cardiac electrophysiologyin vivo.Methods and ResultsThe effects of NAD+precursors on the NAD+metabolome and electrophysiology were studied using HEK293 cells expressing wild-type and mutant NaV1.5, rat neonatal cardiomyocytes (RNCMs), and mice. NR increased INain HEK293 cells expressing NaV1.5 (500 μM: 51 ± 18%, p=0.02, 5 mM: 59 ± 22%, p=0.03) and RNCMs (500 µM: 60 ± 26%, p=0.02, 5 mM: 75 ± 39%, p=0.03) while reducing INa,Lat the higher concentration (RNCMs, 5 mM: −45 ± 11%, p=0.04). NR (5 mM) decreased NaV1.5 K1479 acetylation but increased INain HEK293 cells expressing a mutant form of NaV1.5 with disruption of the acetylation site (NaV1.5-K1479A). Disruption of the PKC phosphorylation site abolished the effect of NR on INa. Furthermore, NAM (5 mM) had no effect on INain RNCMs or in HEK293 cells expressing wild-type NaV1.5, but increased INain HEK293 cells expressing NaV1.5-K1479A. Dietary supplementation with NR for 10-12 weeks decreased QTc in C57BL/6J mice (0.35% NR: −4.9 ± 2.0%, p=0.26; 1.0% NR: −9.5 ± 2.8%, p=0.01).ConclusionsNAD+precursors differentially regulate NaV1.5 via multiple mechanisms. NR increases INa, decreases INa,L, and warrants further investigation as a potential therapy for arrhythmic disorders caused by NaV1.5 deficiency and/or dysfunction.
Dynamics of visual perceptual decision-making in freely behaving mice
Authors: You Wen-Kai , Mysore Shreesh P. 
Published: February 2020

ABSTRACTStudying the temporal dynamics of perceptual decisions offers key insights into the cognitive processes contributing to it. Conducting such investigation in a genetically tractable animal model can facilitate the subsequent unpacking of the mechanistic basis of different stages in perceptual dynamics. Here, we investigated the time course as well as fundamental psychophysical constants governing visual perceptual decision-making in freely behaving mice. We did so by analyzing response accuracy against reaction time (i.e., conditional accuracy), in a series of 2-AFC orientation discrimination tasks in which we varied target size, luminance, duration, and presence of a foil. Our results quantified two distinct stages in the time course of mouse visual decision-making - a ‘sensory encoding’ stage, in which conditional accuracy exhibits a classic tradeoff with response speed, and a subsequent ‘short term memory-dependent’ stage in which conditional accuracy exhibits a classic asymptotic decay following stimulus offset. We estimated the duration of visual sensory encoding as 200-320 ms across tasks, the lower bound of the duration of short-term memory as ~1700 ms, and the briefest duration of visual stimulus input that is informative as ≤50 ms. Separately, by varying stimulus onset delay, we demonstrated that the conditional accuracy function and RT distribution can be independently modulated, and found that the duration for which mice naturally withhold from responding is a quantitative metric of impulsivity. Taken together, our results establish a quantitative foundation for investigating the neural circuit bases of visual decision dynamics in mice.SIGNIFICANCE STATEMENTThis study presents a quantitative breakdown of the time course of visual decision-making in mice during naturalistic behavior. It demonstrates parallel stages in mouse visual perceptual decision dynamics to those in humans, estimates their durations, and shows that mice are able to discriminate well under challenging visual conditions – with stimuli that are brief, low luminance, and small. These results set the stage for investigating the neural bases of visual perceptual decision dynamics and their dysfunction in mice.
Epidemiological characteristics of 1212 COVID-19 patients in Henan, China
Authors: Wang Pei , Lu Jun-an , Jin Yanyu , Zhu Mengfan , Wang Lingling , Chen Shunjie 
Published: February 2020

AbstractBased on publicly released data for 1212 patients, we investigated the epidemiological characteristics of COVID-19 in Henan of China. The following findings are obtained: 1) COVID-19 patients in Henan show gender (55% vs 45%) and age (81% aged between 21 and 60) preferences, possible causes were explored; 2) Statistical analysis on 483 patients reveals that the estimated average, mode and median incubation periods are 7.4, 4 and 7 days; Incubation periods of 92% patients were no more than 14 days; 3) The epidemic of COVID-19 in Henan has undergone three stages and showed high correlations with the numbers of patients that recently return from Wuhan; 4) Network analysis on the aggregate outbreak phenomena of COVID-19 revealed that 208 cases were clustering infected, and various people’s Hospital are the main force in treating patients. The related investigations have potential implications for the prevention and control of COVID-19.
Comparison of throat swabs and sputum specimens for viral nucleic acid detection in 52 cases of novel coronavirus (SARS-Cov-2) infected pneumonia (COVID-19)
Authors: Lin Chenyao , Xiang Jie , Yan Mingzhe , Li Hongze , Huang Shuang , Shen Changxin 
Published: February 2020

AbstractBackgroundIn December 2019, a novel coronavirus (SARS-CoV-2) infected pneumonia (COVID-19) occurred in Wuhan, China. Diagnostic test based on real-time reverse transcription polymerase chain reaction assay (qRT-PCR) was the main means of confirmation, and sample collection was mostly throat swabs, which was easy to miss the diagnosis. It is necessary to seek specimen types with higher detection efficiency and accuracy.MethodsPaired specimens of throat swabs and sputum were obtained from 54 cases, and RNA was extracted and tested for 2019-nCoV (equated with SARS-CoV-2) by qRT-PCR assay.ResultsThe positive rates of 2019-nCoV from sputum specimens and throat swabs were 76.9% and 44.2%, respectively. Sputum specimens showed a significantly higher positive rate than throat swabs in detecting viral nucleic acid using qRT-PCR assay (P=0.001).ConclusionsThe detection rates of 2019-nCoV from sputum specimens are significantly higher than throat swabs. We suggest that sputum would benefit for the detection of 2019-nCoV in patients who produce sputum. The results can facilitate the selection of specimens and increase the accuracy of diagnosis.
Evolving epidemiology of novel coronavirus diseases 2019 and possible interruption of local transmission outside Hubei Province in China: a descriptive and modeling study
Authors: Zhang Juanjuan , Litvinova Maria , Wang Wei , Wang Yan , Deng Xiaowei , Chen Xinghui , Li Mei , Zheng Wen , Yi Lan , Chen Xinhua , Wu Qianhui , Liang Yuxia , Wang Xiling , Yang Juan , Sun Kaiyuan , Longini Ira M. , Halloran M. Elizabeth , Wu Peng , Cowling Benjamin J. , Merler Stefano , Viboud Cecile , Vespignani Alessandro , Ajelli Marco , Yu Hongjie 
Published: February 2020

AbstractBackgroundThe COVID-19 epidemic originated in Wuhan City of Hubei Province in December 2019 and has spread throughout China. Understanding the fast evolving epidemiology and transmission dynamics of the outbreak beyond Hubei would provide timely information to guide intervention policy.MethodsWe collected individual information on 8,579 laboratory-confirmed cases from official publically sources reported outside Hubei in mainland China, as of February 17, 2020. We estimated the temporal variation of the demographic characteristics of cases and key time-to-event intervals. We used a Bayesian approach to estimate the dynamics of the net reproduction number (Rt) at the provincial level.ResultsThe median age of the cases was 44 years, with an increasing of cases in younger age groups and the elderly as the epidemic progressed. The delay from symptom onset to hospital admission decreased from 4.4 days (95%CI: 0.0-14.0) until January 27 to 2.6 days (0.0-9.0) from January 28 to February 17. The mean incubation period was estimated at 5.2 days (1.8-12.4) and the mean serial interval at 5.1 days (1.3-11.6). The epidemic dynamics in provinces outside Hubei was highly variable, but consistently included a mix of case importations and local transmission. We estimate that the epidemic was self-sustained for less than three weeks with Rt reaching peaks between 1.40 (1.04-1.85) in Shenzhen City of Guangdong Province and 2.17 (1.69-2.76) in Shandong Province. In all the analyzed locations (n=10) Rt was estimated to be below the epidemic threshold since the end of January.ConclusionOur findings suggest that the strict containment measures and movement restrictions in place may contribute to the interruption of local COVID-19 transmission outside Hubei Province. The shorter serial interval estimated here implies that transmissibility is not as high as initial estimates suggested.
Characterization of exome variants and their metabolic impact in 6,716 American Indians from Southwest US
Authors: In Kim Hye , Gosalia Nehal , Ye Bin ,   Regeneron Genetics Center, Köroğlu Çiğdem , Hanson Robert L. , Hsueh Wen-Chi , Knowler William C. , Baier Leslie J. , Bogardus Clifton , Shuldiner Alan R. , Van Hout Cristopher V. 
Published: February 2020

AbstractApplying whole exome sequencing (WES) to populations with unique genetic architecture has the potential to reveal novel genes and variants associated with traits and diseases. We sequenced and analyzed the exomes of 6,716 individuals from an American Indian population in Southwest US (Southwestern American Indian, or SWAI) with well-characterized metabolic traits. We found that individuals of SWAI have distinct allelic architecture compared to individuals with European and East Asian ancestry, with many predicted loss-of-function (pLOF) and nonsynonymous variants that were highly enriched or private in SWAI. We evaluated gene-level associations with metabolic traits using pLOF and nonsynonymous variants in SWAI. Many of the candidate genes from previous GWAS studies for body mass index, type 2 diabetes, and plasma lipid levels were associated with respective traits in SWAI. Notably, these associations were mainly driven by pLOF and nonsynonymous variants that are unique or highly enriched in American Indians, many of which have not been observed in other populations or functionally characterized. Our study illustrates the utility and potential of WES in American Indians to prioritize candidate effector genes within GWAS loci and to find novel variants in known diseases genes with potential clinical impact.
A unified neurocomputational bilateral model of spoken language production in healthy participants and recovery in post-stroke aphasia
Authors: Chang Ya-Ning , Ralph Matthew A. Lambon 
Published: February 2020

AbstractUnderstanding the processes underlying normal, impaired and recovered language performance has been a long-standing goal for cognitive and clinical neuroscience. Many verbally-described hypotheses about language lateralisation and recovery have been generated. However, they have not been considered within a single, unified and implemented computational framework, and the literatures on healthy participants and patients are largely separated. These investigations also span different types of data, including behavioural results and fMRI brain activations, which augment the challenge for any unified theory. Consequently, many key issues, apparent contradictions and puzzles remain to be solved. We developed a neurocomputational, bilateral pathway model of spoken language production, designed to provide a unified framework to simulate different types of data from healthy participants and aphasic patients. The model encapsulates key computational principles (differential computational capacity, emergent division of labour across pathways, experience-dependent plasticity-related recovery) and provides an explanation for the bilateral yet asymmetric lateralisation of language in healthy participants, chronic aphasia after left rather than right hemisphere lesions, and the basis of partial recovery in patients. The model provides a formal basis for understanding the relationship between behavioural performance and brain activation. The unified model is consistent with the degeneracy and variable neuro-displacement theories of language recovery, and adds computational insights to these hypotheses regarding the neural machinery underlying language processing and plasticity-related recovery following damage.Significance StatementStudies of healthy and impaired language have generated many verbally-described hypotheses. Whilst these verbal descriptions have advanced our understanding of language processing, some explanations are mutually incompatible and it is unclear how they work mechanistically. We constructed a neurocomputational bilateral model of spoken language production to simulate a range of phenomena in healthy participants and patients with aphasia simultaneously, including language lateralisation, impaired performance after left but not right damage, and hemispheric involvement in plasticity-dependent recovery. The model demonstrates how seemly contradictory findings can be simulated within a single framework. To our knowledge, this provides the first coherent mechanistic account of language lateralisation and recovery from post-stroke aphasia.
Control of spontaneous activity patterns by inhibitory signaling in the developing visual cortex
Authors: Leighton Alexandra H. , Houwen Gerrit J. , Cheyne Juliette E. , Maldonado Paloma P. , De Winter Fred , Lohmann Christian 
Published: February 2020

SummaryDuring early development, even before the senses are active, bursts of activity travel across the nervous system. This spontaneously generated activity drives the refinement of synaptic connections, preparing young networks for patterned sensory input. Synaptic fine-tuning relies not only on the presence of spontaneous activity, but also on the specific characteristics of these activity patterns, such as their frequency, amplitude and synchronicity. Here, we provide evidence that these crucial characteristics are shaped by the relative balance of excitation and inhibition, where patterns with distinct characteristics have different excitatory/inhibitory ratios. Inhibition can control whether cells participate during a spontaneous event, as pharmacogenetic suppression of the somatostatin (SST) expressing subtype of inhibitory interneurons increased cell recruitment and lateral spread of events.
Association of radiologic findings with mortality of patients infected with 2019 novel coronavirus in Wuhan, China
Authors: Yuan Mingli , Yin Wen , Tao Zhaowu , Tan Weijun , Hu Yi 
Published: February 2020

AbstractBackgroundRadiologic characteristics of 2019 novel coronavirus (2019-nCoV) infected pneumonia (NCIP) which had not been fully understood are especially important for diagnosing and predicting prognosis.PurposeTo summarize the clinical and radiologic characteristics of NCIP cases and analyze the association of radiologic findings with mortality cases.Material and methodsWe retrospective studied 27 consecutive patients who were confirmed NCIP, the clinical characteristics and CT image findings were collected, and the association of radiologic findings with mortality of patients was evaluated.Results27 patients included 12 men and 15 women, with median age of 60 years (IQR 47-69). 17 patients discharged in recovered condition and 10 patients died in hospital. The median age of mortality group was higher compared to survival group (68 (IQR 63-73) vs 55 (IQR 35-60), P = 0.003). The comorbidity rate in mortality group was significantly higher than in survival group (80% vs 29%, P = 0.018). The predominant CT characteristics consisted of ground glass opacity (67%), bilateral sides involved (86%), both peripheral and central distribution (74%), and lower zone involvement (96%). The median CT score of mortality group was higher compared to survival group (30 (IQR 7-13) vs 12 (IQR 11-43), P = 0.021), with more frequency of consolidation (40% vs 6%, P = 0.047) and air bronchogram (60% vs 12%, P = 0.025). An optimal cutoff value of a CT score of 24.5 had a sensitivity of 85.6% and a specificity of 84.5% for the prediction of mortality.Conclusions2019-nCoV was more likely to infect elderly people with chronic comorbidities. CT findings of NCIP were featured by predominant ground glass opacities mixed with consolidations, mainly peripheral or combined peripheral and central distributions, bilateral and lower lung zones being mostly involved. A simple CT scoring method was capable to predict mortality.