bluuebunny/crossref_metadata_2025_split huggingface dataset:
ANGPTL8 protein-truncating variant and the risk of coronary disease, type 2 diabetes and adverse effects
Authors: Helkkula Pyry , Kiiskinen Tuomo , Havulinna Aki S. , Karjalainen Juha , Koskinen Seppo , Salomaa Veikko , FinnGen  , Daly Mark J. , Palotie Aarno , Surakka Ida , Ripatti Samuli 
Published: June 2020

AbstractProtein-truncating variants (PTVs) affecting dyslipidemia risk may point to therapeutic targets for cardiometabolic disease. Our objective was to identify PTVs that associated with both lipid levels and cardiometabolic disease risk and assess their possible associations with risks of other diseases. To achieve this aim, we leveraged the enrichment of PTVs in the Finnish population and tested the association of low-frequency PTVs in 1,209 genes with serum lipid levels in the Finrisk Study (n = 23,435). We then tested which of the lipid-associated PTVs also associated with risks of cardiometabolic diseases or 2,264 disease endpoints curated in the FinnGen Study (n = 176,899). Three PTVs were associated with both lipid levels and the risk of cardiometabolic disease: triglyceride-lowering variants in ANGPTL8 (−24.0[-30.4 to −16.9] mg/dL per rs760351239-T allele, P = 3.4× 10−9) and ANGPTL4 (−14.4[-18.6 to −9.8] mg/dL per rs746226153-G allele, P = 4.3 × 10−9) and the HDL cholesterol-elevating variant in LIPG (10.2[7.5 to 13.0] mg/dL per rs200435657-A allele, P = 5.0 × 10−13). The risk of type 2 diabetes was lower in carriers of ANGPTL8 (odds ratio [OR] = 0.67[0.47-0.92], P = 0.01), ANGPTL4 (OR = 0.70[0.60-0.82], P = 1.4× 10−5) and LIPG (OR = 0.67[0.48-0.91], P = 0.01) PTVs than in noncarriers. Moreover, the odds of coronary artery disease were 44% lower in carriers of a PTV in ANGPTL8 (OR = 0.56[0.38-0.83], P = 0.004). Finally, the phenome-wide scan of the ANGPTL8 PTV showed a markedly higher associated risk of esophagitis (585 cases, OR = 174.3[17.7-1715.1], P = 9.7 × 10−6) and sensorineural hearing loss (12,250 cases, OR = 2.45[1.63-3.68], P = 1.8 × 10−5). The ANGPTL8 PTV carriers were less likely to use statin therapy (53,518 cases, OR = 0.53[0.41-0.71], P = 1.2 × 10−5). Our findings provide genetic evidence of potential long-term efficacy and safety of therapeutic targeting of dyslipidemias.
Private Health Sector in India: Ready and willing, yet underutilized in the Covid-19 pandemic
Authors: Davalbhakta Samira , Sharma Supriya , Gupta Shefali , Agarwal Vishwesh , Pandey Gaurav , Misra Durga Prasanna , Naik Bijaya Nanda , Goel Ashish , Gupta Latika , Agarwal Vikas 
Published: June 2020

AbstractBackgroundThe private medical sector is a resource that must be estimated for efficient inclusion into public healthcare during pandemics.MethodsA survey was conducted among private healthcare workers to ascertain their views on the potential resources that can be accessed from the private sector and methods to do the same.ResultsThere were 213 respondents, 80% of them being doctors. Nearly half (47.4%) felt that the contribution from the private medical sector has been suboptimal. Areas suggested for improved contributions by the private sector related to patient care (71.8%) and provision of equipment (62.4%), with fewer expectations (39.9%) on the research front. Another area of deemed support was maintaining continuity of care for non-COVID patients using virtual consultation services (77.4%), tele-consultation being the preferred option (60%). 58.2% felt that the Government had not involved the private sector adequately; and 45.1% felt they should be part of policy-making.ConclusionA streamlined pathway to facilitate the private sector to join hands with the public sector for a national cause is the need of the hour. Through our study, we have identified gaps in the current contribution by the private sector and identified areas in which they could contribute, by their own admission.
Construction of High Content Nanobody Library in Mammalian Cells by Linear-double-stranded DNA Based Strategies
Authors: Zhao Yanjie , Su Weijun , Li Shuai 
Published: June 2020

AbstractHere, we developed two novel methods to construct high content nanobody library in mammalian cells. For the first method, we employed alinear-double-stranded DNAbasedAND-gate (LBAG) strategy. Upstream- and downstream-linear-double-stranded DNAs (ldsDNAs), containing identical overlapping sequences, were co-transfected into cultured cell lines to conduct AND-gate calculation to form intact nanobody expression cassette. For the second method, we generated full-length nanobody expression ldsDNA byin vitroligation of restrict cut up- and down-stream ldsDNAs. Then the ldsDNAs were directly transfected into mammalian cells to express nanobody library. Both methods generated over a million different nanobody sequences as revealed by high-throughput sequencing (HTS).
Speech intelligibility with various head-related transfer functions: A computational modeling approach
Authors: Ahrens Axel , Cuevas-Rodriguez Maria , Brimijoin W. Owen 
Published: June 2020

AbstractSpeech intelligibility is known to be affected by the relative spatial position between target and interferers. The benefit of a spatial separation is, along with other factors, related to the head-related transfer function (HRTF). The HRTF is individually different and thus, the cues that improve speech intelligibility might also be different. In the current study an auditory model was employed to predict speech intelligibility with a variety of HRTFs. The predicted speech intelligibility was found to vary across HRTFs. Thus, individual listeners might have different access to cues that are important for speech intelligibility.
Active foot placement control ensures stable gait: Effect of constraints on foot placement and ankle moments
Authors: van Leeuwen A.M. , van Dieën J.H. , Daffertshofer A. , Bruijn S.M. 
Published: June 2020

AbstractStep-by-step foot placement control, relative to the center of mass (CoM) kinematic state, is generally considered a dominant mechanism for maintenance of gait stability. By adequate (mediolateral) positioning of the center of pressure with respect to the CoM, the ground reaction force generates a moment that prevents falling. In healthy individuals, foot placement is complemented mainly by ankle moment control ensuring stability. To evaluate possible compensatory relationships between step-by-step foot placement and complementary ankle moments, we investigated the degree of (active) foot placement control during steady-state walking, and under either foot placement-, or ankle moment constraints. Thirty healthy participants walked on a treadmill, while full-body kinematics, ground reaction forces and EMG activities were recorded. As a replication of earlier findings, we first showed step-by-step foot placement is associated with preceding CoM state and hip ab-/adductor activity during steady-state walking. Tight control of foot placement appears to be important at normal walking speed because there was a limited change in the degree of foot placement control despite the presence of a foot placement constraint. At slow speed, the degree of foot placement control decreased substantially, suggesting that tight control of foot placement is less essential when walking slowly. Step-by-step foot placement control was not tightened to compensate for constrained ankle moments. Instead compensation was achieved through increases in step width and stride frequency.
Neuro-computational mechanisms of action-outcome learning under moral conflict
Authors: Fornari L. , Ioumpa K. , Nostro A. D. , Evans N. J. , De Angelis L. , Paracampo R. , Gallo S. , Spezio M. , Keysers C. , Gazzola V. 
Published: June 2020

AbstractPredicting how actions result in conflicting outcomes for self and others is essential for social functioning. We tested whether Reinforcement Learning Theory captures how participants learn to choose between symbols that define a moral conflict between financial self-gain and other-pain. We tested whether choices are better explained by model-free learning (decisions based on combined historical values of past outcomes), or model-based learning (decisions based on the current value of separately expected outcomes) by including trials in which participants know that either self-gain or other-pain will not be delivered. Some participants favored options benefiting themselves, others, preventing other-pain. When removing the favored outcome, participants instantly altered their choices, suggesting model-based learning. Computational modelling confirmed choices were best described by model-based learning in which participants track expected values of self-gain and other-pain separately, with an individual valuation parameter capturing their relative weight. This valuation parameter predicted costly helping in an independent task. The expectations of self-gain and other-pain were also biased: the favoured outcome was associated with more differentiated symbol-outcome probability reports than the less favoured outcome. FMRI helped localize this bias: signals in the pain-observation network covaried with pain prediction errors without linear dependency on individual preferences, while the ventromedial prefrontal cortex contained separable signals covarying with pain prediction errors in ways that did and did not reflected individual preferences.
Nectar larceny in the trainbearers (Lesbia, Trochilidae)
Authors: Igić Boris , Nguyen Ivory , Fenberg Phillip B. 
Published: June 2020

ABSTRACTMany flower visitors engage in floral larceny, a suite of so-called ‘illegitimate’ visits in which foragers take nectar without providing pollination services. The data on prevalence of illegitimate visits among hummingbirds, as well as the total proportion of foraging and diet that such visits comprise is broadly lacking. Here, we report the occurrence of nectar larceny in both currently recognized species of trainbearers and analyze the proportion of plant visits categorized by mode of interaction as: primary robbing, secondary robbing, theft, and/or pollination. To the best of our knowledge, we provide the first published report identifying robbing in these species. We augment our original field observations using a trove of data from citizen science databases and literature. Although it is difficult to distinguish primary vs. secondary robbing and theft vs. pollination, we conservatively estimate that ca. 40% of the recorded nectar foraging visits involve nectar robbing. Males appear to engage in robbing marginally more than females, but further studies are necessary to confidently examine the multi-way interactions among sex, species, mode of visitation, and other factors. We discuss the significance of these findings in the context of recent developments in study of nectar foraging, larceny, and pollination from both avian and plant perspectives.
NMDAR-mediated transcriptional control of gene expression during the development of medial ganglionic eminence-derived interneurons
Authors: Mahadevan Vivek , Mitra Apratim , Zhang Yajun , Yuan Xiaoqing , Peltekian Areg , Chittajallu Ramesh , Esnault Caroline , Maric Dragan , Rhodes Christopher , Pelkey Kenneth A. , Dale Ryan , Petros Timothy J. , McBain Chris J. 
Published: June 2020

ABSTRACTMedial ganglionic eminence (MGE)-derived parvalbumin (PV)+, somatostatin (SST)+ and Neurogliaform (NGFC)-type cortical and hippocampal interneurons, have distinct molecular, anatomical and physiological properties. However, the molecular mechanisms regulating their diversity remain poorly understood. Here, via single-cell transcriptomics, we show that the obligate NMDA-type glutamate receptor (NMDAR) subunit geneGrin1mediates subtype-specific transcriptional regulation of gene expression in MGE-derived interneurons, leading to altered subtype abundances. Notably, MGE-specific conditionalGrin1loss results in a systemic downregulation of diverse transcriptional, synaptogenic and membrane excitability regulatory programs. These widespread gene expression abnormalities mirror aberrations that are typically associated with neurodevelopmental disorders, particularly schizophrenia. Our study hence provides a road map for the systematic examination of NMDAR signaling in interneuron subtypes, revealing potential MGE-specific genetic targets that could instruct future therapies of psychiatric disorders.
Nonlinearities in retinal bipolar cells shape the encoding of artificial and natural stimuli
Authors: Schreyer Helene Marianne , Gollisch Tim 
Published: June 2020

AbstractThe retina dissects the visual scene into parallel feature channels, and bipolar cells are speculated to play a key role in this signal separation. Yet, bipolar cells are traditionally viewed as simple, linear neurons. Here, using the salamander retina, we investigated the hypothesis of linear signal processing in bipolar cells by intracellularly recording their voltage signals under artificial and natural visual stimuli. We observed nonlinear representation of contrast and, unexpectedly, also nonlinear spatial integration in a sizable fraction of bipolar cells. Furthermore, linear receptive field models fail to describe responses of nonlinear bipolar cells to spatially structured artificial and natural stimuli. The nonlinear properties occur in the receptive field center and may be cell-type specific, with stronger effects in transient than sustained bipolar cells. Thus, our data suggest that nonlinear signal pooling starts earlier than previously thought, that is, before signal integration in bipolar cells.
TIP60 acetylates H2AZ and regulates doxorubicin-induced DNA damage sensitivity throughRAD51transcription
Authors: Lee Kwok Kin , Zhang Yanzhou , Tirado- Magallanes Roberto , Rajagopalan Deepa , Bhatia Shreshtha Sailesh , Ng Larry , Desi Ng , Tham Cheng Yong , Teo Wen Shiun , Hoppe Michal Marek , Jeyasekharan Anand D. , Tay Yvonne , Chng Wee Joo , Tenen Daniel G. , Benoukraf Touati , Jha Sudhakar 
Published: June 2020

AbstractTIP60, a lysine acetyltransferase and H2AZ, a histone H2A variant are involved in transcription and DNA repair. Recent studies suggest that H2AZ acetylation is dependent on TIP60. Here, we show that TIP60 acetylates both isoforms of H2AZin vitroand in cells. Utilizing ChIP-seq and RNA-seq to identify the genes regulated by TIP60-dependent acetylation of H2AZ, we find that TIP60-dependent acetylation of H2AZ correlates with the expression of genes involved in DNA damage repair, amongst several other pathways. In line with this, TIP60-depleted cells exhibit increased sensitivity to the DNA damage-inducing drug doxorubicin. Restoring the expression level ofRAD51, one of the genes involved in the DNA damage repair pathway, partially rescues the doxorubicin sensitivity due to TIP60 depletion. Overall, our study uncovers a role for TIP60 in regulating doxorubicin-induced DNA damage sensitivity in a manner dependent onRAD51transcription.
Verbal Communication using Intracortical Signals in a Completely Locked In-Patient
Authors: Chaudhary Ujwal , Vlachos Ioannis , Zimmermann Jonas B. , Espinosa Arnau , Tonin Alessandro , Jaramillo-Gonzalez Andres , Khalili-Ardali Majid , Topka Helge , Lehmberg Jens , Friehs Gerhard M. , Woodtli Alain , Donoghue John P. , Birbaumer Niels 
Published: June 2020

AbstractPatients with amyotrophic lateral sclerosis (ALS) can lose all muscle-based routes of communication as motor neuron degeneration progresses, and ultimately, they may be left without any means of communication. While others have evaluated communication in people with remaining muscle control, to the best of our knowledge, it is not known whether neural-based communication remains possible in a completely locked-in state (CLIS). With consent and approval of the participant, family, and legal authority for this study, two 64 microelectrode arrays were implanted in the supplementary and primary motor cortex of a CLIS patient with ALS. The patient modulated neural firing rates based on auditory feedback, and he used this strategy to select letters one at a time to form words and phrases to communicate his needs and experiences. This case study provides novel evidence that brain-based volitional communication is possible even in a completely locked-in state.
High Coxiella burnetii seroconversion rate in veterinary students, the Netherlands, 2006-2010
Authors: de Lange Marit M.A. , van der Hoek Wim , Schneeberger Peter M. , Swart Arno , Heederik Dick J. J. , Schimmer Barbara , Wouters Inge M. 
Published: June 2020

AbstractWe examined seroconversion rates by measuring IgG antibodies against Coxiella burnetii among two cohorts of veterinary students. During follow-up of 118 seronegative veterinary students, 23 students seroconverted. Although the clinical significance of the presence of antibodies is unknown, students should be informed about the potential risks of Q fever.
The computational Patient has diabetes and a COVID
Authors: Barbiero Pietro , Lió Pietro 
Published: June 2020

AbstractMedicine is moving from a curative discipline to a preventative discipline relying on personalised and precise treatment plans. The complex and multi level pathophysiological patterns of most diseases require a systemic medicine approach and are challenging current medical therapies. On the other hand, computational medicine is a vibrant interdisciplinary field that could help move from an organ-centered approach to a process-oriented approach. The ideal computational patient would require an international interdisciplinary effort, of larger scientific and technological interdisciplinarity than the Human Genome Project. When deployed, such a patient would have a profound impact on how healthcare is delivered to patients. Here we present a computational patient model that integrates, refines and extends recent mechanistic or phenomenological models of cardiovascular, RAS and diabetic processes. Our aim is twofold: analyse the modularity and composability of the model-building blocks of the computational patient and to study the dynamical properties of well-being and disease states in a broader functional context. We present results from a number of experiments among which we characterise the dynamic impact of COVID-19 and type-2 diabetes (T2D) on cardiovascular and inflammation conditions. We tested these experiments under different exercise, meal and drug regimens. We report results showing the striking importance of transient dynamical responses to acute state conditions and we provide guidelines for system design principles for the inter-relationship between modules and components in systemic medicine. Finally this initial computational Patient can be used as a toolbox for further modifications and extensions.
State heterogeneity of human mobility and COVID-19 epidemics in the European Union
Authors: Yuan Xiaoling , Hu Kun , Xu Jie , Zhang Xuchen , Bao Wei , Lynch Charles F. , Zhang Lanjing 
Published: June 2020

SummaryHuman mobility was associated with epidemic changes of coronavirus disease 2019 (COVID-19) in China, where strict public health interventions reduced human mobility and COVID-19 epidemics. But its association with COVID-19 epidemics in the European Union (EU) is unclear. In this quasi-experimental study, we modelled the temporal trends in human mobility and epidemics of COVID-19 in the 27 EU states between January 15 and May 9, 2020. COVID-19 and human mobility had 3 trend-segments, including an upward trend in COVID-19 daily incidence and a downward trend in most human mobilities in the middle segment. Compared with the EU states farther from Italy, the state-wide lockdown dates were more likely linked to turning points of human mobilities in the EU states closer to Italy, which were also more likely linked to second turning points of COVID-19 epidemics. Among the examined human mobilities, the second turning points in driving mobility and the first turning points in parks mobility were the best factors that connected lockdown dates and COVID-19 epidemics in the EU states closer to Italy. Our findings highlight the state- and mobility-heterogeneity in the associations of public health interventions and human mobility with changes of COVID-19 epidemics in the EU states.
Relative Coronavirus Disease 2019 Mortality: A Swiss Population-based Study
Authors: Hothorn Torsten , Bopp Matthias , Günthard Huldrych F. , Keiser Olivia , Roelens Maroussia , Weibull Caroline E. , Crowther Michael J. 
Published: June 2020

AbstractObjectiveSeverity of the coronavirus disease 2019 (covid-19) has been assessed in terms of absolute mortality in SARS-CoV-2 positive cohorts. An assessment of mortality relative to mortality in the general population is presented.DesignRetrospective population-based study.SettingIndividual information on symptomatic confirmed SARS-CoV-2 patients and subsequent deaths from any cause were compared to the all-cause mortality in the Swiss population of 2018. Starting February 23, 2020, mortality in covid-19 patients was monitored for 80 days and compared to the population mortality observed in the same time-of-year starting February 23, 2018.Participants5 160 595 inhabitants of Switzerland aged 35 to 95 without covid-19 (general population in spring 2018) and 20 769 persons tested positively for covid-19 (spring 2020).MeasurementsSex- and age-specific mortality rates were estimated using Cox proportional hazards models. Absolute probabilities of death were predicted and risk was assessed in terms of relative mortality by taking the ratio between the sex- and age-specific absolute mortality in covid-19 patients and the corresponding mortality in the 2018 general population.ResultsA confirmed SARS-CoV-2 infection substantially increased the probability of death across all patient groups, ranging from nine (6 to 15) times the population mortality in 35-year old infected females to a 53-fold increase (46 to 59) for 95 year old infected males. The highest relative risks were observed among males and older patients. The magnitude of these effects was smaller compared to increases observed in absolute mortality risk. Male covid-19 patients exceeded the population hazard for males (hazard ratio 1.20, 1.00 to 1.44). Each additional year of age increased the population hazard in covid-19 patients (hazard ratio 1.04, 1.03 to 1.05).LimitationsInformation about the distribution of relevant comorbidities was not available on population level and the associated risk was not quantified.ConclusionsHealth care professionals, decision makers, and societies are provided with an additional population-adjusted assessment of covid-19 mortality risk. In combination with absolute measures of risk, the relative risks presented here help to develop a more comprehensive understanding of the actual impact of covid-19.