bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-SARS-CoV-2 IgG responses are powerful predicting signatures for the outcome of COVID-19 patients
Authors: Lei Qing , Yu Cai-zheng , Li Yang , Hou Hong-yan , Xu Zhao-wei , Yao Zong-jie , Zhang Yan-di , Lai Dan-yun , Ndzouboukou Jo-Lewis Banga , Zhang Bo , Chen Hong , Ouyang Zhu-qing , Xue Jun-biao , Lin Xiao-song , Zheng Yun-xiao , Wang Xue-ning , Jiang He-wei , Zhang Hai-nan , Qi Huan , Guo Shu-juan , He Mei-an , Sun Zi-yong , Wang Feng , Tao Sheng-ce , Fan Xiong-lin 
Published: November 2020

AbstractThe COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. We assumed that antibodies may serve as biomarkers for predicting disease outcome. By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1,034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. We found that nonsurvivors induced higher levels of IgG responses against most of non-structural proteins than survivors on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend < 0.05). Additionally, IgG responses to all of these 10 non-structural/accessory proteins were also associated with the severity of disease, and differential kinetics and serum positive rate of these IgG responses were confirmed in COVID-19 patients of varying severities within 20 days after symptoms onset. The AUCs for these IgG responses, determined by computational cross-validations, were between 0.62 and 0.71. Our findings have important implications for improving clinical management, and especially for developing medical interventions and vaccines.
Non-occupational and occupational factors associated with specific SARS-CoV-2 antibodies among Hospital Workers – a multicentre cross-sectional study
Authors: Kahlert Christian R. , Persi Raphael , Güsewell Sabine , Egger Thomas , Leal-Neto Onicio B. , Sumer Johannes , Flury Domenica , Brucher Angela , Lemmenmeier Eva , Möller J. Carsten , Rieder Philip , Stocker Reto , Vuichard-Gysin Danielle , Wiggli Benedikt , Albrich Werner C. , Flury Baharak Babouee , Besold Ulrike , Fehr Jan , Kuster Stefan P. , McGeer Allison , Risch Lorenz , Schlegel Matthias , Friedl Andrée , Vernazza Pietro , Kohler Philipp 
Published: November 2020

ABSTRACTObjectivesProtecting healthcare workers (HCW) from Coronavirus Disease-19 (COVID-19) is critical to preserve the functioning of healthcare systems. We therefore assessed seroprevalence and identified risk factors for Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2) seropositivity in this population.MethodsBetween June 22nd and August 15th 2020, HCW from institutions in Northern/Eastern Switzerland were screened for SARS-CoV-2 antibodies. We recorded baseline characteristics, non-occupational and occupational risk factors. We used pairwise tests of associations and multivariable logistic regression to identify factors associated with seropositivity.ResultsAmong 4’664 HCW from 23 healthcare facilities, 139 (3%) were seropositive. Non-occupational exposures independently associated with seropositivity were contact with a COVID-19-positive household (adjusted OR=54, 95%-CI: 31-97) and stay in a COVID-19 hotspot (aOR=2.2, 95%-CI: 1.1-3.9). Blood group 0 vs. non-0 (aOR=0.4, 95%-CI: 0.3-0.7), active smoking (aOR=0.5, 95%-CI: 0.3-0.9) and living with children <12 years (aOR=0.3, 95%-CI: 0.2-0.6) were associated with decreased risk. Occupational risk factors were close contact to COVID-19 patients (aOR=2.8, 95%-CI: 1.5-5.5), exposure to COVID-19-positive co-workers (aOR=2.0, 95%-CI: 1.2-3.1), poor knowledge of standard hygiene precautions (aOR=2.0, 95%-CI: 1.3-3.2), and frequent visits to the hospital canteen (aOR=1.9, 95%-CI: 1.2-3.1).ConclusionsLiving with COVID-19-positive households showed by far the strongest association with SARS-CoV-2 seropositivity. We identified several potentially modifiable risk factors, which might allow mitigation of the COVID-19 risk among HCW. The lower risk among those living with children, even after correction for multiple confounders, is remarkable and merits further study.
Awareness, knowledge and trust in the Greek authorities towards COVID-19 pandemic: results from the Epirus Health Study cohort
Authors: Kanellopoulou Afroditi , Koskeridis Fotios , Markozannes Georgios , Bouras Emmanouil , Soutziou Chrysa , Chaliasos Konstantinos , Doumas Michail T , Sigounas Dimitrios E , Tzovaras Vasilios T , Panos Agapios , Stergiou Yiolanda , Mellou Kassiani , Papamichail Dimitrios , Aretouli Eleni , Chatzidimitriou Dimitrios , Chatzopoulou Fani , Bairaktari Eleni , Tzoulaki Ioanna , Evangelou Evangelos , Rizos Evangelos C , Ntzani Evangelia , Vakalis Konstantinos , Tsilidis Konstantinos K 
Published: November 2020

ABSTRACTBackgroundTo assess the level of knowledge and trust in the policy decisions taken regarding the coronavirus disease (COVID-19) pandemic among Epirus Health Study (EHS) participants.MethodsThe EHS is an ongoing and deeply-phenotyped prospective cohort study that has recruited 667 participants in northwest Greece until August 31st, 2020. Level of knowledge on coronavirus (SARS-CoV-2) transmission and COVID-19 severity was labeled as poor, moderate or good. Variables assessing knowledge and beliefs towards the pandemic were summarized overall and by gender, age group (25-39, 40-49, 50-59, ≥60 years) and period of report (before the lifting of lockdown measures in Greece: March 30thto May 3rd, and two post-lockdown time periods: May 4thto June 31st, July 1stto August 31st). An exposure-wide association analysis was conducted to evaluate the associations between 153 explanatory variables and participants’ knowledge. Correction for multiple comparisons was applied using a false discovery rate (FDR) threshold of 5%.ResultsA total of 563 participants (49 years mean age; 60% women) had available information on the standard EHS questionnaire, the clinical and biochemical measurements, and the COVID-19-related questionnaire. Percentages of poor, moderate and good knowledge status regarding COVID-19 were 4.5%, 10.0% and 85.6%, respectively. The majority of participants showed absolute or moderate trust in the Greek health authorities for the management of the epidemic (90.1%), as well as in the Greek Government (84.7%) and the official national sources of information (87.4%). Trust in the authorities was weaker in younger participants and those who joined the study after the lifting of lockdown measures (p-value≤0.001). None of the factors examined was associated with participants’ level of knowledge after correction for multiple testing.ConclusionsHigh level of knowledge about the COVID-19 pandemic and trust in the Greek authorities was observed, possibly due to the plethora of good quality publicly available information and the timely management of the pandemic at its early stages in Greece. Information campaigns for the COVID-19 pandemic should be encouraged even after the lifting of lockdown measures to increase public awareness.
Parkinson’s Disease, Smoking, and Lower Endoscopy
Authors: Davis Susan M. 
Published: November 2020

ABSTRACTParkinson’s disease (PD) is inversely associated with smoking. Whether this association is due to a causal relationship or to confounding by a covariate of smoking is still debated.The Institute for Health Metrics and Evaluation (IHME) released refreshed data on October 15, 2020. This study included that recently released data. The study included populations of the United States and ten U.S. states from 2004 to 2018. The ten U.S. states included the five states with the highest PD incidence rates in 2019 (Maine, Vermont, Kansas, Alaska, Missouri) and the five states with the lowest PD incidence rates in 2019 (Arkansas, Mississippi, South Dakota, Nebraska, Delaware). The study used scatter plots to explore the association between PD incidence and smoking and the association between PD incidence and a covariate of smoking, lower endoscopy utilization.For PD verses smoking, the results indicate that there is an inverse correlation for the United States, but there is no association for the ten states. The coefficient of determination (R2) for the United States was 0.714 and ranged from a low of 0.004 for South Dakota to 0.613 for Mississippi. The average R 2 for the ten states was 0.357.For PD verses lower endoscopy, the results indicate that the best model fit to the data is a polynomial. When the fitting curve examined in the regression analysis was a 3rd order (cubic) polynomial, there was a positive correlation between PD and lower endoscopy for the United States and for all ten states. The R2 for the US was 0.971 and ranged from a low of 0.709 for Alaska to 0.970 for Kansas. The average R2 for the ten states was 0.878.The results suggest that the inverse association between PD incidence and smoking is confounded by a positive association between PD and lower endoscopy utilization. Further investigation of a possible relationship between PD incidence and lower endoscopy utilization is warranted and may provide a means for reducing PD incidence.
Heavy load carrying and musculoskeletal health: An exploratory study of sand miners in Pokhara, Kaski District, Nepal
Authors: Koyuncu Aybüke , Bates Michael N. , Petrin Ziva , Cope Myles , McCoy Sandra I. , Prata Ndola , Sijali Tula Ram , Harris-Adamson Carisa 
Published: November 2020

ABSTRACTBackgroundTrends in urbanization contribute to the growing global demand for raw construction materials. The health effects of load carrying among occupational groups that mine and carry sand and stone used for construction of roads and buildings remains poorly understood.MethodsWe conducted an exploratory cross-sectional study among a convenience sample of sand miners working at an excavation site on the Seti River in Pokhara, Nepal. Load carrying weight, duration, and frequency were used to categorize miners as having “low” or “high” load-carrying exposures. Probable musculoskeletal disorders (MSDs) were identified using self-reported symptoms of moderate to severe musculoskeletal pain, as well as physical examinations.ResultsThe average loads carried by female and male sand miners weighed 66.3 kg and 87.3 kg, respectively. Among all participants (N=42), 45.2% reported moderate to severe musculoskeletal pain in at least one body region and 16 (38.1%) had probable MSDs identified using specified case criteria. The prevalence of MSDs was lower among miners carrying, on average, heavier loads compared to those carrying lighter loads (ORa=0.29; 95% CI: 0.05, 1.8), possibly indicative of the healthy worker survival effect. Miners carrying loads for longer durations and frequencies had higher odds of MSDs compared with those carrying for shorter durations and frequencies.ConclusionDespite the pervasiveness of load carrying as an income generating activity throughout the developing world, these populations remain largely excluded from global occupational health agendas. Larger epidemiologic studies are needed to justify action to protect the health and safety of these unrecognized and understudied groups.
Full activation of an α7-α3β4 nicotinic receptor complex avoids receptor desensitization in human chromaffin cells
Authors: Jiménez-Pompa Amanda , Sanz-Lázaro Sara , Medina-Polo José , González-Enguita Carmen , Blázquez Jesús , McIntosh J. Michael , Albillos Almudena 
Published: November 2020

Abstractα7 nicotinic receptors have been involved in numerous pathologies. A hallmark of these receptors is their extremely fast desensitization, a process not fully understood yet. Here we show that human native α7 and α3β4 nicotinic receptors physically interact in human chromaffin cells of adrenal glands. The full activation of this α7-α3β4 receptor complex avoids subtypes receptor desensitization, leading to gradual increase of currents with successive acetylcholine pulses. Instead, full and partial activation with choline of α7 and α3β4 subtypes, respectively, of this linked receptor leads to α7 receptor desensitization. Therefore choline, a product of the acetylcholine hydrolysis, acts as a brake by limiting the increase of currents by acetylcholine. Very importantly, the efficiency of the α7-α3β4 interaction diminishes in subjets older than 50 years, accordingly increasing receptor desensitization and decreasing nicotinic currents. These results open a new line of research to achieve improved therapeutic treatments for nicotinic receptors related diseases.
Multilevel Twin Models: Geographical Region as a Third Level Variable
Authors: Tamimy Zenab , Kevenaar Sofieke T. , Hottenga Jouke Jan , Hunter Michael D. , de Zeeuw Eveline L. , Neale Michael C. , van Beijsterveldt Catharina E.M. , Dolan Conor V. , van Bergen Elsje , Boomsma Dorret I. 
Published: November 2020

AbstractThe classical twin model can be reparametrized as an equivalent multilevel model. The multilevel parameterization has underexplored advantages, such as the possibility to include higher-level clustering variables in which lower levels are nested. When this higher-level clustering is not modeled, its variance is captured by the common environmental variance component. In this paper we illustrate the application of a 3-level multilevel model to twin data by analyzing the regional clustering of 7-year-old children’s height in the Netherlands. Our findings show that 1.8%, of the phenotypic variance in children’s height is attributable to regional clustering, which is 7% of the variance explained by between-family or common environmental components. Since regional clustering may represent ancestry, we also investigate the effect of region after correcting for genetic principal components, in a subsample of participants with genome-wide SNP data. After correction, region did no longer explain variation in height. Our results suggest that the phenotypic variance explained by region actually represent ancestry effects on height.
Recovering genomes and phenotypes using allele-specific gene expression
Authors: Gürsoy Gamze , Lu Nancy , Wagner Sarah , Gerstein Mark 
Published: November 2020

AbstractWith the recent increase in RNA sequencing efforts using large cohorts of individuals, studying allele-specific gene expression is becoming increasingly important. Here, we report that, despite not containing explicit variant information, a list of allele-specific gene names of an individual is enough to recover key variants and link the individual back to their genome or phenotype. This creates a privacy conundrum.
Dissociable effects of subliminal incentives on initiation and velocity control of goal-directed eye movements
Authors: Hinze Vasko Kilian , Uslu Ozge , Antono Jessica Emily , Wilke Melanie , Pooresmaeili Arezoo 
Published: November 2020

AbstractOver the last decades, several studies have demonstrated that conscious and unconscious reward incentives both affect performance in physical and cognitive tasks, suggesting that goal-pursuit can arise from an unconscious will. Whether the planning of goal-directed saccadic eye movements during an effortful task can also be affected by subliminal reward cues has not been systematically investigated. We employed a novel task where participants had to make several eye movements back and forth between a fixation point and a number of peripheral targets. The total number of targets visited by the eyes in a fixed amount of time determined participants’ monetary gain. The magnitude of the reward at stake was briefly shown at the beginning of each trial and was masked by pattern images superimposed in time. We found that when reward cues were fully visible and thus consciously perceived, higher reward enhanced all saccade parameters. However, a dissociation was observed between the effects of subliminal rewards on saccade initiation and peak velocities. While truly subliminal reward cues did increase the number of saccades, they did not enhance saccades’ peak velocity. Additionally, participants who had reached a truly subliminal level of reward perception showed a decrement in accuracy as a function of reward across all visibility levels, as saccade endpoint error was larger when higher reward incentives were expected. This suboptimal speed-accuracy trade-off did not occur in the supraliminal group. These results suggest that although saccades’ initiation can be triggered by subconscious mechanisms, conscious awareness is required to optimally adjust the velocity and accuracy of eye movements based on the expected rewards.
Distinct population code for movement kinematics and changes of ongoing movements in human subthalamic nucleus
Authors: London Dennis , Fazl Arash , Katlowitz Kalman , Soula Marisol , Pourfar Michael H , Mogilner Alon Y , Kiani Roozbeh 
Published: November 2020

AbstractThe subthalamic nucleus (STN) is theorized to globally suppress movement through connections with downstream basal ganglia structures. Current theories are supported by increased STN activity when subjects withhold an uninitiated action plan, but a critical test of these theories requires studying STN responses when an ongoing action is replaced with an alternative. Here, we perform this test using an extended reaching task with instructions to switch movement trajectory mid-action. We show that STN activity decreases during action switches, contrary to prevalent theories. Further, beta oscillations in the local field potential in STN, which are associated with movement inhibition do not show increased power or entraining of neuronal firing during switches. We report an inhomogeneous population neural code in STN, with one sub-population encoding movement kinematics and direction and another encoding unexpected action switches. We suggest an elaborate neural code in STN that contributes to planning actions and changing the plans.
Local topology, bifurcations and mutation hot-spots in proteins with SARS-CoV-2 spike protein as an example
Authors: Peng Xubiao , Niemi Antti J 
Published: November 2020

AbstractNovel topological methods are introduced to protein research. The aim is to identify hot-spot sites where a bifurcation can change the local topology of the protein backbone. Since the shape of a protein is intimately related to its biological function, a mutation that takes place at such a bifurcation hot-spot has an enhanced capacity to change the protein’s biological function. The methodology applies to any protein but it is developed with the SARS-CoV-2 spike protein as a timely example. First, topological criteria are introduced to identify and classify potential mutation hot-spot sites along the protein backbone. Then, the expected outcome of a substitution mutation is estimated for a general class of hot-spots, by a comparative analysis of the backbone segments that surround the hot-spot sites. This analysis employs the statistics of commensurable amino acid fragments in the Protein Data Bank, in combination with general stereochemical considerations. It is observed that the notorious D614G substitution of the spike protein is a good example of such a mutation hot-spot. Several topologically similar examples are then analyzed in detail, some of them are even better candidates for a mutation hot-spot than D614G. The local topology of the recently observed N501Y mutation is also inspected, and it is found that this site is prone to a different kind of local topology changing bifurcation.
Synaptic integration of subquantal neurotransmission by co-localized G protein coupled receptors in presynaptic terminals
Authors: Church Emily , Hamid Edaeni , Zurawski Zack , Potcoava Mariana , Flores-Barrera Eden , Caballero Adriana , Tseng Kuei Y. , Alford Simon 
Published: November 2020

AbstractIn presynaptic terminals, membrane-delimited Gi/o-mediated presynaptic inhibition is ubiquitous and acts through Gβγ to inhibit Ca2+ entry, or directly at SNARE complexes to inhibit Ca2+-dependent synaptotagmin-SNARE complex interactions. At CA1-subicular presynaptic terminals 5-HT1B and GABAB receptors colocalize. GABAB receptors inhibit Ca2+ entry, whereas 5-HT1B receptors target SNARE complexes. We demonstrate in male and female rats that GABAB receptors receptors alter Pr, whereas 5-HT1B receptors reduce evoked cleft glutamate concentrations allowing differential inhibition of AMPA and NMDA receptor EPSCs. This reduction in cleft glutamate concentration was confirmed by imaging glutamate release using a genetic sensor (iGluSnFR).Simulations of glutamate release and postsynaptic glutamate receptor currents were made. We tested effects of changes in vesicle numbers undergoing fusion at single synapses, relative placement of fusing vesicles and postsynaptic receptors, and the rate of release of glutamate from a fusion pore. Experimental effects of Pr changes, consistent with GABAB receptor effects, were straightforwardly represented by changes in numbers of synapses. The effects of 5-HT1B receptor-mediated inhibition are well-fit by simulated modulation of the release rate of glutamate into the cleft. Colocalization of different actions of GPCRs provide synaptic integration within presynaptic terminals. Train-dependent presynaptic Ca2+ accumulation forces frequency-dependent recovery of neurotransmission during 5-HT1B receptor activation. This is consistent with competition between Ca2+-synaptotagmin and Gβγ at SNARE complexes. Thus, stimulus trains in 5-HT1B receptor agonist unveil dynamic synaptic modulation and a sophisticated hippocampal output filter that itself is modulated by colocalized GABAB receptors which alter presynaptic Ca2+. In combination these pathways allow complex presynaptic integration.Significance StatementTwo G protein coupled receptors colocalize at presynaptic sites, to mediate presynaptic modulation by Gβγ, but one – a GABAB receptor inhibits Ca2+ entry while another – a 5-HT1B receptor competes with Ca2+-synaptotagmin binding to the synaptic vesicle machinery. We have investigated downstream effects of signaling and integrative properties of these receptors. Their effects are profoundly different. GABAB receptors alter Pr leaving synaptic properties unchanged, while 5-HT1B receptors fundamentally change properties of synaptic transmission, modifying AMPA receptor but sparing NMDA receptor responses. Co-activation of these receptors allows synaptic integration because of convergence of GABAB receptor alteration on Ca2+ and the effect of this altered Ca2+ signal on 5-HT1B receptor signaling. This presynaptic convergence provides a novel form of synaptic integration.