bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antibody landscape against SARS-CoV-2 proteome revealed significant differences between non-structural/ accessory proteins and structural proteins
Authors: Li Yang , Xu Zhaowei , Lei Qing , Lai Dan-yun , Hou Hongyan , Jiang He-wei , Zheng Yun-xiao , Wang Xue-ning , Wu Jiaoxiang , Ma Ming-liang , Zhang Bo , Chen Hong , Yu Caizheng , Xue Jun-biao , Zhang Hai-nan , Qi Huan , Guo Shu-juan , Zhang Yandi , Lin Xiaosong , Yao Zongjie , Sheng Huiming , Sun Ziyong , Wang Feng , Fan Xionglin , Tao Sheng-ce 
Published: December 2020

SummaryThe immunogenicity of SARS-CoV-2 proteome is largely unknown, especially for non-structural proteins and accessory proteins. Here we collected 2,360 COVID-19 sera and 601 control sera. We analyzed these sera on a protein microarray with 20 proteins of SARS-CoV-2, built an antibody response landscape for IgG and IgM. We found that non-structural proteins and accessory proteins NSP1, NSP7, NSP8, RdRp, ORF3b and ORF9b elicit prevalent IgG responses. The IgG patterns and dynamic of non-structural/ accessory proteins are different from that of S and N protein. The IgG responses against these 6 proteins are associated with disease severity and clinical outcome and declined sharply about 20 days after symptom onset. In non-survivors, sharp decrease of IgG antibodies against S1 and N protein before death was observed. The global antibody responses to non-structural/ accessory proteins revealed here may facilitate deeper understanding of SARS-CoV-2 immunology.HighlightsAn antibody response landscape against SARS-CoV-2 proteome was constructedNon-structural/accessory proteins elicit prevalent antibody responses but likely through a different mechanism to that of structural proteinsIgG antibodies against non-structural/accessory proteins are more associated with disease severity and clinical outcomeFor non-survivors, the levels of IgG antibodies against S1 and N decline significantly before death
Novel Oral Anticoagulants versus Vitamin K Antagonists for Patients with Left Ventricular Thrombus: A Systematic Review and Meta-Analysis
Authors: Chen Runzhen , Zhou Jinying , Liu Chen , Zhou Peng , Li Jiannan , Wang Ying , Zhao Xiaoxiao , Chen Yi , Song Li , Zhao Hanjun , Yan Hongbing 
Published: December 2020

AbstractBackgroundAlthough vitamin K antagonists (VKAs) are recommended as first-line anticoagulants for patients with left ventricular thrombus (LVT), accumulating evidence suggests novel oral anticoagulants (NOACs) could be safe alternatives for VKAs. Efficacy and safety of NOACs should be assessed to justify their usage for LVT patients.DesignWe performed a meta-analysis of observational studies to evaluate the efficacy and safety of NOACs as compared to VKAs in LVT patients.MethodsPubMed and EMBASE databases were searched for articles published until November 12, 2020. Two reviewers independently extracted relevant information from articles and assessed the study quality. Pooled effects were estimated using Mantel–Haenssel method and presented as risk ratios (RR) using fixed-effect model. Reporting followed the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guideline.ResultsA total of 2467 LVT patients from 13 studies were included. Compared with VKAs, NOACs showed similar efficacy in prevention of stroke or systemic embolism (RR: 0.96, 95% confidence interval [CI]:0.80-1.16, P = 0.68) and thrombus resolution (RR: 0.88, 95% CI: 0.72-1.09, P = 0.20), but significantly reduced the risk of stroke (RR: 0.68, 95% CI: 0.47-1.00, P < 0.05). For safety outcomes, NOACs users showed similar risk of any bleedings (RR: 0.94, 95% CI: 0.67-1.31, P = 0.70), but lower risk of clinically relevant bleedings (RR: 0.35, 95% CI: 0.13-0.92, P = 0.03) compared with VKAs users.ConclusionsCompared with VKAs, NOACs acquired similar efficacy and safety profile for patients with LVT, but could reduce the risk of strokes and clinically relevant bleedings.
Characterisation of multimodal network organisation after focal prefrontal lesions in humans
Authors: Noonan MP , Geddes MR , Mars RB , Fellows LK 
Published: December 2020

AbstractLesion research in humans and non-human primates classically maps the behavioral effects of focal damage to the directly-injured brain region. However, given the interconnectedness of the brain, it has long been known that such damage can also have distant effects. Modern imaging methods provide new ways to assess those effects. Further, triangulating across these methods in a lesion model may shed light on the biological basis of structural and functional networks in the healthy brain. We characterised network organization assessed with multiple MRI imaging modalities in 13 patients with chronic focal damage affecting either superior or inferior frontal gyrus (SFG, IFG) and 18 demographically-matched healthy Controls. We first defined structural and functional network parameters for the two frontal regions-of-interest in healthy Controls, and then used voxel-based morphology (VBM) and tract-based spatial statistics (TBSS) analyses to investigate structural grey matter (GM) and white matter (WM) differences between patients and Controls. The functional and structural networks defined in healthy participants were then used to constrain interpretation of the whole brain network effects in patients. Finally, we applied dual regression to examine the differences in functional coupling to large-scale resting state networks (RSNs), focusing on the RSNs which most overlapped structurally with the lesion sites. Overall, the results show that lesions are associated with widespread within-network GM loss at sites distal from the lesion, yet leave WM and RSNs relatively preserved. Lesions to either prefrontal region had a very similar impact on structural networks, but SFG lesions had larger impact on RSNs than did IFG lesions. The findings provide evidence for causal contributions of specific prefrontal regions to structural and functional brain networks in humans, relevant to interpreting connectomic findings in studies of healthy people or those with psychiatric illnesses.
Post Hoc Evaluation of Probabilistic Model Forecasts: A COVID-19 Case Study
Authors: Colonna Kyle J. , Cooke Roger M. , Evans John S. 
Published: December 2020

AbstractTo combat the spread of coronavirus disease 2019 (COVID-19), decision-makers and the public may desire forecasts of the cases, hospitalizations, and deaths that are likely to occur. Thankfully, dozens of COVID-19 forecasting models exist and many of their forecasts have been made publicly available. However, there has been little published peer-reviewed information regarding the performance of these models and what is available has focused mostly on the performance of their central estimates (i.e., predictive performance). There has been little reported on the accuracy of their uncertainty estimates (i.e., probabilistic performance), which could inform users how often they would be surprised by observations outside forecasted confidence intervals. To address this gap in knowledge, we borrow from the literature on formally elicited expert judgment to demonstrate one commonly used approach for resolving this issue. For two distinct periods of the pandemic, we applied the Classical Model (CM) to evaluate probabilistic model performance and constructed a performance-weighted ensemble based on this evaluation. Some models which exhibited good predictive performance were found to have poor probabilistic performance, and vice versa. Only two of the nine models considered exhibited superior predictive and probabilistic performance. Additionally, the CM-weighted ensemble outperformed the equal-weighted and predictive-weighted ensembles. With its limited scope, this study does not provide definitive conclusions on model performance. Rather, it highlights the evaluation methodology and indicates the utility associated with using the CM when assessing probabilistic performance and constructing high performing ensembles, not only for COVID-19 modeling but other applications as well.Significance StatementCoronavirus disease 2019 (COVID-19) forecasting models can provide critical information for decision-makers and the public. Unfortunately, little information on their performance has been published, particularly regarding the accuracy of their uncertainty estimates (i.e., probabilistic performance). To address this research gap, we demonstrate the Classical Model (CM), a commonly used approach from the literature on formally elicited expert judgment, which considers both the tightness of forecast confidence intervals and frequency in which confidence intervals contain the observation. Two models exhibited superior performance and the CM-based ensemble consistently outperformed the other constructed ensembles. While these results are not definitive, they highlight the evaluation methodology and indicate the value associated with using the CM when assessing probabilistic performance and constructing high performing ensembles.
Detailed Analysis of Surface Infection Barrier on Hands: Relationship with Morbidity to Infection Diseases and Identification of Antimicrobial Components
Authors: Nishioka Yuki , Nagano Kenichi , Koga Yoshitaka , Okada Yasuhiro , Mori Ichiro , Hayase Atsuko , Mori Takuya , Manabe Kenji 
Published: December 2020

AbstractAlthough the surface of hands in humans is known to harbor high levels of antimicrobial activity, reports investigating the relationship between antimicrobial activity and morbidity in infectious diseases are lacking. Additionally, the precise components involved in this activity are not known. Therefore, in this study, a method was developed to quantitatively measure the antimicrobial activity of the components found on the surface of hands, which was then compared with the medical history of the participants for infectious diseases. As a result, the antimicrobial activity of the surface of the hands was found to be positively associated with the history of infection in individuals. Furthermore, a comprehensive analysis of the components on the surface of hands indicated that organic acids and antimicrobial peptides are highly correlated with antimicrobial activity. The high amounts of lactic acid found on the surface of hands suggested it is an important factor in the hand surface infection barrier. Here we showed that the application of lactic acid within the range of the amounts present on the hand surface was found to significantly improve the antimicrobial activity of the hands. Taken together, these results demonstrate that this new method can be used to quantify antimicrobial activity, which opens new avenues for the development of hand hygiene practices by enhancing the antimicrobial activity on the surface of hands using natural ingredients against pathogens.
The association between socioeconomic status and pandemic influenza: systematic review and meta-analysis
Authors: Mamelund Svenn-Erik , Shelley-Egan Clare , Rogeberg Ole 
Published: December 2020

AbstractBackgroundThe objective was to document whether and to what extent there was an association between socioeconomic status (SES) and disease outcomes in the last five influenza pandemics.Methods/Principle FindingsThe review included studies published in English, Danish, Norwegian and Swedish. Records were identified through systematic literature searches in six databases. Results are summarized narratively and using meta-analytic strategies. We found studies only for the 1918 and 2009 pandemics. Of 14 studies on the 2009 pandemic including data on both medical and social risk factors, after controlling for medical risk factors 8 demonstrated independent impact of SES. A random effect analysis of 46 estimates from 35 studies found a pooled mean odds ratio of 1.4 (95% CI: 1.2 – 1.7), comparing the lowest to the highest SES, but with substantial effect heterogeneity across studies –reflecting differences in outcome measures and definitions of case and control samples. Analyses by pandemic period (1918 or 2009) and by level of SES measure (individual or ecological) indicate no differences along these dimensions. Studies using healthy controls tend to find low SES associated with worse influenza outcome, and studies using infected controls find low SES associated with more severe outcomes. Studies comparing severe outcomes (ICU or death) to hospital admissions are few but indicate no clear association. Studies with more unusual comparisons (e.g., pandemic vs seasonal influenza, seasonal influenza vs other patient groups) report no or negative associations.Conclusions/SignificanceResults show that social risk factors help to explain pandemic outcomes in 1918 and in 2009 although the mechanisms and types of social vulnerabilities leading to disparities in outcomes may differ over time. Studies of the 2009 pandemic also showed that social vulnerability could not always be explained by medical risk factors. To prepare for future pandemics, we must consider social along with medical vulnerability.The protocol for this study has been registered in PROSPERO (ref. no 87922) and has been published (1).
Optimal test allocation strategy during the COVID-19 pandemic and beyond
Authors: Du Jiacong , Beesley Lauren J , Lee Seunggeun , Zhou Xiang , Dempsey Walter , Mukherjee Bhramar 
Published: December 2020

AbstractTesting for active SARS-CoV-2 infections is key to controlling the spread of the virus and preventing severe disease. A central public health challenge is defining test allocation strategies in the presence of limited resources. Inthis paper, we provide a mathematical framework for defining anoptimal strategy for allocating viral tests. The framework accounts for imperfect test results, selective testing in certain high-risk patient populations, practical constraints in terms of budget and/or total number of available tests, and the purpose of testing. Our method is not only useful for detecting infected cases, but can also be used for long-time surveillance to monitor for new outbreaks, which will be especially important during ongoing vaccine distribution across the world. In our proposed approach, tests can be allocated across population strata defined by symptom severity and other patient characteristics, allowing the test allocation plan to prioritize higher risk patient populations. We illustrate our framework using historical data from the initial wave of the COVID-19 outbreak in New York City. We extend our proposed method to address the challenge of allocating two different types of tests with different costs and accuracy (for example, the expensive but more accurate RT-PCR test versus the cheap but less accurate rapid antigen test), administered under budget constraints. We show how this latter framework can be useful to reopening of college campuses where university administrators are challenged with finite resources for community surveillance. We provide a R Shiny web application allowing users to explore test allocation strategies across a variety of pandemic scenarios. This work can serve as a useful tool for guiding public health decision-making at a community level and adapting to different stages of an epidemic, and it has broader relevance beyond the COVID-19 outbreak.
The potential impact of including pre-school aged children in the praziquantel mass-drug administration programmes on theS.haematobiuminfections in Malawi: a modelling study
Authors: Hawryluk Iwona , Mangal Tara , Nguluwe Andrew , Kambalame Chikonzero , Banda Stanley , Magaleta Memory , Juziwelo Lazarus , Hallett Timothy B. 
Published: December 2020

AbstractBackgroundMass drug administration (MDA) of praziquantel is an intervention used in the treatment and prevention of schistosomiasis. In Malawi, MDA happens annually across high-risk districts and covers around 80% of school aged children and 50% of adults. The current formulation of praziquantel is not approved for use in the preventive chemotherapy for children under 5 years old, known as pre-school aged children (PSAC). However, a new formulation for PSAC will be available by 2022. A comprehensive analysis of the potential additional benefits of including PSAC in the MDA will be critical to guide policy-makers.MethodsWe developed a new individual-based stochastic transmission model ofSchistosoma haematobiumfor the 6 highest prevalence districts of Malawi. The model was used to evaluate the benefits of including PSAC in the MDA campaigns, with respect to the prevalence of high-intensity infections (> 500 eggs per ml of urine) and reaching the elimination target, meaning the prevalence of high-intensity infections under 5% in all sentinel sites. The impact of different MDA frequencies and coverages is quantified by prevalence of high-intensity infection and number of rounds needed to decrease that prevalence below 1%.ResultsIncluding PSAC in the MDA campaigns can reduce the time needed to achieve the elimination target forS. haematobiuminfections in Malawi by one year. The modelling suggests that in the case of a lower threshold of high-intensity infection, currently set by WHO to 500 eggs per ml of urine, including PSAC in the preventive chemotherapy programmes for 5 years can reduce the number of the high-intensity infection case years for pre-school aged children by up to 9.1 years per 100 children.ConclusionsRegularly treating PSAC in the MDA is likely to lead to overall better health of children as well as a decrease in the severe morbidities caused by persistent schistosomiasis infections and bring forward the date of elimination. Moreover, mass administration of praziquantel to PSAC will decrease the prevalence among the SAC, who are at the most risk of infection.
Distinct Neuropeptide-Receptor Modules Regulate a Sex-Specific Behavioral Response to a Pheromone
Authors: Reilly Douglas K. , McGlame Emily J. , Vandewyer Elke , Robidoux Annalise M. , Northcott Haylea T. , Joyce William , Alkema Mark J. , Gegear Robert J. , Beets Isabel , Srinivasan Jagan 
Published: December 2020

AbstractDioecious species are a hallmark of the animal kingdom, with opposing sexes responding differently to identical sensory cues. Here, we study the response ofC. elegans’to the small-molecule pheromone, ascr#8, which elicits opposing behavioral valences in each sex. We identify a novel neuropeptide-neuropeptide receptor (NP/NPR) module that is active in males, but not in hermaphrodites. Using a novel paradigm of neuropeptide rescue that we established, we leverage bacterial expression of individual peptides to rescue the sex-specific response to ascr#8. Concurrent biochemical studies confirmed individual FLP-3 peptides differentially activate two divergent receptors, NPR-10 and FRPR-16. Interestingly, the two of the peptides that rescued behavior in our feeding paradigm are related through a conserved threonine, suggesting that a specific NP/NPR combination sets a male state, driving the correct behavioral valence of the ascr#8 response. Receptor expression within pre-motor neurons reveals novel coordination of male-specific and core locomotory circuitries.
White matter integrity and nicotine dependence in smokers: evaluating vertical and horizontal pleiotropy
Authors: Ye Zhenyao , Mo Chen , Hatch Kathryn , Liu Song , Gao Si , Hong Elliot , Kochunov Peter , Chen Shuo , Ma Tianzhou 
Published: December 2020

AbstractSmoking is a heritable behavior and nicotine dependency is complex mechanism supported by both positive and negative reinforcements. We hypothesized that cerebral white matter (WM) may mediate the individual dependency on nicotine integrity because its integrity is altered in smokers and shows dose-related response to nicotine administration. Two vertical and one horizontal pleiotropy pathways that combined individual genetic variations, measure of WM integrity by fractional anisotropy (FA), and nicotine dependence were evaluated in a large epidemiological sample (N=12,264 and 4,654 participants that have genetic, FA measure and nicotine dependence data available for smoking status and cigarettes per day (CPD), respectively) collected UK Biobank. We started by selecting the candidate genetic regions including genetic risk factors associated with smoking from genome-wide association study (GWAS) for causal pathway analysis. Then we identified pleiotropic loci that influence both nicotine dependence and WM integrity from these regions. We tested a horizontal pleiotropy pathway: (A) genetic risk factors associated with smoking were independently affecting both nicotine dependence and WM integrity. We also evaluated two vertical pleiotropy that assumed that individual genetic factors associated with nicotine dependence impacted B) impacted WM integrity which in turn led to higher nicotine dependence vs. C) led to nicotine dependence and resulting white matter alterations. There were 10 and 23 candidate pleiotropic variants identified for smoking status and CPD traits. All these variants exhibited vertical pleiotropy. For smoking status, the genetic effect on smoking status was mediated by FA measures over multiple brain regions. The variants were located in a geneSARDH, which catalyzes the oxidative demethylation of sarcosine that plays a role in reducing tolerance effect on nicotine. Conversely, CPD was a significant mediator in the vertical pleiotropy pathway to FA. The identified variants were located in geneIREB2, that was reported as a susceptibility gene for both neurodegeneration and smoking-induced diseases.
Hidden limbs in the “limbless skink”Brachymeles lukbani:developmental observations
Authors: Smith-Paredes Daniel , Griffith Oliver , Fabbri Matteo , Yohe Laurel , Blackburn Daniel G. , Siler Cameron D. , Bhullar Bhart-Anjan S. , Wagner Günter P. 
Published: December 2020

AbstractReduced limbs and limblessness have evolved independently in many lizard clades. Skinks exhibit a wide range of limb-reduced morphologies, but only some species have been used to study the embryology of limb reduction (i.g., digit reduction inChalcidesand limb reduction inScelotes). The genusBrachymeles, a Southeast Asian clade of skinks, includes species with a range of limb morphologies, from pentadactyl to functionally as well as structurally limbless species. Adults of the small, snake-like speciesBrachymeles lukbanishow no sign of external limbs in the adult except for small depressions where they might be expected to occur. Embryos ofB. lukbaniin early stages of development, on the other hand, show a truncated but well-developed limb with a stylopod and a zeugopod, but no signs of an autopod. As development proceeds, the limb’s small size persists even while the embryo elongates. These observations are made based on external morphology. We used florescent whole-mount immunofluorescence to visualize the morphology of skeletal elements and muscles within the embryonic limb ofB. lukabni. Early stages have a humerus and separated ulna and radius cartilages; associated with these structures are dorsal and ventral muscle masses as those found in the embryos of other limbed species. While the limb remains small, the pectoral girdle grows in proportion to the rest of the body, with well-developed skeletal elements and their associated muscles. In later stages of development, the small limb is still present under the skin but there are few indications of its presence, save for the morphology of the scale covering it. The adult morphology consists of a well-developed pectoral girdle, small humerus, extremely reduced ulna and radius, and well-developed limb musculature connected to the pectoral girdle. These muscles form in association with a developing limb during embryonic stages, a hint that “limbless” lizards that possesses these muscles may have or have had at least transient developing limbs, as we find inB. lukbani.Overall, the observed pattern of ontogenetic reduction, leading to an externally limbless adult in which a limb rudiment is hidden and covered under the trunk skin, is a situation called cryptomelia. The results of this work add to our growing understanding of clade-specific patterns of limb reduction and the convergent evolution of limbless phenotypes through different developmental processes.