bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy
Authors: Lesurf Robert , Said Abdelrahman , Akinrinade Oyediran , Breckpot Jeroen , Delfosse Kathleen , Liu Ting , Yao Roderick , McKenna Fintan , Noche Ramil R. , Oliveros Winona , Mattioli Kaia , Miron Anastasia , Yang Qian , Meng Guoliang , Chan Seng Yue Michelle , Sung Wilson WL , Thiruvahindrapuram Bhooma ,   Genomics England Research Consortium, Lougheed Jane , Oechslin Erwin , Bergin Lynn , Smythe John , Mondal Tapas , Melé Marta , Maass Philipp G. , Ellis James , Scherer Stephen W. , Mital Seema 
Published: October 2020

ABSTRACTCardiomyopathy (CMP) is a heritable genetic disorder. Protein-coding variants account for 20-30% of cases. The contribution of variants in non-coding DNA elements that regulate gene expression has not been explored. We performed whole-genome sequencing (WGS) of 228 unrelated CMP families. Besides pathogenic protein-coding variants in known CMP genes, 5% cases harbored rare loss-of-function variants in novel cardiac genes, with NRAP and FHOD3 being strong candidates. WGS also revealed a high burden of high-risk variants in promoters and enhancers of CMP genes in an additional 20% cases (Odds ratio 2.14, 95% CI 1.60-2.86, p=5.26×10−7 vs 1326 controls) with genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) specifically enriched for regulatory variants (False discovery rate <0.03). These findings were independently replicated in the Genomics England CMP cohort (n=1266). The functional effect of non-coding variants on transcription was functionally validated in patient myocardium and reporter assays in human cardiomyocytes, and that of novel gene variants in zebrafish knockouts. Our results show that functionally active variants in novel genes and in regulatory elements of CMP genes contribute strongly to the genomic etiology of childhood-onset CMP.
Early Crowdfunding Response to the COVID-19 Pandemic
Authors: Saleh Sameh N. , Lehmann Christoph U. , Medford Richard J. 
Published: October 2020

AbstractBackgroundAs the number of COVID-19 cases increased precipitously in the US, policymakers and health officials marshalled their pandemic responses. As the economic impacts multiplied, anecdotal reports noted the increased use of online crowdfunding to defray these costs. We examined the online crowdfunding response in the early stage of the COVID-19 pandemic in the US.MethodsOn May 16, 2020, we extracted all available data available on US campaigns created between January 1 and May 10, 2020 on GoFundMe and identified the subset of COVID-related campaigns using keywords relevant to the COVID-19 pandemic. We explored incidence of COVID-related campaigns by geography, by category, and over time and compared campaign characteristics to non-COVID-related campaigns after March 11 when the pandemic was declared.ResultsWe found that there was a substantial increase in overall GoFundMe online crowdfunding campaigns in March, largely attributable to COVID-related campaigns. However, as the COVID-19 pandemic persisted and progressed, the number of campaigns per COVID-19 cases declined more than tenfold across all states. COVID-related campaigns raised more money, had a longer narrative description, and were more likely to be shared on Facebook than other campaigns in the study period.ConclusionsOnline crowdfunding appears to be a transient stopgap, predicated on the novelty of an emergency rather than the true sustained need of a community. Rather, crowdfunding activity is likely an early marker for communities in acute distress that could be used by governments and aid organizations to guide disaster relief and policy.Trial registrationN/A
The HIV/STI Epidemic Potential of Dynamic Sexual Networks of Men Who Have Sex With Men in Atlanta and San Francisco
Authors: Anderson Emeli J. , Weiss Kevin M. , Morris Martina M. , Sanchez Travis H. , Prasad Pragati , Jenness Samuel M. 
Published: October 2020

ABSTRACTBackgroundThe potential speed through which a pathogen may circulate in a network is a function of network connectivity. Network features like degree (number of ongoing partnerships) determine the cross-sectional network connectivity. The overall transmission potential of a pathogen involves connectivity over time, which can be measured using the forward reachable path (FRP). We modeled dynamic sexual networks of MSM in San Francisco and Atlanta to estimate the FRP as a predictor of HIV/STI epidemic potential.MethodsWe used exponential random graph models to obtain parameter estimates for each city’s sexual network and then simulated the complete networks over time. The FRP was estimated in each city overall and stratified by demographics.ResultsThe overall mean and median FRPs were higher in San Francisco than in Atlanta, suggesting a greater epidemic potential for HIV and STIs in San Francisco. At one year, in both cities, the average FRP among casual partnerships was highest in the youngest age group and lowest in the oldest age group, contrasting with the cross-sectional network parameters we estimated, where the youngest age category had the lowest mean degree and the oldest age category had the highest mean degree.ConclusionsThe FRP results correspond to the observed STI epidemics but not HIV epidemics between the cities. In San Francisco, rates of HIV have been declining over the last few years, whereas they have been steady in Atlanta. The FRP by age group resulted in fundamentally different conclusions about connectivity in the network compared with the cross-sectional network measures.
Nonspecific blood tests as proxies for COVID-19 hospitalization: are there plausible associations after excluding noisy predictors?
Authors: Ishikawa G. , Argenti G. , Fadel C. B. 
Published: October 2020

SUMMARYThis study applied causal criteria in directed acyclic graphs for handling covariates in associations for prognosis of severe COVID-19 (Corona virus disease 19) cases. To identify nonspecific blood tests and risk factors as predictors of hospitalization due to COVID-19, one has to exclude noisy predictors by comparing the concordance statistics (AUC) for positive and negative cases of SARS-CoV-2 (acute respiratory syndrome coronavirus 2). Predictors with significant AUC at negative stratum should be either controlled for their confounders or eliminated (when confounders are unavailable). Models were classified according to the difference of AUC between strata. The framework was applied to an open database with 5644 patients from Hospital Israelita Albert Einstein in Brazil with SARS-CoV-2 RT-PCR (Reverse Transcription – Polymerase Chain Reaction) exam. C-reactive Protein (CRP) was a noisy predictor: hospitalization could have happen due to causes other than COVID-19 even when SARS-CoV-2 RT-PCR is positive and CRP is reactive, as most cases are asymptomatic to mild. Candidates of characteristic response from moderate to severe inflammation of COVID-19 were: combinations of eosinophils, monocytes and neutrophils, with age as risk factor; and creatinine, as risk factor, sharpens the odds ratio of the model with monocytes, neutrophils, and age.
Less severe course of COVID-19 is associated with elevated levels of antibodies against seasonal human coronaviruses OC43 and HKU1 (HCoV OC43, HCoV HKU1)
Authors: Dugas Martin , Grote-Westrick Tanja , Vollenberg Richard , Lorentzen Eva , Brix Tobias , Schmidt Hartmut , Tepasse Phil-Robin , Kühn Joachim 
Published: October 2020

AbstractThe clinical course of COVID-19 is very heterogeneous: Most infected individuals can be managed in an outpatient setting, but a substantial proportion of patients requires intensive care, resulting in a high rate of fatalities. Recently, an association between contact to small children and mild course of COVID-19 was reported. We performed an observational study to assess the impact of previous infections with seasonal coronaviruses on COVID-19 severity. 60 patients with confirmed COVID-19 infections were included (age 30 - 82 years; 52 males, 8 females): 19 inpatients with critical disease, 16 inpatients with severe or moderate disease and 25 outpatients (age and gender matched to inpatients). Patients with critical disease had significantly lower levels of HCoV OC43- (p=0.016) and HCoV HKU1-specific (p=0.023) antibodies at the first encounter compared to other COVID-19 patients. Our results indicate that previous infections with seasonal coronaviruses might protect against a severe course of disease. This finding should be validated in other settings and could contribute to identify persons at risk before an infection.
Impact of COVID-19 Restrictions on People with Hypertension
Authors: Bonner Carissa , Cvejic Erin , Ayre Julie , Isautier Jennifer , Semsarian Christopher , Nickel Brooke , Batcup Carys , Pickles Kristen , Dodd Rachael , Cornell Samuel , Copp Tessa , McCaffery Kirsten 
Published: October 2020

ABSTRACTObjectivesIt is unclear how people with hypertension are responding to the COVID-19 pandemic given their increased risk, and whether targeted public health strategies are needed.DesignThis retrospective case-control study compared people with hypertension to matched healthy controls during COVID-19 lockdown, to determine whether they have higher risk perceptions, anxiety and prevention intentions.MethodsBaseline data from a national survey were collected in April 2020 during COVID-19 lockdown. Of 4362 baseline participants, 466 people reported hypertension with no other chronic conditions, and were randomly matched to healthy controls with similar age, gender, education and health literacy. A subset (n=1369) was followed-up at 2 months after restrictions eased, including 147 participants with hypertension only. Risk perceptions, prevention intentions and anxiety were measured.ResultsAt baseline, perceived seriousness was high for both hypertension and control groups. The hypertension group had higher anxiety than controls; and were more willing to have the influenza vaccine. At follow-up, these differences were no longer present in the longitudinal sub-sample. Perceived seriousness and anxiety had decreased, but vaccine intentions for both influenza and COVID-19 remained high (>80%).ConclusionsAnxiety was above normal levels during the COVID-19 lockdown. This was higher in the hypertension group, who also had higher vaccination intentions. Locations with prolonged restrictions may require targeted mental health screening for vulnerable groups. Despite a decrease in perceived risk and anxiety after 2 months of lockdown restrictions, vaccination intentions for both influenza and COVID-19 remained high, which is encouraging for future prevention of COVID-19.
scATAC-Seq reveals epigenetic heterogeneity associated with an EMT-like process in male germline stem cells and its regulation by G9a
Authors: Liao Jinyue , Suen Hoi Ching , Luk Alfred Chun Shui , Lee Annie Wing Tung , Ng Judy Kin Wing , Chan Ting Hei Thomas , Cheung Man Yee , Chan David Yiu Leung , Qi Huayu , Chan Wai Yee , Hobbs Robin M. , Lee Tin-Lap 
Published: October 2020

AbstractBackgroundEpithelial-mesenchymal transition (EMT) is a phenomenon in which epithelial cells acquire mesenchymal traits. It contributes to organogenesis and tissue homeostasis, as well as stem cell differentiation. Emerging evidence indicates that heterogeneous expression of EMT gene markers presents in sub-populations of germline stem cells (GSCs). However, the functional implications of such heterogeneity are largely elusive.ResultsWe unravelled an EMT-like process in GSCs byin vitroextracellular matrix (ECM) model and single-cell genomics approaches. We found that histone methyltransferase G9a regulated an EMT-like program in GSCin vitroand contributed to neonatal germ cell migrationin vivo.Through modulating ECM, we demonstrated that GSCs exist in interconvertible epithelial-like and mesenchymal-like cell states. GSCs gained higher migratory ability after transition to a mesenchymal-like cell state, which was largely mediated by the TGF-β signaling pathway. Dynamics of epigenetic regulation at the single-cell level was also found to align with the EMT-like process. Chromatin accessibility profiles generated by single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) clustered GSCs into epithelial-like and mesenchymal-like states, which were associated with differentiation status. The high-resolution data revealed regulators in the EMT-like process, including transcription factorsZeb1.We further identified putative enhancer-promoter interactions andcis-co-accessibility networks at loci such asTgfb1, Notch1andLin28a.Lastly, we identified HES1 as the putative target underlying G9a’s regulation.ConclusionOur work provides the foundation for understanding the EMT-like process and a comprehensive resource for future investigation of epigenetic regulatory networks in GSCs.
Capsular polysaccharide switching inStreptococcus suismodulates host cell interactions and virulence
Authors: Okura Masatoshi , Auger Jean-Philippe , Shibahara Tomoyuki , Goyette-Desjardins Guillaume , Calsteren Marie-Rose Van , Maruyama Fumito , Kawai Mikihiko , Osaki Makoto , Segura Mariela , Gottschalk Marcelo , Takamatsu Daisuke 
Published: October 2020

AbstractStreptococcus suisserotype 2 strains can cause severe infections in both swine and humans. The capsular polysaccharide (CPS) ofS. suisdefines various serotypes based on its composition and structure. Though serotype switching from serotype 2 has been suggested to occur betweenS. suisstrains, its impact on pathogenicity and virulence remains unknown. Herein, we experimentally generatedS. suisserotype-switched mutants from a serotype 2 strain (SS2) that express the serotype 3, 4, 7, 8, 9, or 14 CPS (SS2to3, SS2to4, SS2to7, SS2to8, SS2to9, and SS2to14, respectively). The effects of serotype switching were then investigated with regards to classical properties conferred by presence of the serotype 2 CPS, including adhesion to/invasion of porcine tracheal epithelial cells, resistance to phagocytosis by murine macrophages, killing by murine and porcine whole blood, and dendritic cell-derived pro-inflammatory mediator production. Results demonstrated that these properties on host cell interactions were differentially modulated depending on the switched serotypes. Using a mouse model of systemic infection, SS2to8 was demonstrated to be hyper-virulent, with animals rapidly succumbing to septic shock, whereas SS2to3 and SS2to4 were less virulent than SS2 because of a reduced systemic inflammatory host response. By contrast, switching to serotype 7, 9, or 14 CPSs had little to no effect. Finally, development of clinical signs in a porcine model of infection was only observed following infection with SS2, SS2to7, and SS2to8. Taken together, these findings suggest that serotype switching can differentially modulateS. suishost cell interactions and virulence depending on the CPS type expressed.ImportanceStreptococcus suisserotype 2 is the most frequently type associated with swine and zoonotic infections. While the serotype 2 CPS is required for virulence and pathogenesis, little information is available regarding that of other serotypes and how differences in serotype can directly affect host cell interactions and virulence. Herein, we constructed serotype-switched mutants from a serotype 2 strain and demonstrated that serotype switching can shift and modulate theS. suishost cell interactions and virulencein vivo. Among the serotype-switched mutants, the mutant expressing the serotype 8 CPS, whose composition and structure are identical to that of the human pathogenStreptococcus pneumoniaeserotype 19F, was hyper-virulent, whereas mutants expressing the serotype 3 or 4 CPSs had reduced virulence. These results demonstrate that serotype switching can drastically alterS. suisphenotype. Consequently, further importance and attention should be given to the phenomenon of serotype switching and the possible emergence of hyper-virulent isolates.
Validation of a Derived International Patient Severity Algorithm to Support COVID-19 Analytics from Electronic Health Record Data
Authors: Klann Jeffrey G , Weber Griffin M , Estiri Hossein , Moal Bertrand , Avillach Paul , Hong Chuan , Castro Victor , Maulhardt Thomas , Tan Amelia LM , Geva Alon , Beaulieu-Jones Brett K , Malovini Alberto , South Andrew M , Visweswaran Shyam , Omenn Gilbert S , Ngiam Kee Yuan , Mandl Kenneth D , Boeker Martin , Olson Karen L , Mowery Danielle L , Morris Michele , Follett Robert W , Hanauer David A , Bellazzi Riccardo , Moore Jason H , Loh Ne-Hooi Will , Bell Douglas S. , Wagholikar Kavishwar B , Chiovato Luca , Tibollo Valentina , Rieg Siegbert , Li Anthony L.L.J. , Jouhet Vianney , Schriver Emily , Samayamuthu Malarkodi J , Xia Zongqi ,   The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) (CONSORTIA AUTHOR), Kohane Isaac S , Brat Gabriel A , Murphy Shawn N 
Published: October 2020

AbstractIntroductionThe Consortium for Clinical Characterization of COVID-19 by EHR (4CE) includes hundreds of hospitals internationally using a federated computational approach to COVID-19 research using the EHR.ObjectiveWe sought to develop and validate a standard definition of COVID-19 severity from readily accessible EHR data across the Consortium.MethodsWe developed an EHR-based severity algorithm and validated it on patient hospitalization data from 12 4CE clinical sites against the outcomes of ICU admission and/or death. We also used a machine learning approach to compare selected predictors of severity to the 4CE algorithm at one site.ResultsThe 4CE severity algorithm performed with pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of single code categories for acuity were unacceptably inaccurate - varying by up to 0.65 across sites. A multivariate machine learning approach identified codes resulting in mean AUC 0.956 (95% CI: 0.952, 0.959) compared to 0.903 (95% CI: 0.886, 0.921) using expert-derived codes. Billing codes were poor proxies of ICU admission, with 49% precision and recall compared against chart review at one partner institution.DiscussionWe developed a proxy measure of severity that proved resilient to coding variability internationally by using a set of 6 code classes. In contrast, machine-learning approaches may tend to overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold standard outcomes, possibly due to pandemic conditions.ConclusionWe developed an EHR-based algorithm for COVID-19 severity and validated it at 12 international sites.
Motiro: an unified non-supervised framework for statistical analysis of probe-based confocal laser endomicroscopy videos of colorectal mucosa
Authors: Sabino Alan U. , Safatle-Ribeiro Adriana V. , Maluf-Filho Fauze , Ramos Alexandre F. 
Published: October 2020

ABSTRACTObjectiveTo present Motiro, an unified framework for non-supervised statistical analysis endomicroscopy videos of the colorectal mucosa.Materials and MethodsWe wrote an open-source Python wrapper using ImageJ software with OpenCV, Seaborn and NumPy libraries. It generates a mosaic from the video of the mucosa, evaluates morphometric properties of the crypts, their distribution, and return their statistics. Shannon entropy (and Hellinger distance) are used for quantifying variability (and comparing different mucosa).ResultsThe segmentation process applied to normal mucosa of pre(post)- neoadjuvant patient is presented along with the corresponding statistical analysis of morphometric parameters.DiscussionOur analysis provides estimation of morphometric parameters consistent with available methods, is faster, and, additionally, provides statistical characterization of the mucosa morphometry. Motiro enables the analysis of large amounts of endomicroscopy videos for building a normal rectum features dataset to help on: detection of small variability; classification of post-neoadjuvant recovery; decision about surgical intervention necessity.
Frequent testing regimen based on salivary samples for an effective COVID-19 containment strategy
Authors: Plebani Mario , Aita Ada , Cattelan Anna Maria , Bonfante Francesco , Padoan Andrea , Giaquinto Carlo , Basso Daniela 
Published: October 2020

AbstractRapid and accurate diagnostic tests are essential for controlling the ongoing COVID-19 pandemic. Although the current gold standard involves testing of nasopharyngeal swabs specimens by nucleic acid amplification test, such as real-time reverse-transcription polymerase chain reaction (rRT-PCR) to detect the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it presents several limitations that ultimately may translate into a bottleneck in the surveillance regimen. New strategies based on frequent testing using less invasive specimens are urgently needed for containment of the infection. Rapid antigen assay using saliva as a reliable alternative to nasopharyngeal swabs should be proposed as a valuable part of the overall testing strategy.
School closures and SARS-CoV-2. Evidence from Sweden’s partial school closure
Authors: Vlachos Jonas , Hertegård Edvin , Svaleryd Helena 
Published: October 2020

AbstractTo reduce the transmission of SARS-CoV-2 most countries closed schools, despite uncertainty if school closures are an effective containment measure. At the onset of the pandemic, Swedish upper secondary schools moved to online instruction while lower secondary school remained open. This allows for a comparison of parents and teachers differently exposed to open and closed schools, but otherwise facing similar conditions. Leveraging rich Swedish register data, we connect all students and teachers in Sweden to their families and study the impact of moving to online instruction on the incidence of SARS-CoV-2 and COVID-19. We find that among parents, exposure to open rather than closed schools resulted in a small increase in PCR-confirmed infections [OR 1.17; CI95 1.03–1.32]. Among lower secondary teachers the infection rate doubled relative to upper secondary teachers [OR 2.01; CI95 1.52–2.67]. This spilled over to the partners of lower secondary teachers who had a higher infection rate than their upper secondary counterparts [OR 1.29; CI95 1.00–1.67]. When analyzing COVID-19 diagnoses from healthcare visits and the incidence of severe health outcomes, results are similar for teachers but weaker for parents and teachers’ partners. The results for parents indicate that keeping lower secondary schools open had minor consequences for the overall transmission of SARS-CoV-2 in society. The results for teachers suggest that measures to protect teachers could be considered.