bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of a Simplified Risk Score for the Prediction of Critical COVID-19 Illness in Newly Diagnosed Patients
Authors: Werfel Stanislas , Jakob Carolin E. M. , Borgmann Stefan , Schneider Jochen , Spinner Christoph , Schons Maximilian , Hower Martin , Wille Kai , Haselberger Martina , Heuzeroth Hanno , Rüthrich Maria M. , Dolff Sebastian , Kessel Johanna , Heemann Uwe , Vehreschild Jörg Janne , Rieg Siegbert , Schmaderer Christoph 
Published: February 2021

AbstractScores for identifying patients at high risk of progression of the coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), are discussed as key instruments for clinical decision-making and patient management during the current pandemic.Here we used the patient data from the multicenter Lean European Open Survey on SARS-CoV-2 - Infected Patients (LEOSS) and applied a technique of variable selection in order to develop a simplified score to identify patients at increased risk of critical illness or death.A total of 1,946 patients, who were tested positive for SARS-CoV-2 were included in the initial analysis. They were split into a derivation and a validation cohort (n=1,297 and 649, respectively). A stability selection among a total of 105 baseline predictors for the combined endpoint of progression to critical phase or COVID-19-related death allowed us to develop a simplified score consisting of five predictors: CRP, Age, clinical disease phase (uncomplicated vs. complicated), serum urea and D-dimer (abbreviated as CAPS-D score). This score showed an AUC of 0.81 (CI95%: 0.77-0.85) in the validation cohort for predicting the combined endpoint within 7 days of diagnosis and 0.81 (CI95%: 0.77-0.85) during the full follow-up. Finally, we used an additional prospective cohort of 682 patients, who were diagnosed largely after the “first wave” of the pandemic to validate predictive accuracy of the score, observing similar results (AUC for an event within 7 days: 0.83, CI95%, 0.78-0.87; for full follow-up: 0.82, CI95%, 0.78-0.86).We thus successfully establish and validate an easily applicable score to calculate the risk of disease progression of COVID-19 to critical illness or death.
Rapid Impact Analysis of B 1.1.7 Variant on the Spread of SARS-CoV-2 in North Carolina
Authors: DeWitt Michael 
Published: February 2021

AbstractBackgroundSeveral cases of the B1.1.7 variant of the SARS-CoV-2 virus were identified in North Carolina first on January 23, 2021 in Mecklenburg County and later in Guilford County on January 28, 2021.[1,2] This variant has been associated with higher levels of transmissibility.[3–6] This study examines the potential impact of increased transmissibility as the B1.1.7 variant becomes more predominant given current vaccine distribution plans and existing non-pharmaceutical interventions (NPIs).MethodWe explored the anticipated impact on the effective reproduction number for North Carolina and Guilford County given the date of import of B1.1.7. The approximate growth rate in proportion of B1.1.7 observed in the United Kingdom was fit and used to establish the estimate share of B1.1.7 circulating in North Carolina. Using the nowcasted reproduction numbers, a stochastic discrete compartmental model was fit with the current vaccination rates and B1.1.7 transmissibility to estimate the impact on the effective reproduction number.ResultsWe found that the effective reproduction number for North Carolina and Guilford County may exceed one, indicating a return to accelerating spread of infection in April as the proportion of B1.1.7 increases. The effective reproduction number will likely decrease into March, then increase as the proportion of B1.1.7 increases in circulation in the population.ConclusionsExisting non-pharmaceutical interventions will need to remain in effect through the spring. Given the current vaccination rate and these interventions, it is likely that there will be an increase in SARS-CoV-2 infections. The impact of the variant will likely be heterogeneous across North Carolina given the reproduction number and volume of susceptible persons in each county at the time of introduction of the variant. Age-based vaccinations will likely reduce the overall impact on hospitalizations. This analysis underlines the need for population level genetic surveillance to confirm the proportion of variants circulating.
Robust immune responses after one dose of BNT162b2 mRNA vaccine dose in SARS-CoV-2 experienced individuals
Authors: Samanovic Marie I. , Cornelius Amber R. , Gray-Gaillard Sophie L. , Allen Joseph Richard , Karmacharya Trishala , Wilson Jimmy P. , Hyman Sara Wesley , Tuen Michael , Koralov Sergei B. , Mulligan Mark J. , Herati Ramin Sedaghat 
Published: February 2021

ABSTRACTThe use of COVID-19 vaccines will play the major role in helping to end the pandemic that has killed millions worldwide. COVID-19 vaccines have resulted in robust humoral responses and protective efficacy in human trials, but efficacy trials excluded individuals with a prior diagnosis of COVID-19. As a result, little is known about how immune responses induced by mRNA vaccines differ in individuals who recovered from COVID-19. Here, we evaluated longitudinal immune responses to two-dose BNT162b2 mRNA vaccination in 15 adults who recovered from COVID-19, compared to 21 adults who did not have prior COVID-19 diagnosis. Consistent with prior studies of mRNA vaccines, we observed robust cytotoxic CD8+ T cell responses in both cohorts following the second dose. Furthermore, SARS-CoV-2-naive individuals had progressive increases in humoral and antigen-specific antibody-secreting cell (ASC) responses following each dose of vaccine, whereas SARS-CoV-2-experienced individuals demonstrated strong humoral and antigen-specific ASC responses to the first dose but muted responses to the second dose of the vaccine at the time points studied. Together, these data highlight the relevance of immunological history for understanding vaccine immune responses and may have significant implications for personalizing mRNA vaccination regimens used to prevent COVID-19, including booster shots.One Sentence SummaryPrior history of COVID-19 affects adaptive immune responses to mRNA vaccination.
Current quantitative polymerase chain reaction to detect severe acute respiratory syndrome coronavirus 2 may give positive results for other described coronavirus
Authors: Martínez-Murcia Antonio , García-Sirera Adrián , Navarro Aaron , Ros-Tárraga Patricia , Pérez Laura 
Published: February 2021

SUMMARYSome weeks after the first CoVID-19 outbreak, the WHO published some qPCR protocol assays developed by different institutions worldwide. These qPCR designs are being used to detect the presence of SARS-CoV-2 in the population, which allow us to monitore the prevalence of the virus during the pandemic. Moreover, the use of these designs is wide spreading and nowadays they are used to detect SARS-CoV-2 in environmental samples to act as epidemiological surveillance tool. However, at the time of designing the published RT-qPCR assays, a lack of SARS-CoV-2 genomes available may explain a low exclusivity in some cases. In this study, we are reporting experimental data which demonstrate that some of the current qPCR used to detect SARS-CoV-2 may give positive results for other described coronavirus different from SARS-CoV-2.
Dysautonomia in hypermobile Ehlers-Danlos syndrome and hypermobility spectrum disorders is associated with exercise intolerance and cardiac atrophy
Authors: Maya Tania Ruiz , Fettig Veronica , Mehta Lakshmi , Gelb Bruce D. , Kontorovich Amy R. 
Published: February 2021

AbstractDysautonomia is a recognized manifestation in patients with joint hypermobility (JH) disorders. Symptoms can be highly debilitating and commonly include physical deconditioning and poor aerobic fitness. In this study, the prevalence of dysautonomia, range of associated symptoms, patient-reported physical activity levels and echocardiographic features were assessed retrospectively in a cohort of 144 patients (94% female) with hypermobile Ehlers-Danlos syndrome (hEDS) or hypermobility spectrum disorder (HSD). Echocardiographic parameters of LV size and function were compared between patients with and without dysautonomia, as well as to reported values from healthy controls. Dysautonomia was identified in 71% of female and 56% of male subjects and was associated with a high burden of symptomatology, most commonly exercise intolerance (78%). Exercise capacity was limited by dysautonomia, often postural symptoms, in half of all patients. We observed a reduction in physical activity following the onset or significant flare of hEDS/HSD, most strikingly noting the proportion of dysautonomic patients with sedentary lifestyle, which increased from 39% to >80%. JH-related dysautonomia was associated with smaller cardiac chamber sizes, consistent with previous reports in positional orthostatic tachycardia syndrome. Dysautonomia is highly prevalent in patients with hEDS/HSD, exercise intolerance is a key feature and leads to drastic decline in physical activity. Unfavorable cardiac geometry may underlie dysautonomia symptoms and may be due to cardiac atrophy in the setting of aerobic deconditioning.
Effect of using a physical assistance device for movements involving trunk bending
Authors: Jelti Z. , Lebel K. , Bastide S. , Le Borgne P. , Slangen P. , Vignais N. 
Published: February 2021

SUMMARYExoskeletons are a solution to physically relieve workers while allowing them to control the execution of their tasks and assist them(Baltrusch et al.2018).The study investigated in the search for elements able to quantify the action of a physical assistance device (PAD) on the human body for movements responsible for pathologies recognized as occupational diseases.The evaluation of a PAD allows to determine in which framework the exoskeleton can be useful for the realization of the movement. It is specified that a relevant way to insert exoskeletons in a company by always implementing a study or analysis beforehand to ensure its good integration.The objective of the study is to perform several tasks with and without the Posture Harness (HAPO) in order to analyze the kinematics of the movements and the electrical activity of erector muscles of the spine involved in carrying a load at work to understand its effects on the human body.
The envelope cytoplasmic tail regulates HIV-1 assembly and spread
Authors: Snetkov Xenia , Haider Tafhima , Mesner Dejan , Groves Nicholas , Engelenburg Schuyler van , Jolly Clare 
Published: February 2021

AbstractThe HIV-1 envelope (Env) is an essential determinant of viral infectivity, tropism and spread between T cells. Lentiviral Env contain an unusually long 150 amino acid cytoplasmic tail (EnvCT) but the function of the EnvCT and conserved domains within it remain largely uncharacterised. Here we identified a highly conserved tryptophan motif at position 757 (W757) in the LLP-2 alpha helix of the EnvCT as a key determinant for HIV-1 replication and spread between T cells. Strikingly we find that mutating W757 had wide-ranging consequences including altering Env mobility in the plasma membrane, preventing Env and Gag recruitment to sites of cell-cell contact for virological synapse (VS) formation and cell-cell spread, and impeding viral fusion. Notably, W757 was also required for efficient virus budding, revealing a previously unappreciated role for the EnvCT in regulating HIV-1 assembly and egress. We conclude that W757 is a key residue that stabilises the structural integrity and function of Env, consistent with the recent model that this region of the EnvCT acts as a critical supporting baseplate for Env.
POPULATION GENOMIC ANALYSIS OFCRYPTOCOCCUSBRAZILIAN ISOLATES REVEALS AN AFRICAN TYPE SUBCLADE DISTRIBUTION
Authors: Maufrais Corinne , de Oliveira Luciana , Bastos Rafael W. , Moyrand Frédérique , Reis Flavia C. G. , Valero Clara , Gimenez Bianca , Josefowicz Luisa J. , Goldman Gustavo H. , Rodrigues Marcio L. , Janbon Guilhem 
Published: February 2021

AbstractThe genomes of a large number ofCryptococcus neoformansisolates have been sequenced and analyzed in recent years. These genomes have been used to understand the global population structure of this opportunistic pathogen. However, only a small number of South American isolates have been considered in these studies, and the population structure ofC. neoformansin this part of the world remains elusive. Here, we analyzed the genomic sequences of 53 BrazilianCryptococcus isolates and deciphered theC. neoformanspopulation structure in this country. Our data reveal an African-like structure that suggested repeated intercontinental transports from Africa to South America. We also identified a mutator phenotype in one VNBII Brazilian isolate, exemplifying how fast-evolving isolates can shape theCryptococcuspopulation structure. Finally, phenotypic analyses revealed wide diversity but not lineage specificity in the expression of classical virulence traits within the set of isolates.
5-Azacytidine: Effects on the Expression of alpha-Cardiac Actin in Pericytes from Human Adipose Tissue
Authors: Ferreira-Silva Valéria , Baqui Munira M. A. , Molfetta Greice A. , Fontes Aparecida M. , Zanette Dalila I. , Ferreira Fernanda U. , Orellana Maristela D. , Silva Wilson A. , Covas Dimas T. 
Published: February 2021

AbstractDNA methylation patterns are closely related to the chromatin structure, and its remodeling is considered an important mechanism in the control of gene transcription during cell differentiation. In rodent, several studies have related the possibility that multipotent mesenchymal stromal cells (MSCs) undergo cardiomyogenesis. However, it has not been completely elucidated if human adult stem cell exhibits true differentiation potential for a cardiac lineage. In this study, the action of the DNA methylation inhibitor 5-azacytidine (5-aza) was examined in human adipose tissue pericytes (hATPCs: 3G5+) regarding their possible capacity to induce myocytesin vitro. Real-Time PCR revealed that cells treated with 5-aza presented time-dependent decrease in the mRNA expression of α-cardiac actin (α-CA). At 24 h, this diminution was statistically significant; however, there was not a correlation with the highest level of DNA demethylation at the same period using Methylation-Sensitive High Resolution Melting-PCR (MS-HRM-PCR). An evident increase in the α-CA protein expression was observed by Western blotting in hATPCs treated with 5-aza at 24 h. The mRNA expression of α-SMA (α-smooth actin) also showed a time-dependent decrease after the treatment, however, it was not significant. The ultrastructural analysis showed similar structures such as like-cell junctions, caveolae, and actin myofilaments, which aligned in parallel. These phenotypic alterations were found only after the treatment; however, the hTAPCs after 5-aza treatment were not able to form thick myofilaments and consequently sarcomeres. These results indicated that a terminal cardiac differentiation of hTAPCs was not achieved and that the cardiomyogenesis failure could be related to the non-muscle origin of the adipose tissue.
Unexpected distribution of the 4-formylaminooxyvinylglycine (FVG) biosynthetic pathway inPseudomonasand beyond
Authors: Davis Edward W. , Okrent Rachel A. , Manning Viola A. , Trippe Kristin M. 
Published: February 2021

ABSTRACTThe biological herbicide and antibiotic 4-formylaminooxyvinylglycine (FVG) was originally isolated from several rhizosphere-associated strains ofPseudomonas fluorescens. Biosynthesis of FVG is dependent on thegvgbiosynthetic gene cluster inP. fluorescens. In this investigation, we used comparative genomics to identify strains with the genetic potential to produce FVG due to presence of agvggene cluster. These strains primarily belong to two groups ofPseudomonas, P. fluorescensandP. syringae, however, a few strains with thegvgcluster were found outside ofPseudomonas. Mass spectrometry confirmed that all tested strains of theP. fluorescensspecies group produced FVG. However,P. syringaestrains did not produce FVG under standard conditions. Several lines of evidence regarding the transmission of thegvgcluster including a robust phylogenetic analysis suggest that it was introduced multiple times through horizontal gene transfer within thePseudomonaslineage as well as in select lineages ofThiomonas, BurkholderiaandPantoea. Together, these data broaden our understanding of the evolution and diversity of FVG biosynthesis. In the course of this investigation, additional gene clusters containing only a subset of the genes required to produce FVG were identified in a broad range of bacteria, including many non-pseudomonads.
Architecture of cell-cell junctions in situ reveals a mechanism for bacterial biofilm inhibition
Authors: Melia Charlotte E. , Bolla Jani R. , Katharios-Lanwermeyer Stefan , Mihaylov Daniel B. , Hoffmann Patrick C. , Huo Jiandong , Wozny Michael R. , Elfari Louis M. , Böhning Jan , Owens Raymond J. , Robinson Carol V. , O’Toole George A. , Bharat Tanmay A.M. 
Published: February 2021

AbstractMany bacteria, including the major human pathogenPseudomonas aeruginosa, are naturally found in multicellular, antibiotic-tolerant biofilm communities, where cells are embedded in an extracellular matrix of polymeric molecules. Cell-cell interactions withinP. aeruginosabiofilms are mediated by CdrA, a large, membrane-associated adhesin present in the extracellular matrix of biofilms, regulated by the cytoplasmic concentration of cyclic diguanylate. Here, using electron cryotomography of focused-ion beam milled specimens, we report the architecture of CdrA molecules in the extracellular matrix ofP. aeruginosabiofilms at intact cell-cell junctions. Combining ourin situobservations at cell-cell junctions with biochemistry, native mass spectrometry and cellular imaging, we demonstrate that CdrA forms an extended structure that projects from the outer membrane to tether cells together via polysaccharide binding partners. We go on to show the functional importance of CdrA using custom single-domain antibody (nanobody) binders. Nanobodies targeting the tip of functional cell-surface CdrA molecules could be used to inhibit bacterial biofilm formation or disrupt pre-existing biofilms in conjunction with bactericidal antibiotics. These results reveal a functional mechanism for cell-cell interactions within bacterial biofilms and highlight the promise of using inhibitors targeting biofilm cell-cell junctions to prevent or treat problematic, chronic bacterial infections.
Enhanced habit formation in Tourette syndrome: dopamine release and striatal disinhibition modulate shortcut connections in a hierarchical model of cortico-basal ganglia loops
Authors: Scholl Carolin , Baladron Javier , Vitay Julien , Hamker Fred H. 
Published: February 2021

AbstractIn the Gilles de la Tourette syndrome, tics are often considered as habitual responses towards unwanted premonitory urges. Support for the relationship between tics and habits comes from devaluation protocols, which reveal that unmedicated Tourette patients show an increased tendency towards responses to devalued outcomes. We use a neuro-computational model of hierarchically organized cortico-basal ganglia-thalamo-cortical loops to shed more light on enhanced habit formation of Tourette patients. In our model, habitual behavior emerges from cortico-thalamic shortcut connections, where enhanced habit formation can be linked to faster plasticity in the shortcut or to a stronger feedback from the shortcut to the basal ganglia. Irregular activity in such shortcut connections may have different pathophysiological origins. Based on our model, we explore decreased local striatal inhibition, which may correspond to a loss of inhibitory interneurons, and increased dopaminergic modulation of striatal medium spiny neurons as causes for irregular shortcut plasticity or activation. Both lead to higher rates of response towards devalued outcomes in our model, similar to what is observed in Tourette patients. Our results support the view of tics in Tourette syndrome as maladaptive habits. We suggest to reveal more shortcuts between cortico-basal ganglia-thalamo-cortical loops in the human brain and study their potential role in the development of the Tourette syndrome.
Using induced pluripotent stem cells to investigate human neuronal phenotypes in 1q21.1 deletion and duplication syndrome
Authors: Chapman Gareth , Alsaqati Mouhamed , Lunn Sharna , Singh Tanya , Linden Stefanie C , Linden David E. J. , van den Bree Marianne B.M. , Ziller Mike , Owen Michael J , Hall Jeremy , Harwood Adrian J. , Syed Yasir Ahmed 
Published: February 2021

AbstractCopy Number Variation (CNV) at the 1q21.1 locus is associated with a range of neurodevelopmental and psychiatric disorders in humans, including abnormalities in head size and motor deficits. Yet, the functional consequences of these CNVs (both deletion and duplication) on neuronal development remain unknown. To determine the impact of CNV at the 1q21.1 locus on neuronal development, we generated induced pluripotent stem cells from individuals harbouring 1q21.1 deletion or duplication and differentiated them into functional cortical neurons. We show that neurons with 1q21.1 deletion or duplication display reciprocal phenotype with respect to proliferation, differentiation potential, neuronal maturation, synaptic density, and functional activity. Deletion of the 1q21.1 locus was also associated with an increased expression of lower cortical layer markers. This difference was conserved in the mouse model of 1q21.1 deletion, which displayed altered corticogenesis. Importantly, we show that neurons with 1q21.1 deletion and duplication are associated with differential expression of calcium channels and demonstrate that physiological deficits in neurons with 1q21.1 deletion or duplication can be pharmacologically modulated by targeting Ca2+channel activity. These findings provide biological insight into the neuropathological mechanism underlying 1q21.1 associated brain disorder and indicate a potential target for therapeutic interventions.