bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARS-CoV-2 reinfections with BA.1 (Omicron) variant among fully vaccinated individuals in the northeast of Brazil
Authors: Neto Francisco P. F. , Teixeira Diego G. , Cunha Dayse C. S. da , Morais Ingryd C. , Tavares Celisa P. M. , Gurgel Genilson P. , Nascimento Sanderson D. do , Santos David C. dos , Sales Alexandre de O. , Jerônimo Selma M.B. 
Published: April 2022

AbstractBackgroundThe first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Rio Grande do Norte, northeast Brazil, was diagnosed on March 12, 2020; thereafter, the pattern of COVID-19 followed the multiple waves as seen elsewhere. Those waves were mostly due to the SARS-CoV-2 virus mutations leading to emergence of variants of concern (VoC). The introduction of new VoCs in a population context of prior SARS-CoV-2 infections or after vaccination has been a challenge in understanding the kinetics of the protective immune response against SARS-CoV-2. The aim of this study was to investigate the outbreak of SARS-CoV-2 reinfections observed in mid-January 2022 in Rio Grande do Norte state, Brazil when the omicron variant was introduced.Methodology/Principal findingsFrom a total of 172,965 individuals with mild to severe respiratory symptoms, 58,097 tested positive for SARS-CoV-2 between March 2020 through mid-February 2022. Of those previously infected, 444 had documented a second SARS-CoV-2 infection and 9 of these reinfection cases were selected for sequencing. Genomic analysis revealed that virus lineages diverged between primary and the reinfection, with the latter caused by the Omicron (BA.1) variant among individuals fully vaccinated against SARS-CoV-2.Conclusions/SignificanceOnce all subjects whose samples were sequenced had prior SARS-CoV-2 infection and were also fully vaccinated, our data suggest that the Omicron variant evades natural and vaccine-induced immunities, confirming the continuous need to decrease transmission and to develop effective blocking vaccines.Author summaryThe pattern of the COVID-19 pandemic has been characterized by multiple waves of cases with a variety of outcomes from asymptomatic, to moderate or to severe fatal cases. By December 2021, about 75.3% of Rio Grande do Norte population, northeast Brazil, had already been fully vaccinated against SARS-CoV-2 and a decrease in newer detection cases was seen to about 8% of the suspected ones. Nevertheless, with the introduction of the Omicron variant at the end of 2021, the number of new SARS-CoV-2 infections reached its highest peak since the start of the pandemic with 75% of the suspected cases testing positive. From March 2020 to February 2022, we confirmed 444 reinfection cases among the ones tested, of which 62.3% (n=277) occurred during the Omicron outbreak, from December 2021 to early February 2022. Of the reinfection cases, 9 were sequenced and genetic analysis showed that they belong to a BA.1 lineage, which seems to have been introduced multiple times into the region. The primary isolates varied. Thus, our data suggest that the Omicron variant evades immunity provided from either natural infection from any other SARS-CoV-2 variants or from different types of vaccines.
Real-World Evidence of the Effectiveness and Safety of Generic Tofacitinib in Rheumatoid Arthritis Patients: A Retrospective, Single-Centre Analysis from Western India
Authors: Phatak Sanat , Khenat Aditya , Malandkar Mansi , Amin Sanjiv 
Published: April 2022

AbstractBackgroundGeneric tofacitinib has been available in India for more than a year and is widely used in rheumatoid arthritis (RA) therapy. There is scarce real-world data on its effectiveness and safety from India, especially given infection endemicity.MethodsWe retrospectively analysed records (demographic and clinical information, haematology and biochemistry, adverse events) of patients prescribed generic tofacitinib from a single centre in Mumbai, India. Disease activity was calculated using the disease activity score-28 and erythrocyte sedimentation rate (DAS28-ESR) and other tools, and we used paired T-tests for significant response. We defined clinical tofacitinib failure as a composite outcome, including clinician’s decision to change to an alternative disease-modifying anti-rheumatic drug (DMARD) or flare after self-withdrawal. We performed logistic regression and survival analysis for determinants of clinical failure.ResultsWe reviewed records of 102 patients (92 female; median age: 53 years) with mean RA duration of 146 months. Thirteen had prior treatment with innovator tofacitinib. There was significant improvement in disease activity parameters at a mean duration of 186 days. No serious adverse events were reported; 4 patients had tuberculosis and 19 patients had mild COVID-19 while on treatment. Clinical failure was seen in 25 patients, and mean time to failure on survival analysis was 357 days. No baseline characteristic predicted clinical failure.InterpretationGeneric tofacitinib showed good effectiveness and a tolerable adverse effect profile, despite tuberculosis endemicity andCOVID-19.. Setting up registries would be valuable in gaining more data on generic tofacitinib.Key points-There is scarce data from India regarding the use of tofacitinib in rheumatoid arthritis, despite widespread use-In this retrospective analysis of 102 patients at a single centre, we found tofacitinib monotherapy was efficacious and tolerable.-Tuberculosis was detected in four and nineteen patients had mild covid.
Outpatient and Home Pulmonary Rehabilitation Program Post COVID-19: A study protocol for clinical trial
Authors: Oliveira Luis V. F. , Oliveira Miriã C. , Lino Maria E. M. , Carrijo Marilucia M. , Afonso João Pedro R. , Moura Ricardo S. , Fonseca Adriano L. , Fonseca Daniela R. P. , Oliveira Luis Felipe R. J. , Galvão Letícia S. , Reis Bianca M. , Diniz Raphael H. C. O. , Bernardes Rubens R. , Póvoa Elisângela R. P. , Silva Anderson S. , Santos Dante B. , Maldaner Vinicius Z , Coutinho Jean Carlos , Modesto Guilherme Pacheco , Oliveira-Silva Iransé , Lopes Martins Rodrigo A. B. , Lopes Martins Patrícia S. L. , Oliveira Claudia S. , Júnior Gerson Cipriano , Vieira Rodolfo P , Palma Renata K. , Alves Larissa R. , Insalaco Giuseppe 
Published: April 2022

AbstractBackgroundThe coronavirus disease 2019 (COVID-19) is a widespread, highly contagious inflammatory process that causes respiratory, physical and psychological dysfunction. COVID-19 mainly affects the respiratory system and evolves in the acute phase from mild cases with common symptoms, such as fever, cough, and fatigue, to the moderate-to-severe form, causing massive alveolar damage resulting in dyspnea and hypoxemia that can rapidly progress to pneumonia, and acute respiratory distress syndrome. The acute form usually causes severe pulmonary sequelae such as pulmonary fibrosis or progression to organ failure, leading to worsening metabolic dysfunction and/or death.PurposeTo verify the effects of an outpatient and home pulmonary rehabilitation program (PRP) on clinical symptoms, pulmonary function, physical activity level, functional status, autonomic activity, peripheral muscle strength, static and functional balance, functional mobility, anxiety and depression, post-traumatic stress, health-related quality of life, and survival of patients with sequelae from COVID-19.MethodsThis study will be a cohort, parallel, two-arm multicentric study, to be carried out in three clinical centers, with blind evaluation, with 06 weeks of training and follow-up. This study was designed according to the recommendations of the CONSORT statement. To be involved in this clinical study, according to the inclusion criteria, women and men aged between 16 and 75 years affected by COVID-19. The proposed PRP is based on the guidelines recommended by the Global Initiative for Chronic Obstructive Lung Disease and, consists of a combination of aerobic and muscle strengthening exercises, lasting six weeks, with a frequency of three times a week.DiscussionIn patients infected with COVID-19 with persistent symptoms and sequelae, PRP mainly seeks to improve dyspnea, relieve anxiety and depression, prevent, and reduce complications and/or dysfunctions, reduce morbidity and mortality, and improve health-related quality of life.Trial registrationThis study was registered at clinicaltrials.gov (ID: COVID-19 PULMONARY REHAB NCT04982042).
Second round of the interlaboratory comparison (ILC) exercise of SARS-CoV-2 molecular detection assays being used by 45 veterinary diagnostic laboratories in the US
Authors: Deng Kaiping , Uhlig Steffen , Goodman Laura B. , Ip Hon S. , Killian Mary Lea , Nemser Sarah M. , Ulaszek Jodie , Kiener Shannon , Kmet Matthew , Frost Kirstin , Hettwer Karina , Colson Bertrand , Nichani Kapil , Schlierf Anja , Tkachenko Andriy , Mlalazi-Oyinloye Mothomang , Scott Andrew , Reddy Ravinder , Tyson Gregory H. 
Published: April 2022

AbstractThe coronavirus disease 2019 (COVID-19) pandemic presents a continued public health challenge across the world. Veterinary diagnostic laboratories in the U.S. use real-time reverse transcriptase PCR (RT-PCR) for animal testing, and many are certified for testing human samples, so ensuring laboratories have sensitive and specific SARS-CoV-2 testing methods is a critical component of the pandemic response. In 2020, the FDA Veterinary Laboratory Investigation and Response Network (Vet-LIRN) led the first round of an Inter-Laboratory Comparison (ILC) Exercise to help laboratories evaluate their existing real-time RT-PCR methods for detecting SARS-CoV-2. The ILC1 results indicated that all participating laboratories were able to detect the viral RNA spiked in buffer and PrimeStore molecular transport medium (MTM). The current ILC (ILC2) aimed to extend ILC1 by evaluating analytical sensitivity and specificity of the methods used by participating laboratories to detect three SARS-CoV-2 variants (B.1, B.1.1.7 (Alpha) and B.1.351 (Beta)). ILC2 samples were prepared with RNA at levels between 10 to 10,000 copies per 50 μL MTM. Fifty-seven sets of results from 45 laboratories were qualitatively and quantitatively analyzed according to the principles of ISO 16140-2:2016. The results showed that over 95% of analysts detected the SARS-CoV-2 RNA in MTM at 500 copies or higher for all three variants. In addition, 81% and 92% of the analysts achieved a Level of Detection (LOD95eff. vol.) below 20 copies in the assays with nucleocapsid markers N1 and N2, respectively. The analytical specificity of the evaluated methods was over 99%. The study allowed participating laboratories to assess their current method performance, identify possible limitations, and recognize method strengths as part of a continuous learning environment to support the critical need for reliable diagnosis of COVID-19 in potentially infected animals and humans.
Implications of red state/blue state differences in COVID-19 death rates
Authors: Adams Mary L. 
Published: April 2022

AbstractThe study objective was to explore state death rates pre- and post- 4/19/2021 (date vaccines were assumed available) and the relative contributions of 3 factors to state death rates post- 4/19/2021: 1) vaccination rates, 2) prevalence of obesity, hypertension, diabetes, COPD, cardiovascular disease, and asthma and 3) red vs. blue states, to better understand options for reducing deaths. The ratio of red to blue state deaths/million was 1.6 pre-4/19/2021 and 2.3 between 4/19 and 2/28/2022 resulting in >222,000 extra deaths in red states or 305/ day. Adjusted betas from linear regression showed state vaccination rates had the strongest effect on death rates while red vs. blue states explained more of the difference in state death rates (60% vs. 46% for vaccination rates) with mean vaccination rates ~10% higher in blue states. Results suggest that increasing vaccination rates in red states could potentially save thousands of lives as the pandemic continues.
Molecular mechanisms of microbiome modulation by the eukaryotic secondary metabolite azelaic acid
Authors: Shibl Ahmed A. , Ochsenkühn Michael A. , Mohamed Amin R. , Isaac Ashley , Coe Lisa S. Y. , Yun Yejie , Skrzypek Grzegorz , Raina Jean-Baptiste , Seymour Justin R. , Afzal Ahmed J. , Amin Shady A. 
Published: April 2022

AbstractPhotosynthetic eukaryotes, such as microalgae and plants, foster fundamentally important relationships with their microbiome based on the reciprocal exchange of chemical currencies. Among these, the dicarboxylate metabolite azelaic acid (Aze) appears to play an important, but heterogeneous, role in modulating these microbiomes, as it is used as a carbon source for some heterotrophs but is toxic to others. However, the ability of Aze to promote or inhibit growth, as well as its uptake and assimilation mechanisms into bacterial cells are mostly unknown. Here, we use transcriptomics, transcriptional factor coexpression networks, uptake experiments, and metabolomics to unravel the uptake, catabolism and toxicity of Aze on two microalgal-associated bacteria,PhycobacterandAlteromonas, whose growth is promoted or inhibited by Aze, respectively. We identify the first putative Aze transporter in bacteria, a ‘C4-TRAP transporter’, and show that Aze is assimilated through fatty acid degradation, with further catabolism occurring through the glyoxylate and butanoate metabolism pathways when used as a carbon source.Phycobactertook up Aze at an initial uptake rate of 3.8×10-9nmol cell-1hr-1and utilized it as a carbon source in concentrations ranging from 10 μM-1mM, suggesting a broad range of acclimation to Aze availability. For inhibited bacteria, we infer that Aze inhibits the ribosome and/or protein synthesis and that a suite of efflux pumps is utilized to shuttle Aze outside the cytoplasm. We demonstrate that seawater amended with Aze becomes enriched in bacterial families that can catabolise Aze, which appears to be a different mechanism from that in soil, where modulation by the host plant is required. This study enhances our understanding of carbon cycling in the oceans and how microscale chemical interactions can structure marine microbial populations. In addition, our findings unravel the role of a key chemical currency in the modulation of eukaryote-microbiome interactions across diverse ecosystems.
NS1 from Two Zika Virus Strains Differently Interact with a Membrane: A Plausible Explanation for their Differential Virulence
Authors: Poveda-Cuevas Sergio A. , Barroso da Silva Fernando L. , Etchebest Catherine 
Published: April 2022

ABSTRACTZika virus (ZIKV) from Uganda (UG) expresses a phenotype related to fetal loss whereas the variant from Brazil (BR) induces microcephaly in neonates. The differential virulence has a direct relation to biomolecular mechanisms that make one strain more aggressive than the other. The non-structural protein 1 (NS1) is a key viral toxin to comprehend these viral discrepancies because of its versatility in many processes of the virus life cycle. Here, we aim to examine through coarse-grained models and molecular dynamics simulations the protein-membrane interactions for both NS1ZIKV-UG and NS1ZIKV-BR dimers. A first evaluation allowed us to establish that the NS1 proteins, in the membrane presence, explore new conformational spaces when compared to systems simulated without a lipid bilayer. These events derive from both differential coupling patterns and discrepant binding affinities to the membrane. The N-terminal domain, intertwined loop, and greasy finger proposed previously as binding membrane regions were also computationally confirmed by us. The anchoring sites have aromatic and ionizable residues that manage the assembly of NS1 toward the membrane, especially for the Ugandan variant. Furthermore, the protein-membrane interaction induces perturbation in the distal part related to putative epitopes. These results open up new strategies for the treatment of flaviviruses.Abstract Figure
DeepTMHMM predicts alpha and beta transmembrane proteins using deep neural networks
Authors: Hallgren Jeppe , Tsirigos Konstantinos D. , Pedersen Mads Damgaard , Almagro Armenteros José Juan , Marcatili Paolo , Nielsen Henrik , Krogh Anders , Winther Ole 
Published: April 2022

AbstractTransmembrane proteins span the lipid bilayer and are divided into two major structural classes, namely alpha helical and beta barrels. We introduce DeepTMHMM, a deep learning protein language model-based algorithm that can detect and predict the topology of both alpha helical and beta barrels proteins with unprecedented accuracy. DeepTMHMM (https://dtu.biolib.com/DeepTMHMM) scales to proteomes and covers all domains of life, which makes it ideal for metagenomics analyses.
IMPatienT: an Integrated web application to digitize, process and explore Multimodal PATIENt daTa
Authors: Meyer Corentin , Romero Norma Beatriz , Evangelista Teresinha , Cadot Brunot , Laporte Jocelyn , Jeannin-Girardon Anne , Collet Pierre , Chennen Kirsley , Poch Olivier 
Published: April 2022

ABSTRACTMedical acts, such as imaging, lead to the production of several medical text report that describes the relevant findings. This induces multimodality in patient data by linking image data to free-text and consequently, multimodal data have become central to drive research and improve diagnosis. However, the exploitation of patient data is challenging as the ecosystem of analysis tools is fragmented depending on the type of data (images, text, genetics), the task (processing, exploration) and domains of interest (clinical phenotype, histology). To address the challenges, we present IMPatienT (Integrated digitalMultimodalPATIENt daTa), a simple, flexible and open-source web application to digitize, process and explore multimodal patient data. IMPatienT has a modular architecture to: (i) create a standard vocabulary for a domain, (ii) digitize and process free-text data, (iii) annotate images and perform image segmentation, and (iv) generate a visualization dashboard and perform diagnosis suggestions. We showcased IMPatienT on a corpus of 40 simulated muscle biopsy reports of congenital myopathy patients. As IMPatienT relies on a user-designed vocabulary, it can be adapted to any domain of research and can be used as a patient registry for exploratory data analysis (EDA). A demo instance of the application is available athttps://impatient.lbgi.fr/.
Hypothalamic gene network dysfunction is associated with cognitive decline and body weight loss in Alzheimer’s disease mice
Authors: Dai M , Dunn AR , Hadad N , Zhang J-G , Poirion OB , Korgan AC , White BS , Philip VM , Neuner SM , O’Connell KMS , Kaczorowski CC 
Published: April 2022

AbstractRecent studies, both clinical and experimental, indicate that many neurodegenerative disorders including Alzheimer’s disease (AD) often display coexisting metabolic dysfunctions, which may exacerbate neurological symptoms. The hypothalamus is a brain region highly involved in maintaining metabolic and other homeostatic processes and is known to be involved in the etiology of AD, although the role of hypothalamic dysfunction in the onset, progression, and severity of AD is poorly understood. In this study, we demonstrate that our new model of genetic diversity in AD, the AD-BXDs, exhibits non-cognitive symptoms consistent with hypothalamic dysfunction and examined hypothalamic bulk RNA sequencing data in the AD-BXD panel to investigate how the AD transgene impacts gene expression profiles in the hypothalamus. Mostly notably, we identified strong neuroinflammatory signatures from the hypothalamus in the AD-BXDs as early as six months of age. A functionally unknown WGCNA module showed correlation to female body weight and contextual fear acquisition. Eigengene expression of microglial/macrophagic modules and their hub gene expressions were correlated to cognitive phenotypes. From these analyses, we nominatedPlekandLaptm5as new targets to attenuate neuroinflammation in AD.
Growth form matters – crustose lichens are sensitive to forest management on dead wood
Authors: Kantelinen Annina , Purhonen Jenna , Halme Panu , Myllys Leena 
Published: April 2022

AbstractLichens have a vital role in forest ecosystems and they are a threatened group in boreal forests. However, the conservation ecology of the total lichen community has very rarely been studied. Here we studied lichen species and communities, including macrolichens (= foliose and fruticose growth forms) and rarely studied crustose lichens, on decaying wood in boreal spruce-dominated forests in Finland. We also studied obligate lignicoles that grow only on dead wood and are mostly crustose in growth form. Species richness and community composition were examined on decaying logs and natural or cut stumps of Picea abies at different decay stages (2–5) in 14 stands, half of which were natural or seminatural and half recently managed. We used thorough search to yield a species list as close to complete as possible. Our study questions were: 1) Are species richness and lichen communities different in natural and managed forests, and if so, are there differences between macrolichens, crustose lichens and obligate lignicoles in how they respond to forest management? 2) How does the decay stage and dead wood type affect the lichens, i.e. are there differences between stumps and logs? We found a total of 127 lichen species. Most (75%) of the recorded lichen species were crustose. With a generalized linear model we found that crustose lichens and obligate lignicoles had a higher species richness in natural than managed forests, but macrolichen richness was not significantly affected by forest management. Utilizing non-metric multidimensional scaling we discovered that site level community composition of macrolichens, crustose lichens and obligate lignicoles was also significantly different between natural and managed forests. We found that on dead wood unit level the decay stage had a significant effect on species richness and community composition, so that the species richness of all studied groups declined during the decay process. The dead wood type (stump vs. log) had a significant effect on species richness of macrolichens and obligate lignicoles, as well as on the communities of crustose lichens.
Evolution of selfish multicellularity collective organisation of individual spatio-temporal regulatory strategies
Authors: Vroomans Renske M.A. , Colizzi Enrico Sandro 
Published: April 2022

AbstractBackgroundThe unicellular ancestors of modern-day multicellular organisms were remarkably complex. They had an extensive set of regulatory and signalling genes, an intricate life cycle and could change their behaviour in response to environmental changes. At the transition to multicellularity, some of these behaviours were co-opted to organise the development of the nascent multicellular organism. Here, we focus on the transition to multicellularity before the evolution of stable cell differentiation, to reveal how the emergence of clusters affects the evolution of cell behaviour.ResultsWe construct a computational model of a population of cells that can evolve the regulation of their behavioural state – either division or migration – in a unicellular or multicellular context. They compete for reproduction and for resources to survive in a seasonally changing environment. We find that the evolution of multicellularity strongly determines the co-evolution of cell behaviour, by altering the competition dynamics between cells. When adhesion cannot evolve, cells compete for survival by rapidly migrating towards resources before dividing. When adhesion evolves, emergent collective migration alleviates the pressure on individual cells to reach resources. This allows cells to selfishly maximise replication. Migrating adhesive clusters display striking patterns of spatio-temporal cell state changes that visually resemble animal development.ConclusionsOur model demonstrates how emergent selection pressures at the onset of multicellularity can drive the evolution of cellular behaviour to give rise to developmental patterns.