bluuebunny/crossref_metadata_2025_split huggingface dataset:
First cases of infection with the 21L/BA.2 Omicron variant in Marseille, France
Authors: Colson Philippe , Delerce Jérémy , Beye Mamadou , Levasseur Anthony , Boschi Céline , Houhamdi Linda , Tissot-Dupont Hervé , Yahi Nouara , Million Matthieu , La Scola Bernard , Fantini Jacques , Raoult Didier , Fournier Pierre-Edouard 
Published: February 2022

ABSTRACTThe SARS-CoV-2 21K/BA.1, 21L/BA.2, and BA.3 Omicron variants have recently emerged worldwide. To date, the 21L/BA.2 Omicron variant has remained very minority globally but became predominant in Denmark instead of the 21K/BA.1 variant. Here we describe the first cases diagnosed with this variant in south-eastern France. We identified thirteen cases using variant-specific qPCR and next-generation sequencing between 28/11/2021 and 31/01/2022, the first two cases being diagnosed in travellers returning from Tanzania. Overall, viral genomes displayed a mean (±standard deviation) number of 65.9±2.5 (range, 61-69) nucleotide substitutions and 31.0±8.3 (27-50) nucleotide deletions, resulting in 49.6±2.2 (45-52) amino acid substitutions (including 28 in the spike protein) and 12.4±1.1 (12-15) amino acid deletions. Phylogeny showed the distribution in three different clusters of these genomes, which were most closely related to genomes from England and South Africa, from Singapore and Nepal, or from France and Denmark. Structural predictions pointed out a significant enlargement and flattening of the 21L/BA.2 N-terminal domain surface compared with that of the 21K/BA.2 Omicron variant, which may facilitate initial viral interactions with lipid rafts. Close surveillance is needed at global, country and center scales to monitor the incidence and clinical outcome of the 21L/BA.2 Omicron variant.
Symptoms and severity in vaccinated and unvaccinated patients hospitalised with SARS-CoV-2 delta (B.1.617.2) variant infection
Authors: Epaulard Olivier , Abgrall Sophie , Lefebvre Maeva , Faucher Jean-François , Michon Jocelyn , Frentiu Emilia , Janssen Cécile , Charbonnier Gabrielle , Fresse Audrey , Laurent Simon , Sandjakian Lena , Casez Pierre , Mahamat Aba , Béraud Guillaume 
Published: February 2022

AbstractBackgroundThe diffusion of the SARS-CoV-2 delta (B.1.617.2) variant and the waning of immune response after primary Covid-19 vaccination favoured the breakthrough SARS-CoV-2 infections in vaccinated subjects. To assess the impact of vaccination, we determined the severity of infection in hospitalised patients according to vaccine status.MethodsWe retrospectively analysed data from patients hospitalised in 10 centres with a SARS-CoV-2 infection (delta variant) from July to November 2021: i) all patients who had completed their primary vaccination at least 14 days before hospital admission; and ii) the same number of completely unvaccinated patients. We assessed the impact of vaccination and other risk factors through logistic regression.FindingsWe included 955 patients (474 vaccinated and 481 unvaccinated). Vaccinated patients were significantly older, more frequently males, and with more comorbidities. They were less often admitted for Covid-19 (59·3% vs. 75·1%, p<0·001), showed fewer lung lesions, and required oxygen less frequently (57·5% vs. 73·0%, p<0·001), at a lower flow (3·0 vs. 6·0 L/min, p<0·001), and for a shorter duration (3 vs. 6 days, p<0·001). They less frequently required intensive care unit admission (16·2 % vs. 36·0 %, p<0·001). Mortality at day 28 was not different between the two groups (16·7% vs. 12.2%, p=0·075), but multivariate logistic regression showed that vaccination significantly decreased the risk of negative outcomes, including mortality, even when considering older patients, and those with comorbidities.ConclusionsAmong patients hospitalised with a delta variant SARS-CoV-2 infection, vaccination was associated with less severe forms, even in the presence of comorbidities.
Innovative Randomized Phase 1 Study and Dosing Regimen Selection to Accelerate and Inform Pivotal COVID-19 Trial of Nirmatrelvir
Authors: Singh Ravi Shankar P. , Toussi Sima S. , Hackman Frances , Chan Phylinda L. , Rao Rohit , Allen Richard , Van Eyck Lien , Pawlak Sylvester , Kadar Eugene P. , Clark Frances , Shi Haihong , Anderson Annaliesa S. , Binks Michael , Menon Sandeep , Nucci Gianluca , Bergman Arthur 
Published: February 2022

ABSTRACTBackgroundCOVID-19 is a continued leading cause of hospitalization and death. Safe and efficacious COVID-19 antivirals are needed urgently. Nirmatrelvir (PF-07321332), the first orally bioavailable, SARS-CoV-2 Mpro inhibitor against the coronaviridae family, has demonstrated potent preclinical antiviral activity and benign safety profile.MethodsWe report safety, tolerability, and pharmacokinetic data of nirmatrelvir with and without ritonavir as a pharmacokinetic enhancer, from an accelerated randomized, double-blind, placebo-controlled, phase 1 study. Two interleaving single-ascending dose (SAD) cohorts were evaluated in a 3-period crossover. Multiple-ascending dose (MAD) with nirmatrelvir/ritonavir twice daily (BID) dosing was evaluated over 10 days in 5 parallel cohorts. Safety was assessed, including in a supratherapeutic exposure cohort. Dose and dosing regimen for clinical efficacy evaluation in phase 2/3 clinical trials were supported by integrating modelling and simulations of SAD/MAD data with nonclinical data and a quantitative systems pharmacology model (QSP).ResultsIn SAD, MAD, and supratherapeutic exposure cohorts, nirmatrelvir/ritonavir was safe and well tolerated. Nirmatrelvir exposure and half-life were considerably increased by ritonavir, enabling selection of nirmatrelvir/ritonavir dose and regimen for phase 2/3 trials (300/100 mg BID), to achieve concentrations continuously above those required for 90% inhibition of viral replication in vitro. The QSP model suggested that a 5-day regimen would significantly decrease viral load in SARS-CoV-2-infected patients and prevent development of severe disease, hospitalization, and death.ConclusionsAn innovative and seamless trial design expedited establishment of phase 1 safety and pharmacokinetics of nirmatrelvir/ritonavir, enabling high confidence in phase 2/3 dose selection and accelerated pivotal trials’ initiation. NCT04756531
DMARD disruption, disease flare, and prolonged symptom duration after acute COVID-19 among participants with rheumatic disease: A prospective study
Authors: Di Iorio Michael , Cook Claire E. , Vanni Kathleen M.M. , Patel Naomi J. , D’Silva Kristin M. , Fu Xiaoqing , Wang Jiaqi , Prisco Lauren C. , Kowalski Emily , Zaccardelli Alessandra , Martin Lily W. , Qian Grace , Hsu Tiffany Y-T. , Wallace Zachary S. , Sparks Jeffrey A. 
Published: February 2022

ABSTRACTObjectiveTo describe disease-modifying antirheumatic drug (DMARD) disruption, rheumatic disease flare/activity, and prolonged COVID-19 symptom duration among COVID-19 survivors with systemic autoimmune rheumatic diseases (SARDs).MethodsWe surveyed patients with SARDs after confirmed COVID-19 at Mass General Brigham to investigate post-acute sequelae of COVID-19. We obtained data on demographics, clinical characteristics, COVID-19 symptoms/course, and patient-reported measures. We examined baseline predictors of prolonged COVID-19 symptom duration (defined as lasting ≥28 days) using logistic regression.ResultsWe analyzed surveys from 174 COVID-19 survivors (mean age 52 years, 81% female, 80% White, 50% rheumatoid arthritis) between March 2021 and January 2022. Fifty-one percent of 127 respondents on any DMARD reported a disruption to their regimen after COVID-19 onset. For individual DMARDs, 56-77% had any change, except for hydroxychloroquine (23%) and rituximab (46%). SARD flare after COVID-19 was reported by 41%. Global patient-reported disease activity was worse at the time of survey than before COVID-19 (mean 6.6±2.9 vs. 7.6±2.3, p<0.001). Median time to COVID-19 symptom resolution was 14 days (IQR 9,29). Prolonged symptom duration of ≥28 days occurred in 45%. Hospitalization for COVID-19 (OR 3.54, 95%CI 1.27-9.87) and initial COVID-19 symptom count (OR 1.38 per symptom, 95%CI 1.17-1.63) were associated with prolonged symptom duration. Respondents experiencing prolonged symptom duration had higher RAPID3 scores (p=0.007) and more pain (p<0.001) and fatigue (p=0.03) compared to those without prolonged symptoms.ConclusionDMARD disruption, SARD flare, and prolonged symptom duration were common in this prospective study of COVID-19 survivors, suggesting substantial impact on SARDs after acute COVID-19.
Genome-wide association reveals host-specific genomic traits in Escherichia coli
Authors: Tiwari Sumeet K. , van der Putten Boas C.L. , Fuchs Thilo M. , Vinh Trung N. , Bootsma Martin , Oldenkamp Rik , La Ragione Roberto , Matamoros Sebastien , Hoa Ngo T. , Berens Christian , Leng Joy , Álvarez Julio , Ferrandis-Vila Marta , Ritchie Jenny M. , Fruth Angelika , Schwarz Stefan , Domínguez Lucas , Ugarte-Ruiz María , Bethe Astrid , Huber Charlotte , Johanns Vanessa , Stamm Ivonne , Wieler Lothar H. , Ewers Christa , Fivian-Hughes Amanda , Schmidt Herbert , Menge Christian , Semmler Torsten , Schultsz Constance 
Published: February 2022

AbstractEscherichia coli is an opportunistic pathogen that can colonize or infect various host species. There is a significant gap in our understanding to what extent genetic lineages of E. coli are adapted or restricted to specific hosts. In addition, genomic determinants underlying such host specificity are unknown.By analyzing a randomly sampled collection of 1198 whole-genome sequenced E. coli isolates from four countries (Germany, UK, Spain, and Vietnam), obtained from five host species (human, pig, cattle, chicken, and wild boar) over 16 years, from both healthy and diseased hosts, we demonstrate that certain lineages of E. coli are frequently detected in specific hosts. We report a novel nan gene cluster, designated nan-9, putatively encoding acetylesterases and determinants of uptake and metabolism of sialic acid, to be associated with the human host as identified through genome wide association studies. In silico characterization predicts nan-9 to be involved in sialic acid (Sia) metabolism. In vitro growth experiments with a representative Δnan E. coli mutant strain, using sialic acids 5-N-acetyl neuraminic acid (Neu5Ac) and N-glycolyl neuraminic acid (Neu5Gc) as the sole carbon source, indicate an impaired growth behaviour compared to the wild-type. In addition, we identified several additional E. coli genes that are potentially associated with adaptation to human, cattle and chicken hosts, but not for the pig host. Collectively, this study provides an extensive overview of genetic determinants which may mediate host specificity in E. coli. Our findings should inform risk analysis and epidemiological monitoring of (antimicrobial resistant) E. coli.
Parasites make hosts more profitable but less available to predators
Authors: Prosnier Loïc , Loeuille Nicolas , Hulot Florence D. , Renault David , Piscart Christophe , Bicocchi Baptiste , Deparis Muriel , Lam Matthieu , Médoc Vincent 
Published: February 2022

AbstractParasites are omnipresent, and their eco-evolutionary significance has aroused much interest from scientists. Parasites may affect their hosts in many ways with changes in density, appearance, behaviour and energy content, likely to modify their value to predators (profitability) within the optimal foraging framework. Consequently, parasites could impact predators’ diet and the trophic links through food webs. Here, we investigate the consequences of the infection by the iridovirus Daphnia iridescent virus 1 (DIV-1) on the reproductive success, mortality, appearance, mobility, and biochemical composition of water fleas (Daphnia magna), a widespread freshwater crustacean. We do predation tests and compare search time, handling time and feeding preference between infected and uninfectedDaphniawhen preyed upon byNotonectasp., a common aquatic insect. Our findings show that infection does not change fecundity but reduces lifespan and thereby constrains fitness. InfectedDaphniashow reduced mobility and increased color reflectance in the UV and visible domains, which potentially affects their appearance and thus vulnerability to predators. Infection increases body size and the amount of proteins but does not affect carbohydrate and lipid contents. Although infectedDaphniaare longer to handle, they are preferred over uninfected individuals by aquatic insects. Taken together, our findings show that DIV-1 infection could makeDaphniamore profitable to predators (24% energy increase), a positive effect that should be balanced with a lower availability due to the higher mortality of infected specimens. We also highlight that exposure to infection in asymptomatic individuals leads to ecological characteristics that differ from both healthy and symptomatic infected individuals.Recommender:Luis SchiesariReviewers:Thierry De Meeus and Eglantine Mathieu-BégnéCite as:Prosnier L., N. Loeuille, F.D. Hulot, D. Renault, C. Piscart, B. Bicocchi, M, Deparis, M. Lam, & V. Médoc. (2023).Parasites make hosts more profitable but less available to predators. BioRxiv, ver. 4 peer-reviewed and recommended by Peer Community in Ecology.https://doi.org/10.1101/2022.02.08.479552
A Systematic Approach for Explaining Time and Frequency Features Extracted by CNNs from Raw EEG Data
Authors: Ellis Charles A. , Miller Robyn L. , Calhoun Vince D. 
Published: February 2022

AbstractIn recent years, the use of convolutional neural networks (CNNs) for raw electroencephalography (EEG) analysis has grown increasingly common. However, relative to earlier machine learning and deep learning methods with manually extracted features, CNNs for raw EEG analysis present unique problems for explainability. As such, a growing group of methods have been developed that provide insight into the spectral features learned by CNNs. However, spectral power is not the only important form of information within EEG, and the capacity to understand the roles of specific multispectral waveforms identified by CNNs could be very helpful. In this study, we present a novel model visualization-based approach that adapts the traditional CNN architecture to increase interpretability and combines that inherent interpretability with a systematic evaluation of the model via a series of novel explainability methods. Our approach evaluates the importance of spectrally distinct first-layer clusters of filters before examining the contributions of identified waveforms and spectra to cluster importance. We evaluate our approach within the context of automated sleep stage classification and find that, for the most part, our explainability results are highly consistent with clinical guidelines. Our approach is the first to systematically evaluate both waveform and spectral feature importance in CNNs trained on EEG data.
TEMPRANILLOhomologs in apple regulate flowering time in the woodland strawberryFragaria vesca
Authors: Dejahang Ata , Maghsoudi Naeimeh , Mousavi Amir , Farsad-Akhtar Nader , Hernandez Luis Matias , Pelaz Soraya , Folta Kevin , Mahna Nasser 
Published: February 2022

AbstractMany economically valuable fruit trees belong to theRosaceaefamily. The long juvenile period of fruit trees makes their breeding costly and time-consuming. Therefore, flowering time regulation and shortening the juvenile phase have been a breeding priority for genetic improvement of fruit tree crops.TEMPRANILLOgenes act as floral inhibitors in Arabidopsis and so, two orthologs of this gene were isolated here from apple (Malus domestica) and functionally analysed in Arabidopsis and woodland strawberry by being overexpressed in both model plants, and partially silenced in strawberry. The overexpression ofMdTEMgenes down-regulatedFvFT1, FvGA3OX1, andFvGA3OX2genes in strawberry. The overexpression lines exhibited delayed flowering, both in terms of days to flowering and the number of leaves at flowering.RNAi-mediatedsilencing ofTEMresulted in early flowering plants. These plants flowered approximately five days earlier than wild type plants with a lower number of leaves. However, the overexpression ofMdTEMgenes could not functionally rescue theArabidopsismutants. According to the results, it can be concluded thatMdTEM1andMdTEM2are orthologs ofFvTEMgene, which play an important role in regulating the juvenile phase and flowering time through controllingFTand GA biosynthetic gene expression.
Transformation of alignment files improves performance of variant callers for long-read RNA sequencing data
Authors: de Souza Vladimir B. C. , Jordan Ben T. , Tseng Elizabeth , Nelson Elizabeth A. , Hirschi Karen K. , Sheynkman Gloria , Robinson Mark D. 
Published: February 2022

AbstractLong-read RNA sequencing (lrRNA-seq) produces detailed information about full-length transcripts, including novel and sample-specific isoforms. Furthermore, there is opportunity to call variants directly from lrRNA-seq data. However, most state-of-the-art variant callers have been developed for genomic DNA. Here, there are two objectives: first, we perform a mini-benchmark on GATK, DeepVariant, Clair3, and NanoCaller primarily on PacBio Iso-Seq, data, but also on Nanopore and Illumina RNA-seq data; second, we propose a pipeline to process spliced-alignment files, making them suitable for variant calling with DNA-based callers. With such manipulations, high calling performance can be achieved using DeepVariant on Iso-seq data.
Maternally inherited siRNAs initiate piRNA cluster formation
Authors: Luo Yicheng , He Peng , Kanrar Nivedita , Toth Katalin Fejes , Aravin Alexei A. 
Published: February 2022

AbstractPIWI-interacting RNAs (piRNAs) guide repression of transposable elements in germlines of animals. In Drosophila, piRNAs are produced from heterochromatic genomic loci, called piRNA clusters, that act as a repositories of information about genome invaders. piRNA generation by dual-strand clusters depend on the chromatin-bound Rhino-Deadlock-Cutoff (RDC) complex, which is deposited on clusters guided by piRNAs, forming a feed-forward loop in which piRNAs promote their own biogenesis. However, how piRNA clusters are formed initially, before cognate piRNAs are present, remained unknown. Here we report spontaneous de novo formation of a piRNA cluster from repetitive transgenic sequences. We show that cluster formation occurs gradually over several generations and requires continuous trans-generational transmission of small RNAs from mothers to their progeny. We discovered that maternally-supplied siRNAs are responsible for triggering de novo cluster activation in progeny. In contrast, the siRNA pathway is dispensable for cluster function after its establishment. These results revealed an unexpected cross-talk between the siRNA and piRNA pathways and suggest a mechanism for de novo formation of piRNA clusters triggered by production of siRNAs.Highlights-A transcribed repetitive transgene is spontaneously converted into dual-strand piRNA cluster-Establishment of piRNA cluster occurs over multiple generations and requires cytoplasmic inheritance of cognate small RNA from mothers-Cognate siRNAs initiate the activation of piRNA cluster, but are dispensable after its establishment
The Chromosome-level Genome of Dracaena cochinchinesis Provides Insights into its Biological Features and the Mechanism of Dragon’s Blood Formation
Authors: Xu Yanhong , Zhang Kaijian , Zhang Zhonglian , Liu Yang , Lv Feifei , Sun Peiwen , Gao Shixi , Wang Qiuling , Yu Cuicui , Jiang Jiemei , Li Chuangjun , Song Meifang , Gao Zhihui , Sui Chun , Li Haitao , Jin Yue , Guo Xinwei , Wei Jianhe 
Published: February 2022

ABSTRACTDracaena, a remarkably long-lived and slowly maturing species, is famous all over the world for the production of dragon’s blood, a precious traditional medicine used by different cultures since ancient times. However, lacking a high-quality genome,the molecular mechanisms underlying these traits are largely unknown and that greatly restricts the protection and regeneration of the rare and endangered plant resources. Here, we sequenced and assembled a chromosome-level genome of the Dracaena cochinchinensis, the first to be sequenced of Dracaena Vand. ex L. The D. cochinchinensis genome covering 1.21 Gb with a scaffold N50 of 50.06 Mb, and encodes 31,619 predicted protein-coding genes. We found D. cochinchinensis has undergone two whole genome duplications (WGDs) and two long terminal repeats (LTRs) insertion burst events. The expansion of cis-zeatin O-glucosyltransferase (cZOGT) and small auxin up-regulated RNA (SAUR) genes is account for its longevity and slow growth. In flavonoids biosynthesis pathway, transcription factors bHLH and MYB were predicted as the core regulators, and ROS as the specific signal molecule during the process of injury-induced dragon’s blood formation. Our study not only provides high-quality genomic knowledge of D. cochinchinensis, but also deciphered the mystery of its longevity, and preliminarily elucidated the molecular mechanism of dragon’s blood formation, which will facilitate the resource protection and sustainable utilization of Dracaena.SHORT SUMMARYThis study reports a chromosome-level genome assembly for D. cochinchinensis, the first genome of Dracaena Vand. ex L. It 29 provides valuable genetic resources and creates a large scope for studying Dracaena. We found the significant expansion of genes associated with its longevity and slow growth, and genes in flavonoids biosynthesis were first completely identified. Moreover, transcription factors bHLH and MYB as the core regulator of flavonoids biosynthesis, and ROS as the specific signal molecule during the process of injury-induced dragon’s blood formation were also identified. These results not only deciphered the mystery of its longevity, but also elucidated the molecular mechanism of dragon[s blood formation preliminarily, which will facilitate the resource protection and sustainable utilization of Dracaena.
Modulation of RNA polymerase processivity affects double-strand break repair in the presence of a DNA end-binding protein
Authors: Sivaramakrishnan Priya , Bradley Catherine C. , Artsimovitch Irina , Hagstrom Katelin M. , Ramirez Laura Deus , Wen Alice Xueyin , Cooke Matthew Brandon , Shaulsky Maya , Herman Christophe , Halliday Jennifer A. 
Published: February 2022

ABSTRACTHomologous recombination is the predominant double-strand DNA break repair pathway in Escherichia coli. A recent report of non-homologous end joining involving the Ku-like Gam protein of bacteriophage Mu (MuGam) has sparked interest in understanding the functions of DNA end-binding proteins in bacteria. MuGam binds to DNA ends, but how it interferes with DNA repair or transcription in live bacteria remains elusive. In E. coli, RNA polymerase secondary channel interactors, such as the Gre factors, play a role in coordinating transcription with DNA replication and break repair. Here we show that MuGam inhibits break repair by slowing down DNA resection and impeding recombination in living cells. Loss of GreA restores break repair in the presence of MuGam by allowing for increased DNA resection due to a potential release of MuGam from the DNA. Using MuGam as a DNA break sensor, we found that breaks are generated when translation is inhibited, more so in the presence of GreA, supporting the model where transcription-translation uncoupling increases transcription/replication collisions. Significantly, this work reveals that modulation of RNA polymerase can impact DNA break repair in presence of a Ku-like protein.