bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivostructure of the Ty1 retrotransposon RNA genome
Authors: Andrzejewska Angelika , Zawadzka Małgorzata , Gumna Julita , Garfinkel David J , Pachulska-Wieczorek Katarzyna 
Published: February 2021

AbstractLong terminal repeat (LTR)-retrotransposons constitute a significant part of eukaryotic genomes and influence their function and evolution. Like other RNA viruses, LTR-retrotransposons efficiently utilize their RNA genome to interact with host cell machinery during replication. Here, we provide the first genome-wide RNA secondary structure model for a LTR-retrotransposon in living cells. Using SHAPE probing, we explore the secondary structure of the yeast Ty1 retrotransposon RNA genome in its native in vivo state and under defined in vitro conditions. Comparative analyses reveal the strong impact of the cellular environment on folding of Ty1 RNA. In vivo, Ty1 genome RNA is significantly less structured and more dynamic but retains specific well-structured regions harboring functional cis-acting sequences. Ribosomes participate in the unfolding and remodeling of Ty1 RNA, and inhibition of translation initiation stabilizes Ty1 RNA structure. Together, our findings support the dual role of Ty1 genomic RNA as a template for protein synthesis and reverse transcription. This study also contributes to understanding how a complex multifunctional RNA genome folds in vivo, and strengthens the need for studying RNA structure in its natural cellular context.
Anti-myeloperoxidase and proteinase 3 antibodies for nephritis flare prediction in anti-neutrophil cytoplasmic antibody–associated vasculitis
Authors: Rodríguez Eva , Latzke Belén , Sierra Milagros , Romera Ana María , Siedel Diego , Agraz Irene , Soler María José , García-Carro Clara , Draibe Juliana , de la Prada Francisco José , Villacorta Javier , Buxeda Anna , Sierra-Ochoa Adriana , Lozano Inés , Durán Xavier , Barrios Clara , Pascual Julio 
Published: February 2021

Abstract

Background
The value of myeloperoxidase (MPO) and proteinase 3 (PR3) antibody titres in the assessment of renal disease activity and flare prediction in patients with anti-neutrophil cytoplasmic antibody–associated vasculitis (AAV) is not well known.

Methods
We performed a retrospective study including 113 AVV patients with renal biopsy–proven pauci-immune necrotizing glomerulonephritis from seven Spanish hospitals. The main inclusion criteria were assessment of MPO antibodies using multiplex flow immunoassay and PR3 antibody measurements using immunoassay chemiluminescence with an identical range of values for all participating centres.

Results
Serum MPO antibodies 3 ± 1.2 months before relapse were higher in patients who relapsed [19.2 ± 12.2 versus 3.2 ± 5.1 antibody index (AI); P &lt; 0.001]. The discrimination value of MPO antibodies 3 months before renal relapse had an area under the receiver operating characteristics curve (AUC) of 0.82 [95% confidence interval (CI) 0.73–0.92; P &lt; 0.001]. ΔMPO antibodies (change in antibodies titration 6 months before relapse) were higher in patients who relapsed (8.3 ± 12 versus 0.9 ± 3.1 AI; P = 0.001). The discrimination value of ΔMPO had an AUC of 0.76 (95% CI 0.63–0.88; P &lt; 0.001). The positive predictive value of renal relapse in PR3 patients is 100% and the negative predictive value of renal relapse in patients with PR3-positive titres is 57.1%. Serum PR3 antibodies were higher in patients who relapsed 2.8 ± 1.4 months before relapse (58.6 ± 24.6 versus 2.0 ± 0.6 AI; P &lt; 0.001).

Conclusions
MPO level monitoring using multiplex flow immunoassay and PR3 measurements using immunoassay chemiluminescence are useful and sensitive tools for the prediction of renal relapse in the follow-up of AAV patients with renal disease and relevant surrogate markers of renal disease activity.
Clinical characterization of primary hyperoxaluria type 3 in comparison with types 1 and 2
Authors: Singh Prince , Viehman Jason K , Mehta Ramila A , Cogal Andrea G , Hasadsri Linda , Oglesbee Devin , Olson Julie B , Seide Barbara M , Sas David J , Harris Peter C , Lieske John C , Milliner Dawn S 
Published: February 2021

Abstract

Background
Primary hyperoxaluria (PH) type 3 (PH3) is caused by mutations in the hydroxy-oxo-glutarate aldolase 1 gene. PH3 patients often present with recurrent urinary stone disease in the first decade of life, but prior reports suggested PH3 may have a milder phenotype in adults. This study characterized clinical manifestations of PH3 across the decades of life in comparison with PH1 and PH2.

Methods
Clinical information was obtained from the Rare Kidney Stone Consortium PH Registry (PH1, n = 384; PH2, n = 51; PH3, n = 62).

Results
PH3 patients presented with symptoms at a median of 2.7 years old compared with PH1 (4.9 years) and PH2 (5.7 years) (P = 0.14). Nephrocalcinosis was present at diagnosis in 4 (7%) PH3 patients, while 55 (89%) had stones. Median urine oxalate excretion was lowest in PH3 patients compared with PH1 and PH2 (1.1 versus 1.6 and 1.5 mmol/day/1.73 m2, respectively, P &lt; 0.001) while urine calcium was highest in PH3 (112 versus 51 and 98 mg/day/1.73 m2 in PH1 and PH2, respectively, P &lt; 0.001). Stone events per decade of life were similar across the age span and the three PH types. At 40 years of age, 97% of PH3 patients had not progressed to end-stage kidney disease compared with 36% PH1 and 66% PH2 patients.

Conclusions
Patients with all forms of PH experience lifelong stone events, often beginning in childhood. Kidney failure is common in PH1 but rare in PH3. Longer-term follow-up of larger cohorts will be important for a more complete understanding of the PH3 phenotype.
Structural Alteration of Rice Pectin Affects Cell Wall Mechanical Strength and Pathogenicity of the Rice Blast Fungus Under Weak Light Conditions
Authors: Ohara Takashi , Takeuchi Haruki , Sato Junya , Nakamura Atsuko , Ichikawa Hiroaki , Yokoyama Ryusuke , Nishitani Kazuhiko , Minami Eiichi , Satoh Shinobu , Iwai Hiroaki 
Published: February 2021

Abstract
Pectin, a component of the plant cell wall, is involved in cell adhesion and environmental adaptations. We generated OsPG-FOX rice lines with little pectin due to overexpression of the gene encoding a pectin-degrading enzyme [polygalacturonase (PG)]. Overexpression of OsPG2 in rice under weak light conditions increased the activity of PG, which increased the degradation of pectin in the cell wall, thereby reducing adhesion. Under weak light conditions, the overexpression of OsPG decreased the pectin content and cell adhesion, resulting in abnormally large intercellular gaps and facilitating invasion by the rice blast fungus. OsPG2-FOX plants had weaker mechanical properties and greater sensitivity to biotic stresses than wild-type (WT) plants. However, the expression levels of disease resistance genes in non-infected leaves of OsPG2-FOX were more than twice as high as those of the WT and the intensity of disease symptoms was reduced, compared with the WT. Under normal light conditions, overexpression of OsPG2 decreased the pectin content, but did not affect cell adhesion and sensitivity to biotic stresses. Therefore, PG plays a role in regulating intercellular adhesion and the response to biotic stresses in rice.
Mesozooplankton biomass, grazing and trophic structure in the bluefin tuna spawning area of the oceanic Gulf of Mexico
Authors: Landry Michael R , Swalethorp Rasmus 
Published: February 2021

Abstract
We investigated size-fractioned biomass, isotopes and grazing of mesozooplankton communities in the larval habitat of Atlantic bluefin tuna (ABT) in the oceanic Gulf of Mexico (GoM) during the peak spawning month of May. Euphotic-zone biomass ranged from 101 to 513 mg C m−2 during the day and 216 to 798 mg C m−2 at night. Grazing varied from 0.1 to 1.0 mg Chla m−2 d−1, averaging 1–3% of phytoplankton Chla consumed d−1. Carnivorous taxa dominated the biomass of &gt; 1-mm zooplankton (78% day; 60% night), while only 13% of smaller zooplankton were carnivores. δ15N enrichment between small and large sizes indicates a 0.5–0.6 trophic-step difference. Although characteristics of GoM zooplankton are generally similar to those of remote oligotrophic subtropical regions, zooplankton stocks in the ABT larval habitat are disproportionately high relative to primary production, compared with HOT and BATS averages. Growth-grazing balances for phytoplankton were resolved with a statistically insignificant residual, and trophic fluxes from local productivity were sufficient to satisfy C demand of suspension feeding mesozooplankton. While carnivore C demand was met by local processes in the central GoM, experiments closer to the coastal margin suggest the need for a lateral subsidy of zooplankton biomass to the oceanic region.
COVID-19: transitioning from in class to online teaching in a heartbeat—Research Methods in Applied Biology
Authors: von Keyserlingk Marina A G 
Published: February 2021

Abstract
At the start of the COVID-19 pandemic, Universities around the world were forced to rapidly transition from face-to-face learning environments to online learning. This paper describes this transition through the lens of a professor responsible for a third year Applied Biology class focused on providing undergraduates with research experience. The paper also describes an innovative format used to engage undergraduates in research but also suggests that the creation of safe learning spaces in the virtual world may be key to successful delivery of these types of courses. Lastly, in times of rapid change professors need, on occasion, take a step back and simply listen to their students.
Evolution of ACE2 and SARS-CoV-2 Interplay Across 247 Vertebrates
Authors: Zhang Tao , Wu Qunfu , Ma Yicheng , Liu Wenjing , Zhou Chengang , Zhang Zhigang 
Published: February 2021

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cause the most serious pandemics of Coronavirus Disease 2019 (COVID-19), which threatens human health and public safety. SARS-CoV-2 spike (S) protein uses angiotensin-converting enzyme 2 (ACE2) as recognized receptor for its entry into host cell that contributes to the infection of SARS-CoV-2 to hosts. Using computational modeling approach, this study resolved the evolutionary pattern of bonding affinity of ACE2 in 247 jawed vertebrates to the spike (S) protein of SARS-CoV-2. First, high-or-low binding affinity phenotype divergence of ACE2 to the S protein of SARS-CoV-2 has appeared in two ancient species of jawed vertebrates,Scyliorhinus torazame(low-affinity, Chondrichthyes) andLatimeria chalumnae(high-affinity, Coelacanthimorpha). Second, multiple independent affinity divergence events recur in fishes, amphibians-reptiles, birds, and mammals. Third, high affinity phenotypes go up in mammals, possibly implying the rapid expansion of mammals might accelerate the evolution of coronaviruses. Fourth, we found natural mutations at eight amino acid sites of ACE2 can determine most of phenotype divergences of bonding affinity in 247 vertebrates and resolved their related structural basis. Moreover, we also identified high-affinity or low-affinity-associated concomitant mutation group.The group linked to extremely high affinity may provide novel potentials for the development of human recombinant soluble ACE2 (hrsACE2) in treating patients with COVID-19 or for constructing genetically modified SARS-CoV-2 infection models promoting vaccines studies. These findings would offer potential benefits for the treatment and prevention of SARS-CoV-2.
Dynamics of SARS-CoV-2-specific antibodies during and after COVID19: Lessons from a biobank in Argentina
Authors: Longueira Yésica , Polo María Laura ,   InViV working group, Turk Gabriela , Laufer Natalia ,   Biobanco de Enfermedades Infecciosas Colección COVID19 working group
Published: February 2021

ABSTRACTBackgroundBiobanks are instrumental for accelerating research. Early in SARS-CoV-2 pandemic, the Argentinean Biobank of Infectious Diseases (BBEI) initiated the COVID19 collection and started its characterization.MethodsBlood samples from subjects with confirmed SARS-CoV-2 infection either admitted to health institutions or outpatients, were enrolled. Highly exposed seronegative individuals, were also enrolled. Longitudinal samples were obtained in a subset of donors, including persons who donated plasma for therapeutic purposes (plasma donors). SARS-CoV-2-specific IgM and IgG levels, IgG titers and IgG viral neutralization capacity were determined.FindingsOut of 825 donors, 57.1% were females and median age was 41 years (IQR 32-53 years). Donors were segregated as acute or convalescent donors, and mild versus moderate/severe disease donors. Seventy-eight percent showed seroconversion to SARS-CoV-2 specific antibodies. Specific IgM and IgG showed comparable positivity rates in acute donors. IgM detectability rate declined in convalescent donors while IgG detectability remained elevated in early (74,8%) and late (83%) convalescent donors. Among donors with follow-up samples, IgG levels seemed to decline more rapidly in plasma donors. IgG levels were higher with age, disease severity, number of symptoms, and was more durable in moderate/severe disease donors. Levels and titers of anti-spike/RBD IgG strongly correlated with neutralization activity against WT virus.InterpretationThe BBEI-COVID19 collection served a dual role in this SARS-CoV-2 global crisis. First, it feed researchers and developers transferring samples and data to fuel research projects. Second, it generated highly needed local data to understand and frame the regional dynamics of the infection.FundingThis work was supported by a grant from the Agencia Nacional de Promoción de la Investigación, el Desarrollo Tecnológico y la Innovación (Agencia I+D+i) from Argentina through an extraordinary funding opportunity to improve the national response to COVID19 (Proyecto COVID N° 11, IP 285).
Standard and anomalous waves of COVID-19: A multiple-wave growth model for epidemics
Authors: Vasconcelos Giovani L. , Brum Arthur A. , Almeida Francisco A. G. , Macêdo Antônio M. S. , Duarte-Filho Gerson C. , Ospina Raydonal 
Published: February 2021

ABSTRACTWe apply a generalized logistic growth model, with time dependent parameters, to describe the fatality curves of the COVID-19 disease for several countries that exhibit multiple waves of infections. In the case of two waves only, the model parameters vary as a function of time according to a logistic function, whose two extreme values, i.e., for early and late times, characterize the first and second waves, respectively. For the multiple-wave model, the time-dependency of the parameters is likewise described by a multi-step logistic function with N intermediate plateaus, representing the N waves of the epidemic. We show that the theoretical curves are in excellent agreement with the empirical data for all countries considered here, namely: Brazil, Canada, Germany, Iran, Italy, Japan, Mexico, South Africa, Sweden, and US. The model also allows for predictions about the time of occurrence and severity of the subsequent waves. It is shown furthermore that the subsequent waves of COVID-19 can be generically classified into two main types, namely, standard and anomalous waves, according as to whether a given wave starts well after or well before the preceding one has subsided, respectively.
Site-specific decrease in cortical reactivity during sensory trick in cervical dystonia patients
Authors: Thirugnanasambandam Nivethida , Singh Shivangi , Cho Hyun Joo , Shitara Hitoshi , Panyakaew Pattamon , Lee Sang Wook , Hallett Mark 
Published: February 2021

AbstractBackgroundSensory tricks (SeT) are various maneuvers that can alleviate dystonic contractions and are a characteristic feature of cervical dystonia (CD). The neurophysiology underlying SeT, however, remains largely unknown. Reducing the abnormal cortical facilitation and modulating the abnormal cortical and subcortical oscillatory activity are mechanisms that have been proposed. The supplementary motor area (SMA) and primary sensorimotor cortices are thought to be relevant to this phenomenon.ObjectiveIn the current study, using concurrent EEG recording during transcranial magnetic stimulation (TMS) of the SMA and primary motor cortex (M1), we aimed at determining the changes in cortical reactivity and oscillatory changes induced by SeT.MethodsWe recruited 13 patients with CD who exhibited SeT and equal number of age- and gender-matched healthy controls. Single TMS pulses were delivered over the SMA and M1 either at rest or during SeT. 32-channel EEG was recorded, and TMS-evoked potentials (TEP) were obtained. Further, time-frequency analysis was performed on the induced data. Correlation analysis for significant neurophysiological parameters was done with clinical measures.ResultsWe found that SeT induced a significant decrease in the amplitude of TEP elicited from M1 stimulation at ∼210-260ms in patients, which correlated with symptom duration. Post hoc analysis of EMG activity in the neck muscles revealed that this effect on TEP was present only in the subset of patients with effective SeT.ConclusionOur results suggest that SeT reduces cortical reactivity over M1 approximately 200ms after stimulation. This adds support to the idea that reduced cortical facilitation underlies the phenomenon.
Improving the Prediction of Clinical Success Using Machine Learning
Authors: Munos Bernard , Niederreiter Jan , Riccaboni Massimo 
Published: February 2021

AbstractIn pharmaceutical research, assessing drug candidates’ odds of success as they move through clinical research often relies on crude methods based on historical data. However, the rapid progress of machine learning offers a new tool to identify the more promising projects. To evaluate its usefulness, we trained and validated several machine learning algorithms on a large database of projects. Using various project descriptors as input data we were able to predict the clinical success and failure rates of projects with an average balanced accuracy of 83% to 89%, which compares favorably with the 56% to 70% balanced accuracy of the method based on historical data. We also identified the variables that contributed most to trial success and used the algorithm to predict the success (or failure) of assets currently in the industry pipeline. We conclude by discussing how pharmaceutical companies can use such model to improve the quantity and quality of their new drugs, and how the broad adoption of this technology could reduce the industry’s risk profile with important consequences for industry structure, R&D investment, and the cost of innovation
A cautionary note on recall vaccination in ex-COVID-19 subjects
Authors: Levi Riccardo , Azzolini Elena , Pozzi Chiara , Ubaldi Leonardo , Lagioia Michele , Mantovani Alberto , Rescigno Maria 
Published: February 2021

AbstractCurrently approved COVID-19 vaccines based on mRNA or adenovirus require a first jab followed by recall immunization. There is no indication as to whether individuals who have recovered from COVID-19 should be vaccinated, and if so, if they should receive one or two vaccine doses. Here, we tested the antibody response developed after the first dose of the mRNA based vaccine encoding the SARS-CoV-2 full-length spike protein (BNT162b2) in 124 healthcare professionals of which 57 had a previous history of COVID-19 (ExCOVID). Post-vaccine antibodies in ExCOVID individuals increase exponentially within 7-15 days after the first dose compared to naïve subjects (p<0.0001). We developed a multivariate Linear Regression (LR) model with l2 regularization to predict the IgG response for SARS-COV-2 vaccine. We found that the antibody response of ExCOVID patients depends on the IgG pre-vaccine titer and on the symptoms that they developed during the disorder, with anosmia/dysgeusia and gastrointestinal disorders being the most significantly positively correlated in the LR. Thus, one vaccine dose is sufficient to induce a good antibody response in ExCOVID subjects. This poses caution for ExCOVID subjects to receive a second jab both because they may have a overreaction of the inflammatory response and also in light of the current vaccine shortage.
A claims-based score for the prediction of bleeding in a contemporary cohort of patients receiving oral anticoagulation for venous thromboembolism
Authors: Alonso Alvaro , Norby Faye L. , MacLehose Richard F. , Zakai Neil A. , Walker Rob F. , Adam Terrence J. , Lutsey Pamela L. 
Published: February 2021

ABSTRACTBackgroundCurrent scores for bleeding risk assessment in patients with venous thromboembolism (VTE) undergoing oral anticoagulation (OAC) have limited predictive capacity. We developed and internally validated a bleeding prediction model using healthcare claims data.Methods and ResultsWe selected patients with incident VTE in the 2011-2017 MarketScan databases initiating OAC. Hospitalized bleeding events were identified using validated algorithms in the 180 days after VTE diagnosis. We evaluated demographic factors, comorbidities, and medication use prior to OAC initiation as potential predictors of bleeding using stepwise selection of variables in Cox models ran on 1000 bootstrap samples of the patient population. Variables included in >60% of all models were selected for the final analysis. We internally validated the model using bootstrapping and correcting for optimism. We included 165,434 VTE patients initiating OAC, of which 2,294 had a bleeding event. After undergoing the variable selection process, the final model included 20 terms (15 main effects and 5 interactions). The c-statistic for the final model was 0.68 (95% confidence interval [CI] 0.67-0.69). The internally validated c-statistic corrected for optimism was 0.68 (95%CI 0.67-0.69). For comparison, the c-statistic of the HAS-BLED score in this population was 0.62 (95%CI 0.61-0.63).ConclusionWe have developed a novel model for bleeding prediction in VTE using large healthcare claims databases. Performance of the model was moderately good, highlighting the urgent need to identify better predictors of bleeding to inform treatment decisions.
One Year of Evidence on Mental Health Disorders in China during the COVID-19 Crisis - A Systematic Review and Meta-Analysis
Authors: Chen Xi , Chen Jiyao , Zhang Meimei , Chen Richard Z. , Dong Rebecca Kechen , Dong Zhe , Ye Yingying , Tong Lingyao , Chen Bryan Z. , Zhao Ruiying , Cao Wenrui , Li Peikai , Zhang Stephen X. 
Published: February 2021

ABSTRACTThis paper provides a systematic review and meta-analysis on the prevalence rate of mental health issues of general population, general and frontline healthcare workers (HCWs) in China over one year of the COVID-19 crisis. We systematically searched PubMed, Embase, Web of Science, and Medrxiv at November 16th, 2020, pooled data using random-effects meta-analyses to estimate the prevalence rates, and ran meta-regression to tease out the heterogeneity. The meta-regression results uncovered several predictors of the prevalence rates, including severity, type of mental issues, population, sampling location, and study quality. Pooled prevalence rates are significantly different from, yet largely between, the findings of previous meta-analyses, suggesting the results of our larger study are consistent with yet more accurate than the findings of the smaller, previous meta-analyses. The prevalence rates of distress and insomnia and those of frontline HCWs are higher suggest future research and interventions should pay more attention to those mental outcomes and populations. Our findings suggest a need to examine the prevalence rates at varying levels of severity. The one-year cumulative evidence on sampling locations (Wuhan vs. non-Wuhan) corroborates the typhoon eye effect theory.Trial registrationCRD4202022059