bluuebunny/crossref_metadata_2025_split huggingface dataset:
The maladaptive vascular response in COVID-19 acute respiratory distress syndrome and recovery
Authors: Price David R. , Benedetti Elisa , Hoffman Katherine L. , Gomez-Escobar Luis , Alvarez-Mulett Sergio , Capili Allyson , Sarwath Hina , Parkhurst Christopher N. , Lafond Elyse , Weidman Karissa , Ravishankar Arjun , Cheong Jin Gyu , Batra Richa , Büyüközkan Mustafa , Chetnik Kelsey , Easthausen Imaani , Schenck Edward J. , Racanelli Alexandra C. , Reed Hasina Outtz , Laurence Jeffrey C. , Josefowicz Steven Zvi , Lief Lindsay , Choi Mary E. , Rafii Shahin , Schmidt Frank , Borczuk Alain C. , Krumsiek Jan , Choi Augustine M.K. 
Published: May 2021

ABSTRACTVascular injury is a menacing element of acute respiratory distress syndrome (ARDS) pathogenesis. To better understand the role of vascular injury in COVID-19 ARDS, we used lung autopsy immunohistochemistry and blood proteomics from COVID-19 subjects at distinct timepoints in disease pathogenesis, including a hospitalized cohort at risk of ARDS development (“at risk”, N=59), an intensive care unit cohort with ARDS (“ARDS”, N=31), and a cohort recovering from ARDS (“recovery”, N=12). COVID-19 ARDS lung autopsy tissue revealed an association between vascular injury and platelet-rich microthrombi. This link guided the derivation of a protein signature in the at risk cohort characterized by lower expression of vascular proteins in subjects who died, an early signal of vascular limitation termed the maladaptive vascular response. These findings were replicated in COVID-19 ARDS subjects, as well as when bacterial and influenza ARDS patients (N=29) were considered, hinting at a common final pathway of vascular injury that is more disease (ARDS) then cause (COVID-19) specific, and may be related to vascular cell death. Among recovery subjects, our vascular signature identified patients with good functional recovery one year later. This vascular injury signature could be used to identify ARDS patients most likely to benefit from vascular targeted therapies.
Research priorities for lower limb amputation in patients with vascular disease
Authors: Bosanquet DC , Nandhra S , Wong KHF , Long J , Chetter I , Hinchliffe RJ 
Published: May 2021

AbstractIntroductionLower limb amputation is a life-changing event for patients and can be associated with high mortality and morbidity rates. Research into this critical part of vascular surgery is limited. The Vascular Society of Great Britain and Ireland (VSGBI) in partnership with the James Lind Alliance (JLA) process, aimed to identify and develop key research priorities for amputation.MethodsA modified JLA Priority Setting Partnership was undertaken, encompassing all vascular practice. Two separate Delphi processes to identify research topics were undertaken with healthcare professionals, patients and carers, led by the VSGBI. The priorities were then ranked by the same participants and amalgamated to produce a list for final prioritisation. The final consensus meeting was attended by patients, carers and healthcare professionals from a variety of backgrounds involved in the care of people with amputation. Using a nominal group technique, the top ten research priorities were identified.ResultsA total of 481 clinicians submitted 1231 research questions relating to vascular surgery in general. 63 amputation-specific research questions were combined into 5 final clinical questions. 373 patients or carers submitted 582 research questions related to vascular surgery in general. Nine amputation-specific research questions were identified after combining similar questions. Amalgamating both the clinician and patient questions, 12 questions were discussed at the final prioritisation meeting and the top 10 identified. These related to amputation prevention, supporting rehabilitation, improving clinical outcomes following amputation (preventing/treating pain including phantom limb pain and improving wound healing) and research into information provision for patients undergoing amputation.ConclusionThe top 10 research priority areas in vascular amputation provide guidance for researchers, clinicians, and funders on the direction of future research questions that are important to both healthcare professionals and patients.
COVID-19 Associated Pulmonary Aspergillosis: Systematic Review and Patient-Level Meta-analysis
Authors: Kariyawasam Ruwandi M. , Dingle Tanis C. , Kula Brittany E. , Sligl Wendy I. , Schwartz Ilan S. 
Published: May 2021

AbstractRationalePulmonary aspergillosis may complicate COVID-19 and contribute to excess mortality in intensive care unit (ICU) patients. The incidence is unclear because of discordant definitions across studies.ObjectiveWe sought to review the incidence, diagnosis, treatment, and outcomes of COVID-19-associated pulmonary aspergillosis (CAPA), and compare research definitions.MethodsWe systematically reviewed the literature for ICU cohort studies and case series including ≥ patients with CAPA. We calculated pooled incidence. Patients with sufficient clinical details were reclassified according to 4 standardized definitions (Verweij, White, Koehler, and Bassetti).MeasurementsCorrelations between definitions were assessed with Spearman’s rank test. Associations between antifungals and outcome were assessed with Fisher’s Exact test.Main Results38 studies (35 cohort studies and 3 case series) were included. Among 3,297 COVID-19 patients in ICU cohort studies, 313 were diagnosed with CAPA (pooled incidence 9.5%). 197 patients had patient-level data allowing reclassification. Definitions had limited correlation with one another (ρ=0.330 to 0.621, p<0.001). 38.6% of patients reported to have CAPA did not fulfil any research definitions. Patients were diagnosed after a median of 9 days (interquartile range 5-14) in ICUs. Tracheobronchitis occured in 5.3% of patients examined with bronchoscopy. The mortality rate (50.0%) was high, irrespective of antifungal use (p=0.28); this remained true even when the analysis was restricted to patients meeting standardized definitions for CAPA.ConclusionsThe reported incidence of CAPA is exaggerated by use of non-standard definitions. Further research should focus on identifying patients likely to benefit from antifungals.
Combining serological assays and official statistics to describe the trajectory of the COVID-19 pandemic: results from the EPICOVID19-RS study in Rio Grande do Sul (Southern Brazil)
Authors: Hartwig Fernando P. , Vidaletti Luís Paulo , Barros Aluísio J. D. , Victora Gabriel D. , Menezes Ana M. B. , Mesenburg Marilia A. , Horta Bernardo L. , Silveira Mariângela F. , Victora Cesar G. , Hallal Pedro C. , Struchiner Claudio J. 
Published: May 2021

ABSTRACTBackgroundThe EPICOVID19-RS study conducted 10 population-based surveys in Rio Grande do Sul (Southern Brazil), starting early in the epidemic. The sensitivity of the rapid point-of-care test used in the first eight surveys has been shown to decrease over time after some phases of the study were concluded. The 9th survey used both the rapid test and an enzyme-linked immunosorbent assay (ELISA) test, which has a higher and stable sensitivity.MethodsWe provide a theoretical justification for a correction procedure of the rapid test estimates, assess its performance in a simulated dataset and apply it to empirical data from the EPICOVID19-RS study. COVID-19 deaths from official statistics were used as an indicator of the temporal distribution of the epidemic, under the assumption that fatality is constant over time. Both the indicator and results from the 9th survey were used to calibrate the temporal decay function of the rapid test’s sensitivity from a previous validation study, which was used to estimate the true sensitivity in each survey and adjust the rapid test estimates accordingly.ResultsSimulations corroborated the procedure is valid. Corrected seroprevalence estimates were substantially larger than uncorrected estimates, which were substantially smaller than respective estimates from confirmed cases and therefore clearly underestimate the true infection prevalence.ConclusionCorrecting biased estimates requires a combination of data and modelling assumptions. This work illustrates the practical utility of analytical procedures, but also the critical need for good quality, populationally-representative data for tracking the progress of the epidemic and substantiate both projection models and policy making.
Evaluation of mRNA-1273 against SARS-CoV-2 B.1.351 Infection in Nonhuman Primates
Authors: Corbett Kizzmekia S. , Werner Anne P. , O’ Connell Sarah , Gagne Matthew , Lai Lilin , Moliva Juan I. , Flynn Barbara , Choi Angela , Koch Matthew , Foulds Kathryn E. , Andrew Shayne F. , Flebbe Dillon R. , Lamb Evan , Nurmukhambetova Saule T. , Provost Samantha J. , Bock Kevin W. , Minai Mahnaz , Nagata Bianca M. , Van Ry Alex , Flinchbaugh Zackery , Johnston Timothy S. , Mokhtari Elham Bayat , Mudvari Prakriti , Henry Amy R. , Laboune Farida , Chang Becky , Porto Maciel , Wear Jaclyn , Alvarado Gabriela S. , Boyoglu-Barnum Seyhan , Todd John-Paul M. , Bart Bridget , Cook Anthony , Dodson Alan , Pessaint Laurent , Steingrebe Katelyn , Elbashir Sayda , Andersen Hanne , Wu Kai , Edwards Darin K. , Kar Swagata , Lewis Mark G. , Bortiz Eli , Moore Ian N. , Carfi Andrea , Suthar Mehul S. , McDermott Adrian , Roederer Mario , Nason Martha C. , Sullivan Nancy J. , Douek Daniel C. , Graham Barney S. , Seder Robert A. 
Published: May 2021

ABSTRACTBackgroundVaccine efficacy against the B.1.351 variant following mRNA-1273 vaccination in humans has not been determined. Nonhuman primates (NHP) are a useful model for demonstrating whether mRNA-1273 mediates protection against B.1.351.MethodsNonhuman primates received 30 or 100 µg of mRNA-1273 as a prime-boost vaccine at 0 and 4 weeks, a single immunization of 30 µg at week 0, or no vaccine. Antibody and T cell responses were assessed in blood, bronchioalveolar lavages (BAL), and nasal washes. Viral replication in BAL and nasal swabs were determined by qRT-PCR for sgRNA, and histopathology and viral antigen quantification were performed on lung tissue post-challenge.ResultsEight weeks post-boost, 100 µg x2 of mRNA-1273 induced reciprocal ID50 neutralizing geometric mean titers against live SARS-CoV-2 D614G and B.1.351 of 3300 and 240, respectively, and 430 and 84 for the 30 µg x2 group. There were no detectable neutralizing antibodies against B.1351 after the single immunization of 30 µg. On day 2 following B.1.351 challenge, sgRNA in BAL was undetectable in 6 of 8 NHP that received 100 µg x2 of mRNA-1273, and there was a ∼2-log reduction in sgRNA in NHP that received two doses of 30 µg compared to controls. In nasal swabs, there was a 1-log10 reduction observed in the 100 µg x2 group. There was limited inflammation or viral antigen in lungs of vaccinated NHP post-challenge.ConclusionsImmunization with two doses of mRNA-1273 achieves effective immunity that rapidly controls lower and upper airway viral replication against the B.1.351 variant in NHP.
Evidence for Deleterious Antigenic Imprinting in SARS-CoV-2 Immune Response
Authors: Sen Sanjana R. , Sanders Emily C. , Santos Alicia M. , Bhuvan Keertna , Tang Derek Y. , Gelston Aidan A. , Miller Brian M. , Ricks-Oddie Joni L. , Weiss Gregory A. 
Published: May 2021

AbstractA previous report demonstrated the strong association between the presence of antibodies binding to an epitope region from SARS-CoV-2 nucleocapsid, termed Ep9, and COVID-19 disease severity. Patients with anti-Ep9 antibodies (Abs) had hallmarks of antigenic imprinting (AIM), including early IgG upregulation and cytokine-associated injury. Thus, the immunological memory of a previous infection was hypothesized to drive formation of suboptimal anti-Ep9 Abs in severe COVID-19 infections. This study identifies a putative primary antigen capable of stimulating production of cross-reactive, anti-Ep9 Abs. Binding assays with patient blood samples directly show cross-reactivity between Abs binding to Ep9 and only one bioinformatics-derived, homologous potential antigen, a sequence derived from the neuraminidase protein of H3N2 Influenza A virus. This cross-reactive binding is highly influenza strain specific and sensitive to even single amino acid changes in epitope sequence. The neuraminidase protein is not present in the influenza vaccine, and the anti-Ep9 Abs likely resulted from the widespread influenza infection in 2014. Therefore, AIM from a previous infection could underlie some cases of COVID-19 disease severity.ImportanceInfections with SARS-COV-2 result in diverse disease outcomes, ranging from asymptomatic to fatal. The mechanisms underlying different disease outcomes remain largely unexplained. Previously, our laboratory identified a strong association between the presence of an antibody and increased disease severity in a subset of COVID-19 patients. Here, we report that this severity-associated antibody cross-reacts with viral proteins from an influenza A viral strain from 2014. Therefore, we speculate that antibodies generated against previous infections, like the 2014 influenza A, play a significant role in directing some peoples’ immune responses against SARS-COV-2. Such understanding of the sources and drivers of COVID-19 disease severity can help early identification and pre-emptive treatment.
Smartwatch Facilitated Remote Health Care for Patients Undergoing Transcatheter Aortic Valve Replacement Amid COVID-19 Pandemic
Authors: Liu Xianbao , Fan Jiaqi , Guo Yuchao , Dai Hanyi , Xu Jianguo , Wang Lihan , Hu Po , Lin Xinping , Li Cheng , Zhou Dao , Li Huajun , Wang Jian’an 
Published: May 2021

ABSTRACTBACKGROUNDThe novel coronavirus disease-2019 (COVID-19 Pandemic) has brought difficulties to the management of patients undergoing transcatheter aortic valve replacement (TAVR).OBJECTIVESThis prospective, observational cohort study sought to evaluate the feasibility of a novel, virtual, and remote health care strategy for TAVR patients with smart wearable devices.METHODSA total of 100 consecutive severe aortic stenosis patients who underwent elective transfemoral TAVR were enrolled and each received a HUAWEI smartwatch at least one day before TAVR. Vital signs were continuously tracked and recorded. Single lead electrocardiogram (ECG) was recorded periodically after TAVR. A designated heart team member was to provide remote data-assisted health care to address the medical demand.RESULTSThirty-eight cardiac events were reported in 34 patients after discharge, with most of the events (76.0%) were detected and confirmed by the smartwatch. Six patients were advised and readmitted to the hospital for arrhythmia events, among whom, four received pacemaker implantations. The remaining 28 (82.4%) patients received telemedicine monitoring instead of face-to-face clinical visits, and three of them received new medication treatment under a doctor’s online guidance of doctors. New-onset LBBB was found in 48 patients with transient and recovered spontaneously in 30 patients, while new-onset atrial fibrillation in 4 patients. There were no significant differences in the average weekly heart rates, the ratio of abnormal or low oxygen saturation when compared with the baseline. The average daily steps increased over time significantly (baseline, 870±1353 steps; first week, 1986±2406 steps; second week, 2707±2716 steps; third week, 3059±3036 steps; fourth week, 3678±3485 steps, p < 0.001).CONCLUSIONSSmartwatch can facilitate remote health care for patients undergoing TAVR during COVID-19 and enables a novel remote follow-up strategy. The majority of cardiac clinical events that occurred within 30-day follow-up were detected by the smartwatch, mainly due to the record of conduction abnormality. (SMART Watch Facilitated Early Discharge in Patients undergoing Transcatheter Aortic Valve Replacement, NCT04454177).
Dynamic magnetic resonance imaging of muscle contraction in facioscapulohumeral muscular dystrophy
Authors: Deligianni Xeni , Santini Francesco , Paoletti Matteo , Solazzo Francesca , Bergsland Niels , Savini Giovanni , Faggioli Arianna , Germani Giancarlo , Monforte Mauro , Ricci Enzo , Tasca Giorgio , Pichiecchio Anna 
Published: May 2021

ABSTRACTBackgroundQuantitative muscle MRI (water-T2 and fat mapping) is being increasingly used to assess disease involvement in muscle disorders, while imaging techniques for assessment of the dynamic and elastic muscle properties have not been translated yet into clinics.MethodsHere, we quantitatively characterized muscle deformation (strain) in patients affected by facioscapulohumeral muscular dystrophy (FSHD), a prevalent muscular dystrophy, by applying dynamic MRI synchronized with neuromuscular electrical stimulation (NMES). We evaluated the quadriceps muscles in 34 ambulatory patients and 12 healthy controls, at 6 month intervals.ResultsWe found that while a subgroup of patients behaved similarly to controls, for another subgroup the strain significantly decreased over time (50% over 1.5 years). Dynamic MRI parameters did not correlate with quantitative MRI.ConclusionsIn conclusion, our results suggest that the evaluation of muscle ability to contract by NMES-MRI could be used to explore the elastic properties and monitor muscle involvement in FSHD and other neuromuscular disorders.
Emergence of SARS-CoV-2 variants of concern in the pediatric population of the United States
Authors: Bard Jennifer Dien , Bootwalla Moiz , Leber Amy , Planet Paul , Moustafa Ahmed M. , Harris Rebecca , Chen Pei Ying , Shen Lishuang , Ostrow Dejerianne , Maglinte Dennis , Flores Jessica , Somak Roy , Ranganathan Sarangarajan , Perlman Elizabeth , Zheng Xiaotian , Selvarangan Rangaraj , Banerjee Dithi , Delaney Meghan , Campos Joseph , Michael Drew G. , Vilain Eric , LoTempio Jonathan , Dunn James , Jung Sarah , Dominguez Samuel R. , Judkins Alexander R. , Gai Xiaowu 
Published: May 2021

AbstractThe evolution of SARS-CoV2 virus has led to the emergence of variants of concern (VOC). Children, particularly <12 years old not yet eligible for vaccines, continue to be important reservoirs of SARS-CoV-2 yet VOC prevalence data in this population is lacking. We report data from a genomic surveillance program that includes 9 U.S. children’s hospitals. Analysis of SARS-CoV-2 genomes from 2119 patients <19 years old between 03/20 to 04/21 identified 252 VOCs and 560 VOC signature mutations, most from 10/20 onwards. 75.00% of the VOC signature mutations detected were in children <12 years old, including 32 cases of B.1.1.7 and 346 of B.1.419/B.1417. From 02/21 to 04/21, B.1.1.7 prevalence increased from 1.28% to 72.22% corresponding with the decline of B.1419/B.1417 from 52.57% to 5.56% at one institution. There continues to be a need for ongoing genomic surveillance, particularly among young children who will be the last groups to be vaccinated.
MLC Seq: De novo sequencing of full-length tRNA isoforms by mass ladder complementation
Authors: Yuan Xiaohong , Su Yue , Zhang Xudong , Turkel Spencer J. , Shi Shundi , Wang Xuanting , Choi Eun-Jin , Wu Wenzhe , Liu Haichuan , Viner Rosa , Russo James J. , Li Wenjia , Bao Xiaoyong , Chen Qi , Zhang Shenglong 
Published: May 2021

AbstracttRNAs can exist in distinct isoforms because of different chemical modifications, which confounds attempts to accurately sequence individual tRNA species using next generation sequencing approaches or to quantify different RNA modifications at specific sites on a tRNA strand. Herein, we develop a mass spectrometric (MS) ladder complementation sequencing (MLC-Seq), allowing for direct and simultaneous sequencing of full-length tRNA molecules, including those with low abundance. MLC-seq is achieved by improved instrumentation, and advanced algorithms that identify each tRNA species and related isoforms in an RNA mixture, and assemble full MS ladders from partial ladders with missing ladder components. Using MLC-Seq, we successfully obtained the sequence of tRNA-Phe from yeast and tRNA-Glu from mouse hepatocytes, and simultaneously revealed new tRNA isoforms derived from nucleotide modifications. Importantly, MLC-Seq pinpointed the location and stoichiometry changes of RNA modifications in tRNA-Glu upon the treatment of dealkylated enzyme AlkB, which confirmed its known enzymatic activity and suggested previously unidentified effects in RNA editing.
Genetic Dissection of the RNA Polymerase II Transcription Cycle
Authors: Chou Shao-Pei , Alexander Adriana K. , Rice Edward J. , Choate Lauren A , Cohen Paula E , Danko Charles G. 
Published: May 2021

AbstractHow DNA sequence affects the dynamics and position of RNA Polymerase II (Pol II) during transcription remains poorly understood. Here we used naturally occurring genetic variation in F1 hybrid mice to explore how DNA sequence differences affect the genome-wide distribution of Pol II. We measured the position and orientation of Pol II in eight organs collected from heterozygous F1 hybrid mice using ChRO-seq. Our data revealed a strong genetic basis for the precise coordinates of transcription initiation and promoter proximal pause, allowing us to redefine molecular models of core transcriptional processes. Our results implicate the strength of base pairing between A-T or G-C dinucleotides as key determinants to the position of Pol II initiation and pause. We report evidence that initiation site selection follows a stochastic process similar to brownian motion along the DNA template. We found widespread differences in the position of transcription termination, which impact the primary structure and stability of mature mRNA. Finally, we report evidence that allelic changes in transcription often affect mRNA and ncRNA expression across broad genomic domains. Collectively, we reveal how DNA sequences shape core transcriptional processes at single nucleotide resolution in mammals.
TIR signaling promotes the interactions between EDS1/PAD4 and ADR1-L1 and oligomerization of ADR1-L1
Authors: Wu Zhongshou , Tian Lei , Liu Xueru , Zhang Yuelin , Li Xin 
Published: May 2021

AbstractBoth plants and animals use nucleotide-binding leucine-rich repeat (NLR) immune receptors to perceive pathogens and trigger immunity. Toll/interleukin-1 receptor (TIR)-type plant NLRs (TNLs) require the lipase-like protein family members Enhanced Disease Susceptibility 1 (EDS1)/ Phytoalexin Deficient 4 (PAD4)/ Senescence-Associated Gene 101 (SAG101) and helper NLRs (hNLRs) for downstream signaling, the biochemical mechanisms of which remain unclear. Here, we report that TIR signaling promotes the association of EDS1 and PAD4 with hNLR ACTIVATED DISEASE RESISTANCE 1-Like 1 (ADR1-L1), and the oligomerization of ADR1-L1s for downstream immune activation and cell death.
Presynaptic HCN channels constrain GABAergic synaptic transmission in pyramidal cells of the medial prefrontal cortex
Authors: Cai Wei , Liu Shu-Su , Li Bao-Ming , Zhang Xue-Han 
Published: May 2021

AbstractHyperpolarization-activated cyclic nucleotide-gated (HCN) channels are widely expressed in neurons in the central nervous system. It has been documented that HCN channels regulate the intrinsic excitability of pyramidal cells in the medial prefrontal cortex (mPFC) of rats. Here, we report that HCN channels limited GABAergic transmission onto pyramidal cells in the mPFC. Pharmacological block of HCN channels resulted in a significant increase in the frequency of both spontaneous and miniature inhibitory postsynaptic currents (IPSCs) in mPFC pyramidal cells. Such facilitation effect on mIPSCs required presynaptic Ca2+ influx and reversed by high-dose cAMP. Such facilitation did not exist in the presence of the T-type Ca2+ channel selective blockers. Immunofluorescence staining revealed that HCN channels expressed in presynaptic GABAergic terminals, as well as in both soma and neurite of parvalbumin-expressing (PV-expressing) basket cells in the mPFC. The present results indicate that HCN channels in GABAergic interneurons, most likely PV-expressing basket cells, constrain inhibitory control over layer 5-6 pyramidal cells through restricting presynaptic Ca2+ entry.