bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mitochondrial induced T cell apoptosis and aberrant myeloid metabolic programs define distinct immune cell subsets during acute and recovered SARS-CoV-2 infection
Authors: Thompson Elizabeth A. , Cascino Katherine , Ordonez Alvaro A. , Zhou Weiqiang , Vaghasia Ajay , Hamacher-Brady Anne , Brady Nathan R. , Sun Im-Hong , Wang Rulin , Rosenberg Avi Z. , Delannoy Michael , Rothman Richard , Fenstermacher Katherine , Sauer Lauren , Shaw-Saliba Kathyrn , Bloch Evan M. , Redd Andrew D. , Tobian Aaron AR , Horton Maureen , Smith Kellie , Pekosz Andrew , D’Alessio Franco R. , Yegnasubramanian Srinivasan , Ji Hongkai , Cox Andrea L. , Powell Jonathan D. 
Published: September 2020

AbstractBy interrogating metabolic programs in the peripheral blood mononuclear cells (PBMC) of acutely infected COVID-19 patients, we identified novel and distinct immune cell subsets Our studies identified a non-clonal population of T cells expressing high H3K27me3 and voltage-dependent anion channel (VDAC) with mitochondrial dysfunction and increased susceptibility to cell death. Characterized by dysmorphic mitochondria and increased cytoplasmic cytochromec, apoptosis of these cells was inhibited by preventing VDAC aggregation or blocking caspase activation. Further, we observed a marked increase in Hexokinase II+polymorphonuclear-myeloid derived suppressor cells (PMN-MDSC). While PMN-MDSC were also found in the PBMC of patients with other viral infections, the Hexokinase II+PMN-MDSC were found exclusively in the acute COVID-19 patients with moderate or severe disease. Finally, we identified a population of monocytic MDSC (M-MDSC) expressing high carnitine palmitoyltransferase I (CPT1a) and VDAC, which were present in the PBMC of the acute COVID-19 patients, but not recovered COVID-19 patients and whose presence correlated with severity of disease. Overall, these unique populations of immune cells provide insight into the pathogenesis of SARS-CoV-2 infection and provide a means to predict and track disease severity as well as an opportunity to design and evaluate novel therapeutic regimens.One Sentence SummaryMetabolic programs define unique immune cells among COVID-19 patients with severe diease.
Biochemical and Biophysical Characterization of Respiratory Secretions in Severe SARS-CoV-2 (COVID-19) Infections
Authors: Kratochvil Michael J. , Kaber Gernot , Cai Pamela C. , Burgener Elizabeth B. , Barlow Graham L. , Nicolls Mark R. , Ozawa Michael G. , Regula Donald P. , Pacheco-Navarro Ana E. , Milla Carlos E. , Nagy Nadine , Yang Samuel ,   Stanford COVID-19 Biobank Study Group, Rogers Angela J. , Spakowitz Andrew J. , Heilshorn Sarah C. , Bollyky Paul L. 
Published: September 2020

AbstractThick, viscous respiratory secretions are a major pathogenic feature of COVID-19 disease, but the composition and physical properties of these secretions are poorly understood. We characterized the composition and rheological properties (i.e. resistance to flow) of respiratory secretions collected from intubated COVID-19 patients. We found the percent solids and protein content are all greatly elevated in COVID-19 compared to heathy control samples and closely resemble levels seen in cystic fibrosis (CF), a genetic disease known for thick, tenacious respiratory secretions. DNA and hyaluronan are major components of respiratory secretions in COVID-19 and are likewise abundant in cadaveric lung tissues from these patients. COVID-19 secretions exhibited heterogeneous rheological behaviors with thicker samples showing increased sensitivity to DNase and hyaluronidase treatment. These results highlight the dramatic biophysical properties of COVID-19 respiratory secretions and suggest that DNA and hyaluronan may be viable therapeutic targets in COVID-19 infection.
Saliva as a potential clinical specimen for diagnosis of SARS-CoV-2
Authors: Bhattacharya Debdutta , Parai Debaprasad , Rout Usha Kiran , Nanda Rashmi Ranjan , Kanungo Srikanta , Dash Girish Chandra , Palo Subrat Kumar , Giri Sidharth , Choudhary Hari Ram , Kshatri Jaya Singh , Turuk Jyotirmayee , Mishra Bijay Kumar , Dash Saroj , Pati Sanghamitra 
Published: September 2020

AbstractBackgroundIt is almost nine months, still there is no sign to stop the spreading of the COVID-19 pandemic. Rapid and early detection of the virus is the master key to cease the rapid spread and break the human transmission chain. There are very few studies in search of an alternate and convenient diagnostic tool which can substitute nasopharyngeal swab (NPS) specimen for detection of SARS-CoV-2. We aimed to analyse the comparison and agreement between the feasibility of using the saliva in comparison to NPS for diagnosis of SARS-CoV-2.MethodsA total number of 74 patients were enrolled for this study. We analysed and compared the NPS and saliva specimen collected within 48 h after the symptom onset. We used real time quantitative polymerase chain reaction (RT-qPCR), gene sequencing for the detection and determination SARS-CoV-2 specific genes. Phylogenetic tree was constructed to establish the isolation of viral RNA from saliva. We use Bland-Altman model to identify the agreement between two specimens.FindingsThis study shows a lower CTmean value for the detection of SARS-CoV-2 ORF1 gene (27.07; 95% CI, 25.62 to 28.52) in saliva methods than that of NPS (28.24; 95% CI, 26.62 to 29.85) sampling method. Bland-Altman analysis produces relatively smaller bias and high agreement between these specimen tools. Phylogenetic analysis with the RdRp and Spike gene confirmed the presence of SARS-CoV-2 in the saliva samples.InterpretationIn conclusion, our study highlights that saliva represents a promising tool in COVID-19 diagnosis and would reduce the exposure risk of frontline health workers which is one of biggest concern in primary healthcare settings.
A Comparative Study to Find a Suitable Model for an Improved Real-Time Monitoring of The Interventions to Contain COVID-19 Outbreak in The High Incidence States of India
Authors: Amrutha G.S , Sharma Abhibhav , Sharma Anudeepti 
Published: September 2020

AbstractBackgroundOn March 11, 2020, The World Health Organization (WHO) declared coronavirus disease (COVID-19) as a global pandemic. There emerged a need for reliable models to estimate the imminent incidence and overall assessment of the outbreak, in order to develop effective interventions and control strategies. One such vital metrics for monitoring the transmission trends over time is the time-dependent effective reproduction number (Rt). Rt is an estimate of secondary cases caused by an infected individual at a time t during the outbreak, given that a certain population proportion is already infected. Misestimated Rt is particularly concerning when probing the association between the changes in transmission rate and the changes in the implemented policies. In this paper, we substantiate the implementation of the instantaneous reproduction number (Rins) method over the conventional method to estimate Rt viz case reproduction number (Rins), by unmasking the real-time estimation ability of both methodologies using credible datasets.Materials & MethodsWe employed the daily incidence dataset of COVID-19 for India and high incidence states to estimate Rins and Rcase. We compared the real-time projection obtained through these methods by corroborating those states that are containing high number of COVID-19 cases and are conducting high and efficient COVID-19 testing. The Rins and Rcase were estimated using R0 and EpiEstim packages respectively in R software 4.0.0.ResultsAlthough, both the Rins and Rcase. for the selected states were higher during the lockdown phases (March 25 - June 1, 2020) and subsequently stabilizes co-equally during the unlock phase (June 1-August 23, 2020), Rins demonstrated variations in accordance with the interventions while Rcase. remained generalized and under- & overestimated. A larger difference in Rins and Rcase. estimates was also observed for states that are conducting high testing.ConclusionOf the two methods, Rins elucidated a better real-time progression of the COVID-19 outbreak conceptually and empirically, than that of Rcase. However, we also suggest considering the assumptions corroborated in the implementations which may result in misleading conclusions in the real world.
Joint hypermobility and its relevance to common mental illness in adolescents: a population-based longitudinal study
Authors: Eccles Jessica A , Scott Hannah E , Davies Kevin A , Bond Rod , David Anthony S , Harrison Neil A. , Critchley Hugo D 
Published: September 2020

ABSTRACTImportanceDepression and anxiety are common mood disorders that show higher prevalence in adults with joint hypermobility, a consequence of a constitutional variant of connective tissue structure. In adolescents, an association between mood disorder and hypermobility may enhance the potential understanding of risk factors for emotional disorder and provide opportunities for early intervention approaches.ObjectiveTo test the hypothesis that joint hypermobility, a consequence of constitutional variant of connective tissue, is associated with common mental illness in adolescents.DesignThis was a longitudinal prospective study.SettingThe Avon Longitudinal Study of Parents and Children (ALSPAC) is a prospective ongoing general population birth cohort study based in Avon County, England.ParticipantsThe original data set comprised 6105 individuals from the cohort with data available on joint hypermobility at age 14 years; a sub-sample (n=3803) had later psychiatric assessments.Measurement of ExposureJoint hypermobility was measured by physical examination at age 14 and 18 years, using the Beighton ScaleMain Outcome and MeasuresParticipants were assessed at age 18 years. ICD-10 diagnoses of Depression and Anxiety were obtained using the Clinical Interview Schedule-Revised (CIS-R) and levels of anxiety quantified using the Anxiety Sensitivity Index (ASI)ResultsPresence of generalized joint hypermobility (GJH) at age 14 years predicted depression at 18 years in males (Odds Ratio (OR) 2.10; 95%CI, 1.17-3.76) but not females After accounting for missing data it was determined that this relationship was mediated by heart rate, a potential measure of physiological arousal. Symptomatic hypermobility ((GJH plus chronic widespread pain (CWP)) at age 18 years was further associated with the presence of anxiety disorder (OR 3.13; 95% CI 1.52-6.46) and level of anxiety (Beta = 0.056, t(3315)=3.27), depressive disorder (adjusted OR 3.52; 95%CI, 1.67 – 7.40) and degree of psychiatric symptomatology (Beta 0.096, t(2064)=4.38)Conclusions and relevanceGeneralized joint hypermobility and symptomatic hypermobility are associated with common mental disorders in adolescence. Consideration of hypermobility may provide important opportunities for intervention to mitigate psychiatric disorder.KEY POINTSQuestionIs joint hypermobility related to depression and anxiety in adolescence?FindingsIn this longitudinal study presence of generalized joint hypermobility at 14 predicted subsequent adolescent depression in males only and this relationship was mediated by heart rate. At age 18 symptomatic hypermobility was associated with both presence of anxiety and depression and psychiatric symptom severity.MeaningGeneralized joint hypermobility and symptomatic hypermobility are associated with common mental disorders in adolescence.
LOW BIRTH WEIGHT AS A RISK FACTOR FOR SEVERE COVID-19 IN ADULTS
Authors: Crispi Fàtima , Crovetto Francesca , Larroya Marta , Camacho Marta , Tortajada Marta , Sibila Oriol , Badia Joan Ramon , López Marta , Vellvé Kilian , Garcia Ferran , Trilla Antoni , Faner Rosa , Blanco Isabel , Borràs Roger , Agustí Alvar , Gratacós Eduard 
Published: September 2020

ABSTRACTThe identification of factors predisposing to severe COVID-19 in young adults remains partially characterized. Low birth weight (LBW) alters cardiovascular and lung development and predisposes to adult disease. We hypothesized that LBW is a risk factor for severe COVID-19 in non-elderly subjects. We analyzed a prospective cohort of 397 patients (18-70y) with laboratory-confirmed SARS-CoV-2 infection attended in a tertiary hospital, where 15% required admission to Intensive Care Unit (ICU). Perinatal and current potentially predictive variables were obtained from all patients and LBW was defined as birth weight ≤2,500 g. Age (adjusted OR (aOR) 1.04 [1-1.07], P=0.012), male sex (aOR 3.39 [1.72-6.67], P<0.001), hypertension (aOR 3.37 [1.69-6.72], P=0.001), and LBW (aOR 3.61 [1.55-8.43], P=0.003) independently predicted admission to ICU. The area under the receiver-operating characteristics curve (AUC) of this model was 0.79 [95% CI, 0.74-0.85], with positive and negative predictive values of 29.1% and 97.6% respectively. Results were reproduced in an independent cohort, from a web-based survey in 1,822 subjects who self-reported laboratory-positive SARS-CoV-2 infection, where 46 patients (2.5%) needed ICU admission (AUC 0.74 [95% CI 0.68-0.81]). LBW seems to be an independent risk factor for severe COVID-19 in non-elderly adults and might improve the performance of risk stratification algorithms.
Early-life socioeconomic position and the accumulation of health-related deficits by midlife in the 1958 British birth cohort study
Authors: Rogers Nina T , Blodgett Joanna M , Searle Samuel D , Cooper Rachel , Davis Daniel H J , Pinto Pereira Snehal M 
Published: September 2020

AbstractReducing population levels of frailty is an important goal and preventing its development in mid-adulthood could be pivotal. Childhood socioeconomic position (SEP) is associated with a myriad of adult health outcomes but evidence is limited on associations with frailty. Using 1958 British birth cohort data (N=8711), we aimed to: (i) establish the utility of measuring frailty in mid-life, by examining associations between a 34-item frailty index at 50y (FI50y) and mortality over an eight-year follow-up period and (ii) examine associations between early-life SEP and FI50y and investigate whether these associations were explained by adult SEP. Hazard ratios (HRs) for mortality increased with increasing levels of frailty, e.g., HRsex-adjusted was 4.07(95% CI:2.64,6.25) for highest vs. lowest fifth of FI50y. Lower early-life SEP was associated with higher FI50y: per unit decrease in early-life SEP (on a 4-point scale), FI50y increased by 12.7%(10.85%,14.6%) in a model adjusted for early-life covariates. After additional adjustment for adult occupational class and education, the association attenuated to 5.71%(3.71%,7.70%). Findings suggest that early-life SEP is associated with frailty and that adult SEP only partially explains this association. Results highlight the importance of improving socioeconomic circumstances across the life course to reduce inequalities in frailty from mid-adulthood.
Increased rate of joint hypermobility in autism and related neurodevelopmental conditions is linked to dysautonomia and pain
Authors: Csecs Jenny L L , lodice Valeria , Rae Charlotte L , Brooke Alice , Simmons Rebecca , Dowell Nicholas G , Prowse Fenella , Themelis Kristy , Critchley Hugo D , Eccles Jessica A 
Published: September 2020

ABSTRACTObjectiveAutism, attention deficit hyperactivity disorder (ADHD), and tic disorder (Tourette syndrome; TS) are neurodevelopmental conditions that frequently co-occur and impact psychological, social and emotional functioning. Vulnerability to chronic physical symptoms, including fatigue and pain, are also recognised. The expression of joint hypermobility, reflecting a constitutional variant in connective tissue, predicts vulnerability to psychological symptoms alongside recognised physical symptoms. Here, we tested for increased rates of joint hypermobility, autonomic dysfunction and pain in 109 adults with neurodevelopmental diagnoses.MethodRates of generalized joint laxity in those individuals with neurodevelopmental conditions were compared to those in the general population in UK. Levels of orthostatic intolerance and musculoskeletal symptoms were compared to a neurotypical control group.ResultsAdults with neurodevelopmental diagnoses manifest elevated rates of joint hypermobility (50%) compared to the general population rate of 20% and a matched control population of 10%. Odds ratio for hypermobility in individuals with neurodevelopmental diagnoses, compared to the general population was 4.51 (95%CI 2.17-9.37), with greater odds in females rather than males. Neurodevelopmental patients reported significantly more symptoms of orthostatic intolerance and musculoskeletal skeletal pain than controlsConclusionsIn adults with neurodevelopmental conditions, there is a strong link between the expression of joint hypermobility, autonomic dysfunction and pain, more so than in healthy controls. Increased awareness and understanding of this association may enhance the management of core symptoms and allied difficulties including comorbid stress-sensitive physical symptoms.
Predicting morbidity by Local Similarities in Multi-Scale Patient Trajectories
Authors: Carrasco-Ribelles Lucía A , Pardo-Mas Jose Ramón , Tortajada Salvador , Sáez Carlos , Valdivieso Bernardo , García-Gómez Juan M 
Published: September 2020

AbstractHealthcare predictive models generally rely on static snapshots of patient information. Patient Trajectories (PTs) model the evolution of patient conditions over time and are a promising source of information for predicting future morbidities. However, PTs are highly heterogeneous among patients in terms of length and content, so only aggregated versions that include the most frequent events have been studied. Further, the use of longitudinal multiscale data such as integrating EHR coded data and laboratory results in PT models is yet to be explored. Our hypothesis is that local similarities on small chunks of PTs can identify similar patients with respect to their future morbidities. The objectives of this work are (1) to develop a methodology to identify local similarities between PTs prior to the occurrence of morbidities to predict these on new query individuals; and (2) to validate this methodology to impute risk of cardiovascular diseases (CVD) in patients with diabetes.We have proposed a novel formal definition of PTs based on sequences of multi-scale data over time, so each patient has their own PT including every data available in their EHR. Thus, patients do not need to follow partly or completely one pre-defined trajectory built by the most frequent events in a population but having common events with any another patient. A dynamic programming methodology to identify local alignments on PTs for predicting future morbidities is proposed. The proposed methodology for PT definition and the alignment algorithm are generic to be applied on any additional clinical domain. We tested this solution for predicting CVD in patients with diabetes and we achieved a positive predictive value of 0.33, a recall of 0.72 and a specificity of 0.38. Therefore, the proposed solution in the diabetes use case can result of utmost utility to patient screening.HighlightsLocal similarities between patient trajectories can potentially be used to predict morbid conditions.A formal definition of patient trajectories comprising heterogeneous clinical observations, biomedical tests and time gaps is proposed.A novel dynamic programming methodology is proposed to find similar patients based on the Smith-Waterman alignment algorithm and a set of customized scoring matrices.
PreQual: An automated pipeline for integrated preprocessing and quality assurance of diffusion weighted MRI images
Authors: Cai Leon Y. , Yang Qi , Hansen Colin B. , Nath Vishwesh , Ramadass Karthik , Johnson Graham W. , Conrad Benjamin N. , Boyd Brian D. , Begnoche John P. , Beason-Held Lori L. , Shafer Andrea T. , Resnick Susan M. , Taylor Warren D. , Price Gavin R. , Morgan Victoria L. , Rogers Baxter P. , Schilling Kurt G. , Landman Bennett A. 
Published: September 2020

AbstractPurposeDiffusion weighted MRI imaging (DWI) is often subject to low signal-to-noise ratios (SNRs) and artifacts. Recent work has produced software tools that can correct individual problems, but these tools have not been combined with each other and with quality assurance (QA). A single integrated pipeline is proposed to perform DWI preprocessing with a spectrum of tools and produce an intuitive QA document.MethodsThe proposed pipeline, built around the FSL, MRTrix3, and ANTs software packages, performs DWI denoising; inter-scan intensity normalization; susceptibility-, eddy current-, and motion-induced artifact correction; and slice-wise signal drop-out imputation. To perform QA on the raw and preprocessed data and each preprocessing operation, the pipeline documents qualitative visualizations, quantitative plots, gradient verifications, and tensor goodness-of-fit and fractional anisotropy analyses.ResultsRaw DWI data were preprocessed and quality checked with the proposed pipeline and demonstrated improved SNRs; physiologic intensity ratios; corrected susceptibility-, eddy current-, and motion-induced artifacts; imputed signal-lost slices; and improved tensor fits. The pipeline identified incorrect gradient configurations and file-type conversion errors and was shown to be effective on externally available datasets.ConclusionThe proposed pipeline is a single integrated pipeline that combines established diffusion preprocessing tools from major MRI-focused software packages with intuitive QA.
rec-Y2H matrix screening reveals a vast potential for direct protein-protein interactions among RNA binding proteins
Authors: Lang Benjamin , Yang Jae-Seong , Garriga-Canut Mireia , Speroni Silvia , Gili Maria , Hoffmann Tobias , Tartaglia Gian Gaetano , Maurer Sebastian P. 
Published: September 2020

AbstractRNA-binding proteins (RBPs) are crucial factors of post-transcriptional gene regulation and their modes of action are intensely investigated. At the center of attention are RNA motifs that guide where RBPs bind. However, sequence motifs are often poor predictors of RBP-RNA interactionsin vivo. It is hence believed that many RBPs recognize RNAs as complexes, to increase specificity and regulatory possibilities. To probe the potential for complex formation among RBPs, we assembled a library of 978 mammalian RBPs and used rec-Y2H screening to detect direct interactions between RBPs, sampling > 600 K interactions. We discovered 1994 new interactions and demonstrate that interacting RBPs bind RNAs adjacentlyin vivo. We further find that the mRNA binding region and motif preferences of RBPs can deviate, depending on their adjacently binding interaction partners. Finally, we reveal novel RBP interaction networks among major RNA processing steps and show that splicing impairing RBP mutations observed in cancer rewire spliceosomal interaction networks.Graphical abstract