bluuebunny/crossref_metadata_2025_split huggingface dataset:
The soil in our microbial DNA informs about environmental interfaces across host and subsistence modalities
Authors: Schnorr Stephanie L. 
Published: October 2020

In this study, I use microbiome datasets from global soil samples and diverse hosts to learn whether soil microbial taxa are found in host microbiomes, and whether these observations fit the narrative that environmental interaction influences human microbiomes. A major motivation for conducting host-associated microbiome research is to contribute towards understanding how the environment may influence host physiology. The microbial molecular network is considered a key vector by which environmental traits may be transmitted to the host. Research on human evolution seeks evidence that can inform about the living experiences of human ancestors. This objective is substantially enhanced by recent work on ancient biomolecules from preserved microbial tissues, such as dental calculus, faecal sediments and whole coprolites. A challenge yet is to distinguish authentic biomolecules from environmental contaminants deposited contemporaneously, primarily from soil. However, we do not have sound expectations about the soil microbial elements arriving to host-associated microbiomes in a modern context. One assumption in human microbiome research is that proximity to the natural environment should affect biodiversity or impart genetic elements. I present evidence supporting the assumption that environmental soil taxa are found among host-associated gut taxa, which can recapitulate the surrounding host habitat ecotype. Soil taxa found in gut microbiomes relate to a set of universal ‘core’ taxa for all soil ecotypes, demonstrating that widespread host organisms may experience a consistent pattern of external environmental cues, perhaps critical for development. Observed differentiation of soil feature diversity, abundance and composition among human communities, great apes and invertebrate hosts also indicates that lifestyle patterns are inferable from an environmental signal that is retrievable from gut microbiome amplicon data.This article is part of the theme issue ‘Insights into health and disease from ancient biomolecules’.
Functional diversity of microbial ecologies estimated from ancient human coprolites and dental calculus
Authors: Jacobson David K. , Honap Tanvi P. , Monroe Cara , Lund Justin , Houk Brett A. , Novotny Anna C. , Robin Cynthia , Marini Elisabetta , Lewis Cecil M. 
Published: October 2020

Human microbiome studies are increasingly incorporating macroecological approaches, such as community assembly, network analysis and functional redundancy to more fully characterize the microbiome. Such analyses have not been applied to ancient human microbiomes, preventing insights into human microbiome evolution. We address this issue by analysing published ancient microbiome datasets: coprolites from Rio Zape (n= 7; 700 CE Mexico) and historic dental calculus (n= 44; 1770–1855 CE, UK), as well as two novel dental calculus datasets: Maya (n= 7; 170 BCE-885 CE, Belize) and Nuragic Sardinians (n= 11; 1400–850 BCE, Italy). Periodontitis-associated bacteria (Treponema denticola,Fusobacterium nucleatumandEubacterium saphenum) were identified as keystone taxa in the dental calculus datasets. Coprolite keystone taxa included known short-chain fatty acid producers (Eubacterium biforme, Phascolarctobacterium succinatutens) and potentially disease-associated bacteria (Escherichia,Brachyspira). Overlap in ecological profiles between ancient and modern microbiomes was indicated by similarity in functional response diversity profiles between contemporary hunter–gatherers and ancient coprolites, as well as parallels between ancient Maya, historic UK, and modern Spanish dental calculus; however, the ancient Nuragic dental calculus shows a distinct ecological structure. We detected key ecological signatures from ancient microbiome data, paving the way to expand understanding of human microbiome evolution.This article is part of the theme issue ‘Insights into health and disease from ancient biomolecules’.
The Genomic Landscape of Pediatric Rheumatology Disorders in the Middle East
Authors: Fathalla Basil M , Alsarhan Ali , Afzal Samina , Naofal Maha EL , Tayoun Ahmad Abou 
Published: October 2020

AbstractGenetic investigations for patients with pediatric rheumatological disorders have been limited to classic genotyping testing, mainly MEFV hotspot mutation analysis, for periodic fever. Therefore, the landscape and clinical utility of comprehensive genomic investigations for a wider range of pediatric rheumatological disorders have not been fully characterized in the Middle East. Here seventy-one pediatric patients, of diverse Arab origins, were clinically and genetically assessed for a spectrum of rheumatology-related disease at the only dedicated tertiary children’s hospital in the United Arab Emirates. Clinical genomic investigations included mainly (76%) next generation sequencing-based gene panels and whole exome sequencing, along with rapid sequencing in the intensive care unit (ICU) and urgent setting. The overall positive yield was 46.5% (16.7%-66.7% for specific indications), while dual diagnoses were made in 2 cases (3%). Although the majority (21/33, 64%) of positive findings involved the MEFV gene, the remaining (12/33, 36%) alterations were attributed to eleven other genes/loci. Copy number variants contributed substantially (5/33, 15.2%) to the overall diagnostic yield. Sequencing-based testing, specifically rapid sequencing, had high positive rate and delivered timely results. Genetic findings guided clinical management plans and interventions in most cases (27/33, 81.8%). We highlight unique findings and provide additional evidence that heterozygous loss of function of the IFIH1 gene increases susceptibility to recurrent fevers. Our study highlights the importance of comprehensive genomic investigations in patients with pediatric rheumatological disorders, and provides new insights into the pathogenic variation landscape in this group of disorders.
SARS-CoV-2 seroprevalence and clinical features of COVID-19 in a German liver transplant recipient cohort: a prospective serosurvey study
Authors: Rauber Conrad , Tiwari-Heckler Shilpa , Pfeiffenberger Jan , Mehrabi Arianeb , Lund Frederike , Gath Philip , Mieth Markus , Merle Uta , Rupp Christian 
Published: October 2020

AbstractIn liver transplant (LT) recipients with severe COVID-19 fatal outcome has been reported in a substantial subset of patients. Whether LT recipients are at increased risk for severe COVID-19 compared to the general population is controversial. Here we report the first results of a SARS-CoV-2 serosurvey in a large LT recipient cohort.Taking into account known risk factors, LT recipients a priori represented a high-risk cohort for severe COVID-19 with 101/219 (46.1 %) presenting with more than 2 risk factors for severe COVID-19. Out of 219 LT recipients 8 (3.7%) were either tested positive for nasopharyngeal SARS-CoV-2 RNA or anti-SARS-CoV-2 serum IgG. 5/8 (62.5 %) did not show any clinical signs of infection, 3/8 (37.5%) had self-limited disease, none required hospitalization for COVID-19. 5/8 (67.5%) SARS-CoV-2 positive patients showed high utilization of the healthcare system. 2/8 (25 %) had known exposure to infected health care personal. A majority of 65.4 % often or always avoided outside family social contacts. Face masks were commonly worn by all patients.In summary, LT recipients showed a SARS-CoV-2 seroconversion rate similar to the general population with a substantial percentage of unrecognized infections. The health care system can be the assumed source of infection in most of these cases.
Dynamic characteristics rather than static hubs are important in biological networks
Authors: Kühlwein Silke D. , Ikonomi Nensi , Schwab Julian D. , Kraus Johann M. , Rudolph K. Lenhard , Pfister Astrid S. , Schuler Rainer , Kühl Michael , Kestler Hans A. 
Published: October 2020

AbstractBiological processes are rarely a consequence of single protein interactions but rather of complex regulatory networks. However, interaction graphs cannot adequately capture temporal changes. Among models that investigate dynamics, Boolean network models can approximate simple features of interaction graphs integrating also dynamics. Nevertheless, dynamic analyses are time-consuming and with growing number of nodes may become infeasible. Therefore, we set up a method to identify minimal sets of nodes able to determine network dynamics. This approach is able to depict dynamics without calculating exhaustively the complete network dynamics. Applying it to a variety of biological networks, we identified small sets of nodes sufficient to determine the dynamic behavior of the whole system. Further characterization of these sets showed that the majority of dynamic decision-makers were not static hubs. Our work suggests a paradigm shift unraveling a new class of nodes different from static hubs and able to determine network dynamics.
Genetic and non-genetic factors affecting the expression of COVID-19 relevant genes in the large airway epithelium
Authors: Kasela Silva , Ortega Victor E , Martorella Molly , Garudadri Suresh , Nguyen Jenna , Ampleford Elizabeth , Pasanen Anu , Nerella Srilaxmi , Buschur Kristina L , Barjaktarevic Igor Z , Barr R Graham , Bleecker Eugene R , Bowler Russell P , Comellas Alejandro P , Cooper Christopher B , Couper David J , Criner Gerard J , Curtis Jeffrey L , Han MeiLan K , Hansel Nadia N , Hoffman Eric A , Kaner Robert J , Krishnan Jerry A , Martinez Fernando J , McDonald Merry-Lynn N , Meyers Deborah A , Paine Robert , Peters Stephen P , Castro Mario , Denlinger Loren C , Erzurum Serpil C , Fahy John V , Israel Elliot , Jarjour Nizar N , Levy Bruce D , Li Xingnan , Moore Wendy C , Wenzel Sally E , Zein Joe ,   NHLBI SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS),   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, Langelier Charles , Woodruff Prescott G , Lappalainen Tuuli , Christenson Stephanie A 
Published: October 2020

Introductory paragraphParticular host and environmental factors influence susceptibility to severe COVID-19. We analyzed RNA-sequencing data from bronchial epithelial brushings - a relevant tissue for SARS-CoV-2 infection - obtained from three cohorts of uninfected individuals, and investigated how non-genetic and genetic factors affect the regulation of host genes implicated in COVID-19. We found thatACE2expression was higher in relation to active smoking, obesity, and hypertension that are known risk factors of COVID-19 severity, while an association with interferon-related inflammation was driven by the truncated, non-bindingACE2isoform. We discovered that expression patterns of a suppressed airway immune response to early SARS-CoV-2 infection, compared to other viruses, are similar to patterns associated with obesity, hypertension, and cardiovascular disease, which may thus contribute to a COVID-19-susceptible airway environment. eQTL mapping identified regulatory variants for genes implicated in COVID-19, some of which had pheWAS evidence for their potential role in respiratory infections. These data provide evidence that clinically relevant variation in the expression of COVID-19-related genes is associated with host factors, environmental exposures, and likely host genetic variation.
Evaluation of the accuracy, ease of use and limit of detection of novel, rapid, antigen-detecting point-of-care diagnostics for SARS-CoV-2
Authors: Krüger L.J. , Gaeddert M. , Köppel L. , Brümmer L. E. , Gottschalk C. , Miranda I.B. , Schnitzler P. , Kräusslich H.G. , Lindner A.K. , Nikolai O. , Mockenhaupt F.P. , Seybold J. , Corman V.M. , Drosten C. , Pollock N.R. , Cubas-Atienzar A.I. , Kontogianni K. , Collins A. , Wright A. H. , Knorr B. , Welker A. , de Vos M. , Sacks J.A. , Adams E.R. , Denkinger C.M. ,   for the study team
Published: October 2020

AbstractBackgroundReliable point-of-care (POC) diagnostics not requiring laboratory infrastructure could be a game changer in the COVID-19 pandemic, particularly in the Global South. We assessed performance, limit of detection and ease-of-use of three antigen-detecting, rapid POC tests (Ag-RDT) for SARS-CoV-2.MethodsThis prospective, multi-centre diagnostic accuracy study recruited participants suspected to have SARS-CoV-2 in Germany and the UK. Paired nasopharyngeal swabs (NP) or NP and/or oropharyngeal swabs (OP) were collected from participants (one for clinical RT-PCR and one for Ag-RDT). Performance of each of three Ag-RDTs was compared to RT-PCR overall, and according to predefined subcategories e.g. cycle threshold (CT)-value, days from symptoms onset, etc. In addition, limited verification of the analytical limit-of-detection (LOD) was determined. To understand the usability a System Usability Scale (SUS) questionnaire and ease-of-use (EoU) assessment were performed.ResultsBetween April 17th and August 25th, 2020, 2417 participants were enrolled, with 70 (3.0%) testing positive by RT-PCR. The best-performing test (SD Biosensor, Inc. STANDARD Q) was 76×6% (95% Confidence Interval (CI) 62×8-86×4) sensitive and 99×3% (CI 98×6-99×6) specific. A sub-analysis showed all samples with RT-PCR CT-values <25 were detectable by STANDARD Q. The test was considered easy-to-use (SUS 86/100) and suitable for POC. Bioeasy and Coris showed specificity of 93×1% (CI 91×0%-94×8%) and 95×8% (CI 93×4%-97×4%), respectively, not meeting the predefined target of ≥98%.ConclusionThere is large variability in performance of Ag-RDT with SD Biosensor showing promise. Given the usability at POC, this test is likely to have impact despite imperfect sensitivity; however further research and modelling are needed.
COVID-19 Pandemic in University Hospital: Impact on Medical Training of Medical Interns
Authors: Lim WeiHonn , Teoh Li Ying , Seevalingam Kanesh Kumaran A/L , Kuppusamy Shanggar 
Published: October 2020

AbstractIntroductionCoronavirus 2019 (COVID-19) has strike all nations hard since the end of year 2019, Malaysia unable to escape the fate as well. Healthcare system, financial growth, industrial development and educational programme are stunted. Inevitably, professional training and education are affected which include the medical training of medical interns.MethodsThis is a cross-sectional, pilot study to determine the impact of the pandemic on University Malaya Medical Centre (UMMC) medical interns. A survey which comprises 37-items was used. Data are analysed by Ordinal Logistic Regression Analysis.ResultsMedical interns feel that they lack clinical skills (p = 0.005) and need more exposure in surgical operations (p =0.029). Some are satisfied with the introduction of triage (p = 0.024), online teaching (p = 0.005) and bedside teaching (p=0.023). Most of them think they are fit and ready to handle the pandemic (p = 0.012 and 0.025 respectively) except first year medical interns (p = 0.029). Some feel like their time are wasted (p <0.05) as they are involved in many non-clinical activities (p = 0.003).ConclusionIn summary, COVID-19 has a great impact on medical training amongst medical interns. Alternative measures should be taken to minimize the interruption in training of our future leaders in medical field.
Factors associated with access to virtual care in older adults: A cross-sectional study
Authors: Liu Laura , Goodarzi Zahra , Jones Aaron , Posno Ron , Straus Sharon , Watt Jennifer 
Published: October 2020

AbstractBackgroundDuring the COVID-19 pandemic, virtual care (i.e. telephone or videoconference) has played a critical role. However, concerns were raised regarding equitable access for older adults, in particular, given potential advantages of videoconference-as opposed to telephone-based assessment. Our objective was to describe patient-specific factors associated with different modes of virtual healthcare.MethodsWe reviewed medical records of all patients assessed virtually in the geriatric medicine clinic at St. Michael’s Hospital, Toronto, Canada, between March 17 and July 13, 2020. We derived adjusted odds ratios (OR), risk differences (RD), and marginal and predicted probabilities, with 95% confidence intervals, from a multivariable logistic regression model, which tested the association between having a videoconference assessment (vs. a telephone assessment) and patient age, sex, ability to use a computer, education, frailty (measured on the Clinical Frailty Scale), history of cognitive impairment, and immigration history; language of assessment, and caregiver involvement in assessment.ResultsOur study included 330 patients (227 telephone and 103 videoconference assessments). Frailty (adjusted OR 0.62, 0.45 to 0.85; adjusted RD -0.08, -0.09 to -0.06) and absence of a caregiver (adjusted OR 0.12, 0.06 to 0.24; adjusted RD -0.35, -0.43 to -0.26) were associated with lower odds of videoconference assessment. For example, an 80-year-old woman with mild frailty who immigrated to Canada, speaks English, attained a post-secondary education, does not have cognitive impairment, and uses a computer had a 60% (39% to 80%) predicted probability of videoconference assessment if a caregiver was present compared to 15% (3% to 26%) without a caregiver. Only 32 of 98 (32.7%) patients who could independently use a computer participated in videoconference assessments.ConclusionGiven the recent expansion of virtual care, we must urgently implement and evaluate strategies that optimise equitable access to videoconference-based virtual care for older adults.
Prognostic accuracy of MALDI mass spectrometric analysis of plasma in COVID-19
Authors: Lazari Lucas Cardoso , De Rose Ghilardi Fabio , Rosa-Fernandes Livia , Assis Diego M , Nicolau José Carlos , Santiago Veronica Feijoli , Dalçóquio Talia Falcão , Angeli Claudia B. , Bertolin Adriadne Justi , Marinho Claudio R. F. , Wrenger Carsten , Durigon Edison Luiz , Siciliano Rinaldo Focaccia , Palmisano Giuseppe 
Published: October 2020

AbstractPurposeSARS-CoV-2 infection poses a global public health problem. There is a critical need for improvements in the noninvasive prognosis of COVID-19. We hypothesized that matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF MS) analysis combined with bottom-up proteomic analysis of plasma proteins might identify features to predict high and low risk cases of COVID-19.Patients and MethodsWe used MALDI-TOF MS to analyze plasma small proteins and peptides isolated using C18 micro-columns from a cohort containing a total of 117 cases of high (hospitalized) and low risk (outpatients) cases split into training (n = 88) and validation sets (n= 29). The plasma protein/peptide fingerprint obtained was used to train the algorithm before validation using a blinded test cohort.ResultsSeveral sample preparation, MS and data analysis parameters were optimized to achieve an overall accuracy of 85%, sensitivity of 90%, and specificity of 81% in the training set. In the blinded test set, this signature reached an overall accuracy of 93.1%, sensitivity of 87.5%, and specificity of 100%. From this signature, we identified two distinct regions in the MALDI-TOF profile belonging to the same proteoforms. A combination of 1D SDS-PAGE and quantitative bottom-up proteomic analysis allowed the identification of intact and truncated forms of serum amyloid A-1 and A-2 proteins. Conclusions: We found a plasma proteomic profile that discriminates against patients with high and low risk COVID-19. Proteomic analysis of C18-fractionated plasma may have a role in the noninvasive prognosis of COVID-19. Further validation will consolidate its clinical utility.Key messageWhat is the key question?Do individuals infected with SARS-CoV-2 harboring different degree of disease severity have a plasma protein profile that differentiate them and predict the COVID-19 outcome?What is the bottom line?In a series of 117 patients with COVID-19 divided in hospitalized (60) and outpatients (57), differential expression of serum amyloid A-1 (SAA1) and A-2 (SAA2) predict their outcome.Why read on?The high mortality rate in SARS-CoV-2 infected individuals requires accurate markers for predicting COVID-19 severity. Plasma levels of SAA1 and SAA2 indicate higher risk of hospitalization and can be used to improve COVID-19 monitoring and therapy.
A Mechanism for Severity of Disease in Older Patients with COVID-19: The Nexus between Telomere Length and Lymphopenia
Authors: Benetos Athanase , Lai Tsung-Po , Toupance Simon , Labat Carlos , Verhulst Simon , Gautier Sylvie , Ungeheuer Marie-Noelle , Perret-Guillaume Christine , Levy Daniel , Susser Ezra , Aviv Abraham 
Published: October 2020

AbstractBackgroundLymphopenia due to a plummeting T-cell count is a major feature of severe COVID-19. T-cell proliferation is telomere length (TL)-dependent and TL shortens with age. Older persons are disproportionally affected by severe COVID-19, and we hypothesized that those with short TL have less capacity to mount an adequate T-cell proliferative response to SARS-CoV-2. This hypothesis predicts that among older patients with COVID-19, shorter telomeres of peripheral blood mononuclear cells (PBMCs) will be associated with a lower lymphocyte count.MethodsOur sample comprised 17 COVID-19 and 21 non-COVID-19 patients, aged 87 ± 8 (mean ± SD) and 87 ± 9 years, respectively. We measured TL by the Telomere Shortest Length Assay, a novel method that measures and tallies the short telomeres directly relevant to telomere-mediated biological processes. The primary analysis quantified TL as the proportion of telomeres shorter than 2 kilobases. For comparison, we also quantified TL by Southern blotting, which measures the mean length of telomeres.ResultsLymphocyte count (109/L) was 0.91 ± 0.42 in COVID-19 patients and 1.50 ± 0.50 in non-COVID-19 patients (P < 0.001). In COVID-19 patients, but not in non-COVID-19 patients, lymphocyte count was inversely correlated with the proportion of telomeres shorter than 2 kilobases (P = 0.005) and positively correlated with the mean of telomeres measured by TeSLA (P = 0.03). Lymphocyte counts showed no statistically significant correlations with Southern blotting results in COVID-19 or non-COVID-19 patients.ConclusionsThese results support the hypothesis that a compromised TL-dependent T-cell proliferative response contributes to lymphopenia and the resulting disproportionate severity of COVID-19 among old adults. We infer that infection with SARS-CoV-2 uncovers the limits of the TL reserves of older persons.