bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zooanthroponotic transmission of SARS-CoV-2 and host-specific viral mutations revealed by genome-wide phylogenetic analysis
Authors: Naderi Sana , Chen Peter E. , Murall Carmen Lía , Poujol Raphael , Kraemer Susanne , Pickering Bradley S. , Sagan Selena M. , Jesse Shapiro B. 
Published: June 2022

AbstractSevere Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a generalist virus, infecting and evolving in numerous mammals, including captive and companion animals, free-ranging wildlife, and humans. Transmission among non-human species poses a risk for the establishment of SARS-CoV-2 reservoirs, makes eradication difficult, and provides the virus with opportunities for new evolutionary trajectories, including selection of adaptive mutations and emergence of new variant lineages. Here we use publicly available viral genome sequences and phylogenetic analysis to systematically investigate transmission of SARS-CoV-2 between human and non-human species and to identify mutations associated with each species. We found the highest frequency of animal-to-human transmission from mink, compared with lower transmission from other sampled species (cat, dog, and deer). Although inferred transmission events could be limited by sampling biases, our results provide a useful baseline for further studies. Using genome-wide association studies, no single nucleotide variants (SNVs) were significantly associated with cats and dogs, potentially due to small sample sizes. However, we identified three SNVs statistically associated with mink and 26 with deer. Of these SNVs, ∼⅔ were plausibly introduced into these animal species from local human populations, while the remaining ∼⅓ were more likely derived in animal populations and are thus top candidates for experimental studies of species-specific adaptation. Together, our results highlight the importance of studying animal-associated SARS-CoV-2 mutations to assess their potential impact on human and animal health.ImportanceSARS-CoV-2, the causative agent of COVID-19, can infect many animal species, making eradication difficult because it can be reseeded from different reservoirs. When viruses replicate in different species, they may be faced with different evolutionary pressures and acquire new mutations, with unknown consequences for transmission and virulence in humans. Here we analyzed SARS-CoV-2 genome sequences from cats, dogs, deer, and mink to estimate transmission between each of these species and humans. We found several transmission events from humans to each animal, but relatively few detectable transmissions from animals back to humans, with the exception of mink. We also identified three mutations more likely to be found in mink than humans, and 26 in deer. These mutations could help the virus adapt to life in these different species. Ongoing surveillance of SARS-CoV-2 from animals will be important to understand their potential impacts on both human and animal health.
Predictive analytics that reflect disease burden – the cumulative COMET score
Authors: Monfredi Oliver , Andris Robert T , Lake Douglas E , Moorman J Randall 
Published: June 2022

AbstractPredictive analytics tools variably take into account data from the electronic medical record, lab tests, nursing charted vital signs and continuous cardiorespiratory monitoring data to deliver an instantaneous score that indicates patient risk or instability. Few, if any, of these tools reflect the risk to a patient accumulated over the course of an entire hospital stay. This approach fails to best utilize all of the collated data regarding the risk or instability sustained by the patient, and hence fails to fully characterize this to optimize the ability of treating clinicians to maximize the chances of a favorable outcome. We have built on our instantaneous CoMET predictive analytics score to generate the cumulative CoMET score (cCOMET), which sums all of the instantaneous CoMET scores throughout a hospital admission relative to a baseline expected risk unique to that patient. We have shown that higher cCOMET scores predict mortality, but not length of stay, and that higher baseline CoMET scores predict higher cCoMET scores at discharge/death. cCoMET scores were higher in males in our cohort, and added information to the final CoMET when it came to the prediction of death. In summary, if one is going to go to the trouble and expense of performing repeated measures when performing predictive analytics calculations, we have shown that including all of these measures in a cumulative way adds data to instantaneous predictive analytics, and could improve the ability of clinicians to predict deterioration, and improve patient outcomes in so doing.
Leadless Pacemaker with Transcatheter Aortic Valve Implantation: A Single Center Experience
Authors: Gao Feng , Kherallah Riyad , Koetting Mackenzie , Simpson Leo , Seger John , Koneru Srikanth , Coselli Joseph , Preventza Ourania , Orozco-Sevilla Vicente , Manon Nastasya , Silva Guilherme V 
Published: June 2022

AbstractBackgroundThe safety and efficacy of leadless pacemakers (LP) in transcatheter aortic valve implant (TAVI) patients is not well known due to paucity of data. Herein, we compared outcomes between leadless pacemakers to traditional dual chamber pacemakers (DCP) following TAVI.MethodsA single-center retrospective study was conducted, including a total of 27 patients with LP and 33 patients with DCP after TAVI between November 2013 to May 2021. We compared baseline demographics, pacemaker indications, percent pacing, ejection fractions, and pacemaker related complication rates.ResultsLeading indications for pacemaker implant were complete heart block (74% LP, 73% DCP) and high degree atrioventricular block (26% LP, 21% DCP). No significant differences were observed between LP and DCP in device usage and ejection fraction at 1, 6, and 12 months. Within each pacemaker group, we did not observe a significant reduction in percent ventricular pacing or ejection fraction at follow up. Three DCP patients required rehospitalization for pocket related complications.ConclusionFrom this single-center study, TAVI patients appear to have comparable pacemaker usage and ejection fraction between LP and DCP groups, suggesting that LP may be a reasonable alternative where single ventricular pacing is indicated. Larger studies are required to validate these findings.
An Automated Entrustment Professional Activities Tracking System (EPA-TRAC) That Holistically Capture Competence: A Paradigm Shift to Programmatic Assessment
Authors: Hamed Omayma 
Published: June 2022

AbstractCompetence is a complex phenomenon that requires comprehensive and holistic assessment. This could be only be achieved through a complete assessment program that navigates poles between assessment for learning, assessment of learning and assessment as learning. Assessment of competence is not an easy task; educationists resorted to unfolding competence into sub-sub-competences and assessing them as separate chunks which violated the purpose of competency-based education. This is attributed to the reduction of the rich information from an assessment to a numerical score. In addition, evaluations of chunks from different competency domains are collated together in a compensatory manner rather than in a conjunctive manner resulting in adding oranges to apples with resultant meaningless assessment information. A useful contribution to this whole issue is the introduction of entrustable professional activities (EPAs) which are considered portal for capturing and visualizing competences in a holistic manner. EPAs provide a better language to make education more task-based. This necessitated a different assessment paradigm “Programmatic Assessment”. This assessment paradigm ensures convergence of assessment data points that keep competence integrated into a whole meaningful picture. In this type of assessment model, the trainee has role in gathering, collating and reflecting on the various assessments in an informative way that triangulates evidence and translates them into learning goals. Hence longitudinal, information-rich feedback and reflection are crucial in such assessment system and could be collated in a developmental portfolio. In such model a variety of assessment tools could be used so long as they constitute a high utility index; assessment could be psychometric and workplace-based. Whether scores from psychometric assessments or enaction of feedback and learning goals are used for making judgment, remains the decision of the curriculum and assessment system designers according to context and purpose of assessment. Being complex to realize, an automated system (EPA-TRAC) is developed to capture that assessment system.
Computational and functional characterization of the PI(4,5)P2 binding site of the TRPM3 ion channel
Authors: Zhao Siyuan , Carnevale Vincenzo , Gianti Eleonora , Rohacs Tibor 
Published: June 2022

ABSTRACTTransient Receptor Potential Melastatin 3 (TRPM3) is a heat-activated ion channel expressed in peripheral sensory neurons and the central nervous system. TRPM3 activity depends on the membrane phospholipid phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], but the molecular mechanism of activation by PI(4,5)P2 is not known. As no experimental structure of TRPM3 is available, we built a homology model of the channel in complex with PI(4,5)P2via molecular modeling. We identified putative contact residues for PI(4,5)P2 in the pre-S1 segment, the S4-S5 linker, and the proximal C-terminal TRP-domain. Mutating these residues increased sensitivity to inhibition of TRPM3 by decreasing PI(4,5)P2 levels by phosphatidylinositol 4-kinase inhibition. Changes in ligand-binding affinities via MM/GBSA showed reduced PI(4,5)P2 affinity for the mutants. Mutating PI(4,5)P2 interacting residues also reduced sensitivity for activation by the endogenous ligand pregnenolone sulfate (PregS), pointing to an allosteric interaction between PI(4,5)P2 and PregS. Mutating residues in the PI(4,5)P2 binding site in TRPM8 had similar effects, increased sensitivity to PI(4,5)P2 depletion, and reduced sensitivity to menthol. Mutation of most PI(4,5)P2 interacting residues in TRPM3 also increased sensitivity to inhibition by Gβγ, indicating allosteric interaction between Gβγ and PI(4,5)P2. Disease-associated gain of function TRPM3 mutations on the other hand, resulted in no change of PI(4,5)P2 sensitivity, indicating that mutations did not increase channel activity via increasing PI(4,5)P2 interactions. Our data provide insight into the mechanism of regulation of TRPM3 by PI(4,5)P2, its relationship to endogenous activators and inhibitors of TRPM3, as well as identify similarities and differences between PI(4,5)P2 regulation of TRPM3 and TRPM8.
Evaluation of variant calling algorithms for wastewater-based epidemiology using mixed populations of SARS-CoV-2 variants in synthetic and wastewater samples
Authors: Bassano Irene , Ramachandran Vinoy K. , Khalifa Mohammad S. , Lilley Chris J. , Brown Mathew R. , van Aerle Ronny , Denise Hubert , Rowe William , George Airey , Cairns Edward , Wierzbicki Claudia , Pickwell Natalie D. , Wilson Myles , Carlile Matthew , Holmes Nadine , Payne Alexander , Loose Matthew , Burke Terry A. , Paterson Steve , Wade Matthew J. , Grimsley Jasmine M.S. 
Published: June 2022

AbstractWastewater-based epidemiology (WBE) has been used extensively throughout the COVID-19 pandemic to detect and monitor the spread and prevalence of SARS-CoV-2 and its variants. It has proven an excellent, complementary tool to clinical sequencing, supporting the insights gained and helping to make informed public health decisions. Consequently, many groups globally have developed bioinformatics pipelines to analyse sequencing data from wastewater. Accurate calling of mutations is critical in this process and in the assignment of circulating variants, yet, to date, the performance of variant-calling algorithms in wastewater samples has not been investigated. To address this, we compared the performance of six variant callers (VarScan, iVar, GATK, FreeBayes, LoFreq and BCFtools), used widely in bioinformatics pipelines, on 19 synthetic samples with known ratios of three different SARS-CoV-2 variants (Alpha, Beta and Delta), as well as 13 wastewater samples collected in London between the 15–18 December 2021. We used the fundamental parameters of recall (sensitivity) and precision (specificity) to confirm the presence of mutational profiles defining specific variants across the six variant callers.Our results show that BCFtools, FreeBayes and VarScan found the expected variants with higher precision and recall than GATK or iVar, although the latter identified more expected defining mutations than other callers. LoFreq gave the least reliable results due to the high number of false-positive mutations detected, resulting in lower precision. Similar results were obtained for both the synthetic and wastewater samples.
Travel-related Twenty-eight Days Cyclical Thrombosis and Subgroups of COVID-19 Cardiac Biomarker Data: Novel Review Strategy and Meta-analysis Method
Authors: Kimoto Keiichiro , Yamakuchi Munekazu , Takenouchi Kazunori , Hashiguchi Teruto 
Published: June 2022

AbstractBackgroundsStrange controversies have remained in thrombosis-related fields (traveler’s and COVID-19-related thrombosis), although traveler’s thrombosis is well-known even among non-professionals as “economy class syndrome.” We hypothesized there might be something overlooked behind those strange situations.MethodsSince ordinary review methods (e.g., systematic review or meta-analysis) had already been conducted, we focused on reviewing a “previously published” “chart.” Also, we developed a novel “review method” for the meta-regression analysis result. We applied those to some previously published and well-known data.ResultsWe newly found an approximately 28 days cycle of thrombosis onset over several weeks after travel in a figure. Also, we found an eighteen-day cycle of thrombosis onset in another chart. In COVID-19 cardiovascular biomarker studies, we newly extracted subgroup patterns in a scatterplot (Troponin T and NT-proBNP) that applied simple linear regression analysis. Also, these subgroups had already appeared in the cardiomyopathy study.ConclusionsTraveler’s thrombosis sometimes occurs over two months after leaving the risky in-flight environment. This phenomenon has been explained that the thrombus is formed in a cabin but dislodged after. However, from the cyclic patterns, explaining that the “high-risk period of thrombosis with Oral Contraceptive (OC) use initiation” coincided with “travel” is more reasonable (e.g., honeymoon and OC initiation). Regarding risk-benefit balance, it is conceivable that “spreading the risk” by starting the dosing away from the travel period is essential to ensure safer use because the in-flight environment may have a non-zero effect, and optimal care by a primary care physician (prescriber) is not available during the travel. In COVID-19, there seems to be a complex scatterplot structure that is unsuitable for usually used simple linear fitting. In a literature review, a pattern on a chart should be given more paying attention.
Matrix fibroblast function during alveolarization is dependent on GATA6
Authors: Ushakumary Mereena George , Green Jenna , Riccetti Matthew Richard , Na Cheng-Lun , Mohanraj Divya , Guo Minzhe , Perl Anne-Karina Theresia 
Published: June 2022

AbstractAlveolarization is dependent on myo-, matrix- and lipo- fibroblast functions by interstitial PDGFRa+ fibroblasts. While these fibroblasts are derived from GLI and PDGFRa expressing fibroblasts, the transcriptional control of their functional specification remains unknown. Perinatally, the transcription factor GATA6 is upregulated in PDGFRa+ fibroblasts. To study the role of GATA6 during fibroblast differentiation, we generated PDGFRaCreER/GATA6flx/flx mice and deleted GATA6 in the perinatal period and in adult mice prior to left lobe pneumonectomy. Loss of GATA6 in the PDGFRa+-fibroblasts impaired alveolarization, and extracellular matrix deposition, in association with increased TCF21 expression and lipofibroblast differentiation. Loss of GATA6 in PDGFRa+ fibroblasts resulted in loss of alveolar type 1 (AT1) cells and gain of transitional alveolar type 2 (AT2) cells. Loss of GATA6 was associated with reduced WNT signaling. Restoration of WNT signaling in GATA6 deficient alveolar lung organoids restored AT2 and AT1 cell differentiation. GATA6 induces matrix fibroblast functions and represses lipofibroblast functions, serving as key regulator of fibroblast differentiation during alveolarization and regeneration. Present findings link matrix fibroblast functions with the ability of transitional AT2 cells to differentiate into AT1 cells.Graphical abstractGraphical abstract:
A scalable approach for continuous time Markov models with covariates
Authors: Hatami Farhad , Ocampo Alex , Graham Gordon , Nichols Thomas E. , Ganjgahi Habib 
Published: June 2022

AbstractExisting methods for fitting continuous time Markov models (CTMM) in the presence of covariates suffer from scalability issues due to high computational cost of matrix exponentials calculated for each observation. In this paper we propose an optimization technique for CTMM which uses a stochastic gradient descent algorithm combined with differentiation of the matrix exponential using a Padé approximation which we show then makes fitting large scale data feasible. We compare two methods for computing standard errors, one using Padé expansion, and the other using power series expansion of the matrix exponential. Through simulations we find improved performance relative to existing CTMM methods, and we demonstrate the method on the large-scale multiple sclerosis NO.MS dataset.
A fibrin enhanced thrombosis model for medical devices operating at low shear regimes or large surface areas
Authors: Méndez Rojano Rodrigo , Lai Angela , Zhussupbekov Mansur , Burgreen Greg W. , Cook Keith , Antaki James F. 
Published: June 2022

AbstractOver the past decade, much of the development of computational models of device-related thrombosis has focused on platelet activity. While those models have been successful in predicting thrombus formation in medical devices operating at high shear rates (> 5000 s−1), they cannot be directly applied to low-shear devices, such as blood oxygenators and catheters, where emerging information suggest that fibrin formation is the predominant mechanism of clotting and platelet activity plays a secondary role. In the current work, we augment an existing platelet-based model of thrombosis with a partial model of the coagulation cascade that includes contact activation of factor XII and fibrin production. To calibrate the model, we simulate a backward-facing-step flow channel that has been extensively characterized in-vitro. Next, we perform blood perfusion experiments through a microfluidic chamber mimicking a hollow fiber membrane oxygenator and validate the model against these observations. The simulation results closely match the time evolution of the thrombus height and length in the backward-facing-step experiment. Application of the model to the microfluidic hollow fiber bundle chamber capture both gross features such as the increasing clotting trend towards the outlet of the chamber, as well as finer local features such as the structure of fibrin around individual hollow fibers. Our results are in line with recent findings that suggest fibrin production, through contact activation of factor XII, drives the thrombus formation in medical devices operating at low shear rates with large surface area to volume ratios.Author summaryPatients treated with blood-contacting medical devices suffer from clotting complications. Over the past decades, a great effort has been made to develop computational tools to predict and prevent clot formation in these devices. However, most models have focused on platelet activity and neglected other important parts of the problem such as the coagulation cascade reactions that lead to fibrin formation. In the current work, we incorporate this missing element into a well-established and validated model for platelet activity. We then use this novel approach to predict thrombus formation in two experimental configurations. Our results confirm that to accurately predict the clotting process in devices where surface area to volume ratios are large and flow velocity and shear stresses remain low, coagulation reactions and subsequent fibrin formation must be considered. This new model could have great implications for the design and optimization of medical devices such as blood oxygenators. In the long term, the model could evolve into a functional tool to inform anticoagulation therapies for these patients.
Genomic Surveillance of SARS CoV2 in COVID-19 vaccinated healthcare workers in Lebanon
Authors: Al Kalamouni Habib , Abou Hassan Farouk F. , Bou Hamdan Mirna , Page Andrew J. , Lott Martin , Ghosn Nada , Rady Alissar , Mahfouz Rami , Araj George F. , Dbaibo Ghassan , Zaraket Hassan , Melhem Nada M. , Matar Ghassan M. 
Published: June 2022

AbstractThe emergence of SARS-CoV-2 variants including the Delta and Omicron along with waning of vaccine-induced immunity over time contributed to increased rates of breakthrough infection specifically among healthcare workers (HCWs). SARS-CoV-2 genomic surveillance is an important tool for timely detection and characterization of circulating variants as well as monitoring the emergence of new strains. Our study is the first national SARS-CoV-2 genomic surveillance among HCWs in Lebanon. We collected 250 samples from five hospitals across Lebanon between December 2021 and January 2022. We extracted viral RNA and performed whole genome sequencing using the Illumina NextSeq 500 platform. A total of 133 (57.1%) samples belonging to the Omicron (BA.1.1) sub-lineage were identified, as well as 44 (18.9%) samples belonging to the BA.1 sub-lineage, 28 (12%) belonging to the BA.2 sub-lineage, and only 15 (6.6%) samples belonging to the Delta variant sub-lineage B.1.617.2. These results show that Lebanon followed the global trend in terms of circulating SARS-CoV-2 variants with Delta rapidly replaced by the Omicron variant. This study underscores the importance of continuous genomic surveillance programs in Lebanon for the timely detection and characterization of circulating variants. The latter is critical to guide public health policy making and to timely implement public health interventions.
TE invasion fuels molecular adaptation in laboratory populations of Drosophila melanogaster
Authors: Wang Luyang , Zhang Shuo , Hadjipanteli Savana , Saiz Lorissa , Nguyen Lisa , Silva Efren , Kelleher Erin S. 
Published: June 2022

AbstractTransposable elements are mobile genetic parasites that frequently invade new host genomes through horizontal transfer. Invading TEs often exhibit a burst of transposition, followed by reduced transposition rates as repression evolves in the host. We recreated the horizontal transfer of P-element DNA transposons into a D. melanogaster host, and followed the expansion of TE copies and evolution of host repression in replicate laboratory populations reared at different temperatures. We observed that while populations maintained at high temperatures rapidly go extinct after TE invasion, those maintained at lower temperatures persist, allowing for TE spread and the evolution of host repression. We also surprisingly discovered that invaded populations experienced recurrent insertion of P-elements into a specific long non-coding RNA, lncRNA:CR43651, and that these insertion alleles are segregating at unusually high frequency in experimental populations, indicative of positive selection. We propose that, in addition to driving the evolution of repression, transpositional bursts of invading TEs can drive molecular adaptation.