bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathogen-Host Adhesion between SARS-CoV-2 Spike Proteins from Different Variants and Human ACE2 Probed at Single-Molecule and Single-Cell Levels
Authors: Zhang Xiaoxu , Chen Jialin , Hong Bixia , Xu Haifeng , Pei Pengfei , Chen Long , Tong Yigang , Luo Shi-Zhong , Fan Huahao , He Chengzhi 
Published: June 2022

AbstractPathogen-Host adhesion is considered the first step of infection for many pathogens such as bacteria and virus. The binding of the receptor binding domain (RBD) of SARS-CoV-2 Spike protein (S protein) onto human angiotensin-converting enzyme 2 (ACE2) is considered as the first step for the SARS-CoV-2 to adhere onto the host cells during the infection. Within three years, a number of variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been found all around the world. Here, we investigated the adhesion of S Proteins from different variants and ACE2 using atomic force microscopy (AFM)-based single-molecule force spectroscopy (SMFS) and single-cell force spectroscopy (SCFS). We found that the unbinding force and binding probability of the S protein from Delta variant to the ACE2 was the highest among the variants tested in our study at both single-molecule and single-cell levels. Molecular dynamics simulation showed that ACE2-RBD (Omicron) complex is destabilized by the E484A and Y505H mutations and stabilized by S477N and N501Y mutations, when compared with Delta variant. In addition, a neutralizing antibody, produced by immunization with wild type RBD of S protein, could effectively inhibit the binding of S proteins from wild type, Delta and Omicron variants onto ACE2. Our results provide new insight for the molecular mechanism of the adhesive interactions between S protein and ACE2 and suggest that effective monoclonal antibody can be prepared using wild type S protein against the different variants.
Trans-Radial Electrical Bioimpedance Velocimetry: A Novel Method for Detecting Cardiac Contractility
Authors: Stump Alexandra I. , Dundon Neil M. , Babenko Viktoriya , Macy Alan , Grafton Scott T. 
Published: June 2022

AbstractIncreasing insight into the complex human response to external states can be captured by measuring event-related cardiac sympathetic activity. However existing assays are either confounded by influence from other branches of the autonomic system, or require preprocessing steps that eliminate moment-to-moment capture of fluctuation. We accordingly tested a novel device (TREV) that measures cardiac impedance directly from the radial and ulnar arteries of the human forearm, while healthy human participants performed a small number of trials of a task known to elicit sympathetic drive, a maximum-strength grip task. TREV recorded robust estimates of contractility at each heartbeat, that allowed fully automated beatwise estimations. TREV further reliably described credible group-level departures from baseline aligned with each individual grip in the task. We conclude that the device can be a useful addition to a broadening field exploring event-related sympathetic perturbations.
Measuring circadian rhythms in patients with dementia: protocol for a scoping review
Authors: Gabb Victoria G. , Ince Louise M. , Rudd Sarah , Coulthard Elizabeth 
Published: June 2022

AbstractIntroductionMost physiological processes are under circadian regulation. Disturbances to circadian rhythms are common and often early symptoms in dementia. There is a gap in the literature regarding how and which circadian functions have been, or could optimally be, measured in patients with dementia. This protocol outlines a scoping review to identify which and how circadian variables have been studied in patients with dementia and mild cognitive impairment, and examine whether feasibility, acceptability, appropriateness, and utility in clinical practice has been considered.Methods and analysisThe scoping review will be conducted in accordance with the Joanna Briggs Institute methodology for scoping reviews and will be reported in line with the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). We will systematically search five electronic bibliographic databases (MEDLINE, CINAHL, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL), PsycInfo). There will be no restriction on date of publication or language; corresponding authors will be contacted where relevant non-English articles are identified to request a translation. Search results will be merged using reference management software and duplicates will be removed. To ensure consistency in applying eligibility criteria, 10% of retrieved articles will be checked by each reviewer in the team at the title and abstract screening stage and full texts will be reviewed by at least 2 reviewers. Data from eligible articles will be extracted using a standardised form. Where study outcomes (e.g., patient and public involvement, adherence) have not been described in the article, authors will be contacted in case relevant data is available to share but was omitted from the main report. Results will be presented as a narrative synthesis as study and population heterogeneity will likely prohibit meta-analysis.Ethics and disseminationEthical approval is not required as the scoping review methodology does not involve human or animal participants. This review will provide an extensive overview of established and emerging trends in measurement of circadian rhythms in dementia and identify gaps in the research to inform future clinical and research practice. The review will also highlight whether patient and public involvement, participant burden, and clinical usefulness of methods have been considered in developing protocols. Results will be disseminated in a peer-reviewed publication.
The impact of surgical mask-wearing, contact tracing program, and vaccination on COVID-19 transmission in Taiwan from January 2020 to March 2022: a modelling study
Authors: Filonets Tatiana , Solovchuk Maxim , Gao Wayne 
Published: June 2022

AbstractThe effectiveness of interventions such as public mask-wearing, contact tracing, and vaccination presents an important lesson for control of the further COVID-19 outbreaks without of whole country lockdowns and the restriction of individual movement. We simulated different scenarios of COVID-19 waves in Taiwan from 2020 to the beginning of March 2022 and considered the following interventions: travel restrictions, quarantine of infected individuals, contact tracing, mask-wearing, vaccination, and mass gathering restrictions. We propose an epidemiological compartmental model modified from the susceptible-exposed-infectious-removed (SEIR) model and derive a formula for the basic reproduction number (R0) describing its dependence on all investigated parameters. The simulation results are fitted with the official Taiwanese COVID-19 data. Thus, the results demonstrate that the fast introduction of the interventions and maintaining them at a high level are able the outbreak control without strict lockdowns. By estimation of the R0, it was shown that it is necessary to maintain on high implementation level of both non- and pharmaceutical intervention types to control the COVID-19 transmission. Our results can be useful as advice or recommendation for public health policies, and our model can be applied for other epidemiological simulation studies.
Cross-Cultural Adaptation and Validation of the 5C Scale to Identify Factors Associated With COVID-19 and Influenza Vaccine Hesitancy Among Healthcare Workers in Cape Town, South Africa – A Protocol
Authors: Alobwede Samuel M , Katoto Patrick DMC , Cooper Sara , Lumngwena Evelyn N , Kidzeru Elvis B , Goliath Rene , Jackson Amanda , Wiysonge Charles S , Shey Muki S 
Published: June 2022

AbstractBackgroundHealthcare workers are at an increased risk of acquiring vaccine-preventable diseases and are known to be reliable source of information for the patients and their relatives. Knowledge and attitudes of Healthcare workers about vaccines are thus important determinants of their own vaccination uptake and their intention to recommend vaccinations to their patients. However, culturally adapted tools and studies to address vaccine uptake and hesitancy as well as related behaviours among Healthcare workers in the Global South are limited.MethodsWe propose a mixed methods project to understand the extent and determinants of vaccination hesitancy among Healthcare workers and construct a validated scale to measure this complex and context-specific phenomenon in Cape Town. We will summarise responses as counts and percentages for categorical variables and means with standard deviations (or median with inter quartile ranges) for continuous variables. We will run the Shapiro-Wilks test to assess the normality. Analysis of the variance, chi-square tests, and equivalents will be conducted as appropriate for group comparisons. Logistic regression models will also be performed to assess association between variables.We will focus on the seasonal influenza and COVID-19 vaccine. We will use an existing tool developed and validated in Germany and the United States of America to measure five psychological determinants of vaccination (referred to as the 5C scale), as the basis to develop and validate a scale to measure the scope and determinants of vaccine hesitancy and acceptance among Healthcare workers in Cape Town.Discussion and conclusionThrough this study, we hope to expand the scientific evidence based on vaccination acceptance and demand among Healthcare workers in South Africa and build resources to enable better understanding of, detection, and response to vaccination hesitancy in Cape Town.
TTN truncating variants in hiPSI exons show high penetrance for cardiomyopathy in carriers with atrial fibrillation
Authors: Schiabor Barrett Kelly M. , Cirulli Elizabeth T. , Bolze Alexandre , Rowan Chris , Elhanan Gai , Grzymski Joseph J. , Lee William , Washington Nicole L. 
Published: June 2022

AbstractBackgroundTruncating variants in TTN (TTNtvs) represent the largest known genetic cause of dilated cardiomyopathies (DCM). At the population level, even when limited to TTNtvs in cardiac-specific exons (hiPSI TTNtvs) penetrance estimates for DCM are low. Recent work shows that individuals harboring TTNtvs have a high prevalence of other cardiac conditions aside from heart failure, in particular, atrial fibrillation (Afib).ObjectivesPinpoint the genetic footprint TTN-related diagnoses aside from DCM, such as Afib, and determine if vetting additional significantly-associated phenotypes better stratifies cardiomyopathy risk across TTN carriers.MethodsWe leverage longitudinal EHR and exome sequencing data from two cohorts to determine the penetrance of TTNtvs using multiple gene expression models against Afib, CM, and other cardiac diagnoses.ResultsControlling for CM and Afib, related cardio phenotypes retain only nominal association with TTNtvs. An unbiased sliding window analysis of TTNtvs across the locus confirms the association is specific to hiPSI exons for both CM and Afib, with no meaningful associations in lowPSI exons nor improvements from LOFTEE designations. We find 34% of hiPSI TTNtv carriers with early Afib have a CM diagnosis – a 5-fold increase in risk over non-carriers with early Afib and 47-fold increase over population controls.ConclusionCM and Afib are often coincident in hiPSI TTNtv carriers, which represent varying and progressive manifestations of structurally-based heart failure. We provide statistical support for a hiPSI variant interpretation model for TTNtvs and evidence for the first population-level screening method with clinical utility for cardiomyopathies, especially in relation to an Afib finding.
Hospitalization, death, and probable reinfection in Peruvian healthcare workers infected with SARS-CoV-2: a national retrospective cohort study
Authors: Ramos Willy , Guerrero Nadia , Saldaña Omar Napanga , Medina José , Loayza Manuel , De La Cruz-Vargas Jhony A. , Vargas María , Ordóñez Luis , Seclén Yovana , Álvarez-Antonio Carlos , Arrasco Juan 
Published: June 2022

ABSTRACTOBJECTIVETo determine if occupation is a risk factor for probable reinfection, hospitalization, and death from COVID-19 in Peruvian healthcare workers infected with SARS-CoV-2.MATERIAL AND METHODSRetrospective cohort study. Healthcare workers who presented SARS-CoV-2 infection between March 1, 2020 and August 9, 2021 were included. Occupational cohorts were reconstructed from the following sources of information: the National Epidemiological Surveillance System, molecular tests (NETLAB), results of serology and antigen tests (SICOVID-19), National Registry of Health Personnel (INFORHUS) and National Information System of Deaths (SINADEF). The incidence of probable reinfection, hospitalization, and death from COVID-19 was obtained in the cohorts of health auxiliaries and technicians, nursing staff, obstetricians, physicians, and other healthcare workers. We evaluated whether occupation was a risk factor for probable reinfection, hospitalization, and death from COVID-19 using a log-binomial generalized linear model, obtaining the adjusted relative risk (RR AJ).RESULTS90,672 healthcare workers were included. 8.1% required hospitalization, 1.7% died from COVID-19, and 2.0% had probable reinfection. A similar incidence of probable reinfection was found in the 5 cohorts (1.9%-2.2%). Physicians had a higher incidence of hospitalization (13.2%) and death (2.6%); however, they were also those who presented greater susceptibility linked to non-occupational variables such as age and comorbidities. The multivariate analysis found that physicians (RR=1.691; CI 95: 1.556–1.837) had a higher risk of hospitalization and that the occupation of health technician and assistant was the only one that constituted a risk factor for mortality from COVID-19 (RR =1.240; 95% CI: 1.052–1.463).CONCLUSIONSPeruvian health technicians and auxiliaries have a higher risk of death from COVID-19 linked to their occupation, while doctors have higher mortality due to non-occupational factors. Physicians had a higher risk of hospitalization independent of the presence of comorbidities and age; likewise, all occupations had a similar risk of probable reinfection.
YAP/TAZ mediate TGFβ2-induced Schlemm’s canal cell dysfunction
Authors: Li Haiyan , Singh Ayushi , Perkumas Kristin M. , Stamer W. Daniel , Ganapathy Preethi S. , Herberg Samuel 
Published: June 2022

AbstractPurposeElevated transforming growth factor beta2 (TGFβ2) levels in the aqueous humor have been linked to glaucomatous outflow tissue dysfunction. Potential mediators of dysfunction are the transcriptional co-activators, Yes-associated protein (YAP) and transcriptional coactivator with PDZ binding motif (TAZ). However, the molecular underpinnings of YAP/TAZ modulation in Schlemm’s Canal (SC) cells under glaucomatous conditions are not well understood. Here, we investigate how TGFβ2 regulates YAP/TAZ activity in human SC (HSC) cells using biomimetic extracellular matrix (ECM) hydrogels, and examine whether pharmacologic YAP/TAZ inhibition would attenuate TGFβ2-induced HSC cell dysfunction.MethodsPrimary HSC cells were seeded atop photocrosslinked ECM hydrogels, made of collagen type I, elastin-like polypeptide and hyaluronic acid, or encapsulated within the hydrogels. HSC cells were induced with TGFβ2 in the absence or presence of concurrent actin destabilization or pharmacologic YAP/TAZ inhibition. Changes in actin cytoskeletal organization, YAP/TAZ activity, ECM production, phospho-myosin light chain levels, and hydrogel contraction were assessed.ResultsTGFβ2 significantly increased YAP/TAZ nuclear localization in HSC cells, which was prevented by either filamentous (F)-actin relaxation or depolymerization. Pharmacologic YAP/TAZ inhibition using verteporfin without light stimulation decreased fibronectin expression and reduced actomyosin cytoskeletal rearrangement in HSC cells induced by TGFβ2. Similarly, verteporfin significantly attenuated TGFβ2-induced HSC cell-encapsulated hydrogel contraction.ConclusionsOur data provide evidence for a pathologic role of aberrant YAP/TAZ signaling in HSC cells under simulated glaucomatous conditions, and suggest that pharmacologic YAP/TAZ inhibition has promising potential to improve outflow tissue dysfunction.
Adaptation to starvation requires a flexible circadian clockwork inNeurospora crassa
Authors: Szőke Anita , Sárkány Orsolya , Schermann Géza , Kapuy Orsolya , Diernfellner Axel C. R. , Brunner Michael , Gyöngyösi Norbert , Káldi Krisztina 
Published: June 2022

AbstractThe circadian clock governs rhythmic cellular functions by driving expression of a substantial fraction of the genome and thereby significantly contributes to the adaptation to changing environmental conditions. Using the circadian model organismNeurospora crassa,we show that molecular timekeeping is robust even under severe limitation of carbon sources, however, stoichiometry, phosphorylation and subcellular distribution of the key clock components display drastic alterations. Protein kinase A, protein phosphatase 2A and glycogen synthase kinase are involved in the molecular reorganization of the clock. RNA-seq analysis reveals that the transcriptomic response of metabolism to starvation is highly dependent on the positive clock component WC-1. Moreover, our molecular and phenotypic data indicate that a functional clock facilitates recovery from starvation. We suggest that the molecular clock is a flexible network that allows the organism to maintain a rhythmic physiology and preserve fitness even under long-term nutritional stress.
Superinfection exclusion creates spatially distinct influenza virus populations
Authors: Sims Anna , Tornaletti Laura Burgess , Jasim Seema , Pirillo Chiara , Devlin Ryan , Hirst Jack , Loney Colin , Wojtus Joanna , Sloan Elizabeth , Thorley Luke , Boutell Chris , Roberts Edward , Hutchinson Edward 
Published: June 2022

AbstractInfluenza viruses can interact during coinfections, allowing viral fitness to be altered by genome complementation and competition, and increasing population diversity through reassortment. However, opportunities for these interactions are limited, as coinfection is blocked shortly after primary infection by a process known as superinfection exclusion (SIE). We asked whether SIE, which occurs at the level of individual cells, could limit within-host interactions between populations of influenza viruses as they spread across regions of cells. We first created a simplified model of within-host spread by infecting monolayers of cells with two isogenic influenza A viruses, each encoding a different fluorophore, and measuring the proportion of coinfected cells. In this system SIE begins within 2-4 hours of primary infection, with the kinetics of onset defined by the dose of primary virus. We then asked how SIE controls opportunities for coinfection as viruses spread across a monolayer of cells. We observed that viruses spreading from a single coinfected focus continued to coinfect cells as they spread, as all new infections were of cells that had not yet established SIE. In contrast, viruses spreading towards each other from separately infected foci could only establish minimal regions of coinfection before SIE blocked further coinfection. This patterning was recapitulated in the lungs of infected mice and is likely to apply to other viruses that exhibit SIE. It suggests that the kinetics of SIE onset separate a spreading infection into discrete regions, within which interactions between virus populations can occur freely, and between which they are blocked.ImportanceViral fitness and diversity are altered by genome interactions, which occur when multiple viruses coinfect a cell. This has been extensively studied for influenza A viruses (IAV), which use genome reassortment to adapt to new hosts and create pandemic strains, and whose replication can be compromised by the acquisition of defective-interfering RNAs. Coinfection of an individual cell by IAV is restricted by the gradual onset of superinfection exclusion (SIE). Replication of IAVs within host organisms involve the asynchronous replication of viruses as they spread to infect multiple cells. We found that under these circumstances, SIE creates spatially separated sub-populations of IAV, between which there are limited opportunities for genome interactions. Our work suggests SIE will cause many viruses to segregate into distinct subpopulations within their hosts, constraining the effects of genome interactions on their fitness and evolution.
The performance of deep generative models for learning joint embeddings of single-cell multi-omics data
Authors: Brombacher Eva , Hackenberg Maren , Kreutz Clemens , Binder Harald , Treppner Martin 
Published: June 2022

AbstractRecent extensions of single-cell studies to multiple data modalities raise new questions regarding experimental design. For example, the challenge of sparsity in single-omics data might be partly resolved by compensating for missing information across modalities. In particular, deep learning approaches, such as deep generative models (DGMs), can potentially uncover complex patterns via a joint embedding. Yet, this also raises the question of sample size requirements for identifying such patterns from single-cell multi-omics data. Here, we empirically examine the quality of DGM-based integrations for varying sample sizes. We first review the existing literature and give a short overview of deep learning methods for multi-omics integration. Next, we consider eight popular tools in more detail and examine their robustness to different cell numbers, covering two of the most common multi-omics types currently favored. Specifically, we use data featuring simultaneous gene expression measurements at the RNA level and protein abundance measurements for cell surface proteins (CITE-seq), as well as data where chromatin accessibility and RNA expression are measured in thousands of cells (10x Multiome). We examine the ability of the methods to learn joint embeddings based on biological and technical metrics. Finally, we provide recommendations for the design of multi-omics experiments and discuss potential future developments.
In-silico identification of potential antigenic proteins in Bartonella bacilliformis for the serological diagnosis of Carrions’ disease
Authors: Jimenez-Vasquez Victor , Calvay-Sanchez Karen , Zarate-Sulca Yanina , Ruiz Joaquim , Mendoza-Mujica Giovanna 
Published: June 2022

AbstractThe current methods for inferring antigenic, pathogenic or virulence factors in bacteria include in-silico or computational tools. Bartonella bacilliformis, the causal agent of Carriońs disease (CD) is a Gram-negative microorganism transmitted by the sand fly Lutzomya verrucarum mainly in Peruvian Inter-Andean valleys. A better understanding of the pathogenicity of B. bacilliformis, the implementation of serological diagnostic methods and the development of candidate vaccines for the control of CD could be facilitated by the identification of outer membrane exposed proteins such as outer-membrane beta-barrels (OMBB) and outer-membrane lipoproteins (OMLPP). In this study we present the in-silico identification of OMBBs and OMLPPs in B. bacilliformis. The present analysis identified 32 OMBBs and 9 OMLPPs, of which 15 and 4 are reported for the first time as potential antigenic, pathogenic and virulence-related proteins, respectively. Future implications of this study are discussed and compared with proteins validated by experimental assays.