bluuebunny/crossref_metadata_2025_split huggingface dataset:
Satellite cells deficiency and defective regeneration in dynamin 2‐related centronuclear myopathy
Authors: F. Almeida Camila , Bitoun Marc , Vainzof Mariz 
Published: March 2021

AbstractDynamin 2 (DNM2) is a ubiquitously expressed protein involved in many functions related to trafficking and remodeling of membranes and cytoskeleton dynamics. Mutations in the DNM2 gene cause the autosomal dominant centronuclear myopathy (AD‐CNM), characterized mainly by muscle weakness and central nuclei. Several defects have been identified in the KI‐Dnm2R465W/+ mouse model of the disease to explain the muscle phenotype, including reduction of the satellite cell pool in muscle, but the functional consequences of this depletion have not been characterized until now. Satellite cells (SC) are the main source for muscle growth and regeneration of mature tissue. Here, we investigated muscle regeneration in the KI‐Dnm2R465W/+ mouse model for AD‐CNM. We found a reduced number of Pax7‐positive SCs, which were also less activated after induced muscle injury. The muscles of the KI‐Dnm2R465W/+ mouse regenerated more slowly and less efficiently than wild‐type ones, formed fewer new myofibers, and did not recover its normal mass 15 days after injury. Altogether, our data provide evidence that the muscle regeneration is impaired in the KI‐Dnm2R465W/+ mouse and contribute with one more layer to the comprehension of the disease, by identifying a new pathomechanism linked to DNM2 mutations which may be involved in the muscle‐specific impact occurring in AD‐CNM.
Maternal adiponectin prevents visceral adiposity and adipocyte hypertrophy in prenatal androgenized female mice
Authors: Wu Yanling , Chanclón Belén , Micallef Peter , Stener‐Victorin Elisabet , Wernstedt Asterholm Ingrid , Benrick Anna 
Published: March 2021

AbstractHyperandrogenism is the main characteristic of polycystic ovary syndrome, which affects placental function and fetal growth, and leads to reproductive and metabolic dysfunction in female offspring. Adiponectin acts on the placenta and may exert endocrine effects on the developing fetus. This study aims to investigate if maternal and/or fetal adiponectin can prevent metabolic and reproductive dysfunction in prenatal androgenized (PNA) female offspring. Adiponectin transgenic (APNtg) and wild‐type dams received dihydrotestosterone/vehicle injections between gestational days 16.5‐18.5 to induce PNA offspring, which were followed for 4 months. Offspring from APNtg dams were smaller than offspring from wild‐type dams, independent of genotype. Insulin sensitivity was higher in wild‐type mice from APNtg dams compared to wild‐types from wild‐type dams, and insulin sensitivity correlated with fat mass and adipocyte size. PNA increased visceral fat% and adipocyte size in wild‐type offspring from wild‐type dams, while wild‐type and APNtg offspring from APNtg dams were protected against this effect. APNtg mice had smaller adipocytes than wild‐types and this morphology was associated with an increased expression of genes regulating adipogenesis (Ppard, Pparg, Cebpa, and Cebpb) and metabolism (Chrebp and Lpl). Anogenital distance was increased in all PNA‐exposed wild‐type offspring, but there was no increase in PNA APNtg offspring, suggesting that adiponectin overexpression protects against this effect. In conclusion, elevated adiponectin levels in utero improve insulin sensitivity, reduce body weight and fat mass gain in the adult offspring and protect against PNA‐induced visceral adiposity. In conclusion, these data suggest that PNA offspring benefit from prenatal adiponectin supplementation.
The microbiota plays a critical role in the reactivity of lung immune components to innate ligands
Authors: Marquant Quentin , Laubreton Daphné , Drajac Carole , Mathieu Elliot , Bouguyon Edwige , Noordine Marie‐Louise , Remot Aude , Riffault Sabine , Thomas Muriel , Descamps Delphyne 
Published: March 2021

AbstractThe gut microbiota contributes to shaping efficient and safe immune defenses in the gut. However, little is known about the role of the gut and/or lung microbiota in the education of pulmonary innate immune responses. Here, we tested whether the endogenous microbiota in general can modulate the reactivity of pulmonary tissue to pathogen stimuli by comparing the response of specific‐pathogen‐free (SPF) and germ‐free (GF) mice. Thus, we observed earlier and greater inflammation in the pulmonary compartment of GF mice than that of SPF mice after intranasal instillation to lipopolysaccharide (LPS), a component of Gram‐negative bacteria. Toll‐like receptor 4 (TLR4) was more abundantly expressed in the lungs of GF mice than those of SPF mice at steady state, which could predispose the innate immunity of GF mice to strongly react to the environmental stimuli. Lung explants were stimulated with different TLR agonists or infected with the human airways pathogen, respiratory syncytial virus (RSV), resulting in greater inflammation under almost all conditions for the GF explants. Finally, alveolar macrophages (AM) from GF mice presented a higher innate immune response upon RSV infection than those of SPF mice. Overall, these data suggest that the presence of microbiota in SPF mice induced a process of innate immune tolerance in the lungs by a mechanism which remains to be elucidated. Our study represents a step forward to establishing the link between the microbiota and the immune reactivity of the lungs.
A zebrafish toolbox for biomechanical signaling in cardiovascular development and disease
Authors: Rödel Claudia Jasmin , Abdelilah-Seyfried Salim 
Published: March 2021

Purpose of review
The zebrafish embryo has emerged as a powerful model organism to investigate the mechanisms by which biophysical forces regulate vascular and cardiac cell biology during development and disease. A versatile arsenal of methods and tools is available to manipulate and analyze biomechanical signaling. This review aims to provide an overview of the experimental strategies and tools that have been utilized to study biomechanical signaling in cardiovascular developmental processes and different vascular disease models in the zebrafish embryo. Within the scope of this review, we focus on work published during the last two years.

Recent findings
Genetic and pharmacological tools for the manipulation of cardiac function allow alterations of hemodynamic flow patterns in the zebrafish embryo and various types of transgenic lines are available to report endothelial cell responses to biophysical forces. These tools have not only revealed the impact of biophysical forces on cardiovascular development but also helped to establish more accurate models for cardiovascular diseases including cerebral cavernous malformations, hereditary hemorrhagic telangiectasias, arteriovenous malformations, and lymphangiopathies.

Summary
The zebrafish embryo is a valuable vertebrate model in which in-vivo manipulations of biophysical forces due to cardiac contractility and blood flow can be performed. These analyses give important insights into biomechanical signaling pathways that control endothelial and endocardial cell behaviors. The technical advances using this vertebrate model will advance our understanding of the impact of biophysical forces in cardiovascular pathologies.
Single-cell RNA sequencing to study vascular diversity and function
Authors: Ma Feiyang , Hernandez Gloria E. , Romay Milagros , Iruela-Arispe M. Luisa 
Published: March 2021

Purpose of review
Single-cell RNA sequencing (scRNA-seq) can capture the transcriptional profile of thousands of individual cells concurrently from complex tissues and with remarkable resolution. Either with the goal of seeking information about distinct cell subtypes or responses to a stimulus, the approach has provided robust information and promoted impressive advances in cardiovascular research. The goal of this review is to highlight strategies and approaches to leverage this technology and bypass potential caveats related to evaluation of the vascular cells.

Recent findings
As the most recent technological development, details associated with experimental strategies, analysis, and interpretation of scRNA-seq data are still being discussed and scrutinized by investigators across the vascular field. Compilation of this information is valuable for those using the technology but particularly important to those about to start utilizing scRNA-seq to seek transcriptome information of vascular cells.

Summary
As our field progresses to catalog transcriptomes from distinct vascular beds, it is undeniable that scRNA-seq technology is here to stay. Sharing approaches to improve the quality of cell dissociation procedures, analysis, and a consensus of best practices is critical as information from this powerful experimental platform continues to emerge.
Viral Pneumonia is Associated with Increased Risk and Earlier Development of Post-Inflammatory Pulmonary Fibrosis
Authors: Shojaee Abbas , Siner Jonathan M. , Zinchuk Andrey , Aryan Yalda , Kaminski Naftali , Dela Cruz Charles S. 
Published: March 2021

AbstractSevere inflammatory response, acute respiratory distress syndrome, and death are established serious consequences of the acute phase of severe viral pneumonia. However, the long-term respiratory outcomes of severe viral pneumonia, including its association with pulmonary fibrosis, are less known.ObjectiveTo determine whether viral pneumonia is associated with an increased incidence of post-inflammatory pulmonary fibrosis.DesignWe performed two retrospective observational cohort studies using longitudinal hospitalization records from the States of California (2005-2011) and Florida (2009-2015) for the discovery and validation studies, respectively. Patients who were 85-years-old and younger with at least two hospital encounters but without a prior diagnosis of pulmonary fibrosis were included. International Classification of Diseases-9 (ICD9) codes of primary and secondary diagnoses and procedures were used to identify the exposure: diagnosis of viral pneumonia; the outcome: incidence of post-inflammatory pulmonary fibrosis [PIPF, ICD9: 515]; and the confounders.MethodsChronological age was used as the study time scale. Non-parametric Kaplan-Meier (KM) estimator and semiparametric Cox Proportional Hazard modelling were used to assessing the risk of PIPF. P-values < 10−3 were considered significant.ResultsAmong 9,802,565 patients from California and 8,741,345 patients in Florida cohorts, the prevalence of PIPF was 0.61% and 0.62% over 7 and 6.75 years, respectively. Patients with incident PIPF were older than those without [68(SD: 11) vs. 40(22) years]; among patients with PIPF, those with viral pneumonia diagnosis were younger than those without [63(12) versus 68(11) years]. Incidence of PIPF was higher for those with viral pneumonia diagnosis versus those without [1.6 (CI:1.51-1.69) vs. 0.91 (CI:0.86-0.96)] cases per 1000 person-years in California and in Florida [1.11 (CI:1.06 −1.16) vs, 0.93 (CI:0.89-0.98)]. Viral pneumonia was associated with increased risk of incident PIPF in both California aHR = 1.49 (1.38, 1.61), and Florida aHR of 1.26 (1.20, 1.33) cohorts (Table). Among patients who developed PIPF, the median time to diagnosis was 7.41 (6.16 −8.66) and 4.80 (4.34 - 5.26) years earlier for patients with viral pneumonia versus without in California and Florida cohorts. The association of viral pneumonia was not found for idiopathic pulmonary fibrosis [ICD9: 516.3]. Our findings suggest that patients hospitalized with viral pneumonia may have long term respiratory sequela that is often overlooked and suggest a need for additional studies focusing on phenotyping susceptible patients. This finding is especially important in light of the current COVID-19 pandemic because viral pneumonia is the most common manifestations of the disease, which could lead to subsequent fibrosis.
Persistence of SARS-CoV-2 virus and viral RNA on hydrophobic and hydrophilic surfaces and investigating contamination concentration
Authors: Paton Susan , Spencer Antony , Garratt Isobel , Thompson Katy-Anne , Dinesh Ikshitaa , Aranega-Bou Paz , Stevenson David , Clark Simon , Dunning Jake , Bennett Allan , Pottage Thomas 
Published: March 2021

AbstractThe transmission of SARS-CoV-2 is likely to occur through a number of routes, including contact with contaminated surfaces. Many studies have used RT-PCR analysis to detect SARS-CoV-2 RNA on surfaces but seldom has viable virus been detected. This paper investigates the viability over time of SARS-CoV-2 dried onto a range of materials and compares viability of the virus to RNA copies recovered, and whether virus viability is concentration dependant.Viable virus persisted for the longest time on surgical mask material and stainless steel with a 99.9% reduction in viability by 124 and 113 hours respectively. Viability of SARS-CoV-2 reduced the fastest on a polyester shirt, with a 99.9% reduction within 2.5 hours. Viability on cotton was reduced second fastest, with 99.9% reduction in 72 hours. RNA on all the surfaces exhibited a one log reduction in genome copy recovery over 21 days.The findings show that SARS-CoV-2 is most stable on non-porous hydrophobic surfaces. RNA is highly stable when dried on surfaces with only one log reduction in recovery over three weeks. In comparison, SARS-CoV-2 viability reduced more rapidly, but this loss in viability was found to be independent of starting concentration. Expected levels of SARS-CoV-2 viable environmental surface contamination would lead to undetectable levels within two days. Therefore, when RNA is detected on surfaces it does not directly indicate presence of viable virus even at high CT values.ImportanceThis study shows the impact of material type on the viability of SARS-CoV-2 on surfaces. It demonstrates that the decay rate of viable SARS-CoV-2 is independent of starting concentration. However, RNA shows high stability on surfaces over extended periods. This has implications for interpretation of surface sampling results using RT-PCR to determine the possibility of viable virus from a surface. Unless sampled immediately after contamination it is difficult to align RNA copy numbers to quantity of viable virus on a surface.
Diurnal variation in SARS-CoV-2 PCR test results: Test accuracy may vary by time of day
Authors: McNaughton Candace D. , Adams Nicholas M. , Johnson Carl Hirschie , Ward Michael J. , Lasko Thomas A. 
Published: March 2021

AbstractFalse negative tests for SARS-CoV-2 are common and have important public health and medical implications. We tested the hypothesis that the proportion of positive SARS-CoV-2 real-time polymerase chain reaction (RT-PCR) tests varied by time of day, suggesting variation in viral shedding by time of day. Among 30,000 clinical tests performed among symptomatic and asymptomatic patients in the Vanderbilt Affiliated Healthcare Network from March-June 2020, we found evidence for diurnal variation in the proportion of positive SARS-CoV-2 tests, with a peak around 2pm in the afternoon and 2-fold variation over the day. Variation was most pronounced in outpatient and inpatient testing locations. These findings have important implications for public health testing and vaccination strategies.
Modeling the use of SARS-CoV-2 vaccination to safely relax non-pharmaceutical interventions
Authors: Kraay Alicia N.M. , Gallagher Molly E. , Ge Yang , Han Peichun , Baker Julia M. , Koelle Katia , Handel Andreas , Lopman Benjamin A 
Published: March 2021

AbstractIn response to the COVID-19 pandemic, widespread non-pharmaceutical interventions (NPIs), including physical distancing, mask wearing, and enhanced hygiene, have been implemented. As of March 2021, three effective vaccines have been approved for emergency use in the United States, with several other vaccines in the pipeline. We use a transmission model to study when and how NPIs could be relaxed in the United States with relative safety as vaccination becomes more widespread. We compare different relaxation scenarios where NPIs begin to relax 0-9 months after vaccination begins for both a one dose and two dose strategy, with historical levels of social interactions being reached within 1 month to 1 year. In our model, vaccination can allow widespread relaxation of NPIs to begin safely within 2 to 9 months, greatly reducing deaths and peak health system burden compared to relaxing NPIs without vaccination. Vaccinated individuals can safely begin to relax NPIs sooner than unvaccinated individuals. The extent of delay needed to safely reopen depends primarily on the rate of vaccine rollout, with the degree of protection against asymptomatic infection playing a secondary role. If a vaccination rate of 3 million doses/day can be achieved, similar to the typical rollout speed of seasonal influenza vaccination, NPIs could begin to be safely relaxed in 2-3 months. With a vaccination rate of 1 million doses/day, a 6–9-month delay is needed. A one dose strategy is preferred if relative efficacy is similar to a two-dose series, but the relative benefit of this strategy is minimal when vaccine rollout is fast. Due to the urgent need to pursue strategies that enable safe relaxation of NPIs, we recommend a two-dose strategy with an initial delay of at least 3 months in relaxing restrictions further, and that the speed of vaccine rollout be given immediate priority.
Limits of lockdown: characterising essential contacts during strict physical distancing
Authors: Thomas Amy , Danon Leon , Christensen Hannah , Northstone Kate , Smith Daniel , Nixon Emily , Trickey Adam , Hemani Gibran , Sauchelli Sarah , Finn Adam , Timpson Nicholas , Brooks-Pollock Ellen 
Published: March 2021

ABSTRACTCOVID-19 has exposed health inequalities within countries and globally. The fundamental determining factor behind an individual’s risk of infection is the number of social contacts they make. In many countries, physical distancing measures have been implemented to control transmission of SARS-CoV-2, reducing social contacts to a minimum. Characterising unavoidable social contacts is key for understanding the inequalities behind differential risks and planning vaccination programmes. We utilised an existing English longitudinal birth cohort, which is broadly representative of the wider population (n=6807), to explore social contact patterns and behaviours when strict physical distancing measures were in place during the UK’s first lockdown in March-May 2020. Essential workers, specifically those in healthcare, had 4.5 times as many contacts as non-essential workers [incident rate ratio = 4.42 (CI95%: 3.88–5.04)], whilst essential workers in other sectors, mainly teaching and the police force had three times as many contacts [IRR = 2.84 (2.58–3.13)]. The number of individuals in a household, which is conflated by number of children, increases essential social contacts by 40%. Self-isolation effectively reduces numbers of contacts outside of the home, but not entirely. Together, these findings will aid the interpretation of epidemiological data and impact the design of effective SARS-CoV-2 control strategies, such as vaccination, testing and contact tracing.
Serum Vitamin D levels are associated with increased COVID-19 severity and mortality independent of whole-body and visceral adiposity
Authors: Vanegas-Cedillo Pablo Esteban , Bello-Chavolla Omar Yaxmehen , Ramírez-Pedraza Natalia , Encinas Bethsabel Rodríguez , Pérez Carrión Carolina Isabel , Jasso-Ávila María Isabel , Valladares-García Jorge Carlos , Hernández-Juárez Diana , Vargas-Vázquez Arsenio , Antonio-Villa Neftali Eduardo , Chapa-Ibarguengoitia Monica , de Leon Alfredo Ponce , Sifuentes-Osornio José , Aguilar-Salinas Carlos A. , Mehta Roopa 
Published: March 2021

ABSTRACTINTRODUCTIONCoronavirus disease (COVID-19) is a global pandemic. Vitamin D deficiency has been associated with susceptibility to infectious disease. In this study, the association between COVID-19 outcomes and vitamin D levels in patients attending a COVID-19 reference center in Mexico City are examined.METHODSConsecutive patients with confirmed COVID-19 were evaluated. All patients underwent clinical evaluation and follow-up, laboratory measurements and a thoracic computerized tomography, including the measurement of epicardial fat thickness. Low vitamin D was defined as levels <20ng/mL (<50nmol/L) and deficient Vitamin D as a level ≤12ng/mL (<30nmol/L)RESULTSOf the 551 patients included, low vitamin D levels were present in 45.6% and deficient levels in 10.9%. Deficient Vitamin D levels were associated with mortality (HR 2.11, 95%CI 1.24-3.58, p=0.006) but not with critical COVID-19, adjusted for age, sex, body-mass index and epicardial fat. Using model-based causal mediation analyses the increased risk of COVID-19 mortality conferred by low vitamin D levels was partly mediated by its effect on D-dimer and cardiac ultrasensitive troponins. Notably, increased risk of COVID-19 mortality conferred by low vitamin D levels was independent of BMI and epicardial fat.CONCLUSIONVitamin D deficiency (≤12ng/mL or <30nmol/L), is independently associated with COVID-19 mortality after adjustment for visceral fat (epicardial fat thickness). Low vitamin D may contribute to a pro-inflammatory and pro-thrombotic state, increasing the risk for adverse COVID-19 outcomes.
Seroprevalence of Antibodies to SARS-CoV-2 among Health Care Workers in Kenya
Authors: Etyang Anthony O. , Lucinde Ruth , Karanja Henry , Kalu Catherine , Mugo Daisy , Nyagwange James , Gitonga John , Tuju James , Wanjiku Perpetual , Karani Angela , Mutua Shadrack , Maroko Hosea , Nzomo Eddy , Maitha Eric , Kamuri Evanson , Kaugiria Thuranira , Weru Justus , Ochola Lucy B. , Kilimo Nelson , Charo Sande , Emukule Namdala , Moracha Wycliffe , Mukabi David , Okuku Rosemary , Ogutu Monicah , Angujo Barrack , Otiende Mark , Bottomley Christian , Otieno Edward , Ndwiga Leonard , Nyaguara Amek , Voller Shirine , Agoti Charles , Nokes David James , Ochola-Oyier Lynette Isabella , Aman Rashid , Amoth Patrick , Mwangangi Mercy , Kasera Kadondi , Ng’ang’a Wangari , Adetifa Ifedayo , Kagucia E. Wangeci , Gallagher Katherine , Uyoga Sophie , Tsofa Benjamin , Barasa Edwine , Bejon Philip , Scott J. Anthony G. , Agweyu Ambrose , Warimwe George 
Published: March 2021

ABSTRACTBackgroundFew studies have assessed the seroprevalence of antibodies against SARS-CoV-2 among Health Care Workers (HCWs) in Africa. We report findings from a survey among HCWs in three counties in Kenya.MethodsWe recruited 684 HCWs from Kilifi (rural), Busia (rural) and Nairobi (urban) counties. The serosurvey was conducted between 30thJuly 2020 and 4thDecember 2020. We tested for IgG antibodies to SARS-CoV-2 spike protein using ELISA. Assay sensitivity and specificity were 93% (95% CI 88-96%) and 99% (95% CI 98-99.5%), respectively. We adjusted prevalence estimates using Bayesian modeling to account for assay performance.ResultsCrude overall seroprevalence was 19.7% (135/684). After adjustment for assay performance seroprevalence was 20.8% (95% CI 17.5-24.4%). Seroprevalence varied significantly (p<0.001) by site: 43.8% (CI 35.8-52.2%) in Nairobi, 12.6% (CI 8.8-17.1%) in Busia and 11.5% (CI 7.2-17.6%) in Kilifi. In a multivariable model controlling for age, sex and site, professional cadre was not associated with differences in seroprevalence.ConclusionThese initial data demonstrate a high seroprevalence of antibodies to SARS-CoV-2 among HCWs in Kenya. There was significant variation in seroprevalence by region, but not by cadre.