bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of the Quality, Reliability, and Educational Content of YouTube Videos as an Information Source for Soft Contact Lenses
Authors: Yildiz Merve Beyza , Yildiz Elvin , Balci Sevcan , Özçelik Köse Alev
Published: April 2021

Objectives:

To evaluate the quality, reliability, and educational content of YouTube videos related to soft contact lenses (CL).

Methods:

An online YouTube search was performed for the terms contact lens and other common CL-related terms contact lens insertion and removal, contact lens wearing, and contact lens care. The first 50 videos were evaluated for each term. Videos were evaluated using three checklists (the modified DISCERN criteria, the Journal of the American Medical Association [JAMA] criteria, and Global Quality Score [GQS]). Video popularity was also evaluated using the video power index (VPI). Videos were classified into three groups according to the source of the upload; group 1: universities/occupational organizations, group 2: medical ad/profit-oriented companies, and group 3: independent users.

Results:

From among the 200 videos analyzed, 79 were included. The mean mDISCERN score of the videos was 2.34±1.39, the mean JAMA score was 1.20±0.99, and the mean GQS value was 3.47±1.28. There were positive correlations between the three checklists (P<0.001). Video power index was not correlated with each score. The videos in group 1 (13.9%) had the highest scores whereas videos in group 3 (41.8%) had the lowest scores. There was no significant difference between the video sources according to the VPI.

Conclusion:

Although some YouTube videos contain useful information for CL wearers, most videos have poor quality and reliability and contain insufficient information. Eye care providers should be aware of these sources and steer CL users to information sources that provide accurate and reliable information and do not contain misleading information.
Investigation of the Peripapillary Choriocapillaris in Normal Tension Glaucoma, Primary Open-angle Glaucoma, and Control Eyes
Authors: Bhalla Mahadev , Heisler Morgan , Mammo Zaid , Ju Myeong Jin , Sarunic Marinko V. , Navajas Eduardo V. , Warner Simon , Schendel Steven , Gill Kulbir S.
Published: April 2021

Precis:

The peripapillary choriocapillaris (CC) was observed to be significantly impaired in normal tension glaucoma (NTG) subjects compared with normal controls using optical coherence tomography angiography (OCTA).

Purpose:

The aim was to quantitatively evaluate the peripapillary CC in NTG, primary open-angle glaucoma (POAG), and control eyes using OCTA.

Materials and Methods:

Ninety eyes (30 controls, 30 NTG, and 30 POAG) from 73 patients were imaged using the Zeiss Plex Elite 9000. Five repeat 3×3 mm OCTA scans were acquired both nasally and temporally to the optic disc and subsequently averaged. Four CC flow deficit (FD) measures were calculated using the fuzzy C-means approach: FD density (FDD), mean FD size (MFDS), FD number (FDN), and FD area (FDA).

Results:

Temporal NTG CC parameters were associated with visual field index and mean deviation (P<0.05). The control group showed a significantly lower nasal FDD (nasal: 3.79±1.26%, temporal: 4.48±1.73%, P=0.03), FDN (nasal: 156.43±38.44, temporal: 178.40±45.68, P=0.02), and FDA (nasal: 0.22±0.08, temporal: 0.26±0.10, P=0.03) when compared with temporal optic disc. The NTG group showed a significantly higher FDD (NTG: 5.04±2.38%, control: 3.79±1.26%, P=0.03), FDN (NTG: 185.90±56.66, control: 156.43±38.44, P=0.04), and FDA (NTG: 0.30±0.14 mm2, control: 0.22±0.08 mm2, P=0.03) nasal to the optic disc compared with controls.

Conclusions:

Association between CC parameters and glaucoma severity in NTG, but not POAG subjects, suggests vascular abnormalities may be a potential factor in the multifactorial process of glaucoma damage in NTG patients.
A Case Report of Methylobacterium radiotolerans Bacteremia and Brain Abscesses
Authors: Tang Wesley , Desai Alpa , Desai Kunal
Published: April 2021

Methylobacterium radiotolerans is a ubiquitous organism found in the environment and is considered an opportunistic pathogen of low virulence in humans. Most human infections from M. radiotolerans have been reported in immunocompromised hosts and have been reported mainly as bloodstream infections related to central venous catheters. We present the first known case of M. radiotolerans as a causative agent of multiple brain abscesses in an immunocompromised host.
Leadership in Healthcare: Transitioning From Clinical Professional to Healthcare Leader
Authors: Perez Jessica
Published: April 2021

EXECUTIVE SUMMARY

Clinical professionals may not have the necessary evidence-based knowledge regarding specific leadership styles to succeed in a leadership role. This article examines the various leadership styles that can be adopted by a clinical professional who transitions into a leadership role. The Path-Goal theory developed by Robert House in 1971 was used as the theoretical lens for this study. Twenty scholarly, peer-reviewed articles written in English and published between 2015 and 2020 were analyzed and synthesized to develop the findings. The findings showed that employee retention was positively associated with transformational and authentic leadership styles; organizational commitment was positively associated with transformational, transactional, and authentic leadership styles; and job satisfaction was positively associated with transformational and authentic leadership styles. In particular, a transformational leadership style demonstrated higher rates of employee retention and job satisfaction than did transactional and laissez-faire leadership styles. The authentic and transformational leadership styles each saw increased job satisfaction and commitment, but a correlation between the authentic leadership style and those benefits was less evident. Clinical professionals should apply the transformational leadership style to become effective leaders.
Use of Contact Lenses in an Industrial Environment
Authors: Saito Kenji , Hovis Jeff K.
Published: April 2021

Industrial workers can come into contact with harmful agents that are transmitted via the eye in the form of an aerosol droplet or splash. Contact lenses do not provide ocular protection from hazards. This guidance from the American College of Occupational and Environmental Medicine addresses the use of contact lenses and personal protective equipment by the industrial worker and provides recommendations for contact lens use in an eye-hazardous environment.
Association of Parent Workplace Injury With Emotional and Behavioral Problems in Children
Authors: Asfaw Abay , Sauter Steven L. , Swanson Naomi , Beach Cheryl M. , Sauter Diana L.
Published: April 2021

Objective:

Investigate associations between occupational injury to parents and the psychological well-being of their children.

Methods:

We used multiple logistic regression to examine effects of occupational injury to parents on measures of psychological well-being among their children using National Health Interview Survey data from 2012 through 2016.

Results:

Children of injured workers exhibited greater impairment than children of workers who had not sustained injuries for four of five measures of emotional and behavioral functioning that were hypothesized to differentiate these two child groups. A significant group difference was not observed for a sixth behavioral measure that was expected to be insensitive to parent occupational injury.

Conclusion:

Study findings heighten concern over downstream effects of occupational injury and signal need for more expansive investigation of these effects and mitigation strategies among children of injured workers.
Brief Report: Prevalence Trend of Transmitted Drug Resistance in a Prospective Cohort of Thai People With Acute HIV Infection
Authors: Muccini Camilla , Pinyakorn Suteeraporn , Sirivichayakul Sunee , Kroon Eugene , Sacdalan Carlo , Crowell Trevor A. , Trichavaroj Rapee , Ananworanich Jintanat , Vasan Sandhya , Phanuphak Nittaya , Colby Donn J. ,   On Behalf of the RV254 Study Group
Published: April 2021

Background:

The greater availability of different antiretroviral therapy regimens in developing countries may influence the emergence of transmitted drug resistance (TDR). People with acute HIV infection (AHI) represent the best opportunity for real-time monitoring of TDR. This study assessed the TDR prevalence trends over time in a Thai cohort of predominantly men who have sex with men (MSM) with AHI.

Methods:

At the time of RV254/SEARCH010 study (NCT00796146) enrollment and before starting ART, HIV genotyping was used to identify mutations in the reverse transcriptase and protease genes. Testing for TDR mutations was obtained by a validated in-house method with TRUGENE assay in a subset. Genotype sequences were analyzed using the Stanford University HIV Drug Resistance Database.

Results:

Genotyping was performed for 573 participants with AHI. Their median age was 26 years (interquartile range 22–31), 97.4% were men, and 94.1% were MSM. Overall TDR prevalence was 7.0%, declining from 12.5% in 2009–2010 to 4.8% in 2017–2018. A declining resistance prevalence to nonnucleoside reverse transcriptase inhibitor emerged from 9.4% in 2009–2010 to 3.5% in 2017–2018 and to nucleoside reverse transcriptase inhibitor from 6.3% to 2.1%. Protease inhibitor resistance showed a decreased TDR level from 3.1% in 2009–2010 to 1.4% in 2017–2018.

Conclusions:

We report an encouraging declining trend in TDR prevalence in a Thai cohort of mainly MSM from 2009 to 2018; in 2017–2018, we observed a low TDR prevalence according to the World Health Organization definition.
Brief Report: “I Didn't Really Have a Primary Care Provider Until I Got PrEP”: Patients' Perspectives on HIV Preexposure Prophylaxis as a Gateway to Health Care
Authors: Sewell Whitney C. , Powell Victoria E. , Ball-Burack Maya , Mayer Kenneth H. , Ochoa Aileen , Marcus Julia L. , Krakower Douglas S.
Published: April 2021

Background:

HIV prevention is the primary goal of preexposure prophylaxis (PrEP); however, ancillary benefits may exist, including PrEP as an entry point to primary care.

Objective:

To explore PrEP users' perspectives on how PrEP use relates to broader engagement in health care.

Design:

In-depth qualitative interviews.

Participants:

We recruited PrEP users aged 18 years or older from a social media group for people interested in PrEP information and a Boston community health center specializing in health care for sexual and gender minorities.

Approach:

Inductive content analysis to identify emergent themes.

Key results:

All 25 participants were men who have sex with men, whose mean age was 34 years, and 84% were White. Three major themes emerged: (1) accessing PrEP was a strong motivator for initial and continued engagement in health care, which for some evolved over time into accessing comprehensive primary care; (2) provider awareness and attitudes about PrEP influenced participants' ongoing engagement in health care; and (3) PrEP engendered a positive sense of control over users' personal health, giving them agency in reducing their risk of HIV and engaging in other aspects of their health. Quarterly PrEP visits helped participants establish and maintain a relationship with a primary care provider, access non–HIV-related care services, and feel empowered to keep themselves healthy.

Conclusions:

The benefits of PrEP extend beyond HIV prevention to broader engagement in health care, including new relationships with primary care providers and use of other preventive health care services. To maximize those benefits, efforts are needed to ensure that providers are aware, nonjudgmental, and supportive of PrEP use.
Therapeutically Targeting Microvascular Leakage in Experimental Hemorrhagic SHOCK: A Systematic Review and Meta-Analysis
Authors: van Leeuwen Anoek L.I. , Borgdorff Marieke P. , Dekker Nicole A.M. , van den Brom Charissa E.
Published: April 2021

Background:

Microvascular leakage is proposed as main contributor to disturbed microcirculatory perfusion following hemorrhagic shock and fluid resuscitation, leading to organ dysfunction and unfavorable outcome. Currently, no drugs are available to reduce or prevent microvascular leakage in clinical practice. We therefore aimed to provide an overview of therapeutic agents targeting microvascular leakage following experimental hemorrhagic shock and fluid resuscitation.

Methods:

PubMed, EMBASE.com, and Cochrane Library were searched in January 2021 for preclinical studies of hemorrhagic shock using any therapeutic agent on top of standard fluid resuscitation. Primary outcome was vascular leakage, defined as edema, macromolecule extravasation, or glycocalyx degradation. Drugs were classified by targeting pathways and subgroup analyses were performed per organ.

Results:

Forty-five studies, published between 1973 and 2020, fulfilled eligibility criteria. The included studies tested 54 different therapeutics mainly in pulmonary and intestinal vascular beds. Most studies induced trauma besides hemorrhagic shock. Forty-four therapeutics (81%) were found effective to reduce microvascular leakage, edema formation, or glycocalyx degradation in at least one organ. Targeting oxidative stress and apoptosis was the predominantly effective strategy (SMD: −2.18, CI [−3.21, −1.16], P < 0.0001). Vasoactive agents were found noneffective in reducing microvascular leakage (SMD: −0.86, CI [−3.07, 1.36], P = 0.45).

Conclusion:

Pharmacological modulation of pathways involved in cell metabolism, inflammation, endothelial barrier regulation, sex hormones and especially oxidative stress and apoptosis were effective in reducing microvascular leakage in experimental hemorrhagic shock with fluid resuscitation. Future studies should investigate whether targeting these pathways can restore microcirculatory perfusion and reduce organ injury following hemorrhagic shock.

Systematic review registration number:

CRD42018095432.
Central vein sign and iron rim in multiple sclerosis: ready for clinical use?
Authors: Preziosa Paolo , Rocca Maria A. , Filippi Massimo
Published: April 2021

Purpose of review

To summarize recent evidence from the application of susceptibility-based MRI sequences to investigate the ‘central vein sign’ (CVS) and ‘iron rim’ as biomarkers to improve the diagnostic work-up of multiple sclerosis (MS) and predict disease severity.

Recent findings

The CVS is a specific biomarker for MS being detectable from the earliest phase of the disease. A threshold of 40% of lesions with the CVS can be optimal to distinguish MS from non-MS patients. Iron rim lesions, reflecting chronic active lesions, develop in relapsing-remitting MS patients and persist in progressive MS. They increase in size in the first few years after their formation and then stabilize. Iron rim lesions can distinguish MS from non-MS patients but not the different MS phenotypes. The presence of at least four iron rim lesions is associated with an earlier clinical disability, higher prevalence of clinically progressive MS and more severe brain atrophy. Automated methods for CVS and iron rim lesion detection are under development to facilitate their quantification.

The assessment of the CVS and iron rim lesions is feasible in the clinical scenario and provides MRI measures specific to MS pathological substrates, improving diagnosis and prognosis of these patients.
Genetic analysis of lung cancer reveals novel susceptibility loci and germline impact on somatic mutation burden
Authors: Gabriel Aurélie AG , Atkins Joshua R , Penha Ricardo CC , Smith-Byrne Karl , Gaborieau Valerie , Voegele Catherine , Abedi-Ardekani Behnoush , Milojevic Maja , Olaso Robert , Meyer Vincent , Boland Anne , François Deleuze Jean , Zaridze David , Mukeriya Anush , Swiatkowska Beata , Janout Vladimir , Schejbalová Miriam , Mates Dana , Stojšić Jelena , Ognjanovic Miodrag , Witte John S , Rashkin Sara R , Kachuri Linda , Hung Rayjean J , Kar Siddhartha , Brennan Paul , Sertier Anne-Sophie , Ferrari Anthony , Viari Alain , Johansson Mattias , Amos Christopher I , Foll Matthieu , McKay James D
Published: April 2021

Germline genetic variants are involved in lung cancer (LC) susceptibility. Previous genome-wide association studies (GWAS) have implicated genes involved in smoking propensity and DNA repair but further work is required to identify additional LC susceptibility variants and to investigate LC disease development dynamics.

We have undertaken a family history-based genome-wide association (GWAx) study of LC, analysing 48,843 European cases with a parent/sibling with LC compared to 195,387 controls from the UK Biobank. This was meta-analysed with previously described LC GWAS results. We performed Polygenic Risk Scores (PRS) analyses and further evaluated the PRS influence on the somatic environment in exome (N=736) and genome sequencing (N=61) profiled cohorts.

Eight novel loci were identified including DNA repair genes (CHEK1, MDM4), metabolic genes (CYP1A1) and variants that were also associated with smoking propensity, such as both subunits of the neuronal α4β2 nicotinic acetylcholine receptor (CHRNA4 and CHRNB2). PRS analysis demonstrated that variants related to eQTLs and/or smoking propensity are enriched for susceptibility variants, including variants below genome-wide significant threshold. PRS of LC variants related to smoking propensity were associated with somatic mutation burden in two case cohorts, with individuals with higher polygenic genetic risk having increased numbers of somatic mutations in their lung tumours.

This study has expanded the number of susceptibility loci linked with LC and provided insights into the molecular mechanisms by which these susceptibility variants contribute to the development of lung cancer.
KLF3 and PAX6 are candidate driver genes in late-stage, MSI-hypermutated endometrioid endometrial carcinomas
Authors: Rudd Meghan L. , Hansen Nancy F. , Zhang Xiaolu , Urick Mary Ellen , Zhang Suiyuan , Merino Maria J. ,   National Institutes of Health Intramural Sequencing Center Comparative Sequencing Program, Mullikin James C. , Brody Lawrence C. , Bell Daphne W.
Published: April 2021

Endometrioid endometrial carcinomas (EECs) are the most common histological subtype of uterine cancer. Late-stage disease is an adverse prognosticator for EEC. The purpose of this study was to analyze EEC exome mutation data to identify late-stage-specific statistically significantly mutated genes (SMGs), which represent candidate driver genes potentially associated with disease progression. We exome sequenced 15 late-stage (stage III or IV) non-ultramutated EECs and paired non-tumor DNAs; somatic variants were called using Strelka, Shimmer, Somatic Sniper and MuTect. Additionally, somatic mutation calls were extracted from The Cancer Genome Atlas (TCGA) data for 66 late-stage and 270 early-stage (stage I or II) non-ultramutated EECs. MutSigCV (v1.4) was used to annotate SMGs in the two late-stage cohorts and to derive p-values for all mutated genes in the early-stage cohort. To test whether late-stage SMGs are statistically significantly mutated in early-stage tumors, q-values for late-stage SMGs were re-calculated from the MutSigCV (v1.4) early-stage p-values, adjusting for the number of late-stage SMGs tested. We identified 14 SMGs in the combined late-stage EEC cohorts. When the 14 late-stage SMGs were examined in the TCGA early-stage data, only KLF3 and PAX6 failed to reach significance as early-stage SMGs, despite the inclusion of enough early-stage cases to ensure adequate statistical power. Within TCGA, nonsynonymous mutations in KLF3 and PAX6 were, respectively, exclusive or nearly exclusive to the microsatellite instability (MSI)-hypermutated molecular subgroup and were dominated by insertions-deletions at homopolymer tracts. In conclusion, our findings are hypothesis-generating and suggest that KLF3 and PAX6, which encode transcription factors, are MSI target genes and late-stage-specific SMGs in EEC.
Local emergence and decline of a SARS-CoV-2 variant with mutations L452R and N501Y in the spike protein
Authors: Mallm Jan-Philipp , Bundschuh Christian , Kim Heeyoung , Weidner Niklas , Steiger Simon , Lander Isabelle , Börner Kathleen , Bauer Katharina , Hübschmann Daniel , Benes Vladimir , Rausch Tobias , de Azevedo Nayara Trevisan Doimo , Telzerow Anja , Jost Katharina Laurence , Parthé Sylvia , Schnitzler Paul , Boutros Michael , Müller Barbara , Bartenschlager Ralf , Kräusslich Hans-Georg , Rippe Karsten
Published: April 2021

Variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are replacing the initial wild-type strain, jeopardizing current efforts to contain the pandemic. Amino acid exchanges in the spike protein are of particular concern as they can render the virus more transmissible or reduce vaccine efficacy. Here, we conducted whole genome sequencing of SARS-CoV-2 positive samples from the Rhine-Neckar district in Germany during January-March 2021. We detected a total of 166 samples positive for a variant with a distinct mutational pattern in the spike gene comprising L18F, L452R, N501Y, A653V, H655Y, D796Y and G1219V with a later gain of A222V. This variant was designated A.27.RN according to its phylogenetic clade classification. It emerged in parallel with the B.1.1.7 variant, increased to >50% of all SARS-CoV-2 variants by week five. Subsequently it decreased to <10% of all variants by calendar week eight when B.1.1.7 had become the dominant strain. Antibodies induced by BNT162b2 vaccination neutralized A.27.RN but with a two-to-threefold reduced efficacy as compared to the wild-type and B.1.1.7 strains. These observations strongly argue for continuous and comprehensive monitoring of SARS-CoV-2 evolution on a population level.
Pre-pandemic mental and physical health as predictors of COVID-19 vaccine hesitancy: evidence from a UK-wide cohort study
Authors: Batty G. David , Deary Ian J. , Altschul Drew
Published: April 2021

Importance

Although several predictors of COVID-19 vaccine hesitancy have been identified, the role of physical health has not been well-examined, and the association with mental health is unknown.

Objective

To examine the association of pre-pandemic mental health, physical health, and shielding with vaccine hesitancy after the announcement of the successful testing of the Oxford University/AstraZeneca vaccine.

Design, Setting, and Participants

We used individual-level data from a pandemic-focused investigation (COVID Survey), a prospective cohort study nested within the UK Understanding Society (Main Survey) project. In the week immediately following the announcement of successful testing of the first efficacious inoculation (November/December 2020), data on vaccine intentionality were collected in 12,035 individuals aged 16-95 years. Pre-pandemic, study members had responded to enquiries about diagnoses of mental and physical health, completed the 12-item General Health Questionnaire for symptoms of psychological distress (anxiety and depression), and indicated whether they or someone in their household was shielding.

Main outcome measures

Self-reported intention to take up a vaccination for COVID-19. To summarise our results, we computed odds ratios with accompanying 95% confidence intervals for indices of health and shielding adjusted for selected covariates.

Results

In an analytical sample of 11,955 people (6741 women), 15.4% indicated that they were vaccine hesitant. Relative to their disease-free counterparts, shielding was associated with a 24% lower risk of being hesitant (odds ratio; 95% confidence interval: 0.76; 0.59, 0.96), after adjustment for a range of covariates which included age, education, and ethnicity. Corresponding results for cardiometabolic disease were 22% (0.78; 0.64, 0.95), and for respiratory disease were 26% (0.74; 0.59, 0.93). Having a pre-pandemic diagnosis of anxiety or depression, or a high score on the distress symptom scale, were all unrelated to the willingness to take up a vaccine.

Conclusions and relevance

People who have been prioritised for COVID-19 vaccination owing to a physical condition are more likely to take it up. These effects were not apparent for indices of mental health.
Comprehensive genome-wide association study of different forms of hernia identifies more than 80 associated loci
Authors: Fadista João , Skotte Line , Karjalainen Juha , Abner Erik , Sørensen Erik , Ullum Henrik , Werge Thomas ,   iPSYCH-group, Esko Tõnu , Milani Lili , Palotie Aarno , Daly Mark ,   FinnGen, Melbye Mads , Feenstra Bjarke , Geller Frank
Published: April 2021

Hernias are characterized by protrusion of an organ or tissue through its surrounding cavity and often require surgical repair. We identified 65,492 cases for five hernia types in the UK Biobank and performed genome-wide association study scans for these five types and two combined groups. The results showed associated variants in all scans. Inguinal hernia had the most associations and we conducted a replication study with 23,803 additional cases from four study groups giving 84 independently associated variants. Identified variants from all scans were collapsed into 81 independent loci. Further testing showed that 26 loci were associated with more than one hernia type, suggesting substantial overlap between the underlying genetic mechanisms. Pathway analysis identified several genes with a strong link to collagen and/or elastin (ADAMTS6, ADAMTS16, ADAMTSL3, LOX, ELN) in the vicinity of associated loci for inguinal hernia, which substantiates an essential role of connective tissue morphology.
Evaluation of serological tests for detecting SARS-CoV-2 antibodies: implementation in assessing post vaccination status
Authors: Mahmoud Sally A. , Ganesan Subhashini , Naik Shivaraj , Bissar Safaa , Zamil Isra , Zaher Walid Abbas
Published: April 2021

Background

The anti-SARS-CoV-2 immunological assays have promising applications in the control and surveillance of the current COVID-19 pandemic. Therefore, large number of serological assays are developed in the commercial market to measure SARS-CoV-2 antibodies, which requires evaluation before their application in large scale.

Objectives

To evaluate the performances of commercially available serological assays for detecting SARS-CoV-2 antibodies.

Methods

The study compared the performances of six different methods for detection of antibodies against SARS-CoV-2 which includes (i) Genscript SARS-CoV-2 surrogate virus neutralization test kit [Test A] (ii) Diasorin - SARS-CoV-2 S1/S2 IgG detection [Test B] (iii) Alinity SARS-CoV-2 IgG II [Test C] (iv) Diasorin – SARS-CoV-2 TrimericS IgG [Test D] (v) Roche Elecsys Anti-SARS-CoV-2 – cobas [Test E] (vi) AESKULISA (AESKU Enzyme Linked Immunosorbent Assay) [Test F] against the gold standard Plaque Reduction Neutralization Test (PRNT).

Results

Test E had the highest sensitivity and Test A had the highest specificity The ROC for tests A, C, D and E showed optimum cut-offs that differed from the manufacturer’s recommendation. Test D had the best performance considering all the performance indicators with the highest agreement with the PRNT results. Parallel testing of test A with test D and test B had the optimum performance.

Conclusion

Serological assays that are commercially available are very promising and show good agreement with the standard PRNT results. Studies on large samples for optimization of the assay cut-off values and cost-effective evaluations on parallel testing methods are needed to make recommendations on these commercial assays.

Importance

Serological assays that are commercially available are very promising and this paper adds new knowledge about the optimization of these kits for evaluating post vaccination antibodies status. It highlights the positive and negative aspects of each of these assays in terms of sensitivity, specificity, positive and negative predictive values, and the agreement of results with the standard neutralization test. When serological assays are being used to assess post-vaccine immune status, a balance of all parameters needs to be considered rather than emphasizing only on high specificity. This is particularly relevant in the current situation where vaccination is happening around the globe, high sensitivity assays will result in reporting a lower percentage of false negative reports and avoids panic about lack of vaccine response. It is important that we understand the strengths and limitations of commercially available serological assays for better application of these tests to understand immune response and the duration of protection post vaccination.
Age-varying genetic associations and implications for bias in Mendelian randomization
Authors: Labrecque Jeremy A , Swanson Sonja A
Published: April 2021

Estimates from conventional Mendelian randomization (MR) analyses can be biased when the genetic variants proposed as instruments vary over age in their relationship with the exposure. For four exposures commonly studied using MR, we assessed the degree to which their relationship with genetic variants commonly used as instruments varies by age using flexible, spline-based models in UK Biobank data. Using these models, we then estimated how biased MR estimates would be due to age-varying relationships using plasmode simulations. We found that most genetic variants had age-varying relationships with the exposure for which they are a proposed instrument. Body mass index and LDL cholesterol had the most variation while alcohol consumption had very little. This variation over age led to small potential biases in some cases (e.g. alcohol consumption and C-reactive protein) and large potential biases for many proposed instruments for BMI and LDL.
Heterotypic Aβ interactions facilitate amyloid assembly and modify amyloid structure
Authors: Konstantoulea Katerina , Guerreiro Patricia , Ramakers Meine , Louros Nikolaos , Aubrey Liam , Houben Bert , Michiels Emiel , De Vleeschouwer Matthias , Lampi Yulia , Ribeiro Luís F. , de Wit Joris , Xue Wei-Feng , Schymkowitz Joost , Rousseau Frederic
Published: April 2021

It is still unclear why pathological amyloid deposition initiates in specific brain regions, nor why specific cells or tissues are more susceptible than others. Amyloid deposition is determined by the self-assembly of short protein segments called aggregation-prone regions (APRs) that favour cross-β structure. Here we investigated whether Aβ amyloid assembly can be modified by heterotypic interactions between Aβ APRs and short homologous segments in otherwise unrelated human proteins. We identified heterotypic interactions that accelerate Aβ assembly, modify fibril morphology and affect its pattern of depositionin vitro. Moreover, we found that co-expression of these proteins in an Aβ reporter cell line promotes Aβ amyloid aggregation. Importantly, reanalysis of proteomics data of Aβ plaques from AD patients revealed an enrichment in proteins that share homologous sequences to the Aβ APRs, suggesting heterotypic amyloid interactions may occur in patients. Strikingly, we did not find such a bias in plaques from overexpression models in mouse. Based on these data, we propose that heterotypic APR interactions may play a hitherto unrealised role in amyloid-deposition diseases.
No reproductive fitness benefits of dear enemy behaviour in a territorial songbird
Authors: Reichert Michael S. , Crane Jodie M.S. , Davidson Gabrielle L. , Dillane Eileen , Kulahci Ipek G. , O’Neill James , van Oers Kees , Sexton Ciara , Quinn John L.
Published: April 2021

Territorial animals often respond less aggressively to neighbours than strangers. This ‘dear enemy’ effect is hypothesized to be adaptive by reducing unnecessary aggressive interactions with non-threatening individuals. A key prediction of this hypothesis, that individual fitness will be affected by variation in the speed and the extent to which individuals reduce their aggression towards neighbours relative to strangers, has never been tested. We used a series of song playbacks to measure the change in response of male great tits to a simulated establishment of a neighbour on an adjacent territory during early stages of breeding, as an assay of individuals’ tendencies to form dear enemy relationships. Males reduced their approach to the speaker and sang fewer songs on later playback repetitions. However, only some males exhibited dear enemy behaviour by responding more strongly to a subsequent stranger playback, and when the playback procedure was repeated on a subset of males, there was some indication for consistent differences among individuals in the expression of dear enemy behaviour. We monitored nests and analysed offspring paternity to determine male reproductive success. Individuals that exhibited dear enemy behaviour towards the simulated neighbour did not suffer any costs associated with loss of paternity, but there was also no evidence of reproductive benefits, and no net effect on reproductive fitness. The general ability to discriminate between neighbours and strangers is likely adaptive, but benefits are probably difficult to detect because of the indirect link between individual variation in dear enemy behaviour and reproductive fitness, and because of the complex range of mechanisms affecting relations with territorial neighbours.
An enveloped virus-like particle vaccine expressing a stabilized prefusion form of the SARS-CoV-2 spike protein elicits potent immunity after a single dose
Authors: Fluckiger Anne-Catherine , Ontsouka Barthelemy , Bozic Jasminka , Diress Abebaw , Ahmed Tanvir , Berthoud Tamara , Tran Anh , Duque Diane , Liao Mingmin , McCluskie Michael , Diaz-Mitoma Francisco , Anderson David E. , Soare Catalina
Published: April 2021

Development of efficacious single dose vaccines would substantially aid efforts to stop the uncontrolled spread of the COVID-19 pandemic. We evaluated enveloped virus-like particles (eVLPs) expressing various forms of the SARS-CoV-2 spike protein and several adjuvants in an effort to identify a COVID-19 vaccine candidate efficacious after a single dose. The eVLPs expressing a modified prefusion form of SARS-CoV-2 spike protein were selected as they induced the highest antibody binding titers and neutralizing activity after a single injection in mice. Formulation of SARS-CoV-2 S eVLPs with aluminum phosphate resulted in balanced induction of IgG2 and IgG1 isotypes and antibody binding and neutralization titers were undiminished for more than 3 months after a single immunization. A single dose of this candidate, VBI-2902a (prefusion S eVLPs formulated with aluminum phosphate), protected Syrian golden hamsters from challenge with SARS-CoV-2 and supports the on-going clinical evaluation of VBI-2902a as a potential single dose vaccine against COVID-19.

Highlights

VBI-2902a is a VLP-based vaccine candidate against SARS-COV-2

VBI-2902a contains VLPs pseudotyped with a modified prefusion SARS-COV-2 S in Alum.

VBI-2902a induces robust neutralization antibody response against SARS-COV-2 S

VBI-2902a protects hamsters from SARS-CoV-2 induced lung inflammation

A single dose of VBI-2902a provides protective benefit in hamsters
ZAF – The First Open Source Fully Automated Feeder for Aquatic Facilities
Authors: Lange Merlin , Solak AhmetCan , Vijay Kumar Shruthi , Kobayashi Hirofumi , Yang Bin , Royer Loic A.
Published: April 2021

In the past few decades, aquatic animals have become popular model organisms in biology, spurring a growing need for establishing aquatic facilities. Zebrafish are widely studied and relatively easy to culture using commercial systems. However, a challenging aspect of maintaining aquatic facilities is animal feeding, which is both time- and resource-consuming. We have developed an open-source fully automatic daily feeding system, Zebrafish Automatic Feeder (ZAF). ZAF is reliable, provides a standardized amount of food to every tank, is cost-efficient and easy to build. The advanced version, ZAF+, allows for the precise control of food distribution as a function of fish density per tank, and has a user-friendly interface. Both ZAF and ZAF+ are adaptable to any laboratory environment and facilitate the implementation of aquatic colonies. Here we provide all blueprints and instructions for building the mechanics, electronics, fluidics, as well as to setup the control software and its user-friendly graphical interface. Importantly, the design is modular and can be scaled to meet different user needs. Furthermore, our results show that ZAF and ZAF+ do not adversely affect zebrafish culture, enabling fully automatic feeding for any aquatic facility.
Identification and correction of phase switches with Hi-C data in the Nanopore and HiFi chromosome-scale assemblies of the dikaryotic leaf rust fungusPuccinia triticina
Authors: Duan Hongyu , Jones Ashley W. , Hewitt Tim , Mackenzie Amy , Hu Yiheng , Sharp Anna , Lewis David , Mago Rohit , Upadhyaya Narayana M. , Rathjen John P. , Stone Eric A. , Schwessinger Benjamin , Figueroa Melania , Dodds Peter N. , Periyannan Sambasivam , Sperschneider Jana
Published: April 2021

Background

Most animals and plants have more than one set of chromosomes and package these haplotypes into a single nucleus within each cell. In contrast, many fungal species carry multiple haploid nuclei per cell. Rust fungi are such species with two nuclei (karyons) that contain a full set of haploid chromosomes each. The physical separation of haplotypes in dikaryons means that, unlike in diploids, Hi-C chromatin contacts between haplotypes are false positive signals.

Results

We generate the first chromosome-scale, fully-phased assembly for the dikaryotic leaf rust fungusPuccinia triticinaand compare Nanopore MinION and PacBio HiFi sequence-based assemblies. We show that false positive Hi-C contacts between haplotypes are predominantly caused by phase switches rather than by collapsed regions or Hi-C read mis-mappings. We introduce a method for phasing of dikaryotic genomes into the two haplotypes using Hi-C contact graphs, including a phase switch correction step. In the HiFi assembly, relatively few phase switches occur, and these are predominantly located at haplotig boundaries and can be readily corrected. In contrast, phase switches are widespread throughout the Nanopore assembly. We show that haploid genome read coverage of 30-40 times using HiFi sequencing is required for phasing of the leaf rust genome (~0.7% heterozygosity) and that HiFi sequencing resolves genomic regions with low heterozygosity that are otherwise collapsed in the Nanopore assembly.

Conclusions

This first Hi-C based phasing pipeline for dikaryons and comparison of long-read sequencing technologies will inform future genome assembly and haplotype phasing projects in other non-haploid organisms.
Copy-number alterations reshape the classification of diffuse intrinsic pontine gliomas. First exome sequencing results of the BIOMEDE trial
Authors: Kergrohen Thomas , Castel David , Le Teuff Gwenael , Tauziède-Espariat Arnault , Lechapt-Zalcman Emmanuèle , Nysom Karsten , Blomgren Klas , Leblond Pierre , Bertozzi Anne-Isabelle , De Carli Emilie , Faure-Conter Cécile , Chappe Celine , Entz-Werlé Natacha , Moussa Angokai , Ghermaoui Samia , Barret Emilie , Picot Stephanie , Sabourin-Cousin Marjorie , Beccaria Kevin , Vassal Gilles , Varlet Pascale , Puget Stephanie , Grill Jacques , Debily Marie-Anne
Published: April 2021

Diffuse intrinsic pontine gliomas (DIPG) is an incurable neoplasm occurring mainly in children for which no progress was made in the last decades. The randomized phase II BIOMEDE trial compared three drugs (everolimus, dasatinib, erlotinib) combined with irradiation. The present report describes whole exome sequencing (WES) results for the first 100 patients randomized.

Copy-number-Alteration (CNA) unsupervised clustering identified four groups with different outcomes and biology. This classification improved prognostication compared to models based on known biomarkers (Histone H3 and TP53 mutations). The cluster presenting complex genomic rearrangements was associated with significantly worse outcome and TP53 dysfunction. Mutation and CNA signatures confirmed the frequent alteration in DNA repair machinery. With respect to potential targetable pathways, PI3K/AKT/mTOR activation occurred in all the samples through multiples mechanisms. In conclusion, WES at diagnosis was feasible in most patients and provides a better patient stratification and theranostic information for precision medicine.
Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy
Authors: Tourret Marie , Talvard-Balland Nana , Lambert Marion , Ben Youssef Ghada , Chevalier Mathieu F. , Bohineust Armelle , Yvorra Thomas , Morin Florence , Azarnoush Saba , Lantz Olivier , Dalle Jean-Hugues , Caillat-Zucman Sophie
Published: April 2021

Background

Mucosal associated invariant T (MAIT) cells are semi-invariant T cells that recognize microbial antigens presented by the highly conserved MR1 molecule. MAIT cells are predominantly localized in the liver and barrier tissues and are potent effectors of anti - microbial defense. MAIT cells are very few at birth and accumulate gradually over a period of about 6 years during infancy. The cytotoxic potential of MAIT cells, as well as their newly described regulatory and tissue repair functions, open the possibility of exploiting their properties in adoptive therapy. A prerequisite for their use as “universal” cells would be a lack of alloreactive potential, which remains to be demonstrated.

Methods

We used ex vivo, in vitro and in vivo models to determine if human MAIT cells contribute to allogeneic responses.

Results

We show that recovery of MAIT cells after allogeneic hematopoietic stem cell transplantation recapitulates their slow physiological expansion in early childhood, independent of recovery of conventional T cells. In vitro, signals provided by allogeneic cells and cytokines do not induce sustained MAIT cell proliferation. In vivo, human MAIT cells do not expand nor accumulate in tissues in a model of T-cell mediated xenogeneic graft-versus-host disease (GVHD) in immunodeficient mice.

Conclusions

Altogether, these results provide evidence that MAIT cells are devoid of alloreactive potential and pave the way for harnessing their translational potential in universal adoptive therapy overcoming barriers of HLA disparity.
Interdental and subgingival microbiota may affect the tongue microbial ecology and oral malodour in health, gingivitis and periodontitis
Authors: Stephen Abish S. , Dhadwal Narinder , Nagala Vamshidhar , Gonzales-Marin Cecilia , Gillam David G. , Bradshaw David J. , Burnett Gary R. , Allaker Robert P.
Published: April 2021

Background and Objective

Oral malodour is often observed in gingivitis and chronic periodontitis patients, and the tongue microbiota is thought to play a major role in malodorous gas production, including Volatile Sulfur Compounds (VSCs) such as hydrogen sulfide (H2S) and methanethiol (CH3SH). This study aimed to examine the link between the presence of VSCs in mouth air (as a marker of oral malodour) and the oral bacterial ecology in the tongue and periodontal niches of healthy, gingivitis and periodontitis patients.

Methods

Participants were clinically assessed using plaque index, bleeding on probing (BOP) and periodontal probing depths, and VSC concentrations in their oral cavity measured using a portable gas chromatograph. Tongue scrapings, subgingival and interdental plaque were collected from healthy individuals (n=22), and those with gingivitis (n=14) or chronic periodontitis (n=15). The bacterial 16S rRNA gene region V3-V4 in these samples was sequenced and the sequences analysed using the Minimum Entropy Decomposition pipeline.

Results

Elevated VSC concentrations and CH3SH:H2S were observed in periodontitis compared to health. Significant ecological differences were observed in the tongue microbiota of healthy subjects with high plaque scores compared to low plaque scores, suggesting a possible connection between the microbiota of the tongue and the periodontium and that key dysbiotic changes may be initiated in the clinically healthy who have higher dental plaque accumulation. Greater subgingival bacterial diversity was positively associated with H2S in mouth air. Periodontopathic bacteria known to be prolific VSC producers increased in abundance on the tongue associated with increased bleeding on probing (BOP) and total percentage of periodontal pockets >6mm, supporting the suggestion that the tongue may become a reservoir for periodontopathogens.

Conclusion

This study highlights the importance of the periodontal microbiota in malodour and has detected dysbiotic changes in the tongue microbiota in periodontitis.
COMPARISON OF PERFORMANCE CHARACTERISTICS BETWEEN LATERAL FLOW, ELISA AND ELECTROCHEMILUMINESCENCE IMMUNOASSAYS FOR THE DETECTION OF SARS-COV-2 ANTIBODIES AMONG HEALTHCARE WORKERS
Authors: Shincy M R , Govindan Vandana , Sudhakar H H , Venkatesha V T , Padmapriya K , Ravikumar K L
Published: April 2021

Background

Medical professionals and researchers have been urging the need for wide and rapid testing of citizens in order to plan measures that can contain the spread of the virus. Antibody tests play an important role throughout the patient care pathway and are vital for the management and surveillance of the virus. Although RT-PCR is considered as the gold standard, serological tests based on antibodies are helpful for on-time detection. We performed one to one assessment of point-of-care lateral flow assay (POCTs), enzyme immunoassay (EIAs), electrochemiluminescence immunoassay (CLIA), to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) IgG antibody.

Materials and Methods

611 healthcare workers were recruited between November and December 2020 at Central Research Laboratory, KIMS. Collected serum samples were analysed according to manufacturer’s protocol. The Standard Q IgG/IgM combo assay, Anti-SARS CoV-2 Human IgG ELISA, and the Elecsys® to measure the IgG titer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results

The kits displayed a sensitivity of 61.2%,79.5%, 91.8% and specificity of 61.7%,64.1%,80.2% for the Standard Q IgG/IgM combo assay, Anti-SARS CoV-2 Human IgG ELISA, and the Elecsys® in order.

Conclusion

Our results indicate high sensitivity and specificity for the Elecsys® assay compared to Anti-SARS CoV-2 Human IgG ELISA, the Standard Q IgG/IgM combo assay.
TranSyT, an innovative framework for identifying transport systems
Authors: Lagoa Davide , Faria José P. , Liu Filipe , Cunha Emanuel , Henry Christopher S. , Dias Oscar
Published: April 2021

The importance and rate of development of genome-scale metabolic models have been growing for the last years, increasing the demand for software solutions that automate several steps of this process. However, since TRIAGE’s release, software development for automatic integration of transport reactions into models has stalled. Here we present the Transport Systems Tracker (TranSyT), the next iteration of TRIAGE. Unlike its predecessor,TranSyTdoes not rely on manual curation to expand its internal database, derived from highly-curated records retrieved from the Transporters Classification Database and complemented with information from other data sources.TranSyTcompiles information regarding transporters families, transport proteins, and derives reactions into its internal database, making it available for rapid annotation of complete genomes. All transport reactions have GPR associations and can be exported with identifiers from four different metabolite databases.TranSyTis currently available as a plugin formerlinv4.0 and an app for KBase.