bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Different Phyllosphere Sample Types for Parallel Metabarcoding of Fungi and Oomycetes in Vitis vinifera
Authors: Behrens Falk H. , Fischer Michael
Published: February 2022

Metabarcoding is an effective and cost-efficient approach to study environmental microbiomes and has become a standard method in studying microbial community structures and relative species abundance. In grapevine research on leaf microbial communities, two kinds of sample types, either leaf wash sediments representing the phyllosphere microbiome from leaf surfaces or leaf tissue samples, e.g., leaf disks, including phyllosphere and endosphere microorganisms, are used to characterize leaf microbiomes. The goal of this study was to analyze the advantages and disadvantages of these sample preparation methods for the characterization of the phyllosphere microbiome by fungal metabarcoding with both sample types being processed from the exact same set of leaves. We used a metabarcoding strategy, which can detect Fungi and Oomycetes, facilitating the parallel analysis of these communities. At each sampling time point, species richness was shown to be higher in leaf wash samples, and differences in the community structure between samples was smaller for this sample type as well. Furthermore, by comparing read count abundance to qPCR measured relative proportions of selected amplicon sequence variants, a higher congruence was observed for leaf wash samples. Therefore, metabarcoding analyses of leaf samples using leaf wash sediments outperform analyses using leaf disks and should be applied to characterize phyllosphere fungal communities. As a second goal, we show that the direct comparison of metabarcoding libraries of both sample types prepared from the exact same set of leaves also provides a new strategy to identify endophytes that may not be culturable.

[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
The Effect of Male Sexual Abstinence Periods on the Clinical Outcomes of Fresh Embryo Transfer Cycles Following Assisted Reproductive Technology: A Meta-Analysis
Authors: Li Jinhong , Shi Qingquan , Li Xiaohong , Guo Junliang , Zhang Long , Quan Yi , Ma Ming , Yang Yihong
Published: February 2022

(Abstracted from Am J Mens Health 2020;14:1557988320933758)

Sexual abstinence period (SAP) is an important component affecting semen quality analysis in the evaluation of infertile men. The World Health Organization guidelines currently suggest 2 to 7 days of SAP, the European Society of Human Reproduction and Embryology suggests 3 to 4 days of SAP, and recent studies have reported that less than 2 days of SAP can result in higher pregnancy rates after assisted reproductive technology (ART).
Mortality and PICU Hospitalization Among Pediatric Gunshot Wound Victims in Chicago
Authors: Rhine Maya A. , Hegermiller Emma M. , Kane Jason M. , Slidell Mark B. , Mayampurath Anoop , McQueen Alisa A. , Mbadiwe Nina , Pinto Neethi P.
Published: February 2022

IMPORTANCE:

Firearm injury accounts for significant morbidity with high mortality among children admitted to the PICU. Understanding risk factors for PICU admission is an important step toward developing prevention and intervention strategies to minimize the burden of pediatric gunshot wound (GSW) injury.

OBJECTIVES:

The primary objective of this study was to characterize outcomes and the likelihood of PICU admission among children with GSWs.

DESIGN, SETTING, AND PARTICIPANTS:

Retrospective cohort study of GSW patients 0–18 years old evaluated at the University of Chicago Comer Children’s Hospital Pediatric Trauma Center from 2010 to 2017.

MAIN OUTCOMES AND MEASURES:

Demographic and injury severity measures were acquired from an institutional database. We describe mortality and hospitalization characteristics for the cohort. We used logistic regression models to test the association between PICU admission and patient characteristics.

RESULTS:

During the 8-year study period, 294 children experienced GSWs. We did not observe trends in overall mortality over time, but mortality for children with GSWs was higher than all-cause PICU mortality. Children 0–6 years old experienced longer hospitalizations compared with children 13–16 years old (5 vs 3 d; p = 0.04) and greater frequency of PICU admission (83.3% vs 52.9%; p = 0.001). Adjusting for severity of illness, children less than 7 years old were four-fold more likely to be admitted to the PICU than children 13–16 years old (aOR range, 3.9–4.6).

CONCLUSIONS AND RELEVANCE:

Despite declines in pediatric firearm mortality across the United States, mortality did not decrease over time in our cohort and was higher than all-cause PICU mortality. Younger children with GSWs experience longer hospitalizations and require PICU care more often than older children. Our findings suggest that the youngest victims of firearm-related injury may be particularly at-risk of the long-term sequelae of critical illness and injury.
Central Auditory Processing and the Relationship to Perceived Hearing Difficulty: The Jackson Heart Study
Authors: Shepherd Brandon , Spankovich Christopher , Bishop Charles E. , Su Dan , Valle Karen , Schweinfurth John
Published: February 2022

Objective:

There are limited population-based studies of central auditory processing (CAP). We aimed to determine the relationship between CAP measures and perceived hearing difficulty (PHD) despite normal pure-tone audiometry in an African-American population.

Study Design:

Cross-sectional.

Setting:

Jackson Heart Study (JHS), Jackson, MS.

Subjects:

Participants of an African-American cohort (26% men; age 54.2, standard deviations [SD] 9.2) who self-reported hearing difficulty despite normal hearing sensitivity defined as audiometric pure-tone average (PTA-4: average of 500, 1000, 2000, and 4000 Hz) less than or equal to 25 dBHL (n = 911) or across all tested frequencies (PT-AF: 250–8000 Hz) less than or equal to 25 dBHL (n = 516).

Methods:

The Quick Speech-in-Noise (QuickSIN) and Dichotic Digits, Double Pairs (DDT2) tests were used to assess CAP. Logistic regression was used to examine the association between measures of CAP and PHD; adjusted for age, sex, education, and pure tone audiogram.

Results:

PHD was present in 251 (28%) and 137 (27%) of participants using the PTA-4 and PT-AF models, respectively. Fully adjusted regression models revealed that each one-point increase in QuickSIN increased the odds of reporting PHD by 13.7% (odds ratio [OR] 1.14, p < 0.01, 95% CI: 1.08, 1.19) using the PTA-4 model and 15.0% (OR 1.15, p < 0.01, 95% CI: 1.08, 1.23) using the PT-AF model. For DDT2 testing, each 1% reduction in score, increased the odds of reporting PHD by 7.7% (OR 0.92, p < 0.01, 95% CI: 0.88, 0.97) in a fully adjusted PTA-4 model and 6.6% (OR 0.93, p = 0.04, 95% CI: 0.87, 0.99) in the PT-AF model.

Conclusion:

CAP deficits were associated with increased odds of PHD in normal hearing participants within the JHS cohort.
Assessing the Quality of Patient Information for Vestibular Schwannoma on the Open Source Video Sharing Platform YouTube
Authors: Oh Lawrence , Phan Kevin , Jufas Nicholas E. , Patel Nirmal P.
Published: February 2022

Background:

Patients frequently use the internet to gain information and make decisions about their health conditions. This work aims to assess the quality of information about Vestibular Schwannoma on a popular video sharing platform, YouTube (Alphabet Inc.).

Objectives:

To assess quality of the most popular vestibular schwannoma videos using recognized scoring systems and whether video quality metrics correlated with video popularity based on metadata analysis.

Setting:

Public domain.

Study Design:

Cross-sectional Study

Methods:

The YouTube website was systematically searched on separate days with a formal search strategy to identify videos relevant to vestibular schwannoma. Each video was viewed and scored by three independent assessors, using scores for quality and disease specific accuracy. Popularity metrics were analyzed and compared to video quality. Patient surveys were conducted to further assess their perspectives of the included videos.

Results:

A total of 23 YouTube videos were included. In terms of Essential and Ideal Video Completeness Criteria, the mean scores ranged from 4.8 to 5.0 (out of 12), indicating moderate video quality. The average DISCERN score ranged from 30.0 to 36.7, indicating lower reliability. The mean JAMA scores ranged from 1.96 to 2.48, indicating average quality. Based on metrics including DISCERN and JAMA instruments, the information in the YouTube videos were of low to average quality and reliability. Rater scoring was reliable. Viewer engagement correlated poorly with video quality except for JAMA metrics.

Conclusion:

Video quality on YouTube with respect to Vestibular Schwannoma is of low to average quality. Viewer engagement and popularity correlated poorly with video quality. Clinicians should direct their patients to high quality videos and should consider uploading their own high-quality videos.
Moxibustion for diarrhea in COVID-19
Authors: Liu Ningning , Xu Yingxue , Zhang Dongbin , Wang Lianzhu , Hou Yi , Ji Jiafu
Published: February 2022

Background:

Coronavirus disease 2019 (COVID-19) is an acute respiratory infectious disease that is often accompanied by diarrhea, patients with symptoms such as diarrhea are more likely to develop severe pneumonia, while diarrhea is the most prominent among atypical symptoms. The incidence of diarrhea in COVID-19 patients is 2.0% to 49.5%. Moxibustion has been proven to have a therapeutic effect on diarrhea; however, there is no high-quality evidence on moxibustion for diarrhea in COVID-19 patients. This study was designed to evaluate the effectiveness and safety of moxibustion for the treatment of diarrhea in patients with COVID-19.

Methods:

Randomized controlled trials from December 2019 to December 2021 will be included without restrictions on language or publication date. PubMed, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Databases, China National Knowledge Infrastructure, Wanfang database, and VIP database will be searched. Two researchers will independently select studies, extract data and evaluate study quality. Cochrane risk of bias tool for randomized trials will be used to assess the risk of bias of included studies. Statistical analyses will be performed using the Review Manager V.5.3 and stata 14.0.

Results:

The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.

Conclusion:

This study will provide evidence for whether moxibustion therapy is beneficial to the treatment of diarrhea in COVID-19.

Ethics and dissemination:

Ethical approval is not required for this study. The systematic review will be published in a peer-reviewed journal, presented at conferences, and shared on social media platforms. This review would be disseminated in a peer-reviewed journal or conference presentations.

Prospero registration number:

CRD42022302933.
Aesthetics and Technology Integration in a Community-Based Primary Care Nursing Curriculum
Authors: DeGrande Heather , Acker Katelijne , Monahan Laura , Fomenko Julie , McMillan Sheryl Robinson , Baldwin Sara , Aubrey Margaret , Hoff Julie Anne
Published: February 2022

Background:

Reconceptualized nursing education can prepare registered nurses to practice at the full scope of licensure on interprofessional teams across care continua while enhancing the quality of health care systems.

Problem:

Traditional nursing programs minimally address primary care competencies. Rapidly changing managed care models demand nurses develop knowledge, skills, and attitudes to effectively deliver population health, primary care, care coordination, and disease prevention/management services across care continua.

Approach:

A faculty team built an innovative concept and competency-based accelerated bachelor of science in nursing primary care–focused curriculum integrating behavioral health, aesthetic knowing, and technology.

Outcomes:

The curriculum was implemented twice, with the third cohort mid-program. Program evaluation is ongoing.

Conclusion:

A paradigm shift in nursing education may improve population-based biobehavioral wellness, disease prevention, and chronic disease management. Future research should focus on how this innovative curricular approach builds essential nursing competencies and enhances digital fluency, observation, communication, empathy, and critical thinking skills.
Virtual Health Assessment Laboratory Course Delivery and Nursing Student Clinical Judgment
Authors: Vihos Jill , Chute Andrea , Carlson Sue , Buro Karen , Velupillai Nirudika , Currie Tami
Published: February 2022

Background:

It is essential to explore virtual learning experiences to identify their impact on nursing students' learning.

Purpose:

The purpose of this study was to investigate the relationship between the virtual delivery of a health assessment laboratory course and nursing students' clinical judgment.

Methods:

Using a mixed-methods explanatory sequential design, the investigators appraised the final laboratory examinations of both in-person and virtual delivery cohorts using the Lasater Clinical Judgment Rubric (LCJR) and then interviewed faculty members.

Results:

The LCJR total mean scores (mean = 10.64) and mean scores for Effective Noticing (mean = 3.48) were higher for the virtual delivery students. The faculty reported that virtual delivery advances students' critical appraisal skills related to subjective assessment but advocated for in-person delivery to develop physical examination techniques.

Conclusion:

Although the mean clinical judgment scores were higher for the students whose course delivery was virtual, in-person experiences are necessary to develop psychomotor techniques to prepare students for clinical practice.
Women's Mental Health Services and Pregnancy: A Review
Authors: Ghahremani Taylor , Magann Everett F. , Phillips Amy , Ray-Griffith Shona L. , Coker Jessica L. , Stowe Zackary N.
Published: February 2022

Importance

The importance of women's mental health services is becoming more evident as we learn more about the impact of mental health on maternal and perinatal outcomes.

Objective

The purpose of this review is to identify the importance of mental health issues arising during pregnancy including prevention, timely diagnosis and treatment, and referral to specialized services.

Evidence Acquisition

A literature search was undertaken using the search engines PubMed, CINAHL, and PsycINFO. The search terms were as follows: “mental health services” or “behavioral health” or “mental health counseling” or “psychological” and “delivery of health care” and “pregnancy” or “pregnant.” The years searched were January 2000 to November 2020. The search was limited to English language.

Results

Of the 255 abstracts identified and reviewed, 35 full-text articles were the basis of this review. Literature summarizing the availability and models of care for mental health services for pregnant women is limited. After reviewing the literature, the themes of depression and anxiety in the antepartum and postpartum periods that emerged as mental health issues, especially during adolescent pregnancies, the coronavirus pandemic, intimate partner violence, and pregnancy loss, are of primary importance to obstetrical providers. All of these issues can have a significant impact on maternal and neonatal outcomes and should be addressed during routine practice.

Conclusions and Relevance

Maternal mental health is garnering deserved attention and has enormous implications on maternal and infant outcomes. Obstetrical providers should be comfortable with screening, identification, and basic treatment algorithms including when to refer to specialized services.

Relevance Statement

Mental health issues during pregnancy and the postpartum period can be profound with severe maternal and perinatal consequences.

Target Audience

Obstetricians and gynecologists, family physicians, psychiatrists.

Learning Objectives

After completing this activity, the learner should be better able to identify the mental health services that are available for pregnant women; outline the common mental illnesses that are present during adolescent pregnancies; explain the risk factors that have been linked with perinatal depression; and describe the management and potential complications of pregnant patients presenting with mental illness.
Just-in-Time In Situ Simulation Training as a Preparedness Measure for the Perioperative Care of COVID-19 Patients
Authors: Zucco Liana , Chen Michael J. , Levy Nadav , Obeidat Salameh S. , Needham Matthew J. , Hyatt Allison , Keane Jeffrey R. , Pollard Richard J. , Mitchell John D. , Ramachandran Satya Krishna
Published: February 2022

Introduction

Routine workflows were redesigned during the first surge of the COVID-19 pandemic to standardize perioperative management of patients and minimize the risk of viral exposure and transmission to staff members. Just-in-time (JIT), in situ simulation training was adopted to implement urgent change, the value of which in a public health crisis has not previously been explored.

Methods

Implementation of workflow changes in the setting of the COVID-19 pandemic was accomplished through JIT, in situ simulation training, delivered over a period of 3 weeks to participants from anesthesia, nursing, and surgery, within our healthcare network. The perceived value of this training method was assessed using a postsimulation training survey, composed of Likert scale assessments and free-text responses. The impact on change in practice was assessed by measuring compliance with new COVID-19 workflows for cases of confirmed or suspected COVID-19 managed in the operating room, between March and August 2020.

Results

Postsimulation survey responses collected from 110 of 428 participants (25.7%) demonstrated significant positive shifts along the Likert scale on perceived knowledge of new workflow processes, comfort in adopting them in practice and probability that training would have an impact on future practice (all Ps < 0.001). Free-text responses reflected appreciation for the training being timely, hands-on, and interprofessional. Compliance with new COVID workflows protocols in practice was 95% (121 of 127 cases) and was associated with lower than expected healthcare worker test positive rates (<1%) within the network during this same period.

Conclusions

These findings support JIT, in situ simulation training as a preparedness measure for the perioperative care of COVID-19 patients and demonstrate the value of this approach during public health crises.
Novel Word Recognition in Childhood Stuttering
Authors: Lescht Erica , Venker Courtney E. , McHaney Jacie R. , Bohland Jason W. , Hampton Wray Amanda
Published: February 2022

Language skills have long been posited to be a factor contributing to developmental stuttering. The current study aimed to evaluate whether novel word recognition, a critical skill for language development, differentiated children who stutter from children who do not stutter. Twenty children who stutter and 18 children who do not stutter, aged 3–8 years, completed a novel word recognition task. Real-time eye gaze was used to evaluate online learning. Retention was measured immediately and after a 1-hr delay. Children who stutter and children who do not stutter exhibited similar patterns of online novel word recognition. Both groups also had comparable retention accuracy. Together, these results revealed that novel word recognition and retention were similar in children who stutter and children who do not stutter. These patterns suggest that differences observed in previous studies of language in stuttering may not be driven by novel word recognition abilities in children who stutter.
Understanding the Speaker's Experience of Stuttering Can Improve Stuttering Therapy
Authors: Tichenor Seth E. , Herring Caryn , Yaruss J. Scott
Published: February 2022

This article highlights the value for speech–language pathologists of considering the overall stuttering condition—including speakers' experiences during and around moments of stuttering—in treatment with individuals who stutter. We first highlight a framework for conceptualizing the entirety of the stuttering condition. We then present recent research and clinical perspectives about stuttering to support the claim that speech–language pathologists who account for individual differences in how their clients experience stuttering are better positioned to treat stuttering more effectively. Ultimately, this will yield better treatment outcomes and help clinicians achieve greater gains in quality of life for their clients who stutter.
COVID-19: the case for aerosol transmission
Authors: Tellier Raymond
Published: February 2022

The COVID-19 pandemic is the most severe pandemic caused by a respiratory virus since the 1918 influenza pandemic. As is the case with other respiratory viruses, three modes of transmission have been invoked: contact (direct and through fomites), large droplets and aerosols. This narrative review makes the case that aerosol transmission is an important mode for COVID-19, through reviewing studies about bioaerosol physiology, detection of infectious SARS-CoV-2 in exhaled bioaerosols, prolonged SARS-CoV-2 infectivity persistence in aerosols created in the laboratory, detection of SARS-CoV-2 in air samples, investigation of outbreaks with manifest involvement of aerosols, and animal model experiments. SARS-CoV-2 joins influenza A virus as a virus with proven pandemic capacity that can be spread by the aerosol route. This has profound implications for the control of the current pandemic and for future pandemic preparedness.
In situcell-surface conformation of the TCR-CD3 signaling complex
Authors: Natarajan Aswin , Wang Wenjuan , Flores Manuel Becerra , Li Tianqi , Shin Hye Won , Beesam Saikiran , Cardozo Timothy , Krogsgaard Michelle
Published: February 2022

T cells play a vital role in adaptive immune responses to infections, inflammation and cancer and are dysregulated in autoimmunity. Antigen recognition by T cells – a key step in adaptive immune responses – is performed by the T cell receptor (TCR)-CD3 complex. The extracellular molecular organization of the individual CD3 subunits (CD3δε and CD3 γε) around the αβTCR is critical for T cell signaling. Here, we incorporated unnatural amino acid (UAA) photo-crosslinkers at specific mouse TCRα, TCRβ, CD3δ and CD3γ sites, based on previous mutagenesis, NMR spectroscopy and cryo-EM evidence, and crosslinking allowing us to identify nearby interacting CD3 or TCR subunits on the mammalian cell surface. Using this approach, we show that CD3γ and CD3ε, belonging to CD3γε heterodimer crosslinks to Cβ FG loop and Cβ G strand, respectively and CD3δ crosslinks to Cβ CC’ loop and Cα DE loop. Together with computational docking, we identify that inin situcell-surface conformation, the CD3 subunits exists in CD3ε’-CD3γ-CD3ε-CD3δ arrangement around the αβ TCR. This unconventional technique, which uses the native mammalian cell surface microenvironment, includes the plasma membrane and excludes random, artificial crosslinks, captures a dynamic, biologically relevant, cell-surface conformation of the TCR-CD3 complex, which is compatible with the reported static cryo-EM structure’s overall CD3 subunits arrangement, but with key differences at the TCR-CD3 interface, which may be critical for experiments in T cell model systems.
Allometric scaling of a superposition eye optimises sensitivity and acuity in large and small hawkmoths
Authors: Stöckl Anna , Grittner Rebecca , Taylor Gavin , Rau Christoph , Bodey Andrew J , Kelber Almut , Baird Emily
Published: February 2022

Animals vary widely in body size across and within species. This has consequences in large and small individuals for the function of organs and body parts. How these scale in relation to body size reveals evolutionary investment strategies, often resulting in trade-offs between functions. Eyes exemplify these trade-offs, as they are limited by their absolute size in two key performance features: sensitivity and spatial acuity. Previous studies of the 3D structure of apposition compound eyes, which are ideal models for allometric studies due to their size polymorphism, revealed that allometric scaling improves both local resolution and visual sensitivity in larger bumblebees (Taylor et al., 2019). Here, we build on the established methods and results to investigate allometric scaling in superposition compound eyes – the second prominent eye type in insects – for the first time. Our research highlights a surprising strategy to cope with the challenge of trading off sensitivity and spatial resolution in small eyes, as we show that the eyes of the hummingbird hawkmoth retain an optimal balance of these performance measures across all body sizes.
Phenome-wide association analysis of substance use disorders in a deeply phenotyped sample
Authors: Kember Rachel L. , Hartwell Emily E. , Xu Heng , Rotenberg James , Almasy Laura , Zhou Hang , Gelernter Joel , Kranzler Henry R.
Published: February 2022

Background

Substance use disorders (SUDs) are associated with a variety of co-occurring psychiatric disorders and other SUDs, which partly reflects genetic pleiotropy. Polygenic risk scores (PRS) and phenome-wide association studies (PheWAS) are useful in evaluating pleiotropic effects. The comparatively low prevalence of SUDs and lack of detailed information available in electronic health records limits their informativeness for such analyses.

Methods

We used the deeply-phenotyped Yale-Penn sample [(N=10,610; 46.3% African ancestry (AFR), 53.7% European ancestry (EUR)], recruited for genetic studies of substance dependence, to examine pleiotropy for 4 major substance-related traits: alcohol use disorder (AUD), opioid use disorder (OUD), smoking initiation (SMK), and lifetime cannabis use (CAN). The sample includes both affected and control subjects interviewed using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA), a comprehensive psychiatric interview.

Results

In AFR individuals PRS for AUD, and in EUR individuals PRS for AUD, OUD, and SMK, were associated with their respective primary DSM diagnoses. These PRS were also associated with additional phenotypes involving the same substance. PheWAS analyses of PRS in EUR individuals identified associations across multiple phenotypic domains, including phenotypes not commonly assessed in PheWAS analyses, such as family environment and early childhood experiences.

Conclusions

Smaller, deeply-phenotyped samples can complement large biobank genetic studies with limited phenotyping by providing greater phenotypic granularity. These efforts allow associations to be identified between specific features of disorders and genetic liability for SUDs, which help to inform our understanding of the pleiotropic pathways underlying them.
Grandparental Childcare During the Pandemic and Effects on Mental Health: Evidence From England
Authors: Di Gessa Giorgio , Bordone Valeria , Arpino Bruno
Published: February 2022

Objectives

Policies aiming at reducing rates of hospitalisation and death from COVID-19 encouraged older people to reduce physical interactions. For grandparents in England, this meant that provision of care for grandchildren was allowed only under very limited circumstances. Evidence also suggests that reduced face-to-face interactions took a toll on mental health during the pandemic. This study aims to investigate whether changes in grandchild care provision during the pandemic impacted grandparents’ mental health.

Methods

Using pre-pandemic data from Wave 9 (2018/19) and the second Covid-19 sub-study (November/December 2020) of the English Longitudinal Study of Ageing, we first describe changes in grandparenting since the start of the pandemic to then investigate, using regression models, associations between changes in grandparenting and mental health (depression, quality of life, life satisfaction) during the pandemic, while controlling for pre-pandemic levels of the outcome variables. Results: About 10% of grandparents stopped altogether to look after grandchildren during the pandemic, with 22% reporting an overall decrease in the amount of grandchild care provided and 20% an increase or similar levels. Compared to grandparents who mostly maintained unchanged their grandchild care provision, those who stopped altogether and those who mostly reduced the amount of grandchild care provided were more likely to report poorer mental health, even accounting for pre-pandemic health.

Discussion

While measures to limit physical contact and shield older people were necessary to reduce the spread of COVID-19, policymakers should acknowledge potential adverse consequences for mental health among grandparents who experienced changes in their roles as grandchild caregivers.
Immune responses after twofold SARS-CoV-2 immunisation in elderly residents and Health Care Workers in nursing homes and homes with assisted living support - Proposal for a correlate of protection
Authors: Schiffner Julia , Eisemann Nora , Baltus Hannah , Jensen Sina , Wunderlich Katharina , Schüßeler Stefan , Eicker Charlotte , Teegen Bianca , Boniakowsky Doreen , Solbach Werner , Mischnik Alexander
Published: February 2022

In the present study, we were interested in the decline over time of anti SARS-CoV-2 antibodies and SARS-CoV-2 specific T-cell responses after two doses of mRNA vaccines in total and by age group and comorbidity. The second goal was to suggest an immunological correlate for protection on an individual basis and to describe the probability of protection over time after second vaccination.

We analysed blood samples from 228 residents (median age 83.8 years) and from 273 Health Care Workers (HCW; median age 49.7 years) of five nursing homes and one home for the elderly with assisted living support. Participants had received two vaccinations. The blood samples were analysed for SARS-CoV-2 specific antibody and T-cell responses. We compared outcomes in the HCW and residents in the respective institutions. No breakthrough infections occurred during the study period. The initial immune responses in the younger participants were about 30 % higher than in the older ones. Over time, all parameters dropped continuously in all groups within the maximum observation period of 232 days. Comorbidities such as coronary heart disease or diabetes mellitus reduced the initial immune responses, regardless of age. In contrast to an almost linear decline in antibody levels, we observed that the interferon-gamma response remained at a constant level between about day 120 and 180, only to decline further thereafter.

Based on our data, we propose on an individual level a correlate of protection: Persons who have a neutralizing capacity of 75 % (which would correspond to approx. 200 BAU/ml) and an interferon-gamma response above 200 mIU/ml should be considered to be protected resp. sufficiently immunized.
MTPpilot: an interactive software for visualization of NGS results in molecular tumor boards
Authors: Kahraman A. , Arnold F. M. , Hanimann J. , Nowak M. , Pauli C. , Britschgi C. , Moch H. , Zoche M.
Published: February 2022

Comprehensive targeted Next Generation Sequencing (NGS) panels are routinely used in modern molecular cancer diagnostics. In molecular tumor boards the detected genomic alterations are often discussed to decide the next treatment options for the cancer patient. With the increasing size and complexity of NGS panels, the discussion of these results becomes increasingly complex, especially if they are reported in a text-based form, as it is the standard in current molecular pathology. We developed the Molecular Tumor Profiling pilot (MTPpilot) software to enable an efficient and quick analysis and visualization of complex NGS results, thanks to a combination of automated annotations and interactive tools. The software is tailored for the use at molecular tumor boards to aid clinical decision making. It is freely available as a web-application at https://www.mtppilot.org.
PENet: Continuous-Valued Pulmonary Edema Severity Prediction On Chest X-ray Using Siamese Convolutional Networks
Authors: Akbar Md Navid , Wang Xin , Erdoğmuş Deniz , Dalal Sandeep
Published: February 2022

For physicians to take rapid clinical decisions for patients with congestive heart failure, the assessment of pulmonary edema severity in chest radiographs is vital. While deep learning has been promising in detecting the presence or absence, or even discrete grades of severity, of such edema, prediction of the continuous-valued severity yet remains a challenge. Here, we propose PENet, a deep learning framework to assess the continuous spectrum of pulmonary edema severity from chest X-rays. We present different modes of implementing this network, and demonstrate that our best model outperforms that of earlier work (mean area under the curve of 0.91 over 0.87, for nine comparisons), while saving training data and computation.
Distinct Core Glycan and O-Glycoform Utilization of SARS-CoV-2 Omicron Variant Spike Protein RBD Revealed by Top-Down Mass Spectrometry
Authors: Roberts David S. , Mann Morgan , Li Brad H. , Kim Donguk , Brasier Allan R. , Jin Song , Ge Ying
Published: February 2022

The SARS-CoV-2 Omicron (B.1.1.529) variant possesses numerous spike (S) mutations particularly in the S receptor-binding domain (S-RBD) that significantly improve transmissibility and evasion of neutralizing antibodies. But exactly how the mutations in the Omicron variant enhance viral escape from immunological protection remains to be understood. The S-RBD remains the principal target for neutralizing antibodies and therapeutics, thus new structural insights into the Omicron S-RBD and characterization of the post-translational glycosylation changes can inform rational design of vaccines and therapeutics. Here we report the molecular variations and O-glycoform changes of the Omicron S-RBD variant as compared to wild-type (WA1/2020) and Delta (B.1.617.2) variants using high-resolution top-down mass spectrometry (MS). A novel O-glycosite (Thr376) unique to the Omicron variant is identified. Moreover, we have directly quantified the Core 1 and Core 2 O-glycan structures and characterized the O-glycoform structural heterogeneity of the three variants. Our findings reveal high resolution detail of Omicron O-glycoforms and their utilization to provide direct molecular evidence of proteoform alterations in the Omicron variant which could shed light on how this variant escapes immunological protection.
Disparities in Opioid-related Mortality Across United States Census Regions from 1999-2020
Authors: Addimulam Supriyanka , Gupta Swapnil , Mahalingam Sindhuja , Walia Namrata
Published: February 2022

Background

Opioid-related mortality has been on a sharp rise in the decade. This study aims to provide insight into the difference in mortality between white and black population in various census regions of the United States between 1999-2020.

Methods

The data was extracted from multiple cause of death files from CDC Wonder database. The International Classification of Disease (ICD-10) codes used to extract data include F11 (mental and behavioral disorders due to use of opioids); T40.0 (Opium); T40.1 (Heroin); T40.2 (Other opioids); T40.3 (Methadone); T40.4 (Other synthetic narcotics). The regression analysis was conducted using Joinpoint statistical software.

Results

The black population in the Midwest census region showed the highest age-adjusted mortality in the year 2020 (46.14 per 100,000). This was followed by the black (32.71 per 100,000) and white population (30.5 per 100,000) in the northeast census regions respectively. Overall, the opioid-related mortality followed a similar trend across all census regions. Except south census region where age-adjusted mortality was comparable between the black and white populations, blacks had higher opioid-related mortality in all other census regions.

Conclusion

This study provides concise evidence of inequality in opioid-related deaths among various US census regions. Policy changes focused to certain regions are required to significantly address the underlying factors related to disparities in opioid-related mortality among the black population.
Profiling of the most reliable mutations from sequenced SARS-CoV-2 genomes scattered in Uzbekistan
Authors: Ayubov Mirzakamol S. , Buriev Zabardast T. , Mirzakhmedov Mukhammadjon K. , Yusupov Abdurakhmon N. , Usmanov Dilshod E. , Shermatov Shukhrat E. , Ubaydullaeva Khurshida A. , Abdurakhmonov Ibrokhim Y.
Published: February 2022

Due to rapid mutations in the coronavirus genome over time and re-emergence of multiple novel variants of concerns (VOC), there is a continuous need for a periodic genome sequencing of SARS-CoV-2 genotypes of particular region. This is for on-time development of diagnostics, monitoring and therapeutic tools against virus in the global pandemics condition. Toward this goal, we have generated 18 high-quality whole-genome sequence data from 32 SARS-CoV-2 genotypes of PCR-positive COVID-19 patients, sampled from the Tashkent region of Uzbekistan. The nucleotide polymorphisms in the sequenced sample genomes were determined, including nonsynonymous (missense) and synonymous mutations in coding regions of coronavirus genome. Phylogenetic analysis grouped fourteen whole genome sample sequences (1, 2, 4, 5, 8, 10-15, 17, 32) into the G clade (or GR sub-clade) and four whole genome sample sequences (3, 6, 25, 27) into the S clade. A total of 128 mutations were identified, consisting of 45 shared and 83 unique mutations. Collectively, nucleotide changes represented one unique frameshift mutation, four upstream region mutations, six downstream region mutations, 50 synonymous mutations, and 67 missense mutations. The sequence data, presented herein, is the first coronavirus genomic sequence data from the Republic of Uzbekistan, which should contribute to enrich the global coronavirus sequence database, helping in future comparative studies. More importantly, the sequenced genomic data of coronavirus genotypes of this study should be useful for comparisons, diagnostics, monitoring, and therapeutics of COVID-19 disease in local and regional levels.
IL11 stimulates ERK/P90RSK to inhibit LKB1/AMPK and activate mTOR in hepatocytes, the stroma and cancer cells
Authors: Widjaja Anissa A. , Ting Joyce Goh Wei , Viswanathan Sivakumar , Tan Jessie , Shekeran Shamini G , Carling David , Wen Lim Wei , Cook Stuart A.
Published: February 2022

Interleukin 11 (IL11) stimulates stromal cell activation but also causes hepatocyte metabolic dysfunction. The mechanisms underlying these seemingly unrelated processes are not known. Here we report that IL11-stimulated ERK/P90RSK activity causes the sequential phosphorylation of LKB1 (STK11) at S325 and S428, leading to its inactivation. This leads to a reduction in AMPK activity whilst concomitantly activating mTOR in human fibroblasts, hepatic stellate cells, hepatocytes and cancer cells. In fibroblasts and hepatic stellate cells, IL11-mediated LKB1/AMPK inhibition causes myofibroblast transformation whereas in hepatocytes it inhibits autophagy and fatty acid oxidation and is toxic. Across cell types, the self-amplifying loop of autocrine IL11 activity was inhibited by AMPK activation with metformin, AICAR or 991. In mice on a western diet with fructose, anti-IL11 therapy or hepatocyte-specific deletion of Il11ra1 rescues LKB1/AMPK activity and reduces NASH. In contrast, restoration of IL11 signalling in hepatocytes of mice with global Il11ra1 deletion inactivates LKB1/AMPK and exacerbates NASH. These data show that LKB1, an important tumour suppressor and master kinase, is not constitutively active and identify the IL11/LKB1/AMPK/mTOR axis as a point of signalling convergence for epithelial homeostasis, fibrogenesis, immunometabolism and cancer.
Pneumolysin promotes host cell necroptosis and bacterial competence during pneumococcal meningitis as shown by whole animal dual RNA-seq
Authors: Jim Kin Ki , Aprianto Rieza , Domenech Arnau , Kurushima Jun , van de Beek Diederik , Vandenbroucke-Grauls Christina M.J.E. , Bitter Wilbert , Veening Jan-Willem
Published: February 2022

Pneumolysin is a major virulence factor of Streptococcus pneumoniae that plays a key role in interaction with the host during invasive disease. How pneumolysin influences these dynamics between host and pathogen interaction during early phase of central nervous system infection in pneumococcal meningitis remains unclear. Using a whole animal in vivo dual RNA-seq approach, we identified pneumolysin-specific transcriptional responses in both S. pneumoniae and zebrafish (Danio rerio) during early pneumococcal meningitis. By functional enrichment analysis we identified host pathways known to be activated by pneumolysin, and discovered the importance of necroptosis for host survival. Inhibition of this pathway using the drugs necrostatin-5 or GSK’872 increased host mortality during pneumococcal meningitis. On the pathogen’s side, we find that pneumolysin-dependent competence activation is crucial for intra-host replication and virulence and that not all bacteria activate competence at the same time. Altogether, this study provides new insights into pneumolysin-specific transcriptional responses and identifies key pathways involved in pneumococcal meningitis.

GRAPHICAL ABSTRACT

HIGHLIGHTS

Pneumolysin-specific host and bacterial responses as identified by whole animal dual RNA-seq, available at https://veeninglab.com/dual-danio

Discovery of a functional necroptosis or necroptosis-like pathway in zebrafish

Heterogeneity in competence development during infection

Competence development is an important virulence determinant
Predictions of Skin Permeability Using Molecular Dynamics Simulation from Two-Dimensional Sampling of Spatial and Alchemical Perturbation Reaction Coordinates
Authors: Lundborg Magnus , Wennberg Christian , Lidmar Jack , Hess Berk , Lindahl Erik , Norlén Lars
Published: February 2022

A molecular level understanding of skin permeation may rationalize and streamline product development, and improve quality and control, of transdermal and topical drug delivery systems. It may also facilitate toxicity and safety assessment of cosmetics, skin care products. Here, we present new molecular dynamics simulation approaches that make it possible to efficiently sample the free energy and local diffusion coefficient across the skin’s barrier structure and predict skin permeability and the effects of chemical penetration enhancers. In particular, we introduce a new approach to use two-dimensional reaction coordinates with so-called Accelerated Weight Histograms, where we combine sampling along spatial coordinates with an alchemical perturbation virtual coordinate. We present predicted properties for twenty permeants, and demonstrate how our approach improves correlation with ex vivo/in vitro skin permeation data. For the compounds included in this study, the ob-tained mean square difference was 0.8 cm2 h−2.
Oligodendrocyte precursor cells engulf synaptic inputs in an experience- and microglia-dependent manner
Authors: Auguste Yohan S.S. , Ferro Austin , Dixon Jessica , Vrudhula Uma , Kahng Jessica , Nichitiu Anne-Sarah , Cheadle Lucas
Published: February 2022

Oligodendrocyte precursor cells (OPCs) are a highly proliferative class of non-neuronal progenitors that largely give rise to myelinating oligodendrocytes. Although OPCs persist across the lifespan, their functions beyond oligodendrogenesis remain to be fully characterized. Here, we show that OPCs contribute to neural circuit remodeling by internalizing presynaptic thalamocortical inputs in both the developing and adult mouse visual cortex. Inputs internalized by OPCs localize to lysosomal compartments, consistent with OPC engulfment of synapses occuring through phagocytosis. We further show that engulfment by OPCs is heightened during experience-dependent plasticity, and that this experience-dependent increase in engulfment requires microglia. These data identify a new function for OPCs beyond the generation of oligodendrocytes and reveal that distinct non-neuronal populations collaborate to modulate synaptic connectivity.
Estimating the net effect of functional traits on fitness across species and environments
Authors: Siefert Andrew , Laughlin Daniel C.
Published: February 2022

Functional traits affect the demographic performance of individuals in their environment, leading to fitness differences that scale up to drive population dynamics and community assembly. Understanding the links between traits and fitness is therefore critical for predicting how populations and communities respond to environmental change. However, the net effects of traits on species fitness are largely unknown because we have lacked a framework for estimating fitness across multiple species and environments.

We present a modeling framework that integrates trait effects on demographic performance over the life cycles of individuals to estimate the net effect of traits on species fitness. This approach involves 1) modeling trait effects on individual demographic rates (growth, survival, and recruitment) as multidimensional performance surfaces that vary with individual size and environment and 2) integrating these effects into a population model to project population growth rates (i.e., fitness) as a function of traits and environment. We illustrate our approach by estimating performance surfaces and fitness landscapes for trees across a temperature gradient in the eastern United States.

Functional traits (wood density, specific leaf area, and maximum height) interacted with individual size and temperature to influence tree growth, survival, and recruitment rates, generating demographic trade-offs and shaping the contours of fitness landscapes. Tall tree species had high survival, growth, and fitness across the temperature gradient. Wood density and specific leaf area had interactive effects on demographic performance, resulting in fitness landscapes with multiple peaks.

With this approach it is now possible to empirically estimate the net effect of traits on fitness, leading to improved understanding of the selective forces that drive community assembly and permitting generalizable predictions of population and community dynamics in changing environments.