bluuebunny/crossref_metadata_2025 huggingface dataset:
Awareness, Perception and Practice of COVID 19 Prevention among Residents of a State in the South-South Region of Nigeria: Implications for Public Health Control Efforts
Authors: Owhonda Golden , Maduka Omosivie , Nwadiuto Ifeoma , Tobin-West Charles , Azi Esther , Ojimah Chibianotu , Alasia Datonye , Olofinuka Ayo-Maria , Agala Vetty , Paul John Nwolim , Nria Doris , Okafor Chinenye , Ndekwu Ifeoma , Opara Chikezie , Newsom Chris
Published: October 2020

Background

This research explored awareness, perception, and practice of COVID 19 prevention among residents of communities in all the local government areas (districts) in Rivers State during the early stages of the pandemic response.

Design

This was a descriptive cross-sectional survey which employed an interviewer-administered four-page questionnaire built into the Open Data Kit application for android phones. Knowledge and practice scores were computed by scoring every correct response/action as 1 and wrong responses as 0. Knowledge was graded as excellent for scores of ≥80%, good for scores of 50-79% and poor for scores of <50%. Respondents who washed all critical parts of the hand were categorized as having correct handwashing practice.

Setting

Rivers State in the South-South region of Nigeria had recorded over 2000 cases of COVID 19 as of 18th August 2020, ranking 5th among the high burden states in Nigeria. As with any epidemic of an infectious nature, panic, fear, and misconceptions are rife. Risk communication utilizes multi-faceted activities geared towards facilitating correct and consistent knowledge and prevention practice.

Participants

Study involved 1,294 adult community residents in the 23 districts of the state.

Results

The respondents were aged between 18 and 80 years with average age of 39.6 years (SD = 11.9 years). A total of 710 (54.9%) were male, 476 (36.8%) were unemployed with 685 (52.9%) having secondary education. Almost all respondents 1,271 (98.2%) had heard about COVID 19. The three most common sources of information about COVID 19 were radio jingles 1102 (86.7%), television adverts 940 (74.0%) and announcements in Church 612 (48.2%). Overall, 608 (47.0%) of the respondents had poor knowledge of COVID 19. About 1167 (90.2%) of the respondents who were aware of COVID 19 acknowledged that COVID 19 is a problem in the state while 443 (34.9%) respondents believed they were unlikely contract the virus. Only 505 (39.0%) of the respondents washed all critical parts of the hand correctly.

Conclusions

Risk communication interventions during pandemics need to be based on an understanding of the gaps in knowledge, attitude, perceptions, and practice. Broadcast media has a pivotal role to play in risk communication for behaviour change for the control of current and future epidemics in this population.
α4β2* Nicotinic Cholinergic Receptor Target Engagement in Parkinson Disease Gait-Balance Disorders
Authors: Albin Roger L. , Müller Martijn L.T.M. , Bohnen Nicolaas I. , Spino Cathie , Sarter Martin , Koeppe Robert A. , Szpara Ashley , Kim Kamin , Lustig Cindy , Dauer William T.
Published: October 2020

Objective

Attentional function deficits secondary to degeneration of brain cholinergic systems are significant contributors to gait-balance deficits in Parkinson disease (PD). As an initial step towards assessing if α4β2* nicotinic acetylcholine receptor (nAChR) stimulation improves attention and gait-balance function, we assessed target engagement of the α4β2* nAChR partial agonist varenicline.

Methods

Non-demented PD participants with cholinergic deficits were identified with [18F]fluoroethoxybenzamicol positron emission tomography (PET). α4β2* nAChR occupancy after subacute oral varenicline treatment was measured with [18F]flubatine PET. With a dose selected from the receptor occupancy experiment, varenicline effects on gait, balance, and cognition were assessed in a double-masked placebo-controlled crossover study. Primary endpoints were normal pace gait speed and a measure of postural stability.

Results

All varenicline doses (0.25 mg per day, 0.25 mg b.i.d., 0.5 mg b.i.d., and 1.0 mg b.i.d.) produced 60% - 70% receptor occupancy. We selected 0.5 mg po b.i.d for the crossover study. Thirty-three (of thirty-four) participants, completed the crossover study with excellent tolerability. Varenicline had no significant impact on the postural stability measure and caused slower normal pace gait speed. Varenicline narrowed the difference in normal pace gait speed between dual task and no dual task gait conditions, reduced dual task cost, and improved performance on a sustained attention test. We obtained identical conclusions in 28 participants in whom treatment compliance was confirmed by plasma varenicline measurements.

Interpretation

Varenicline occupied a significant fraction of α4β2* nicotinic acetylcholine receptors, was tolerated well, enhanced attentional function, and altered gait performance. These results are consistent with relevant target engagement. Varenicline or similar agents may be worth further evaluation for mitigation of gait and balance disorders in PD.
Presence Of Infection By Mycobacterium Avium Subsp. Paratuberculosis In The Blood Of Patients With Crohn’s Disease And Control Subjects Shown By Multiple Laboratory Culture And Antibody Methods
Authors: Kuenstner J. Todd , Potula Raghava , Bull Tim J. , Grant Irene R. , Foddai Antonio , Naser Saleh , Bach Horacio , Zhang Peilin , Yu Daohai , Lu Xiaoning , Shafran Ira
Published: October 2020

Mycobacterium avium subspecies paratuberculosis (MAP) has long been suspected to be involved in the etiology of Crohn’s disease (CD). An obligate intracellular pathogen, MAP persists and influences host macrophages. The primary goals of this study were to assess the degree of viable culturable MAP bacteremia in humans, definite identification of the organisms cultured and to assess if CD patients have a significantly higher rate of MAP infection compared to controls. A secondary goal was to compare the efficacy of three culture methods plus a phage assay and four antibody assays performed in separate laboratories, to detect MAP from the parallel samples. Culture and serological MAP testing was performed blind on whole blood samples obtained from 201 subjects including 61 CD patients, two patients with CD and concurrent ulcerative colitis (UC), 14 patients with UC only and 140 non-CD controls. Viable MAP bacteremia was detected in a significant number of study subjects across all groups. This included Pozzato culture (124/201 or 62% of all subjects, 35/61 or 57% of CD patients), Phage assay (113/201 or 56% of all subjects, 28/61 or 46% of CD patients), TiKa culture (64/201 or 32% of all subjects, 22/61 or 36% of CD patients) and MGIT culture (36/201 or 18% of all subjects, 15/61 or 25% of CD patients). A link between MAP detection and CD was observed with MGIT culture and one of the antibody methods (Hsp65) confirming previous studies. Other detection methods showed no association between any of the groups tested. Nine subjects with positive Phage assay (8/9) or MAP culture (1/9) were again positive with the Phage assay one year later. This study highlights viable MAP bacteremia is widespread in the study population including CD patients, those with other autoimmune conditions and asymptomatic healthy subjects.
Derivation and validation of a clinical severity score for acutely ill adults with suspected COVID-19: The PRIEST observational cohort study
Authors: Goodacre Steve , Thomas Ben , Sutton Laura , Bursnall Matthew , Lee Ellen , Bradburn Mike , Loban Amanda , Waterhouse Simon , Simmonds Richard , Biggs Katie , Marincowitz Carl , Schutter Jose , Connelly Sarah , Sheldon Elena , Hall Jamie , Young Emma , Bentley Andrew , Challen Kirsty , Fitzimmons Chris , Harris Tim , Lecky Fiona , Lee Andrew , Maconochie Ian , Walter Darren
Published: October 2020

Objectives

We aimed to derive and validate a triage tool, based on clinical assessment alone, for predicting adverse outcome in acutely ill adults with suspected COVID-19 infection.

Methods

We undertook a mixed prospective and retrospective observational cohort study in 70 emergency departments across the United Kingdom (UK). We collected presenting data from 22445 people attending with suspected COVID-19 between 26 March 2020 and 28 May 2020. The primary outcome was death or organ support (respiratory, cardiovascular, or renal) by record review at 30 days. We split the cohort into derivation and validation sets, developed a clinical score based on the coefficients from multivariable analysis using the derivation set, and the estimated discriminant performance using the validation set.

Results

We analysed 11773 derivation and 9118 validation cases. Multivariable analysis identified that age, sex, respiratory rate, systolic blood pressure, oxygen saturation/inspired oxygen ratio, performance status, consciousness, history of renal impairment, and respiratory distress were retained in analyses restricted to the ten or fewer predictors. We used findings from multivariable analysis and clinical judgement to develop a score based on the NEWS2 score, age, sex, and performance status. This had a c-statistic of 0.80 (95% confidence interval 0.79-0.81) in the validation cohort and predicted adverse outcome with sensitivity 0.98 (0.97-0.98) and specificity 0.34 (0.34-0.35) for scores above four points.

Conclusion

A clinical score based on NEWS2, age, sex, and performance status predicts adverse outcome with good discrimination in adults with suspected COVID-19 and can be used to support decision-making in emergency care.

Registration

ISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533
Pathophysiology-based subphenotyping of individuals at elevated risk for type 2 diabetes
Authors: Wagner Robert , Heni Martin , Tabak Adam G. , Machann Jürgen , Schick Fritz , Randrianarisoa Elko , de Angelis Martin Hrabě , Birkenfeld Andreas L. , Stefan Norbert , Peter Andreas , Häring Hans-Ulrich , Fritsche Andreas
Published: October 2020

The state of intermediate hyperglycemia is indicative of elevated risk of developing type 2 diabetes1. However, the current definition of prediabetes neither reflects subphenotypes of pathophysiology of type 2 diabetes nor is it predictive of future metabolic trajectories. We used partitioning on variables derived from oral glucose tolerance tests, MRI measured body fat distribution, liver fat content, and genetic risk in a cohort of extensively phenotyped individuals who are at increased risk for type 2 diabetes2,3to identify six distinct clusters of subphenotypes. Three of the identified subphenotypes have increased glycemia (clusters 3, 5 and 6), but only individuals in clusters 5 and 3 have immanent diabetes risks. By contrast, those in cluster 6 have moderate risk of type 2 diabetes, but an increased risk of kidney disease and all-cause mortality. Findings were replicated in an independent cohort using simple anthropomorphic and glycemic constructs4. This proof-of-concept study demonstrates that pathophysiological heterogeneity exists before diagnosis of type 2 diabetes and highlights a group of individuals who have an increased risk of complications without rapid progression to overt type 2 diabetes.
SARS-CoV-2 sequencing reveals rapid transmission from college student clusters resulting in morbidity and deaths in vulnerable populations
Authors: Richmond Craig S. , Sabin Arick P. , Jobe Dean A. , Lovrich Steven D. , Kenny Paraic A.
Published: October 2020

College reopening decisions during the SARS-CoV-2 pandemic represent a trade-off between competing risks to students, faculty and staff, and college finances. Additionally, risks taken in reopening colleges can impose significant burdens on individuals living in surrounding communities. Many colleges that reopened for in-person instruction have reported frequent SARS-CoV-2 outbreaks. La Crosse County, Wisconsin experienced a substantial SARS-CoV-2 outbreak (2,002 cases in September 2020) that coincided with the return to in-person instruction at three local academic institutions. Genomic sequencing of SARS-CoV-2 cases in La Crosse during that period found rapid expansion of two viral substrains. Although the majority of cases were among college-age individuals, from a total of 111 genomes sequenced we identified rapid transmission of the virus into more vulnerable populations. Eight sampled genomes represented two independent transmission events into two skilled nursing facilities, resulting in two fatalities. Our study highlights the very significant risks imposed by college administrator reopening decisions, not just on college-associated populations, but on vulnerable individuals in surrounding communities.
The alternative complement pathway is activated in protoporphyria patients during sun exposure
Authors: Granata Francesca , Duca Lorena , Brancaleoni Valentina , Fustinoni Silvia , De Luca Giacomo , Motta Irene , Graziadei Giovanna , Di Pierro Elena
Published: October 2020

The homeostasis of tissues in chronic disease is an important function of the alternative pathway (AP) of the complement system (CS). However, if not controlled, it may also be detrimental to healthy cells.

Protoporphyria (PP) is a rare disease that causes photosensitivity at the visible light due to the accumulation of Protoporphyrin-IX in the dermis. The aim of this study was to deep the knowledge about the involvement of AP in PP photoreaction.

Global radiation and UV data were provided from regional agency of environmental protection (ARPA). Properdin, Factor H (FH) and C5 levels were assessed in the serum collected during winter and summer from 19 PP patients and 13 controls..

Properdin in winter and summer reflected a positive increase compared to controls. The values in summer were higher than winter. The C5 results were altered only in summer. The outcome was reversed for FH: in the winter, it was higher compared to the summer. A positive correlation was reported between properdin and C3 in summer; a negative tendency between Factor B (FB) and FH was detected.

This study substantiated the differential involvement of AP depending on the increase in light exposure during the season, which was demonstrated with ARPA data. The enhanced systemic response could justify the malaise sensation of patients after long light exposure and can be exploited to elucidate the new therapeutic approach.
Rapid detection of SARS-CoV-2 antibodies in oral fluids
Authors: MacMullan Melanie A. , Chellamuthu Prithvi , Mades Aubree , Das Sudipta , Turner Fred , Slepnev Vladimir I , Ibrayeva Albina
Published: October 2020

Current commercially available methods for reliably detecting antibodies against SARS-CoV-2 remain expensive and inaccessible due to the need for whole blood collection by highly trained phlebotomists using personal protective equipment (PPE). We evaluated an antibody detection approach utilizing the OraSure® Technologies’ Oral Antibody Collection Device (OACD) and their proprietary SARS-CoV-2 total antibody detection enzyme-linked immunosorbent assay (ELISA). We found that the OraSure® test for total antibody detection in oral fluid had comparable sensitivity and specificity to serum-based ELISAs while presenting a more affordable and accessible system with the potential for self-collection.
Scrutiny for Child Abuse and Neglect During the COVID-19 Pandemic
Authors: Catillon Maryaline , Mandl Kenneth D.
Published: October 2020

The extant infrastructure for child abuse surveillance, dependent on reporting by schools and healthcare professionals, has been disrupted by the pandemic. Using Google Trends and MediaCloud data, we find a drop in Internet searches and news reports about child abuse and neglect during the pandemic, which may reflect decreased scrutiny.
COVID-19 vaccination rate and protection attitudes can determine the best prioritisation strategy to reduce fatalities
Authors: Rodríguez Jorge , Patón Mauricio , Acuña Juan M
Published: October 2020

Background

The unprecedented rapid development of vaccines against the SARS-CoV-2 virus creates in itself a new challenge for governments and health authorities: the effective vaccination of large numbers of people in a short time and, possibly, with shortage of vaccine doses. To whom vaccinate first and in what sequence, if any at all, to avoid the most fatalities remains an open question.

Methods

A compartmental model considering age-related groups was developed to evaluate and compare vaccine distribution strategies in terms of the total avoidable fatalities. Population groups are established based on relevant differences in mortality (due to e.g. their age) and risk-related traits (such as their behaviour and number of daily person-to-person interactions). Vaccination distribution strategies were evaluated for different vaccine effectiveness levels, population coverage and vaccination rate using data mainly from Spain.

Findings

Our results show that, if children could also be included in the vaccination, a rollout by priority to groups with the highest number of daily person-to-person interactions can achieve large reductions in total fatalities. This is due to the importance of the avoided subsequent infections inflicted on the rest of the population by highly interactive individuals. If children are excluded from the vaccination, the differences between priority strategies become smaller and appear highly depending on rollout rate, coverage and the levels of self-protection and awareness exercised by the population.

Interpretation

These results are in possible contradiction with several published plans for COVID-19 vaccination and highlight the importance of conducting an open comprehensive and thorough analysis of this problem leaving behind possible preconceptions.
Implementing a Telemedicine Curriculum for Internal Medicine Residents during a Pandemic: The Cleveland Clinic Experience
Authors: Savage David J. , Gutierrez Omar , Montane Bryce , Singh Achintya Dinesh , Yudelevich Eric , Mahar Jamal , Brateanu Andrei , Khatri Lakshmi , Fleisher Catherine , Jolly Stacey
Published: October 2020

Introduction

Telemedicine is an important element of healthcare. However, until the COVID-19 pandemic, training in telemedicine was not a substantial element of most residency programs. Social distancing measures changed this. The Cleveland Clinic Internal Medicine Residency Program (IMRP) is one of the largest programs in the United States, which made the task of developing and adopting an effective, expedited telemedicine curriculum challenging. Our goal was to implement a system for teaching telemedicine care skills and supervising the care provided by residents during virtual visits.

Methods

This study was started in April 2020. We developed and implemented a resident-led curriculum and training program for providing telemedicine care in less than five weeks. This entailed creating a formal training program for residents, creating a resource guide for the different video communication tools, and training preceptors to safely supervise care in this new paradigm. We also created an assessment instrument in our education evaluation system that allows residents to receive feedback on their performance during virtual appointments.

Results

Over 2000 virtual visits were performed by residents in a span of 10 weeks. Of 148 residents, 38% responded to the pre-participation survey. A majority had no prior telemedicine experience and expressed only slight comfort with the modality.

Discussion

Through collaboration with experienced residents and faculty, we expeditiously developed an enhancement to our ambulatory care curriculum to teach residents how to provide virtual care and help faculty with supervision. We share our insights on this experience for other residency programs to utilize.
Antimicrobial resistance surveillance: can we estimate resistance in bloodstream infections from other types of specimen?
Authors: Vihta Karina-Doris , Gordon Nicola Claire , Stoesser Nicole , Quan T. Phuong , Tyrrell Carina SB , Vongsouvath Manivanh , Ashley Elizabeth A , Chansamouth Vilada , Turner Paul , Ling Clare L , Eyre David , White Nicholas J , Crook Derrick , Peto Tim , Walker Ann Sarah
Published: October 2020

Synopsis

Background

Antimicrobial resistance (AMR) surveillance of bloodstream infections is challenging in low- and middle-income countries (LMICs), limited laboratory capacity preventing routine patient-level susceptibility testing. Other specimen types could provide an effective approach to surveillance.

Objectives

Our study aims to systematically evaluate the relationship between resistance prevalence in non-sterile sites and bloodstream infections.

Methods

Associations between resistance rates in Escherichia coli and Staphylococcus aureus isolates from blood and other specimens were estimated in Oxfordshire, UK, 1998-2018, comparing proportions resistant in each calendar year using time series cross-correlations and across drug-years. We repeated analysis across publicly-available data from four high-income and 12 middle-income countries, and in three hospitals/programmes in LMICs.

Results

8102 E. coli bloodstream infections, 322087 E. coli urinary tract infections, 6952 S. aureus bloodstream infections and 112074 S. aureus non-sterile site cultures were included from Oxfordshire. Resistance trends over time in blood versus other specimens were strongly correlated (maximum cross-correlation 0.51-0.99, strongest associations in the same year for 18/27 pathogen-drug combinations). Resistance prevalence was broadly congruent across drug-years for each species. 276/312 (88%) species-drug-years had resistance prevalence in other specimen types within ±10% of that blood isolates. Results were similar across multiple countries and hospitals/programmes in high/middle/low income-settings.

Conclusions

Resistance in bloodstream and less invasive infections are strongly related over time, suggesting the latter could be a surveillance tool for AMR in LMICs. These infection sites are easier to sample and cheaper to obtain the necessary numbers of susceptibility tests, providing more cost-effective evidence for decisions including empiric antibiotic recommendations.
Indolent Presentations of Leukemic Lung Disease in Acute Myeloid Leukemia
Authors: Kunitomo Yukiko , Lee Seohyuk , Avery Chace C. , Valda Toro Patricia L. , Cohen Avi J. , Ehtashimi-Afshar Solmaz , Kahn Peter A. , Siddon Alexa , Boddu Prajwal , Datta Rupak , Dela Cruz Charles S. , Gautam Samir
Published: October 2020

Background

Patients with active acute myelogenous leukemia (AML) are at risk for leukemic infiltration (LI) into the lung and acute tumor lysis pneumopathy (ATLP) following chemotherapy. Fulminant presentations of these leukemic lung diseases are well-described, but indolent forms have not yet been studied. Therefore, we sought to elucidate the clinical features of mild-to-moderate LI and ATLP.

Methods

A retrospective cohort analysis was performed on 51 hospitalized patients with AML, circulating blast count ≥3%, non-critical illness, and receipt of bronchoscopy between 2015-2019. Diagnoses of LI and ATLP were made via retrospective chart review by a multidisciplinary team of physicians.

Results

19 cases of leukemic lung disease were identified: 14 with LI and 5 with ATLP. The clinical presentations closely resembled pneumonia, with the majority demonstrating respiratory symptoms (63%), hypoxemia (63%), fever (84%), and pulmonary opacities (100%). All patients were presumptively diagnosed with infection, leading to an average of 18 days of broad-spectrum antibiotic therapy and multiple instances of delayed chemotherapy in treatment candidates. Although most patients were near the end-of-life (90% died within 1 year), transitions to comfort care were infrequent (25%) and hospitalizations were protracted (median 25 days).

Conclusions

LI and ATLP are common yet under-recognized pulmonary complications in patients with active AML. When presenting indolently, these conditions are difficult to distinguish from lung infection, leading to missed diagnosis, inappropriate antibiosis, chemotherapy deferrals, and prolonged hospitalizations. Greater awareness and consensus definitions of LI and ATLP are therefore needed to improve care of this population.
The ADEPT Study, A Comparative Study of Dentists’ Ability to Detect Enamel-only Proximal Caries in Bitewing Radiographs With and Without the use of AssistDent® Artificial Intelligence Software
Authors: Devlin Hugh , Williams Tomos , Graham Jim , Ashley Martin
Published: October 2020

Introduction

Reversal of enamel-only proximal caries by non-invasive treatments is important in preventive dentistry. However, detecting such caries using bitewing radiography is difficult, and the subtle patterns are often missed by dental practitioners.

Aims

To investigate whether the ability of dentists to detect enamel-only proximal caries is enhanced by the use of AssistDent® Artificial Intelligence (AI) software.

Materials and Methods

In the ADEPT (AssistDent Enamel-only Proximal caries assessmenT) study, twenty-three dentists were randomly divided into a control arm, without AI assistance, and an experimental arm in which AI assistance provided on-screen prompts indicating potential enamel-only proximal caries. All participants analysed a set of 24 bitewings in which an expert panel had previously identified 65 enamel-only carious lesions and 241 healthy proximal surfaces.

Results

The control group found 44.3% of the caries, whereas the experimental group found 75.8%. The experimental group incorrectly identified caries in 14.6% of the healthy surfaces compared to 3.7% in the control group. The increase in sensitivity of 71% and decrease in specificity of 11% are statistically significant (p<0.01).

Conclusions

AssistDent® Artificial Intelligence software significantly improves dentists’ ability to detect enamel-only proximal caries and could be considered as a tool to support preventive dentistry in general practice.

Key Points

Enamel-only proximal caries are often missed by dentists when examining bitewing radiographs.

The use of AssistDent® Artificial Intelligence software results in a 71% increase in ability to detect enamel-only proximal caries accompanied by a 11% decrease in specificity.

Artificial Intelligence software could be considered as a tool to support preventive dentistry in general practice.
Whole genome sequencing delineates regulatory and novel genic variants in childhood cardiomyopathy
Authors: Lesurf Robert , Said Abdelrahman , Akinrinade Oyediran , Breckpot Jeroen , Delfosse Kathleen , Liu Ting , Yao Roderick , McKenna Fintan , Noche Ramil R. , Oliveros Winona , Mattioli Kaia , Miron Anastasia , Yang Qian , Meng Guoliang , Chan Seng Yue Michelle , Sung Wilson WL , Thiruvahindrapuram Bhooma ,   Genomics England Research Consortium, Lougheed Jane , Oechslin Erwin , Bergin Lynn , Smythe John , Mondal Tapas , Melé Marta , Maass Philipp G. , Ellis James , Scherer Stephen W. , Mital Seema
Published: October 2020

Cardiomyopathy (CMP) is a heritable genetic disorder. Protein-coding variants account for 20-30% of cases. The contribution of variants in non-coding DNA elements that regulate gene expression has not been explored. We performed whole-genome sequencing (WGS) of 228 unrelated CMP families. Besides pathogenic protein-coding variants in known CMP genes, 5% cases harbored rare loss-of-function variants in novel cardiac genes, with NRAP and FHOD3 being strong candidates. WGS also revealed a high burden of high-risk variants in promoters and enhancers of CMP genes in an additional 20% cases (Odds ratio 2.14, 95% CI 1.60-2.86, p=5.26×10−7 vs 1326 controls) with genes involved in α-dystroglycan glycosylation (FKTN, DTNA) and desmosomal signaling (DSC2, DSG2) specifically enriched for regulatory variants (False discovery rate <0.03). These findings were independently replicated in the Genomics England CMP cohort (n=1266). The functional effect of non-coding variants on transcription was functionally validated in patient myocardium and reporter assays in human cardiomyocytes, and that of novel gene variants in zebrafish knockouts. Our results show that functionally active variants in novel genes and in regulatory elements of CMP genes contribute strongly to the genomic etiology of childhood-onset CMP.
Frontline healthcare workers' experiences with personal protective equipment during the COVID-19 pandemic in the UK: a rapid qualitative appraisal
Authors: Hoernke Katarina , Djellouli Nehla , Andrews Lily Jay , Lewis-Jackson Sasha , Manby Louisa , Martin Sam , Vanderslott Samantha , Vindrola-Padros Cecilia
Published: October 2020

Objectives
To report frontline healthcare workers' (HCWs) experiences with personal protective equipment (PPE) during the COVID-19 pandemic in the UK. To understand HCWs' fears and concerns surrounding PPE, their experiences following its guidance and how these affected their perceived ability to deliver care during the COVID-19 pandemic.

Methods
A rapid qualitative appraisal study combining three sources of data: semi-structured in-depth telephone interviews with frontline HCWs (n=46), media reports (n=39 newspaper articles and 145,000 social media posts) and government PPE policies (n=25). HCWs interviewed were from secondary care, primary care and specialist community clinics. Media and policy data were from across the UK.

Results
A major concern was running out of PPE, putting HCWs and patients at risk of infection. Following national-level guidance was often not feasible when there were shortages, leading to re-use and improvisation of PPE. Frequently changing guidelines generated confusion and distrust. PPE was reserved for high-risk secondary care settings and this translated into HCWs outside these settings feeling inadequately protected. Participants were concerned about inequitable access to PPE for community, lower seniority, female and ethnic minority HCWs. Participants continued delivering care despite the physical discomfort, practical problems and communication barriers associated with PPE use.
Conclusion
This study found that frontline HCWs persisted in caring for their patients despite multiple challenges including inappropriate provision of PPE, inadequate training and inconsistent guidance. In order to effectively care for patients during the COVID-19 pandemic, frontline HCWs need appropriate provision of PPE, training in its use, as well as comprehensive and consistent guidance. These needs must be addressed in order to protect the health and well-being of the most valuable healthcare resource in the COVID-19 pandemic: our HCWs.
Early Crowdfunding Response to the COVID-19 Pandemic
Authors: Saleh Sameh N. , Lehmann Christoph U. , Medford Richard J.
Published: October 2020

Background

As the number of COVID-19 cases increased precipitously in the US, policymakers and health officials marshalled their pandemic responses. As the economic impacts multiplied, anecdotal reports noted the increased use of online crowdfunding to defray these costs. We examined the online crowdfunding response in the early stage of the COVID-19 pandemic in the US.

Methods

On May 16, 2020, we extracted all available data available on US campaigns created between January 1 and May 10, 2020 on GoFundMe and identified the subset of COVID-related campaigns using keywords relevant to the COVID-19 pandemic. We explored incidence of COVID-related campaigns by geography, by category, and over time and compared campaign characteristics to non-COVID-related campaigns after March 11 when the pandemic was declared.

Results

We found that there was a substantial increase in overall GoFundMe online crowdfunding campaigns in March, largely attributable to COVID-related campaigns. However, as the COVID-19 pandemic persisted and progressed, the number of campaigns per COVID-19 cases declined more than tenfold across all states. COVID-related campaigns raised more money, had a longer narrative description, and were more likely to be shared on Facebook than other campaigns in the study period.

Conclusions

Online crowdfunding appears to be a transient stopgap, predicated on the novelty of an emergency rather than the true sustained need of a community. Rather, crowdfunding activity is likely an early marker for communities in acute distress that could be used by governments and aid organizations to guide disaster relief and policy.

Trial registration

N/A
The HIV/STI Epidemic Potential of Dynamic Sexual Networks of Men Who Have Sex With Men in Atlanta and San Francisco
Authors: Anderson Emeli J. , Weiss Kevin M. , Morris Martina M. , Sanchez Travis H. , Prasad Pragati , Jenness Samuel M.
Published: October 2020

Background

The potential speed through which a pathogen may circulate in a network is a function of network connectivity. Network features like degree (number of ongoing partnerships) determine the cross-sectional network connectivity. The overall transmission potential of a pathogen involves connectivity over time, which can be measured using the forward reachable path (FRP). We modeled dynamic sexual networks of MSM in San Francisco and Atlanta to estimate the FRP as a predictor of HIV/STI epidemic potential.

Methods

We used exponential random graph models to obtain parameter estimates for each city’s sexual network and then simulated the complete networks over time. The FRP was estimated in each city overall and stratified by demographics.

Results

The overall mean and median FRPs were higher in San Francisco than in Atlanta, suggesting a greater epidemic potential for HIV and STIs in San Francisco. At one year, in both cities, the average FRP among casual partnerships was highest in the youngest age group and lowest in the oldest age group, contrasting with the cross-sectional network parameters we estimated, where the youngest age category had the lowest mean degree and the oldest age category had the highest mean degree.

Conclusions

The FRP results correspond to the observed STI epidemics but not HIV epidemics between the cities. In San Francisco, rates of HIV have been declining over the last few years, whereas they have been steady in Atlanta. The FRP by age group resulted in fundamentally different conclusions about connectivity in the network compared with the cross-sectional network measures.
Nonspecific blood tests as proxies for COVID-19 hospitalization: are there plausible associations after excluding noisy predictors?
Authors: Ishikawa G. , Argenti G. , Fadel C. B.
Published: October 2020

This study applied causal criteria in directed acyclic graphs for handling covariates in associations for prognosis of severe COVID-19 (Corona virus disease 19) cases. To identify nonspecific blood tests and risk factors as predictors of hospitalization due to COVID-19, one has to exclude noisy predictors by comparing the concordance statistics (AUC) for positive and negative cases of SARS-CoV-2 (acute respiratory syndrome coronavirus 2). Predictors with significant AUC at negative stratum should be either controlled for their confounders or eliminated (when confounders are unavailable). Models were classified according to the difference of AUC between strata. The framework was applied to an open database with 5644 patients from Hospital Israelita Albert Einstein in Brazil with SARS-CoV-2 RT-PCR (Reverse Transcription – Polymerase Chain Reaction) exam. C-reactive Protein (CRP) was a noisy predictor: hospitalization could have happen due to causes other than COVID-19 even when SARS-CoV-2 RT-PCR is positive and CRP is reactive, as most cases are asymptomatic to mild. Candidates of characteristic response from moderate to severe inflammation of COVID-19 were: combinations of eosinophils, monocytes and neutrophils, with age as risk factor; and creatinine, as risk factor, sharpens the odds ratio of the model with monocytes, neutrophils, and age.
Less severe course of COVID-19 is associated with elevated levels of antibodies against seasonal human coronaviruses OC43 and HKU1 (HCoV OC43, HCoV HKU1)
Authors: Dugas Martin , Grote-Westrick Tanja , Vollenberg Richard , Lorentzen Eva , Brix Tobias , Schmidt Hartmut , Tepasse Phil-Robin , Kühn Joachim
Published: October 2020

The clinical course of COVID-19 is very heterogeneous: Most infected individuals can be managed in an outpatient setting, but a substantial proportion of patients requires intensive care, resulting in a high rate of fatalities. Recently, an association between contact to small children and mild course of COVID-19 was reported. We performed an observational study to assess the impact of previous infections with seasonal coronaviruses on COVID-19 severity. 60 patients with confirmed COVID-19 infections were included (age 30 - 82 years; 52 males, 8 females): 19 inpatients with critical disease, 16 inpatients with severe or moderate disease and 25 outpatients (age and gender matched to inpatients). Patients with critical disease had significantly lower levels of HCoV OC43- (p=0.016) and HCoV HKU1-specific (p=0.023) antibodies at the first encounter compared to other COVID-19 patients. Our results indicate that previous infections with seasonal coronaviruses might protect against a severe course of disease. This finding should be validated in other settings and could contribute to identify persons at risk before an infection.
Impact of COVID-19 Restrictions on People with Hypertension
Authors: Bonner Carissa , Cvejic Erin , Ayre Julie , Isautier Jennifer , Semsarian Christopher , Nickel Brooke , Batcup Carys , Pickles Kristen , Dodd Rachael , Cornell Samuel , Copp Tessa , McCaffery Kirsten
Published: October 2020

Objectives

It is unclear how people with hypertension are responding to the COVID-19 pandemic given their increased risk, and whether targeted public health strategies are needed.

Design

This retrospective case-control study compared people with hypertension to matched healthy controls during COVID-19 lockdown, to determine whether they have higher risk perceptions, anxiety and prevention intentions.

Methods

Baseline data from a national survey were collected in April 2020 during COVID-19 lockdown. Of 4362 baseline participants, 466 people reported hypertension with no other chronic conditions, and were randomly matched to healthy controls with similar age, gender, education and health literacy. A subset (n=1369) was followed-up at 2 months after restrictions eased, including 147 participants with hypertension only. Risk perceptions, prevention intentions and anxiety were measured.

Results

At baseline, perceived seriousness was high for both hypertension and control groups. The hypertension group had higher anxiety than controls; and were more willing to have the influenza vaccine. At follow-up, these differences were no longer present in the longitudinal sub-sample. Perceived seriousness and anxiety had decreased, but vaccine intentions for both influenza and COVID-19 remained high (>80%).

Conclusions

Anxiety was above normal levels during the COVID-19 lockdown. This was higher in the hypertension group, who also had higher vaccination intentions. Locations with prolonged restrictions may require targeted mental health screening for vulnerable groups. Despite a decrease in perceived risk and anxiety after 2 months of lockdown restrictions, vaccination intentions for both influenza and COVID-19 remained high, which is encouraging for future prevention of COVID-19.
scATAC-Seq reveals epigenetic heterogeneity associated with an EMT-like process in male germline stem cells and its regulation by G9a
Authors: Liao Jinyue , Suen Hoi Ching , Luk Alfred Chun Shui , Lee Annie Wing Tung , Ng Judy Kin Wing , Chan Ting Hei Thomas , Cheung Man Yee , Chan David Yiu Leung , Qi Huayu , Chan Wai Yee , Hobbs Robin M. , Lee Tin-Lap
Published: October 2020

Background

Epithelial-mesenchymal transition (EMT) is a phenomenon in which epithelial cells acquire mesenchymal traits. It contributes to organogenesis and tissue homeostasis, as well as stem cell differentiation. Emerging evidence indicates that heterogeneous expression of EMT gene markers presents in sub-populations of germline stem cells (GSCs). However, the functional implications of such heterogeneity are largely elusive.

Results

We unravelled an EMT-like process in GSCs byin vitroextracellular matrix (ECM) model and single-cell genomics approaches. We found that histone methyltransferase G9a regulated an EMT-like program in GSCin vitroand contributed to neonatal germ cell migrationin vivo.Through modulating ECM, we demonstrated that GSCs exist in interconvertible epithelial-like and mesenchymal-like cell states. GSCs gained higher migratory ability after transition to a mesenchymal-like cell state, which was largely mediated by the TGF-β signaling pathway. Dynamics of epigenetic regulation at the single-cell level was also found to align with the EMT-like process. Chromatin accessibility profiles generated by single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) clustered GSCs into epithelial-like and mesenchymal-like states, which were associated with differentiation status. The high-resolution data revealed regulators in the EMT-like process, including transcription factorsZeb1.We further identified putative enhancer-promoter interactions andcis-co-accessibility networks at loci such asTgfb1, Notch1andLin28a.Lastly, we identified HES1 as the putative target underlying G9a’s regulation.

Conclusion

Our work provides the foundation for understanding the EMT-like process and a comprehensive resource for future investigation of epigenetic regulatory networks in GSCs.
Capsular polysaccharide switching inStreptococcus suismodulates host cell interactions and virulence
Authors: Okura Masatoshi , Auger Jean-Philippe , Shibahara Tomoyuki , Goyette-Desjardins Guillaume , Calsteren Marie-Rose Van , Maruyama Fumito , Kawai Mikihiko , Osaki Makoto , Segura Mariela , Gottschalk Marcelo , Takamatsu Daisuke
Published: October 2020

Streptococcus suisserotype 2 strains can cause severe infections in both swine and humans. The capsular polysaccharide (CPS) ofS. suisdefines various serotypes based on its composition and structure. Though serotype switching from serotype 2 has been suggested to occur betweenS. suisstrains, its impact on pathogenicity and virulence remains unknown. Herein, we experimentally generatedS. suisserotype-switched mutants from a serotype 2 strain (SS2) that express the serotype 3, 4, 7, 8, 9, or 14 CPS (SS2to3, SS2to4, SS2to7, SS2to8, SS2to9, and SS2to14, respectively). The effects of serotype switching were then investigated with regards to classical properties conferred by presence of the serotype 2 CPS, including adhesion to/invasion of porcine tracheal epithelial cells, resistance to phagocytosis by murine macrophages, killing by murine and porcine whole blood, and dendritic cell-derived pro-inflammatory mediator production. Results demonstrated that these properties on host cell interactions were differentially modulated depending on the switched serotypes. Using a mouse model of systemic infection, SS2to8 was demonstrated to be hyper-virulent, with animals rapidly succumbing to septic shock, whereas SS2to3 and SS2to4 were less virulent than SS2 because of a reduced systemic inflammatory host response. By contrast, switching to serotype 7, 9, or 14 CPSs had little to no effect. Finally, development of clinical signs in a porcine model of infection was only observed following infection with SS2, SS2to7, and SS2to8. Taken together, these findings suggest that serotype switching can differentially modulateS. suishost cell interactions and virulence depending on the CPS type expressed.

Importance

Streptococcus suisserotype 2 is the most frequently type associated with swine and zoonotic infections. While the serotype 2 CPS is required for virulence and pathogenesis, little information is available regarding that of other serotypes and how differences in serotype can directly affect host cell interactions and virulence. Herein, we constructed serotype-switched mutants from a serotype 2 strain and demonstrated that serotype switching can shift and modulate theS. suishost cell interactions and virulencein vivo. Among the serotype-switched mutants, the mutant expressing the serotype 8 CPS, whose composition and structure are identical to that of the human pathogenStreptococcus pneumoniaeserotype 19F, was hyper-virulent, whereas mutants expressing the serotype 3 or 4 CPSs had reduced virulence. These results demonstrate that serotype switching can drastically alterS. suisphenotype. Consequently, further importance and attention should be given to the phenomenon of serotype switching and the possible emergence of hyper-virulent isolates.
Validation of a Derived International Patient Severity Algorithm to Support COVID-19 Analytics from Electronic Health Record Data
Authors: Klann Jeffrey G , Weber Griffin M , Estiri Hossein , Moal Bertrand , Avillach Paul , Hong Chuan , Castro Victor , Maulhardt Thomas , Tan Amelia LM , Geva Alon , Beaulieu-Jones Brett K , Malovini Alberto , South Andrew M , Visweswaran Shyam , Omenn Gilbert S , Ngiam Kee Yuan , Mandl Kenneth D , Boeker Martin , Olson Karen L , Mowery Danielle L , Morris Michele , Follett Robert W , Hanauer David A , Bellazzi Riccardo , Moore Jason H , Loh Ne-Hooi Will , Bell Douglas S. , Wagholikar Kavishwar B , Chiovato Luca , Tibollo Valentina , Rieg Siegbert , Li Anthony L.L.J. , Jouhet Vianney , Schriver Emily , Samayamuthu Malarkodi J , Xia Zongqi ,   The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) (CONSORTIA AUTHOR), Kohane Isaac S , Brat Gabriel A , Murphy Shawn N
Published: October 2020

Abstract

Introduction

The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) includes hundreds of hospitals internationally using a federated computational approach to COVID-19 research using the EHR.

Objective

We sought to develop and validate a standard definition of COVID-19 severity from readily accessible EHR data across the Consortium.

Methods

We developed an EHR-based severity algorithm and validated it on patient hospitalization data from 12 4CE clinical sites against the outcomes of ICU admission and/or death. We also used a machine learning approach to compare selected predictors of severity to the 4CE algorithm at one site.

Results

The 4CE severity algorithm performed with pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of single code categories for acuity were unacceptably inaccurate - varying by up to 0.65 across sites. A multivariate machine learning approach identified codes resulting in mean AUC 0.956 (95% CI: 0.952, 0.959) compared to 0.903 (95% CI: 0.886, 0.921) using expert-derived codes. Billing codes were poor proxies of ICU admission, with 49% precision and recall compared against chart review at one partner institution.

Discussion

We developed a proxy measure of severity that proved resilient to coding variability internationally by using a set of 6 code classes. In contrast, machine-learning approaches may tend to overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold standard outcomes, possibly due to pandemic conditions.

Conclusion

We developed an EHR-based algorithm for COVID-19 severity and validated it at 12 international sites.