bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital based contact tracing of COVID-19 patients and health care workers and risk stratification of exposed health care workers during the COVID-19 Pandemic in Eastern India
Authors: Sahoo Durgesh Prasad , Singh Arvind Kumar , Sahu Dinesh Prasad , Pradhan Somen Kumar , Patro Binod Kumar , Batmanabane Gitanjali , Mishra Baijayantimala , Behera Bijayini , Dash Ambarish , Dora G Susmita , L Anand , S M Azhar , Nair Jyolsna , Panigrahi Sasmita , R Akshaya , Sahoo Bimal Kumar , Sahoo Subhakanta , Sahoo Suchismita
Published: November 2020

Introduction

Contact tracing and subsequent quarantining of Health Care Workers (HCWs) is essential to minimize further transmission of COVID-19 infection. In this study, we have reported the yield of Contact Tracing of COVID-19 Patients and HCWs and risk stratification of exposed HCWs.

Methodology

This is a secondary analysis of routine data collected for contact tracing from 19th March to 31st August 2020 at All India Institute of Medical Sciences, Bhubaneswar, Odisha, India. HCWs exposed to COVID-19 infections were categorized as per the risk stratification guidelines and the high-risk contacts were quarantined for 14 days and tested on 7thday from last day of exposure. The low risk contacts were encouraged to closely monitor their symptoms while continuing to work.

Results

Out of 3411 HCWs exposed to COVID 19 patients (n=269) and HCWs (n=91), 890 (26.1%) were high risk contacts and 2521 (73.9%) were low risk contacts. The test positivity rate of high-risk contact was 3.82% and for low risk contact was 1.90%. Average number of high-risk contacts was significantly higher; for admitted patients (6.6) as compared to HCWs (4.0) and outpatients (0.2), p value = 0.009; for patients admitted in non-COVID areas (15.8) as compared to COVID areas (0.27), p value < 0.001; and when clustering of cases was present (14.3) as compared to isolated cases (8.2); p value < 0.001. Trend analysis (15 days block period) showed a significant decline in number of mean numbers of high-risk contacts during the study period.

Conclusion

Contact tracing and risk stratification was effective and helped in reducing the number of HCWs going for quarantine. There was also a decline in high-risk contacts during study period suggesting role of implementation of hospital based COVID related infection control strategies. This contact tracing and risk stratification approach designed in the current study can also be implemented in other healthcare settings.
Experience from a COVID-19 screening centre of a tertiary care institution: A retrospective hospital-based study
Authors: Pradhan Somen Kumar , Sahu Dinesh Prasad , Sahoo Durgesh Prasad , Singh Arvind Kumar , Patro Binod Kumar , Mohanty Sachidananda
Published: November 2020

Introduction

The COVID-19 pandemic continuing to be a significant public health concern across the whole world, including India. In the absence of any specific treatment or vaccine against COVID-19., the role of efficient testing and reporting has been uncontested so far as the number of cases is rising daily. In order to strengthen the screening activities and to prevent nosocomial infection, facility-based screening centres have been designed and operated at various level of healthcare, including tertiary care institutions.

Methods

The present study has been planned with an objective to understand the patient profile and evaluate the functioning of COVID-19 screening OPD(CS-OPD) at a tertiary care hospital. In this hospital-based retrospective study, data from individuals visiting the COVID-19 screening OPD during the period from 17th March 2020 to 31st July 2020 were collected. We documented and analysed relevant demographic, epidemiological and clinical characteristics of the patients.

Results

A total of 10,735 patients visited the COVID-19 screening OPD during the defined study period out of which 3652 individuals were tested. Majority of the patients, i.e. 65.67% (7050) were male and in 15-59 years age group (84.68%). Most common symptoms among patients visiting CS-OPD was Cough (9.86%). Out of the total, 17.17% (1843) of patient reported to the CS-OPD with contact history of COVID-19 positive patient. On the other hand, 13.49% (1448) of patients were with either domestic or international travel history. The overall testing rate and positivity rate for CS-OPD during this period were found to be 34.02% and 7.94% respectively.

Conclusion

The clinical, demographic and epidemiological characteristics of patients visiting CS-OPD varied across the study period depending upon the containment and testing strategy. The CS-OPD played a crucial role in preventing nosocomial infection and maintaining non-COVID care at the tertiary care hospital.
COVID-19 Medical Vulnerability Indicators: A Local Data Model for Equity in Public Health Decision-Making
Authors: Ong Paul M. , Pech Chhandara , Gutierrez Nataly Rios , Mays Vickie
Published: November 2020

Objective

To develop indicators of vulnerability for coronavirus disease 2019 (covid-19) infection in Los Angeles County (LAC) by race and neighborhood characteristics.

Design

Development of indicators that combines pre-existing medical vulnerabilities with social and built-environment data by zip code tabulation areas (ZCTAs).

Setting

Neighborhoods in LAC categorized by race/ethnicity ranked into quintiles by relative vulnerability: Non-Hispanic white; Black; Latinx; Cambodians, Hmong and Laotians combined (CHL); and Other Asians.

Data Sources

AskCHIS Neighborhood Edition, American Community Survey 2014-2018, and California Department of Parks and Recreation.

Main Outcome Measures

1) Pre-Existing Health Condition, 2) Barriers to Accessing Healthcare, 3) Built Environment Risk, and 4) CDC’s Social Vulnerability.

Results

Neighborhoods most vulnerable to COVID-19 are characterized by significant clustering of racial minorities, low income households and unmet medical needs. An overwhelming 73% of Blacks reside in the neighborhoods with the two highest quintiles of pre-existing health conditions, followed by Latinx (70%) and CHL (60%), while 60% of whites reside in low or the lowest vulnerable neighborhoods. For the Barriers to Accessing Healthcare indicator, 40% of Latinx reside in the highest vulnerability places followed by Blacks, CHL and other Asians (29%, 22%, and 16% respectively), compared with only 7% of Whites reside in such neighborhoods. The Built Environment Indicator finds CHL (63%) followed by Latinx (55%) and Blacks (53%) reside in the neighborhoods designated as high or the highest vulnerability compared to 32% of Whites residing in these neighborhoods. The Social Vulnerability Indicator finds 42% of Blacks and Latinx and 38% of CHL residing in neighborhoods of high vulnerability compared with only 8% of Whites residing these neighborhoods.

Conclusions

Vulnerability to covid-19 infections differs by neighborhood and racial/ethnic groups. Our vulnerability indicators when utilized in decision-making of re-openings or resource distribution such as testing, vaccine distribution, hotel rooms for quarantine and other covid-19-related resources can provide an equity driven data approach for the most vulnerable.
An evaluation of assumptions underlying respondent-driven sampling and the social contexts of sexual and gender minority youth participating in HIV clinical trials in the United States
Authors: Wirtz AL , Iyer J , Brooks D , Hailey-Fair K , Galai N , Beyrer C , Celentano D , Arrington-Sanders R. ,   PUSH Study Group
Published: November 2020

Introduction

Respondent-driven sampling has been an effective sampling strategy for HIV research in many settings, but has had limited success among some youth in the United States. We evaluated a modified RDS approach for sampling Black and Latinx sexual and gender minority youth (BLSGMY) and evaluates how lived experiences and social contexts of BLSGMY youth may impact traditional RDS assumptions.

Methods

RDS was implemented in three cities to engage BLSGMY in HIV prevention or care intervention trials. RDS was modified to include targeted seed recruitment from venues, internet, and health clinics, and provided options for electronic or paper coupons. Qualitative interviews were conducted among a sub-sample of RDS participants to explore their experiences with RDS. Interviews were coded using RDS assumptions as an analytic framework.

Results

Between August 2017 and October 2019, 405 participants were enrolled, 1,670 coupons were distributed, with 133 returned, yielding a 0.079 return rate. The maximum recruitment depth was 4 waves among seeds that propagated. Self-reported median network size was 5 (IQR 2-10) and reduced to 3 (IQR 1-5) when asked how many peers were seen in the past 30 days. Qualitative interviews (n=27) revealed that small social networks, peer trust, and targeted referral of peers with certain characteristics challenged network, random recruitment, and reciprocity assumptions of RDS. HIV stigma and research hesitancy were barriers to participation and peer referral.

Conclusions

Small social networks and varying relationships with peers among BLSGMY challenge assumptions that underlie traditional RDS. Modified RDS approaches, including those that incorporate social media, may support recruitment for community-based research but may challenge assumptions of reciprocal relationships. Research hesitancy and situational barriers must be addressed in recruitment and study designs.
SARS-CoV-2 responsive T cell numbers and anti-Spike IgG levels are both associated with protection from COVID-19: A prospective cohort study in keyworkers
Authors: Wyllie David , Jones Hayley E , Mulchandani Ranya , Trickey Adam , Taylor-Phillips Sian , Brooks Tim , Charlett Andre , Ades AE ,   EDSAB-HOME investigators, Moore Philippa , Boyes John , Hormis Anil , Todd Neil , Reckless Ian , Makin Andrew , Oliver Isabel
Published: November 2020

Immune correlates of protection from COVID-19 are incompletely understood. 2,826 keyworkers had T-SPOT®DiscoverySARS-CoV-2 tests (measuring interferon-γ secreting, SARS-CoV-2 responsive T cells, Oxford Immunotec Ltd), and anti-Spike S1 domain IgG antibody levels (EuroImmun AG) performed on recruitment into a cohort study. 285/2,826 (10.1%) of participants had positive SARS-CoV-2 RT-PCR tests, predominantly associated with symptomatic illness, during 200 days followup. T cell responses to Spike, Nucleoprotein and Matrix proteins (SNM responses) were detected in some participants at recruitment, as were anti-Spike S1 IgG antibodies; higher levels of both were associated with protection from subsequent SARS-CoV-2 test positivity. In volunteers with moderate antibody responses, who represented 39% (252/654) of those with detectable anti-Spike IgG, protection was partial, and higher with higher circulating T cell SNM responses. SARS-CoV-2 responsive T cell numbers predict protection in individuals with low anti-Spike IgG responses; serology alone underestimates the proportion of the population protected after infection.
Longitudinal testing for respiratory and gastrointestinal shedding of SARS-CoV-2 in day care centres in Hesse, Germany. Results of the SAFE KiDS Study
Authors: Hoehl Sebastian , Kreutzer Emilie , Schenk Barbara , Westhaus Sandra , Foppa Ivo , Herrmann Eva , Ettrich India , Schaible Alexander , Rudych Olga , Rabenau Holger , Berger Annemarie , Ciesek Sandra
Published: November 2020

Background

With the pandemic of SARS-CoV-2 ongoing in Europe in July of 2020, day care centres were reopened in the state of Hesse, Germany, after the lockdown. The role young children play in the dynamics of the transmission was unknown.

Methods

We conducted a longitudinal study over a period of 12 weeks (18th of June 2020 to 10th of September, 2020) to screen attendees and staff from day care centres in the state of Hesse, Germany, for both respiratory and gastrointestinal shedding of SARS-CoV-2. 825 children (age range 3 months to 8 years) and 372 staff members from 50 day care centres, which were chosen representatively from throughout the state, participated in the study. Parents were asked to perform both a buccal mucosa and an anal swab on their children once a week. Staff were asked to self-administer the swabs. RT-PCRs for SARS-CoV-2 were performed in a multiple-swab pooling protocol.

Findings

7,366 buccal mucosa swabs and 5,907 anal swabs were analysed. No respiratory or gastrointestinal shedding of SARS-CoV-2 was detected in any of the children. Shedding of SARS-CoV-2 could be detected in two staff members from distinct day care centres. One was asymptomatic at the time of testing, and one was symptomatic.

Interpretation

Respiratory or gastrointestinal shedding of SARS-CoV-2 in children or staff members in day care centres was very rare in the context of low community activity. The data indicate day care centres do not pose a reservoir for SARS-CoV-2 in a low prevalence setting, no inapparent transmissions were observed.

Funding

The study was commissioned by the Hessian Ministry of Social Affairs and Integration and was supported by Roche Diagnostics, Basel, Switzerland.
Predicting the Clinical Management of Skin Lesions using Deep Learning
Authors: Abhishek Kumar , Kawahara Jeremy , Hamarneh Ghassan
Published: November 2020

Automated machine learning approaches to skin lesion diagnosis from images are approaching dermatologist-level performance. However, current machine learning approaches that suggest management decisions rely on predicting the underlying skin condition to infer a management decision without considering the variability of management decisions that may exist within a single condition. We present the first work to explore image-based prediction of clinical management decisions directly without explicitly predicting the diagnosis. In particular, we use clinical and dermoscopic images of skin lesions along with patient metadata from the Interactive Atlas of Dermoscopy dataset (1,011 cases; 20 disease labels; 3 management decisions) and demonstrate that predicting management labels directly is more accurate than predicting the diagnosis and then inferring the management decision (13.73 ± 3.93% and 6.59 ± 2.86% improvement in overall accuracy and AUROC respectively), statistically significant at p < 0.001. Directly predicting management decisions also considerably reduces the over-excision rate as compared to management decisions inferred from diagnosis predictions (24.56% fewer cases wrongly predicted to be excised). Furthermore, we show that training a model to also simultaneously predict the seven-point criteria and the diagnosis of skin lesions yields an even higher accuracy (improvements of 4.68 ± 1.89% and 2.24 ± 2.04% in overall accuracy and AUROC respectively) of management predictions. Finally, we demonstrate our model’s generalizability by evaluating on the publicly available MClass-D dataset and show that our model agrees with the clinical management recommendations of 157 dermatologists as much as they agree amongst each other.
Risk factors for outcomes of COVID-19 patients: an observational study of 795 572 patients in Russia
Authors: Demkina A.E. , Morozov S.P. , Vladzymyrskyy A.V. , Kljashtorny V.G. , Guseva O.I. , Pugachev P.S. , Artemova O.R. , Reshetnikov R.V. , Gombolevskiy V.A. , Ryabinina M.N.
Published: November 2020

Background

Several factors that could affect survival and clinical outcomes of COVID-19 patients require larger studies and closer attention.

Objective

To investigate the impact of factors including whether COVID-19 was clinically or laboratory-diagnosed, influenza vaccination, former or current tuberculosis, HIV, and other comorbidities on the hospitalized patients’ outcomes.

Design

Observational nationwide cohort study.

Patients

All subjects, regardless of age, admitted to 4,251 Russian hospitals indexed in the Federal Register of COVID-19 patients between March 26, 2020, and June 3, 2020. All included patients for which complete clinical data were available were divided into two cohorts, with laboratory- and clinically verified COVID-19.

Measurements

We analyzed patients’ age and sex, COVID-19 ICD-10 code, the length of the hospital stay, and whether they required ICU treatment or invasive mechanical ventilation. The other variables for analysis were: verified diagnosis of pulmonary disease, cardiovascular disease, diseases of the endocrine system, cancer/malignancy, HIV, tuberculosis, and the data on influenza vaccination in the previous six months.

Results

This study enrolled 705,572 COVID-19 patients aged from 0 to 121 years, 50.4% females. 164,195 patients were excluded due to no confirmed COVID-19 (n=143,357) or insufficient and invalid clinical data (n=20,831). 541,377 participants were included in the study, 413,950 (76.5%) of them had laboratory-verified COVID-19, and 127,427 patients (23.5%) with the clinical verification. Influenza vaccination reduced the risk of transfer to the ICU (OR 0.76), mechanical ventilation requirement (OR 0.74), and the risk of death (HR 0.77). TB increased the mortality risk (HR 1.74) but reduced the likelihood of transfer to the ICU (OR 0.27). HIV comorbidity significantly increased the risks of transfer to the ICU (OR 2.46) and death (HR 1.60). Patients with the clinically verified COVID-19 had a shorter duration of hospital stay (HR 1.45) but a higher risk of mortality (HR 1.08) and the likelihood of being ventilated (OR 1.36). According to the previously published data, age, male sex, endocrine disorders, and cardiovascular diseases increased the length of hospital stay, the risk of death, and transfer to the ICU.

Limitations

The study did not include a control group of subjects with no COVID-19. Because of that, some of the identified factors could not be specific for COVID-19.

Conclusions

Influenza vaccination could reduce the severity of the hospitalized patients’ clinical outcomes, including mortality, regardless of age, social, and economic group. The other factors considered in the study did not reduce the assessed risks, but we observed several non-trivial associations that may optimize the management of COVID-19 patients.
Emergence of Novel SARS-CoV-2 Variants in the Netherlands
Authors: Urhan Aysun , Abeel Thomas
Published: November 2020

In this study, we analyzed SARS-CoV-2 genomes in the Netherlands, in the context of global viral population since the beginning of the pandemic. We have identified the most variant sites on the whole genome as well as the stable, conserved ones on the S and N proteins. We found four mutations, S:D614G, NSP12b:P314L, NSP3:F106F, to be the most frequent ones that dominate the SARS-CoV-2 population outside of China. We detected novel variants of SARS-CoV-2 almost unique to the Netherlands that form localized clusters, indicating community spread. We emphasize that while SARS-CoV-2 is evolving, and the number of mutations from the reference sequence is increasing, we observe only little diversity in the new variants as we enter the later stages of the pandemic. Our analyses suggest we have diverged away from the current SARS-CoV-2 reference enough that the reference should be re-evaluated to represent the current viral population more accurately. We assert our work provides valuable information on the genetic diversity of SARS-CoV-2 and its local dynamics in the Netherlands, especially for DNA-based diagnostic, therapeutic or vaccine development against COVID-19. We suggest sequence-based analyses should opt for a consensus representation to adequately cover the genomic variation observed.
Human genomics of the humoral immune response against polyomaviruses
Authors: Hodel F. , Chong A.Y. , Scepanovic P. , Xu Z.M. , Naret O. , Thorball C.W. , Rüeger S. , Marques-Vidal P. , Vollenweider P. , Begemann M. , Ehrenreich H. , Brenner N. , Bender N. , Waterboer T. , Mentzer A. J. , Hill A.V.S. , Hammer C. , Fellay J.
Published: November 2020

Human polyomaviruses are widespread in human populations and are able to cause severe disease in immunocompromised individuals. There remains an incomplete understanding of the potential impact of human genetic variation on inter-individual responses to polyomaviruses.

To identify human genetic determinants of the humoral immune response against polyomaviruses, we performed genome-wide association studies and meta-analyses of qualitative and quantitative immunoglobulin G (IgG) responses against the major capsid protein VP1 of Human polyomavirus 6 (HPyV6), BK virus (BKPyV), JC virus (JCPyV), Merkel Cell Polyomavirus (MCPyV) and WU polyomavirus (WUPyV), in a total of 15,660 individuals of European ancestry from CoLaus, UK Biobank and GRAS, three independent studies.

We observed significant associations for all tested viruses: JCPyV, HPyV6 and MCPyV associated with HLA class II variation; BKPyV and JCPyV with variants in the FUT2 gene, responsible for secretor status; MCPyV with variants in the STING1 gene, involved in interferon induction; and WUPyV with a functional variant in the MUC1 gene, previously associated with risk for gastric cancer.

These results provide insights into the genetic control of a family of very prevalent human viruses, highlighting genes and pathways that play a modulating role in human humoral immunity.
Gender-affirming care, mental health, and economic stability in the time of COVID-19: a global cross-sectional study of transgender and non-binary people
Authors: Jarrett Brooke A. , Peitzmeier Sarah M. , Restar Arjee , Adamson Tyler , Howell Sean , Baral Stefan , Beckham S. Wilson
Published: November 2020

Background

Transgender and non-binary people are disproportionately burdened by barriers to quality healthcare, mental health challenges, and economic hardship. This study examined the impact of the novel coronavirus disease (COVID-19) pandemic and subsequent control measures on gender-affirming care, mental health, and economic stability among transgender and non-binary people globally.

Methods

We collected global cross-sectional data from 964 transgender and non-binary adult users of the Hornet and Her apps from April to August 2020 to characterize changes in gender-affirming care, mental health, and economic stability as a result of the COVID-19 pandemic. We conducted Poisson regression models to assess if access to gender-affirming care and ability to live according to one’s gender were related to depressive symptoms, anxiety, and changes in suicidal ideation.

Results

Individuals resided in 76 countries, including Turkey (27.4%,n=264/964) and Thailand (20.6%,n=205). A majority were non-binary (66.8%,n=644) or transfeminine (29.4%,n=283). Due to the COVID-19 pandemic, 55.0% (n=320/582) reported reduced access to gender- affirming resources, and 38.0% (n=327/860) reported reduced time lived according to their gender. About half screened positive for depression (50.4%,442/877) and anxiety (45.8%,n=392/856). One in six (17.0%,n=112/659) expected losses of health insurance, and 77.0% (n=724/940) expected income reductions. The prevalence of depressive symptoms, anxiety, and increased suicidal ideation were 1.63 (95% CI: 1.36-1.97), 1.61 (95% CI: 1.31-1.97), and 1.74 (95% CI: 1.07-2.82) times higher for individuals whose access to gender- affirming resources was reduced versus not.

Discussion

The COVID-19 pandemic has reduced access to gender-affirming resources and the ability of transgender and non-binary people to live according to their gender worldwide. These reductions may drive the increased depressive symptoms, anxiety, and suicidal ideation reported in this sample. To improve transgender and non-binary health globally, increased access to gender-affirming resources should be achieved through policies (e.g., digital prescriptions), flexible interventions (e.g., telehealth), and support for existing transgender health initiatives.
Applying Machine Learning to Evaluate for Fibrosis in Chronic Hepatitis C
Authors: Akella Aravind , Akella Sudheer
Published: November 2020

Machine learning (ML) is proving to be an appealing analytical tool as modern medicine progresses towards preventative care. Clinical risk prediction models built using ML offer the potential for more effective diagnostic modalities without the need for invasive procedures. With such models, healthcare practitioners may be empowered towards a more preventative approach in management, thus improving clinical outcomes. The management of patients with chronic Hepatitis C is incomplete without considering the presence and extent of liver fibrosis, which is traditionally assessed with biopsy of liver tissue. Although non-invasive testing alternatives to liver biopsy are gaining popularity, they are considered limited due to inadequate accuracy and were designed to be complementary to liver biopsy. In this study, our aim is to build clinical risk models to predict the extent of fibrosis in patients with chronic Hepatitis C using ML algorithms. We developed nine ML algorithms based on an Egyptian cohort dataset, relying only on patient demographics and commonly-obtained serum laboratory values. One of our models was able to evaluate for fibrosis with an accuracy of 0.81, sensitivity of 0.95, and specificity of 0.73. Furthermore, most of our models outperformed many current diagnostic alternatives to liver biopsy for the evaluation of fibrosis in this patient population.
Inflexible Updating of the Self-Other Divide During a Social Context in Autism; Psychophysical, Electrophysiological, and Neural Network Modeling Evidence
Authors: Noel Jean-Paul , Paredes Renato , Terrebonne Emily , Feldman Jacob I. , Woynaroski Tiffany , Cascio Carissa J. , Seriès Peggy , Wallace Mark T.
Published: November 2020

Autism spectrum disorder (ASD) is a heterogenous disorder predominantly characterized by social and communicative differences, but increasingly recognized to also alter (multi)sensory function. To face the heterogeneity and ubiquity of ASD, researchers have proposed models of statistical inference operating at the level of ‘computations’. Here, we attempt to bridge both across domains – from social to sensory – and levels of description – from behavioral computations to neural ensemble activity to a biologically-plausible artificial neural network – in furthering our understanding of autism. We do so by mapping visuo-tactile peri-personal space (PPS), and examining its electroencephalography (EEG) correlates, in individuals with ASD and neurotypical individuals during both a social and non-social context given that (i) the sensory coding of PPS is well understood, (ii) this space is thought to distinguish between self and other, and (iii) PPS is known to remap during social interactions. In contrast to their neurotypical counterparts, psychophysical and EEG evidence suggested that PPS does not remap in ASD during a social context. To account for this observation, we then employed a neural network model of PPS and demonstrate that PPS remapping may be driven by changes in neural gain operating at the level of multisensory neurons. Critically, under the anomalous excitation-inhibition (E/I) regime of ASD, this gain modulation does not result in PPS resizing. Overall, our findings are in line with recent statistical inference accounts suggesting diminished flexibility in ASD, and further these accounts by demonstrating within an example relevant for social cognition that such inflexibility may be due to E/I imbalances.
Constructing Graphs from Genetic Encodings
Authors: Barabási Dániel L. , Czégel Dániel
Published: November 2020

Our understanding of real-world connected systems has benefited from studying their evolution, from random wirings and rewirings to growth-dependent topologies. Long overlooked in this search has been the role of the innate: networks that connect based on identity-dependent compatibility rules. Inspired by the genetic principles that guide brain connectivity, we derive a network encoding process that can utilize wiring rules to reproducibly generate specific topologies. To illustrate the representational power of this approach, we propose stochastic and deterministic processes for generating a wide range of network topologies. Specifically, we detail network heuristics that generate structured graphs, such as feed-forward and hierarchical networks. In addition, we characterize a Random Genetic (RG) family of networks, which, like Erdős-Rényi graphs, display critical phase transitions, however their modular underpinnings lead to markedly different behaviors under targeted attacks. The proposed framework provides a relevant null-model for social and biological systems, where diverse metrics of identity underpin a node’s preferred connectivity.
Plasma proteomics reveals tissue-specific cell death and mediators of cell-cell interactions in severe COVID-19 patients
Authors: Filbin Michael R. , Mehta Arnav , Schneider Alexis M. , Kays Kyle R. , Guess Jamey R. , Gentili Matteo , Fenyves Bánk G. , Charland Nicole C. , Gonye Anna L.K. , Gushterova Irena , Khanna Hargun K. , LaSalle Thomas J. , Lavin-Parsons Kendall M. , Lilly Brendan M. , Lodenstein Carl L. , Manakongtreecheep Kasidet , Margolin Justin D. , McKaig Brenna N. , Rojas-Lopez Maricarmen , Russo Brian C. , Sharma Nihaarika , Tantivit Jessica , Thomas Molly F. , Gerszten Robert E. , Heimberg Graham S. , Hoover Paul J. , Lieb David J. , Lin Brian , Ngo Debby , Pelka Karin , Reyes Miguel , Smillie Christopher S. , Waghray Avinash , Wood Thomas E. , Zajac Amanda S. , Jennings Lori L. , Grundberg Ida , Bhattacharyya Roby P. , Parry Blair Alden , Villani Alexandra-Chloé , Sade-Feldman Moshe , Hacohen Nir , Goldberg Marcia B.
Published: November 2020

COVID-19 has caused over 1 million deaths globally, yet the cellular mechanisms underlying severe disease remain poorly understood. By analyzing several thousand plasma proteins in 306 COVID-19 patients and 78 symptomatic controls over serial timepoints using two complementary approaches, we uncover COVID-19 host immune and non-immune proteins not previously linked to this disease. Integration of plasma proteomics with nine published scRNAseq datasets shows that SARS-CoV-2 infection upregulates monocyte/macrophage, plasmablast, and T cell effector proteins. By comparing patients who died to severely ill patients who survived, we identify dynamic immunomodulatory and tissue-associated proteins associated with survival, providing insights into which host responses are beneficial and which are detrimental to survival. We identify intracellular death signatures from specific tissues and cell types, and by associating these with angiotensin converting enzyme 2 (ACE2) expression, we map tissue damage associated with severe disease and propose which damage results from direct viral infection rather than from indirect effects of illness. We find that disease severity in lung tissue is driven by myeloid cell phenotypes and cell-cell interactions with lung epithelial cells and T cells. Based on these results, we propose a model of immune and epithelial cell interactions that drive cell-type specific and tissue-specific damage in severe COVID-19.
Comparative gene pathway analysis during adolescent binge-EtOH exposure, withdrawal, and following abstinence
Authors: Nato Alejandro Q. , Ata Ul Mustafa Hafiz , Sexton Hannah G. , Moore Scott D. , Denvir James , Primerano Donald A. , Risher Mary-Louise
Published: November 2020

Introduction

Binge drinking is common among adolescents and young adults and is associated with an increased risk of developing alcohol use disorder (AUD) and long-term cognitive deficits. We analyzed RNA-seq data from male Sprague Dawley rats to identify candidate genes that may play a role in the acute and chronic changes in cognitive function during binge-like adolescent alcohol/EtOH exposure and after a period of abstinence.

Methods

At postnatal day (PND) 30, male rats received chronic intermittent EtOH across 16 days. RNA was extracted from hippocampal tissue and sequenced at two acute timepoints, PND 35 and PND 46, and after 24 days forced abstinence (PND 70). We processed RNA-seq data, compiled gene counts, and performed normalization and differential expression analysis (DESeq2). Gene set enrichment analysis was performed through the R package fgsea. Gene sets of the Molecular Signatures Database (MSigDB) collections were used to identify gene pathways that were dysregulated following EtOH exposure. We also evaluated overlapping gene pathways that were affected across all timepoints.

Results

Multiple gene pathway analyses revealed that EtOH has robust effects on neuroinflammation, cellular remodeling, sleep, and bioenergetics. Changes were heavily dependent on whether gene expression was assessed during acute EtOH exposure or after abstinence. Genes involved in sleep regulation were selectively impacted during the acute timepoints, whereas dysregulation of genes involved in bioenergetics were only impacted after abstinence. The most striking changes occurred in genes that regulate neuroinflammatory processes and cellular remodeling.

Conclusion

These data reveal acute and chronic effects of EtOH on multiple gene pathways that persist across analytic approaches and identify genes that have increased sensitivity to EtOH. These findings contribute to our understanding of the temporal effects of adolescent EtOH exposure and how gene pathway dysregulation contributes to the protracted emergence of neuronal remodeling in the hippocampus during a critical period of brain maturation.
Seeking an optimal dosing regimen for OZ439-DSM265 combination therapy for treating uncomplicated falciparum malaria
Authors: Dini Saber , Zaloumis Sophie G , Price David J , Gobeau Nathalie , Kümmel Anne , Cherkaoui Mohammed , Moehrle Joerg J , McCarthy James S , Simpson Julie A
Published: November 2020

The efficacy of Artemisinin-based Combination Therapies (ACTs), the first- line treatments of uncomplicated falciparum malaria, has been declining in malaria endemic countries due to the emergence of malaria parasites resistant to these com- pounds. Novel alternative therapies are needed urgently to prevent the likely surge in morbidity and mortality due to failing ACTs. This study investigates the efficacy of the combination of two novel drugs, OZ439 and DSM265, using a biologically informed within-host mathematical model that accounts for the pharmacodynamic interaction between the two drugs. Model parameters were estimated using data from healthy volunteers infected with falciparum malaria collected from four trials: three that administered OZ439 and DSM265 alone, and the fourth a combination of OZ439-DSM265. Posterior predictive simulations of the model were performed to determine efficacious dosing regimens. One such regimen that predicted at least 90% of infected individuals cured 42 days after the administration of the drugs, while within the tolerable dose range, is 800 mg of OZ439 and 450 mg of DSM265. Our model can be used to inform future phase 2 and 3 clinical trials of OZ439-DSM265, fast-tracking the deployment of this combination therapy in the regions where ACTs are failing.
Altered cortical thickness development in 22q11.2 deletion syndrome and association with psychotic symptoms
Authors: Bagautdinova Joëlle , Zöller Daniela , Schaer Marie , Padula Maria Carmela , Mancini Valentina , Schneider Maude , Eliez Stephan
Published: November 2020

Schizophrenia has been extensively associated with reduced cortical thickness (CT), and its neurodevelopmental origin is increasingly acknowledged. However, the exact timing and extent of alterations occurring in preclinical phases remain unclear. With a high prevalence of psychosis, 22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder that represents a unique opportunity to examine brain maturation in high-risk individuals. In this study, we quantified trajectories of CT maturation in 22q11DS and examined the association of CT development with the emergence of psychotic symptoms. Longitudinal structural MRI data with 1-6 time points were collected from 324 participants aged 5-35 years (N=148 22q11DS, N=176 controls), resulting in a total of 636 scans (N=334 22q11DS, N=302 controls). Mixed model regression analyses were used to compare CT trajectories between participants with 22q11DS and controls. Further, CT trajectories were compared between participants with 22q11DS who developed (N=61, 146 scans), or remained exempt of (N=47; 98 scans) positive psychotic symptoms during development. Compared to controls, participants with 22q11DS showed widespread increased CT, focal reductions in the posterior cingulate gyrus and superior temporal gyrus (STG), and accelerated cortical thinning during adolescence, mainly in fronto-temporal regions. Within 22q11DS, individuals who developed psychotic symptoms showed exacerbated cortical thinning in the right STG. Together, these findings suggest that genetic predisposition for psychosis is associated with increased CT starting from childhood and altered maturational trajectories of CT during adolescence, affecting predominantly fronto-temporal regions. In addition, accelerated thinning in the STG may represent an early biomarker associated with the emergence of psychotic symptoms.
A Novel Primer Probe Set for Detection of SARS-CoV-2 by Sensitive Droplet Digital PCR
Authors: Wang Fang , Pervaiz Umar , Tian Hongwei , Mariam Algahdary Omar Ahmed Omar , Hamid Mahasin Abdallah Mohammed , Wang Degui
Published: November 2020

Background

The current increase in the spread of (SARS-CoV-2) critically needs a multitarget diagnostic assays to promote analytical sensitivity to facilitate the public health actions.

Objective

The aim of this study was to develop a new primer-probe set targeting N gene of SARS-CoV-2 to improve the sensitivity for detection of COVID-19(Corona Virus Disease 2019)in multiplex rRT-PCR (Reversetranscript Realtime PCR) and ddPCR (Droplet Digital PCR).

Results

We designed primers/probes set N(LZU3) targeting the N gene of 2019-nCov and proved its sensitivity in both rRT-PCR and ddPCR. When the quantity of template was 105 copies/reaction, the mean Ct value of N(LZU3) was 32.563, the detection rate was 91.7%. If the quantity of template was 52.5 copies/reaction, the mean Ct value of N(LZU3) was 33.835, and the detection rate was 83.3%, which were similar with that of N(CDC) and N(USA). The calculated lower limit of detection (LOD) of the new primer-probe set N(LZU3) used in rRT-PCR was 118 copies/reaction. We also did one-step ddPCR for detection the same serial dilution of RNA template. It shows good linearity for primer/probe sets N(LZU3). The calculated lower limit of detection (LOD) of N(LZU3) was 22.4 copies/reaction, which was 1.12 copies/ul.

Conclusion

The novel primer-probe set(LZU3) targeting N gene of SARS-CoV-2 could be both used in rRT-PCR and ddPCR with better sensitivity, furthermore, ddPCR method had higer sensitivity than rRT-PCR, hence it could significantly improve SARS-CoV-2 detection efficiency in low virus load and asymptomatic infection.
Characteristics of those most vulnerable to employment changes during the COVID-19 pandemic: a nationally representative cross-sectional study in Wales
Authors: Gray Benjamin J , Kyle Richard G , Song Jiao , Davies Alisha R
Published: November 2020

Background

The public health response to the SARS-CoV-2 (COVID-19) pandemic has had a detrimental impact on employment and there are concerns the impact may be greatest amongst the most vulnerable. We examined the characteristics of those who experienced changes in employment status during the early months of the pandemic.

Methods

Data was collected from a cross-sectional, nationally representative household survey of the working age population (18-64 years) in Wales in May/June 2020 (N=1,379). We looked at changes in employment and being placed on furlough since February 2020 across demographics, contract type, job skill level, health status and household factors. Chi-squared or Fisher’s tests and multinomial logistic regression models examined associations between demographics, subgroups and employment outcomes.

Results

Of our respondents 91.0% remained in the same job in May/June 2020 as they were in February 2020, 5.7% were now in a new job, and 3.3% experienced unemployment. In addition, 24% of our respondents reported being placed on furlough. Non-permanent contract types, individuals who reported low mental wellbeing and household financial difficulties were all significant factors in experiencing unemployment. Being placed on ‘furlough’ was more likely in younger (18-29 years) and older (60-64 years) workers, those in lower skilled jobs and from households with less financial security.

Conclusion

A number of vulnerable population groups were observed to experience detrimental employment outcomes during the initial stage of the COVID-19 pandemic. Targeted support is needed to mitigate against both the direct impacts on employment, and indirect impacts on financial insecurity and health.

What is already known on this subject?

The response to the current global pandemic caused by SARS-CoV-2 (COVID-19) is already having a significant impact on people’s ability to work and employment status.

Emerging UK employment data has raised concerns about the disproportionate impact on specific demographic groups.

What this study adds?

Groups that reported higher proportions of being placed on furlough included younger (18-29 years) and older (50-64 years) workers, people from more deprived areas, in lower skilled jobs, and those from households with less financial security.

Job insecurity in the early months of the COVID-19 pandemic was experienced more by those self-employed or employed on atypical or fixed term contract arrangements compared to those holding permanent contracts.

To ensure that health and wealth inequalities are not exacerbated by COVID-19 or the economic response to the pandemic, interventions should include the promotion of secure employment and target the groups identified as most susceptible to the emerging harms of the pandemic.
Exposure to violence, chronic stress, nasal DNA methylation, and atopic asthma in children
Authors: Yan Qi , Forno Erick , Cardenas Andres , Qi Cancan , Han Yueh-Ying , Acosta-Pérez Edna , Kim Soyeon , Zhang Rong , Boutaoui Nadia , Canino Glorisa , Vonk Judith M. , Xu Cheng-jian , Chen Wei , Oken Emily , Gold Diane R. , Koppelman Gerard H. , Celedón Juan C.
Published: November 2020

Background

Exposure to violence (ETV) or stress may cause asthma through unclear mechanisms.

Methods

Epigenome-wide association study (EWAS) of DNA methylation in nasal epithelium and four ETV or chronic stress measures in 487 Puerto Ricans aged 9-20 years who participated in the Epigenetic Variation and Childhood Asthma in Puerto Ricans study [EVA-PR]). We assessed measures of ETV or chronic stress in children (ETV scale, gun violence, and perceived stress) and their mothers (perceived stress). Each EWAS was conducted using linear regression, with CpGs as dependent variables and the stress/violence measure as a predictor, adjusting for age, sex, the top five principal components, and SVA latent factors. We then selected the top 100 CpGs (by P-value) associated with each stress/violence measure in EVA-PR and conducted a meta-analysis of the selected CpGs and atopic asthma using data from EVA-PR and two additional cohorts (Project Viva and PIAMA).

Results

In the EWAS of stress/violence in EVA-PR, gun violence was associated with methylation of cg18961589 in LINC01164 (β=0.03, P=1.28×10−7), and maternal stress was associated with methylation of cg03402351 in SNN (β=0.04, P=1.69×10−7) and cg19064846 in PTPRN2 (β=0.03, P=3.36×10−7). In a meta-analysis of three cohorts, which included the top CpGs associated with stress/violence in EVA-PR, CpGs in STARD3NL, SLC35F4, TSR3, CDC42SE2, KLHL25, PLCB1, BUD13, OR2B3, GALR1, TMEM196, TEAD4 and ANAPC13 were associated with atopic asthma at FDR-P < 0.05.

Conclusions

ETV and chronic stress may increase the risk of atopic asthma through DNA methylation in airway epithelium, though this needs confirmation in future longitudinal studies.
A comparison of pain registration by Visual Analog Scale and Numeric Rating Scale – a cross-sectional study of primary triage registration
Authors: Kollltveit Jofrid , Osaland Malin , Reimers Marianne , Berle Magnus
Published: November 2020

Background

Pain is a subjective sensation; self-reporting is important for quantifying pain intensity. There are several different validated tools for this, such as Visual Analog Scale and Numeric Rating Scale. In the clinic, these terms are often used as equivalent. The objective of this study was to examine correlation and agreement between the pain registration tools in triage in an emergency department.

Materials and Methods

The study was performed in the Department of Emergency Medicine at Haukeland University Hospital in the period June-August 2019. We registered the pain score with two tools in 200 unselected patients in emergency admission with pain. In addition, we registrered gender, age, triage and general department affiliation.

Results

We found a strong correlation between the pain registration tools by Spearmans correlation test (rho=0,930, p<0,001). There were no significant difference between the pain registration tools within the subgroups. Bland-Altman analysis show agreement between the two pain registration tools.

Conclusions

In an Emergency Department triage is it acceptable to use Visual Analog Scale and Numeric Rating Scale as equivalent, as long as the correct terminology is used.
Role and Dynamics of Vacuolar pH during Cell-in-Cell mediated Death
Authors: Su Yan , Ren He , Tang Meng , Zheng You , Zhang Bo , Wang Chenxi , Hou Xinyu , Niu Zubiao , Gao Lihua , Chen Zhaolie , Luo Tianzhi , Sun Qiang
Published: November 2020

The non-autonomous cell death by entosis was mediated by the so-called cell-in-cell structures, which were believed to kill the internalized cells by a mechanism dependent on acidified lysosomes. However, the precise values and roles of pH critical for the death of the internalized cells remained undetermined yet. We creatively employed keima, a fluorescent protein that displays different excitation spectra in responding to pH changes, to monitor the pH dynamics of the entotic vacuoles during cell-in-cell mediated death. We found that different cells varied in their basal intracellular pH, and the pH was relatively stable for entotic vacuoles containing live cells, but sharply dropped to a narrow range along with the inner cell death. In contrast, the lipidation of entotic vacuoles by LC3 displayed previously underappreciated complex patterns associated with entotic and apoptotic death, respectively. The pH decline seemed to play distinct roles in the two types of inner cell deaths, where apoptosis is preceded with moderate pH decline while a profound pH decline is likely to be determinate for entotic death. Whereas the cancer cells seemed to be lesser tolerant to acidified environments than non-cancerous cells, manipulating vacuolar pH could effectively control inner cell fates and switch the ways whereby inner cell die. Together, this study demonstrated for the first time the pH dynamics of entotic vacuoles that dictate the fates of internalized cells, providing a rationale for tuning cellular pH as a potential way to treat cell-in-cell associated diseases such as cancer.