bluuebunny/crossref_metadata_2025 huggingface dataset:
Medical management of eating disorders: an update
Authors: Voderholzer Ulrich , Haas Verena , Correll Christoph U. , Körner Thorsten
Published: September 2020

Purpose of review

Eating disorders are associated with numerous medical complications. The aim of this study was to review recent progress in improving the medical management of patients with eating disorders.

Recent findings

With close medical monitoring and electrolyte supplementation, accelerated refeeding protocols improve weight restoration without increasing the risk of refeeding syndrome. Olanzapine improves weight restoration better than placebo, without leading to adverse metabolic effects seen in individuals not in starvation. Alterations of the gut microbiome in anorexia nervosa have been demonstrated, but their clinical relevance remains unclear.

Medical complications of eating disorders may facilitate the first contact with health professionals and treatment initiation. Medical complications of anorexia nervosa generally occur due to starvation, malnutrition and their associated physiological effects, whereas medical complications of bulimia nervosa are generally due to purging behaviors. Most medical complications in patients with binge eating disorder are secondary to obesity. Most medical complications of eating disorders can be effectively treated with nutritional management, weight normalization and the termination of purging behaviors. In summary, eating disorders are associated with many medical complications that have to be carefully assessed and managed as early as possible to improve long-term outcomes.
Lithium Is Likely to Persist in the Brain
Authors: Augustin Marc , Karakavuz Rahsan , Riester Luise , Grözinger Michael
Published: September 2020

Electroconvulsive therapy and concomitant lithium therapy remain a matter of debate because of increased rates of adverse events. Current recommendations include monitoring lithium levels and reducing lithium to minimally effective dose. We present a report on protracted effects of lithium intoxication as electroconvulsive therapy 8 days after intoxication and under normal lithium serum levels resulted in a prolonged seizure. Electroencephalogram recordings before stimulation showed electroencephalogram correlates of subsiding lithium intoxication most likely due to protracted lithium influx and efflux of the central nervous system.
Automatic Contact Tracing for Outbreak Detection Using Hospital Electronic Medical Record Data
Authors: DeWitt Michael
Published: September 2020

Contact tracing is a well-known tool for public health professionals to trace and isolate contacts of known infectious persons. During a pandemic contact tracing is critical to ending an outbreak, but the volume of cases makes tracing difficult without adequate staffing tools. Hospitals equipped with electronic medical records can utilize these databases to automatically link cases into possible transmission chains and surface potential new outbreaks. While this automatic contact tracing does not have the richness of contact tracing interviews, it does provide a way for health systems to highlight potential super-spreader events and support their local health departments. Additionally, these data provide insight into how a given infection is spreading locally. These insights can be used to inform policy at the local level.
Disruption of RFX family transcription factors causes autism, attention deficit/hyperactivity disorder, intellectual disability, and dysregulated behavior
Authors: Harris Holly K. , Nakayama Tojo , Lai Jenny , Zhao Boxun , Argyrou Nikoleta , Gubbels Cynthia S. , Soucy Aubrie , Genetti Casie A. , Rodan Lance H. , Tiller George E. , Lesca Gaetan , Gripp Karen W. , Asadollahi Reza , Hamosh Ada , Applegate Carolyn D. , Turnpenny Peter D. , Simon Marleen E.H. , Volker-Touw Catharina (Nienke) M.L. , van Gassen Koen L.I. , van Binsbergen Ellen , Pfundt Rolph , Gardeitchik Thatjana , de Vries Bert B.A. , Imken Ladonna L. , Buchanan Catherine , Willing Marcia , Toler Tomi L. , Fassi Emily , Baker Laura , Vansenne Fleur , Wang Xiadong , Ambrus Julian L. , Fannemel Madeleine , Posey Jennifer E. , Agolini Emanuele , Novelli Antonio , Rauch Anita , Boonsawat Paranchai , Fagerberg Christina R. , Larsen Martin J. , Kibaek Maria , Labalme Audrey , Poisson Alice , Payne Katelyn K. , Walsh Laurence E. , Aldinger Kimberly , Balciuniene Jorune , Skraban Cara , Gray Christopher , Murrell Jill , Bupp Caleb P. , Pascolini Giulia , Grammatico Paola , Broly Martin , Küry Sébastien , Nizon Mathilde , Rasool Iqra Ghulam , Zahoor Muhammad Yasir , Kraus Cornelia , Reis André , Iqbal Muhammad , Uguen Kevin , Audebert-Bellanger Severine , Ferec Claude , Redon Sylvia , Baker Janice , Wu Yunhong , Zampino Guiseppe , Syrbe Steffan , Brosse Ines , Jamra Rami Abou , Dobyns William B. , Cohen Lilian L. , Agrawal Pankaj B. , Beggs Alan , Yu Timothy W.
Published: September 2020

Purpose

We describe a novel neurobehavioral syndrome of autism spectrum disorder, intellectual disability, and attention deficit/hyperactivity disorder associated withde novoor inherited deleterious variants in members of theRFXfamily of genes.RFXgenes are evolutionarily conserved transcription factors that act as master regulators of central nervous system development and ciliogenesis.

Methods

We assembled a cohort of 36 individuals (from 31 unrelated families) withde novomutations inRFX3, RFX4, andRFX7. We describe their common clinical phenotypes and present bioinformatic analyses of expression patterns and downstream targets of these genes as they relate to other neurodevelopmental risk genes.

Results

These individuals share neurobehavioral features including autism spectrum disorder (ASD), intellectual disability, and attention-deficit/hyperactivity disorder (ADHD); other frequent features include hypersensitivity to sensory stimuli and sleep problems.RFX3, RFX4, andRFX7are strongly expressed in developing and adult human brain, and X-box binding motifs as well asRFXChIP-seq peaks are enriched in the cis-regulatory regions of known ASD risk genes.

Conclusion

These results establish deleterious variation inRFX3, RFX4, andRFX7as important causes of monogenic intellectual disability, ADHD and ASD, and position these genes as potentially critical transcriptional regulators of neurobiological pathways associated with neurodevelopmental disease pathogenesis.
Covid-19 epidemic curve in Brazil: A sum of multiple epidemics, whose income inequality and population density in the states are correlated with growth rate and daily acceleration
Authors: de Sousa Pinto Airandes , Rodrigues Carlos Alberto , Sobrinho Carlito Lopes Nascimento , Santos Edval Gomes dos , Cruz Lívia Almeida da , Nunes Paulo Cesar , Costa Matheus Gomes Reis , da Costa Rocha Manoel Otávio
Published: September 2020

Introduction

Recently, we demonstrated that the polynomial interpolation method can be used to accurately calculate the daily acceleration of cases and deaths by Covid-19. The acceleration of new cases is important for the characterization and comparison of epidemic curves. The objective of this work is to measure the diversity of epidemic curves and understand the importance of socioeconomic variables in the acceleration, peak cases and deaths by Covid-19 in Brazilian states.

Methods

This is an ecological study with time series analysis of new cases and deaths by Covid-19 in Brazil and its 27 federation units. Using the polynomial interpolation method, we calculated the daily cases and deaths with the measurement of the respective acceleration. We calculated the correlation coefficient between the epidemic curve data and socioeconomic data.

Results

The combination of daily data and acceleration determined that the states of Brazil are in different stages of the epidemic. Maximum acceleration of peak cases, peak of cases, maximum acceleration of deaths and peak of deaths are associated with the Gini index and population density, but did not correlate with HDI and per capita income.

Conclusion

Brazilian states showed heterogeneous data curves. Density population and socioeconomic inequality are associated with worse control of the epidemic.
RAAS blockers and region-specific variations in COVID-19 outcomes: findings from a systematic review and meta-analysis
Authors: Kaur Upinder , Chakrabarti Sankha Shubhra , Patel Tejas Kumar
Published: September 2020

Background

Coronavirus disease 2019 (COVID-19) has evolved as a global crisis with high mortality seen in elderly and people with cardiometabolic diseases. The use of renin angiotensin aldosterone system (RAAS) blockers in these patients is known to enhance the expression of ACE-2, the chief binding receptor of SARS-CoV-2 and may potentially enhance infectivity.

Objective

To provide a pooled estimate of the effect of RAAS blocker usage on COVID-19 outcomes.

Data Sources

An electronic literature search was performed for published (using MEDLINE/PubMed and Google Scholar) and preprint (using bioRxiv and medRxiv) studies of interest. The last search was conducted on 9th July 2020.

Study Selection

Studies reporting data on RAAS blocker use and COVID-19 mortality and severity were included in the review.

Data Extraction and Synthesis

Mortality data and severity data including hospitalization, intensive care unit (ICU) admission, invasive ventilation, steroid use and acute kidney injury (AKI) were recorded. Pooled Odds ratio (OR) estimates were reported with 95% CIs and level of heterogeneity (I2).

Main Outcomes and Measures

Odds of mortality in users of RAAS blockers with respect to non-users was the primary outcome. Odds of severity, hospitalization, ICU admission, mechanical ventilation, steroid use, and AKI in users with respect to non-users of RAAS blockers were the secondary outcomes.

Results

Of 1348 articles identified, 48 published studies were included in the final analysis, with a total of 26432 patients from 31 studies included in mortality analysis and 20127 patients from 23 studies included in severity analysis. Majority of the studies (41.6%) were from China. No increased risk of mortality (Pooled OR 0.91 (0.65-1.26), I2=89%) or severity (Pooled OR 1.08 (0.79-1.46), I2=88%) was seen with RAAS blockers. The drug class was protective in hypertension (pooled OR 0.63 (0.46-0.86), I2=58%). Severity of COVID-19 outcomes was found to be high for Europeans (Pooled OR 2.08 (1.52-2.85), I2=77%) and US patients (Pooled OR 1.87 (1.62-2.17) in users of RAAS-blockers. A nearly 4 times higher risk of hospitalization, two times higher risk of ICU admission and mechanical ventilation was observed in US patients on RAAS blockers. No net effect on mortality and severity outcomes was seen in Chinese patients. RAAS blocker usage did not have any effect on corticosteroid use and AKI in Chinese patients.

Conclusions and Relevance

Use of RAAS blockers is not associated with increased risk of mortality in COVID-19 patients. Reduced mortality is seen in hypertensive patients with COVID-19 and therefore the drugs should be continued in this subset. US and European patients are at higher risk of severe outcomes. Pharmacogenomic differences may explain the ethnicity related variations.
Disrupting upstream translation in mRNAs leads to loss-of-function associated with human disease
Authors: Lee David S.M. , Park Joseph , Kromer Andrew ,   Regeneron Genetics Center, Rader Daniel J. , Ritchie Marylyn D. , Ghanem Louis R. , Barash Yoseph
Published: September 2020

Ribosome-profiling has uncovered pervasive translation in 5’UTRs, however the biological significance of this phenomenon remains unclear. Using genetic variation from 71,702 human genomes, we assess patterns of selection in translated upstream open reading frames (uORFs) in 5’UTRs. We show that uORF variants introducing new stop codons, or strengthening existing stop codons, are under strong negative selection comparable to protein-coding missense variants. Using these variants, we map and validate new gene-disease associations in two independent biobanks containing exome sequencing from 10,900 and 32,268 individuals respectively, and demonstrate their impact on gene expression in human cells. Our results establish new mechanisms relating uORF variation to loss-of-function of downstream genes, and demonstrate that translated uORFs are genetically constrained regulatory elements in 40% of human genes.
Automated analysis of lexical features in Frontotemporal Degeneration
Authors: Cho Sunghye , Nevler Naomi , Ash Sharon , Shellikeri Sanjana , Irwin David J. , Massimo Lauren , Rascovsky Katya , Olm Christopher , Grossman Murray , Liberman Mark
Published: September 2020

We implemented an automated analysis of lexical aspects of semi-structured speech produced by three patient groups with Frontotemporal degeneration (FTD): behavioral variant FTD (n=74), semantic variant Primary Progressive Aphasia (svPPA, n=42), and nonfluent/agrammatic PPA (naPPA, n=22). With a natural language processing program, we automatically tagged part-of-speech categories of all words and rated nouns for lexical measures, and computed the cross-entropy estimation, which is a measure of word predictability. Our automated analysis was a valid reflection of manual scoring. For svPPA patients, we found fewer unique nouns and more pronouns and wh-words than in the other patient groups and the controls; high abstractness, ambiguity, frequency, and familiarity for nouns they produced; and the lowest cross-entropy estimation among the groups. These measures were associated with cortical thinning in the left temporal lobe. In naPPA patients, we found increased speech errors, which were associated with cortical thinning in the left middle frontal gyrus. bvFTD patients were similar to the controls. Our results underline distinct word use profiles in subgroups of PPA patients and validate our automated method of analyzing FTD patients’ speech.
Improved mTBI outcomes with a BCI Amplified CRT Training: A retrospective chart review
Authors: Cripe C.T. , Mikulecky P. , Cooper Rebecca , Eagan T.
Published: September 2020

This study is a retrospective chart review of 200 clients who participated in a non-verbal restorative Cognitive Remediation Training (rCRT) program. The program was applied to effect proper neural functional remodeling needed to support resilient, flexible and adaptable behaviors after encountering a mild to medium closed head traumatic brain injury (mTBI). The r CRT training program focused on improving functional performance in executive cognitive control networks as defined by fMRI studies. All rCRT training activities were delivered in a semi-game-like manner, incorporating a Brain Computer Interface (BCI) that provided in-the-moment neural network performance integrity metrics (nPIMs) used to adjust the level of play required to properly engage long-term potentiation (LTP) and long term depreciation (LTD) network learning rules.

This study reports on t-test and Reliable Change Index (RCI) changes found within cognitive abilities’ performance metrics derived from the Woodcock Johnson Cognitive Abilities III Test. We compared pre and post scores from seven cognitive abilities considered dependent on executive cognitive control networks against seven non-executive control abilities. We observed significant improvements (p values 10 to 10-22) with large Cohen’s d effect sizes (0.78-1.20) across thirteen cognitive ability domains with a medium effect size (.49) on the remaining. The mean percent change for pooled trained domain was double that observed for pooled untrained domain, at 17.2% versus 8.3%, respectively. To further adjust for practice effects, practice effect RCI values were computed and further supported the effectiveness of the rCRT training (RCI-trained 1.4 - 4.8; untrained RCI 0.08-0.75).
GWAS reveal a role for the central nervous system in regulating weight and weight change in response to exercise
Authors: Watanabe Louis P. , Riddle Nicole C.
Published: September 2020

Body size and weight show considerable variation both within and between species. This variation is controlled in part by genetics, but also strongly influenced by environmental factors including diet and the level of activity experienced by the individual. Due to the increasing obesity epidemic in much of the world, there is considerable interest in the genetic factors that control body weight and how weight changes in response to exercise treatments. Here, we use GWAS in Drosophila to identify the molecular pathways that control weight and exercise-induced weight changes. We find that there is a complex set of molecular pathways controlling weight, with many genes linked to the central nervous system (CNS). Weight was strongly impacted by animal size and body composition. While the CNS appears to be important for weight and exercise-induced weight change, signaling pathways are particularly important for determining how exercise impacts weight.
Combined protein and transcript single cell RNA sequencing in human peripheral blood mononuclear cells
Authors: Vallejo Jenifer , Saigusa Ryosuke , Gulati Rishab , Ghosheh Yanal , Durant Christopher P. , Roy Payel , Ehinger Erik , Suryawanshi Vasantika , Pattarabanjird Tanyaporn , Padgett Lindsey E. , Olingy Claire E. , Hanna David B. , Landay Alan L. , Tracy Russell P. , Lazar Jason M. , Mack Wendy J. , Weber Kathleen M. , Adimora Adaora A. , Hodis Howard N. , Tien Phyllis C. , Ofotokun Igho , Heath Sonya L. , Blanco-Dominguez Rafael , Dinh Huy Q. , Shemesh Avishai , McNamara Coleen A. , Lanier Lewis L. , Hedrick Catherine C. , Kaplan Robert C. , Ley Klaus
Published: September 2020

Cryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single cell (sc)RNA sequencing in PBMCs. Among 31 participants in the WIHS Study, we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs and Louvain clustering, we identified 58 subsets among CD4 T, CD8 T, B, NK cells and monocytes. This resolution was superior to flow cytometry, mass cytometry or scRNA-sequencing without antibodies. Since the transcriptome was not needed for cell identification, combined protein and transcript scRNA-Seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportion. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease. In conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.
Modular barcode beads for microfluidic single cell genomics
Authors: Delley Cyrille L. , Abate Adam R.
Published: September 2020

Barcode beads allow efficient nucleic acid tagging in single cell genomics. Current barcode designs, however, are fabricated with a particular application in mind. Repurposing to novel targets, or altering to add additional targets as information is obtained is possible but the result is suboptimal. Here, we describe a modular framework that simplifies generation of multifunctional beads and allows their easy extension to new targets.

One Sentence Summary

We describe an optimized design for barcoding beads which are useful for single cell RNA and DNA sequencing.
Molecular characterization of non-small cell lung cancer tumors in Latin American patients from Brazil, Chile and Peru uncovers novel potentially driver mutations
Authors: Sepúlveda-Hermosilla Gonzalo , Blanco Alejandro , Freire Matías , Lizana Rodrigo , Cáceres-Molima Javier , Ampuero Diego , Pérez Paola , Ramos Liliana , Aren Osvaldo , Chernilo Sara , Spencer María Loreto , Flores Jacqueline , Bernal Giuliano , Olea Mónica Ahumada , Rasse Germán , Sánchez Carolina , Marcelain Katherine , Rivas Solange , Amorim Maria Galli de , Branco Gabriela , Nunes Diana Noronha , Dias-Neto Emmanuel , Freitas Helano C. , Fernández Cristina ,   NIRVANA Team, Assar Rodrigo , Armisén Ricardo
Published: September 2020

Introduction

Therapies that target activatingEgfr, Alk, Ros1and other mutations have become first-line treatments that improve NSCLC patient’s life expectancy. Latin-American patients are poorly represented in clinical trials and in genomic databases, thus little is known about the prevalence of actionable mutations in this population. This study characterizes, for the first time, the somatic mutations found in 52 actionable genes, and describe a novel set of potentially actionable mutations, in NSCLC patients from Chile, Brazil and Peru, while correlating these genomic occurrences with relevant clinical, demographic and pathology aspects.

Methods

1732 subjects diagnosed with NSCLC were analyzed. DNA and RNA were sequenced using a 52 genes NGS panel. Mutations were annotated using the Variant Effect Predictor, COSMIC, OncoKB and the Cancer Genome Interpreter to categorize somatic mutations.

Results

We found a total of 1713 mutations with 626 (36.5%) novel, potentially driver mutations. 66.1% of these novel mutations were predicted as Tier 1 driver mutations. Actionable mutations forRet and Alkwere more prevalent in Brazil than in Chile, whereasMetexon-14 skipping was significantly enriched in Chile. In Peru,Egfris higher whileKrasis lower. A high number of novels potentially driver mutations in know NSCLC actionable genes, such asAlk, Erbb2, Ret, Met, andRos1, was found.

Conclusions

The analysis of many Latin America subjects revealed a significant number of clinically actionable but also novel somatic mutations in cancer genes highlighting the importance of including less-represented populations in clinical trials and molecular studies.
On Machine Learning-Based Short-Term Adjustment of Epidemiological Projections of COVID-19 in US
Authors: Kefayati Sarah , Roberts Fred , Pethe Sayali , Liu Xuan , Huang Hu , Gopalakrishnan Vishrawas , Madan Piyush , Hu Jianying , Chakraborty Prithwish , Srinivasan Raman , Deshpande Ajay , Jackson Gretchen
Published: September 2020

Epidemiological models have provided valuable information for the outlook of COVID-19 pandemic and relative impact of different mitigation scenarios. However, more accurate forecasts are often needed at near term for planning and staffing. We present our early results from a systemic analysis of short-term adjustment of epidemiological modeling of COVID 19 pandemic in US during March-April 2020. Our analysis includes the importance of various types of features for short term adjustment of the predictions. In addition, we explore the potential of data augmentation to address the data limitation for an emerging pandemic. Following published literature, we employ data augmentation via clustering of regions and evaluate a number of clustering strategies to identify early patterns from the data.

From our early analysis, we used CovidActNow as our underlying epidemiological model and found that the most impactful features for the one-day prediction horizon are population density, workers in commuting flow, number of deaths in the day prior to prediction date, and the autoregressive features of new COVID-19 cases from three previous dates of the prediction. Interestingly, we also found that counties clustered with New York County resulted in best preforming model with maximum of R2= 0.90 and minimum of R2=0.85 for state-based and COVID-based clustering strategy, respectively.
Whole-Exome sequencing identifies a Type 2 Diabetes candidate mutation inPTPRF
Authors: Toonen Erik J.M. , Kwint Michael , Hoischen Alexander , Tack Cees J.
Published: September 2020

Objectives

Identification of genetic factors involved in Type 2 diabetes mellitus (T2DM) has been challenging. While genome-wide association studies (GWAS) have identified over 60 loci associated with T2DM, these variants only explain a small proportion of the total heritability of the disease. Whole-exome sequencing has become a powerful approach to identify genetic variants that are not captured by GWAS. We applied exome sequencing to identify causal genetic variants in a family with a 2-generation history of T2DM characterized by substantial insulin resistance, hypertension and isolated hypertriglyceridemia. Methods: Exome sequencing was performed on genomic DNA of two affected family members. Twenty-four identified variants that were present in both family members were further tested for segregation in all other family members by Sanger sequencing. Results: Three rare missense variants, located in the genesPTPRF, FUCA1andFBXO30, were present in all affected family members but also in one unaffected family member. Protein-protein interaction analysis showed thatPTPRFstrongly interacts with several members of the insulin signaling pathway. Conclusions: Our results suggest that the variant in thePTPRFgene might be causal for an unusual T2DM subtype that is characterized by a severe insulin resistance and isolated hypertriglyceridemia.
Spatial and temporal invasion dynamics of the 2014-2017 Zika and chikungunya epidemics in Colombia
Authors: Charniga Kelly , Cucunubá Zulma M. , Mercado Marcela , Prieto Franklyn , Ospina Martha , Nouvellet Pierre , Donnelly Christl A.
Published: September 2020

Zika virus (ZIKV) and chikungunya virus (CHIKV) were recently introduced into the Americas resulting in significant disease burdens. Understanding their spatial and temporal dynamics at the subnational level is key to informing surveillance and preparedness for future epidemics. We analyzed anonymized line list data on approximately 105,000 Zika virus disease and 412,000 chikungunya fever suspected and laboratory-confirmed cases during the 2014-2017 epidemics. We first determined the week of invasion in each city. Out of 1,122, 288 cities met criteria for epidemic invasion by ZIKA and 338 cities by CHIKV. We estimated that the geographic origin of both epidemics was located in Barranquilla, north Colombia. Using gravity models, we assessed the spatial and temporal invasion dynamics of both viruses to analyze transmission between cities. Invasion risk was best captured when accounting for geographic distance and intermediate levels of density dependence. Although a few long-distance invasion events occurred at the beginning of the epidemics, an estimated distance power of 1.7 (95% CrI: 1.5-2.0) suggests that spatial spread was primarily driven by short-distance transmission. Cities with large populations were more likely to spread disease than cities with smaller populations. Similarities between the epidemics included having the same estimated geographic origin and having the same five parameters estimated in the best-fitting models. ZIKV spread considerably faster than CHIKV.

Author summary

Understanding the spread of infectious diseases across space and time is critical for preparedness, designing interventions, and elucidating mechanisms underlying transmission. We analyzed human case data from over 500,000 reported cases to investigate the spread of the recent Zika virus (ZIKV) and chikungunya virus (CHIKV) epidemics in Colombia. Both viruses were introduced into northern Colombia. We found that intermediate levels of density dependence best described transmission and that transmission mainly occurred over short distances. Our results highlight similarities and key differences between the ZIKV and CHIKV epidemics in Colombia, which can be used to anticipate future epidemic waves and prioritize cities for active surveillance and targeted interventions.
SARS2 simplified scores to estimate risk of hospitalization and death among patients with COVID-19
Authors: Dashti Hesam , Roche Elise C. , Bates David William , Mora Samia , Demler Olga
Published: September 2020

Although models have been developed for predicting severity of COVID-19 based on the medical history of patients, simplified risk prediction models with good accuracy could be more practical. In this study, we examined utility of simpler models for estimating risk of hospitalization of patients with COVID-19 and mortality of these patients based on demographic characteristics (sex, age, race, median household income based on zip code) and smoking status of 12,347 patients who tested positive at Mass General Brigham centers. The corresponding electronic health records were queried from 02/26/2020 to 07/14/2020 to construct derivation and validation cohorts. The derivation cohort was used to fit a generalized linear model for estimating risk of hospitalization within 30 days of COVID-19 diagnosis and mortality within approximately 3 months for the hospitalized patients. On the validation cohort, the model resulted in c-statistics of 0.77 [95% CI: 0.73-0.80] for hospitalization outcome, and 0.72 [95% CI: 0.69-0.74] for mortality among hospitalized patients. Higher risk was associated with older age, male sex, black ethnicity, lower socioeconomic status, and current/past smoking status. The model can be applied to predict risk of hospitalization and mortality, and could aid decision making when detailed medical history of patients is not easily available.
Diagnosing Community-Acquired Pneumonia: diagnostic accuracy study of a cough-centred algorithm for use in primary and acute-care consultations
Authors: Porter Paul , Brisbane Joanna , Abeyratne Udantha , Bear Natasha , Wood Javan , Peltonen Vesa , Della Phillip , Smith Claire , Claxton Scott
Published: September 2020

Background

Community-acquired pneumonia (CAP) is an essential consideration in patients presenting to primary care with respiratory symptoms; however, accurate diagnosis is difficult when clinical and radiologic examinations are not possible, such as during telehealth consultations.

Aim

To develop and test a smartphone-based algorithm for diagnosing CAP without need for clinical examination or radiology inputs.

Design and Setting

A prospective cohort study using data from subjects aged over 12 years presenting with acute respiratory symptoms to a hospital in Western Australia.

Method

Five cough audio-segments were recorded and four patient-reported symptoms (fever, acute cough, productive cough, age) were analysed by the smartphone-based algorithm to generate an immediate diagnostic output for CAP. We recruited independent cohorts to train and test the accuracy of the algorithm.

Diagnostic agreement was calculated against the confirmed discharge diagnosis of CAP by specialist physicians. Specialist radiologists reported medical imaging.

Results

The algorithm had high percent agreement (PA) with the clinical diagnosis of CAP in the total cohort (n=322, Positive PA=86%, Negative PA=86%, AUC=0.95); in subjects 22-65 years (n=192, PPA=86%, NPA=87%, AUC=0.94) and in subjects >65 years (n=86, PPA=86%, NPA=87.5%, AUC=0.94). Agreement was preserved across CAP severity: 85% (80/94) of subjects with CRB-65 scores 1-2, and 87% (57/65) with a score of 0, were correctly diagnosed by the algorithm.

Conclusion

The algorithm provides rapid and accurate diagnosis of CAP. It offers improved accuracy over current protocols when clinical evaluation is difficult. It provides increased capabilities for primary and acute care, including telehealth services, required during the COVID-19 pandemic.

How this fits in?

Diagnosis of community-acquired pneumonia (CAP) in the primary care setting relies upon the identification of clinical features or abnormal vital signs during a clinical examination. We have developed a smartphone-based algorithm which removes the requirement for in-person consultation and provides high-diagnostic agreement with specialist diagnosis of CAP. The algorithm requires the input of five cough-sound segments and four patient-reported symptoms and provides a result in less than one minute. With increasing momentum towards digital-first care under the NHS, tools such as this which allow remote deployment are likely to find increased merit.
Shedding of infectious SARS-CoV-2 from airways in hospitalized COVID-19 patients in relation to serum antibody responses
Authors: Glans Hedvig , Gredmark-Russ Sara , Olausson Mikaela , Falck-Jones Sara , Varnaite Renata , Christ Wanda , Maleki Kimia T. , Karlberg Maria Lind , Broddesson Sandra , Falck-Jones Ryan , Bell Max , Johansson Niclas , Färnert Anna , Smed-Sörensen Anna , Klingström Jonas , Bråve Andreas
Published: September 2020

To understand the risk of transmission of SARS-CoV-2 in hospitalized COVID-19 patients we simultaneously assessed the presence of SARS-CoV-2 RNA, live infectious virus in the airways, and virus-specific IgG and neutralizing antibodies in sera in 36 hospitalized COVID-19 patients. SARS-CoV-2 could be cultured from four patients, all with low or undetectable antibody response. Our data suggests that the level of SARS-CoV-2 antibodies may correlate to risk for shedding live SARS-CoV-2 virus in hospitalized COVID-19 patients.
Neural markers of suppression in impaired binocular vision
Authors: Lygo Freya A. , Richard Bruno , Wade Alex R. , Morland Antony B. , Hess Robert F. , Baker Daniel H.
Published: September 2020

Objective/Purpose

Even after conventional patching treatment, individuals with a history of amblyopia typically lack good stereo vision. This is often attributed to atypical suppression between the eyes, yet the specific mechanism is still unclear. Guided by computational models of binocular vision, we tested explicit predictions about how neural responses to contrast might differ in individuals with impaired binocular vision.

Design

A 5 × 5 factorial repeated measures design was used, in which all participants completed a set of 25 conditions (stimuli of different contrasts shown to the left and right eyes).

Participants

25 individuals with a history of amblyopia, and 19 control participants with typical visual development, participated in the study.

Methods

Neural responses to different combinations of contrast in the left and right eyes, were measured using both electroencephalography (EEG) and functional magnetic resonance imaging (fMRI). Stimuli were sinusoidal gratings with a spatial frequency of 3c/deg, flickering at 4Hz. In the fMRI experiment, we also ran population receptive field and retinotopic mapping sequences, and a phase-encoded localiser stimulus, to identify voxels in primary visual cortex (V1) sensitive to the main stimulus.

Main outcome measures

The main outcome measures were the signal-to-noise ratio of the steady state visual evoked potential, and the fMRIβweights from a general linear model.

Results

Neural responses generally increased monotonically with stimulus contrast. When measured with EEG, responses were attenuated in the weaker eye, consistent with a fixed tonic suppression of that eye. When measured with fMRI, a low contrast stimulus in the weaker eye substantially reduced the response to a high contrast stimulus in the stronger eye. This effect was stronger than when the stimulus-eye pairings were reversed, consistent with unbalanced dynamic suppression between the eyes.

Conclusions

Measuring neural responses using different methods leads to different conclusions about visual differences in individuals with impaired binocular vision. Both of the atypical suppression effects may relate to binocular perceptual deficits, e.g. in stereopsis, and we anticipate that these measures could be informative for monitoring the progress of treatments aimed at recovering binocular vision.
Temporal Analysis of COVID-19 Peak Outbreak
Authors: Tewari Amit
Published: September 2020

Intent of this research is to explore how mathematical models, specifically Susceptible-Infected-Removed (SIR) model, can be utilized to forecast peak outbreak timeline of COVID-19 epidemic amongst a population of interest starting from the date of first reported case. Till the time of this research, there was no effective and universally accepted vaccine to control transmission and spread of this infection. COVID-19 primarily spreads in population through respiratory droplets from an infected person’s cough and sneeze which infects people who are in proximity. COVID-19 is spreading contagiously across the world. If health policy makers and medical experts could get early and timely insights into when peak infection rate would occur after first reported case, they could plan and optimize medical personnel, ventilators supply, and other medical resources without over-taxing the infrastructure. The predictions may also help policymakers devise strategies to control the epidemic, potentially saving many lives. Thus, it can aid in critical decision-making process by providing actionable insights into COVID-19 outbreak by leveraging available data.
Seroprevalence and Correlates of SARS-CoV-2 Antibodies in Healthcare Workers in Chicago
Authors: Wilkins John T. , Gray Elizabeth L. , Wallia Amisha , Hirschhorn Lisa R. , Zembower Teresa R. , Ho Joyce , Kalume Naomi , Agbo Ojoma , Zhu Alex , Rasmussen-Torvik Laura J. , Khan Sadiya S. , Carnethon Mercedes , Huffman Mark , Evans Charlesnika T.
Published: September 2020

Background

Identifying factors associated with SARS-CoV-2 infection among healthcare workers (HCW)s may help health systems optimize SARS-CoV-2 infection control strategies. Methods: We conducted a cross-sectional analysis of baseline data from the Northwestern HCW SARS-CoV-2 Serology Cohort Study. The Abbott Architect Nucleocapsid IgG assay was used to determine seropositivity. Logistic regression models (unadjusted and adjusted for demographics and self-reported community exposure to COVID-19) were fit to quantify the associations between occupation group, healthcare delivery tasks, and community exposure and seropositive status.

Results

6,510 HCWs, including 1,794 nurses, and 904 non-patient facing administrators participated. The majority were women (79.6%), 74.9% were white, 9.7% were Asian, 7.3% were Hispanic and 3.1% were Black. The crude prevalence rate of seropositivity was 4.8% (95% confidence interval (CI): 4.6%-5.2%). Out-of-hospital exposure to COVID-19 occurred in 9.3% of HCWs and was strongly associated with seropositivity (OR=4.7, 95% CI: 3.5-6.4). When compared to administrators, nursing was the only occupation group with a significantly higher adjusted-odds (OR: 1.9, 95% CI: 1.3-2.9) of seropositivity. Exposure to COVID-19 patients was reported by 37.8% of participants and was associated with higher positivity than those not exposed (OR= 2.2, 95% CI: 1.6-3.0). Being exposed to patients receiving high-flow oxygen therapy, and hemodialysis also remained significantly associated with a 45% and 57% higher odds for seropositive status, respectively.

Conclusions

Exposure to COVID-19 patients, and longer duration patient therapies were each associated with higher risk for seropositive status; however, the community burden of COVID-19 remains a significant source of exposure to SARS CoV-2 infection among HCWs in Chicago.
Anakinra and Intravenous IgG versus Tocilizumab in the Treatment of COVID-19 Pneumonia
Authors: Zantah Massa , Castillo Eduardo Dominguez , Gangemi Andrew J. , Patel Maulin , Chowdhury Junad , Verga Steven , Abramian Osheen , Zheng Matthew , Lu Kevin , Lau Arthur , Levinson Justin , Zhao Hauquing , Criner Gerard J. , Caricchio Roberto ,   for the Temple University COVID-19 Research Group
Published: September 2020

Background

COVID-19 can lead to acute respiratory failure and an exaggerated inflammatory response. Studies have suggested promising outcomes using monoclonal antibodies targeting IL-1β (Anakinra) or IL6 (Tocilizumab), however no head to head comparison was done between the two treatments. Herein, we report our experience in treating COVID-19 pneumonia associated with cytokine storm with either subcutaneous Anakinra given concomitantly with intravenous immunoglobulin (IVIG), or intravenous Tocilizumab.

Methods

Comprehensive clinical and laboratory data from patients with COVID-19 pneumonia admitted at our hospital between March and May 2020 were collected. Patients who received either Anakinra/ IVIG or Tocilizumab were selected. Baseline characteristics including oxygen therapy, respiratory status evaluation using ROX index, clinical assessment using NEWS score and laboratory data were collected. Outcomes included mortality, intubation, ICU admission and length of stay. In addition, we compared the change in ROX index, NEWS score and inflammatory markers at days 7 and 14 post initiation of therapy.

Results

84 consecutive patients who received either treatment (51 in the Anakinra/ IVIG group and 33 in the Tocilizumab group) were retrospectively studied. Baseline inflammatory markers were similar in both groups. There was no significant difference regarding to death (21.6% vs 15.2%, p 0.464), intubation (15.7% vs 24.2%, p 0.329), ICU need (57.1% vs 48.5%, p 0.475) or length of stay (13+9.6 vs 14.9+11.6, p 0.512) in the Anakinra/IVIG and Tocilizumab, respectively. Additionally, the rate of improvement in ROX index, NEWS score and inflammatory markers was similar in both groups at days 7 and 14. Furthermore, there was no difference in the incidence of superinfection in both groups.

Conclusion

Treating COVID-19 pneumonia associated with cytokine storm features with either subcutaneous Anakinra/IVIG or intravenous Tocilizumab is associated with improved clinical outcomes in most subjects. The choice of treatment does not appear to affect morbidity or mortality. Randomized controlled trials are needed to confirm our study findings.

Funding

None.
Cohort profile: St. Michael’s Hospital Tuberculosis Database (SMH-TB), a retrospective cohort of electronic health record data and variables extracted using natural language processing
Authors: Landsman David , Abdelbasit Ahmed , Wang Christine , Guerzhoy Michael , Joshi Ujash , Mathew Shaun , Pou-Prom Chloe , Dai David , Pequegnat Victoria , Murray Joshua , Chokar Kamalprit , Banning Michaelia , Mamdani Muhammad , Mishra Sharmistha , Batt Jane
Published: September 2020

Background

Tuberculosis (TB) is a major cause of death worldwide. TB research draws heavily on clinical cohorts which can be generated using electronic health records (EHR), but granular information extracted from unstructured EHR data is limited. The St. Michael’s Hospital TB database (SMHTB) was established to address gaps in EHR-derived TB clinical cohorts and provide researchers and clinicians with detailed, granular data related to TB management and treatment.

Methods

We collected and validated multiple layers of EHR data from the TB outpatient clinic at St. Michael’s Hospital, Toronto, Ontario, Canada to generate the SMH-TB database. SMH-TB contains structured data directly from the EHR, and variables generated using natural language processing (NLP) by extracting relevant information from free-text within clinic, radiology, and other notes. NLP performance was assessed using recall, precision and F1 score averaged across variable labels. We present characteristics of the cohort population using binomial proportions and 95% confidence intervals (CI), with and without adjusting for NLP misclassification errors.

Results

SMH-TB currently contains retrospective patient data spanning 2011 to 2018, for a total of 3298 patients (N=3237 with at least 1 associated dictation). Performance of TB diagnosis and medication NLP rulesets surpasses 93% in recall, precision and F1 metrics, indicating good generalizability. We estimated 20% (95% CI: 18.4-21.2%) were diagnosed with active TB and 46% (95% CI: 43.8-47.2%) were diagnosed with latent TB. After adjusting for potential misclassification, the proportion of patients diagnosed with active and latent TB was 18% (95% CI: 16.8-19.7%) and 40% (95% CI: 37.8-41.6%) respectively

Conclusion

SMH-TB is a unique database that includes a breadth of structured data derived from structured and unstructured EHR data. The data are available for a variety of research applications, such as clinical epidemiology, quality improvement and mathematical modelling studies.
Genetic variation in RCOR1 is associated with tinnitus in UK Biobank
Authors: Wells Helena R.R. , Zainul Abidin Fatin N. , Freidin Maxim B. , Williams Frances M.K. , Dawson Sally J.
Published: September 2020

Tinnitus is a prevalent condition in which perception of sound occurs without an external stimulus. It is often associated with pre-existing hearing loss or noise-induced damage to the auditory system. In some individuals it occurs frequently or even continuously and leads to considerable distress and difficulty sleeping. There is little knowledge of the molecular mechanisms involved in tinnitus which has hindered the development of treatments. Evidence suggests that tinnitus has a heritable component although previous genetic studies have not established specific risk factors. We performed a case-control genome-wide association study for self-reported tinnitus in 172,608 UK Biobank volunteers. Three variants in close proximity to the RCOR1 gene reached genome wide significance: rs4906228 (p=1.7E-08), rs4900545 (p=1.8E-08) and 14:103042287_CT_C (p=3.50E-08). RCOR1 encodes REST Corepressor 1, a component of a co-repressor complex involved in repressing neuronal gene expression in non-neuronal cells. Eleven other independent genetic loci reached a suggestive significance threshold of p<1E-06.
Characteristics of anti-SARS-CoV-2 antibodies in recovered COVID-19 subjects
Authors: Huynh Angela , Arnold Donald M. , Smith James W. , Moore Jane C. , Zhang Ali , Chagla Zain , Harvey Bart J. , Stacey Hannah D. , Ang Jann C. , Clare Rumi , Ivetic Nikola , Chetty Vasudhevan T. , Bowdish Dawn ME , Miller Matthew S. , Kelton John G. , Nazy Ishac
Published: September 2020

Coronavirus Disease 2019 (COVID-19) is a global pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). While detection of SARS-CoV-2 by polymerase chain reaction with reverse transcription (RT-PCR) is currently used to diagnose acute COVID-19 infection, serological assays are needed to study the humoral immune response to SARS-CoV-2. SARS-CoV-2 IgG/A/M antibodies against SARS-CoV-2 spike (S) protein and its receptor-binding domain (RBD) were characterized using an enzyme-linked immunosorbent assay (ELISA) and assessed for their ability to neutralize live SARS-CoV-2 virus in recovered subjects who were RT-PCR-positive (n=153), RT-PCR-negative (n=55), and control samples collected pre-COVID-19 (n=520). Anti-SARS-CoV-2 antibodies were detected in 90.9% of resolved subjects up to 180 days post-symptom onset. Anti-S protein and anti-RBD IgG titers correlated (r= 0.5157 and r = 0.6010, respectively) with viral neutralization. Of the RT-PCR-positive subjects, 22 (14.3%) did not have anti-SARS-CoV-2 antibodies; and of those, 17 had RT-PCR cycle threshold (Ct) values >27, raising the possibility that these indeterminate results are from individuals who were not infected, or had mild infection that failed to elicit an antibody response. This study highlights the importance of serological surveys to determine population-level immunity based on infection numbers as determined by RT-PCR.