bluuebunny/crossref_metadata_2025 huggingface dataset:
Personality impairment in the DSM-5 and ICD-11: Current standing and limitations
Authors: Sleep Chelsea , Lynam Donald R. , Miller Joshua D.
Published: November 2020

Purpose of review

The current review provides an examination of the levels of personality functioning outlined by the International Classification of Diseases-11 and the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders.

Recent findings

Across self-report measures, high convergence is observed, and they evince relatively robust relations with general and pathological traits as well as other clinical symptoms. At the same time, current measures of impairment also demonstrate unstable factor structures, poor discriminant validity (when measures offer subscales aligned with different forms of personality impairment), and tend to account for relatively little unique variance beyond traits. As a result, some have questioned the utility of personality impairment, as currently measured.

The dimensional models of personality psychopathology included in the International Classification of Diseases-11 and 5th edition of the Diagnostic and Statistical Manual of Mental Disorders signify important steps toward an empirically supported and clinically useful diagnostic model; however, self-report measures of impairment are problematic. The authors conclude by calling for the refinement of these measures to more directly assess deficits in various domains of functioning as well as the dimensional models, by assessing traits first, and then examining the nature of the associated personality impairment.
Inference of COVID-19 epidemiological distributions from Brazilian hospital data
Authors: Hawryluk Iwona , Mellan Thomas A. , Hoeltgebaum Henrique , Mishra Swapnil , Schnekenberg Ricardo P. , Whittaker Charles , Zhu Harrison , Gandy Axel , Donnelly Christl A. , Flaxman Seth , Bhatt Samir
Published: November 2020

Knowing COVID-19 epidemiological distributions, such as the time from patient admission to death, is directly relevant to effective primary and secondary care planning, and moreover, the mathematical modelling of the pandemic generally. We determine epidemiological distributions for patients hospitalized with COVID-19 using a large dataset (N= 21 000 − 157 000) from the Brazilian Sistema de Informação de Vigilância Epidemiológica da Gripe database. A joint Bayesian subnational model with partial pooling is used to simultaneously describe the 26 states and one federal district of Brazil, and shows significant variation in the mean of the symptom-onset-to-death time, with ranges between 11.2 and 17.8 days across the different states, and a mean of 15.2 days for Brazil. We find strong evidence in favour of specific probability density function choices: for example, the gamma distribution gives the best fit for onset-to-death and the generalized lognormal for onset-to-hospital-admission. Our results show that epidemiological distributions have considerable geographical variation, and provide the first estimates of these distributions in a low and middle-income setting. At the subnational level, variation in COVID-19 outcome timings are found to be correlated with poverty, deprivation and segregation levels, and weaker correlation is observed for mean age, wealth and urbanicity.
Barriers to Health Behavior Change in People with Type 2 Diabetes: Survey Study
Authors: Mohamdy Oumoukelthoum
Published: November 2020

Structured Abstract

BACKGROUND

Diabetes mellitus DM (type 2) is one of the major chronic disease that creates burden at the population level. A prevalence of 422 million patients with diabetes worldwide is detected 1. UAE population has an increased prevalence of DM; According to International Diabetes Federation (IDF) 17.3% of the UAE population between the ages of 20 and 79 have type 2 diabetes in 2017 2. UAE has been suffering with the health problems that result from obesity and sedentary lifestyle. The purpose of this study is to understand barriers to health behavior among community patients with diabetes mellitus type 2. METHODS: This is a qualitative survey study of 123 adult individuals with type 2 diabetes who are above 18 years old, who participated in a survey that explore their perception about barriers to health behavior change. The survey was distributed online and in 6 health care centers under ministry of health and prevention in the United Arab Emirates. RESULTS: This study finds that the top barrier for behavior change is difficulty to follow healthy schedule (19.4%), workplace condition and timing (14.3%), and laziness (13%). The least barrier was lack of knowledge about healthier behaviors (5.3%). The best way to motivate behavior change was doctor’s advice during regular visit (26.3%), joining support group (18.4%), and receiving electronic tips and reminders on smartphones (15%) CONCLUSION: The outcomes of this study can aid directly in community programs design and implementation, health education campaigns, and health policies. The findings of this study help in understanding real barriers to initiating and sustaining positive health behavior.
GenomeDiver: A platform for phenotype-guided medical genomic diagnosis
Authors: Pearson Nathaniel , Stolte Christian , Shi Kevin , Beren Faygel , Abul-Husn Noura S. , Bertier Gabrielle , Brown Kaitlyn , Odgis Jacqueline A. , Suckiel Sabrina A. , Horowitz Carol R. , Wasserstein Melissa , Gelb Bruce D. , Kenny Eimear E. , Gagnon Charles , Jobanputra Vaidehi , Bloom Toby , Greally John M.
Published: November 2020

Purpose

Making a diagnosis from clinical genomic sequencing requires well-structured phenotypic data to guide genotype interpretation. A patient’s phenotypic features can be documented using the Human Phenotype Ontology (HPO), generating terms used to prioritize genes potentially causing the patient’s disease. We have developed GenomeDiver to provide a user interface for clinicians that allows more effective collaboration with the clinical diagnostic laboratory, with the goal of improving the success of the diagnostic process.

Methods

GenomeDiver is designed to prompt reverse phenotyping of patients undergoing genetic testing, enriching the amount and quality of structured phenotype data for the diagnostic laboratory, and helping clinicians to explore and flag diseases potentially causing their patient’s presentation.

Results

We show how GenomeDiver communicates the clinician’s informed insights to the diagnostic lab in the form of HPO terms for interpretation of genomic sequencing data. We describe our user-driven design process, the engineering of the software for efficiency, security and portability, and an example of the performance of GenomeDiver using simulated genomic testing data.

Conclusions

GenomeDiver is a first step in a new approach to genomic diagnostics that enhances laboratory-clinician interactions, with the goal of directly engaging clinicians to improve the outcome of genomic diagnostic testing.
Seven day continuous ambulatory electrocardiographic telemetric study with pocket electrocardiographic recording device for detecting hydroxychloroquin induced arrhythmias
Authors: Walia Rohit , Prabhakaran Nanda , Kodliwadmath Ashwin , Singh O Budha Charan , Sabbarwal Vikas , Nigam Abhimanyu , Vijay B Kartik , Pai Venkatesh Srinivasa
Published: November 2020

BACKGROUND & AIMS

The use of hydroxycholoroquin for COVID 19 treatment and prophylaxis raised issues concerning its cardiac safety owing to possibility of QT prolongation and arrhythmias.1 There was no study on long term electrocardiographic telemetry monitoring of patients taking hydroxychloroquin and we planned a continuous electrocardiographic holter telemetry of these patients for a period of seven days.

Methods

Healthcare workers taking hydroxycholoroquin as pre exposure prophylaxis, patients taking hydroxychloroquin were monitored by holter electrocardiographic telemetry with continuous beat to beat analysis for seven days with capacity to report any arrhythmic event or significant QT prolongation instantly to medical faculty.

Results

25 participants with mean age 42.4 ± 14.1 years, 40% females. 20% patients needed to stop HCQ. Four patients developed QT prolongation > 500 ms and needed to stop HCQ, one patient had accelerated idioventricular rhythm and stopped treatment. one had short episodes of atrial fibrillation. No malignant arrhythmia or ventricular arrhythmia or torsades were noted. No episode of significant conduction disturbance and arrhythmic death noted. Baseline mean QTc was 423.96 ± 32.18 ms, mean QTc corrected at 24 hours 438.93 ± 37.95, mean QTc 451.879 ± 37.99 at 48 hours, change in baseline mean QTc to max QTc was 30.74 ± 21.75 ms at 48 hours. All those develop QTc prolongation > 500 ms were greater than 50 years of age.

Conclusion

Ambulatory telemetry ECG monitoring seems to detect early QT prolongation and stopping drug timely prevented malignant arrhythmias. HCQ seems to have less risk of QT prolongation in young healthy individuals.
Biobank scale pharmacogenomics informs the genetic underpinnings of simvastatin use
Authors: Wendt Frank R , Koller Dora , Pathak Gita A , Jacoby Daniel , Miller Edward J , Polimanti Renato
Published: November 2020

Background and Purpose

Studying drug metabolizing enzymes, encoded by pharmacogenes (PGx), may inform biological mechanisms underlying the diseases for which a medication is prescribed. Until recently, PGx loci could not be studied at biobank scale. Here we analyze PGx haplotype variation to detect associations with medication use in the UK Biobank.

Methods

In 7,649 unrelated African-ancestry (AFR) and 326,214 unrelated European-ancestry (EUR) participants from the UK Biobank, aged 37-73 at time of recruitment, we associated clinically-relevant PGx haplotypes with 265 (EUR) and 17 (AFR) medication use phenotypes using generalized linear models covaried with sex, age, age2, sex×age, sex×age2, and ten principal components of ancestry. Haplotypes across 50 genes were assigned with Stargazer. Our analyses focused on the association of PGx haplotype dose (quantitative predictor), diplotype (categorical predictor), and rare haplotype burden on medication use.

Results

In EUR,NAT2metabolizer phenotype (OR=1.05, 95% CI: 1.03-1.08, p=7.03×10−6) and activity score (OR=1.09, 95% CI: 1.05-1.14, p=2.46×10−6) were associated with simvastatin use. The dose of N-acetyltransferase 2 (NAT2)*1 was associated with simvastatin use relative toNAT2*5 (NAT2*1 OR=1.04, 95% CI=1.03-1.07, p=1.37×10−5) and was robust to effects of low-density lipoprotein cholesterol (LDL-C) concentration (NAT2*1 given LDL-C concentration: OR=1.07, 95% CI=1.05-1.09, p=1.14×10−8) and polygenic risk for LDL-C concentration (NAT2*1 given LDL-C PRS: OR=1.09, 95% CI=1.04-1.14, p=2.26×10−4). Interactive effects betweenNAT2*1, simvastatin use, and LDL-C concentration (OR: 0.957, 95% CI=0.916-0.998, p=0.045) were replicated in eMERGE PGx cohort (OR: 0.987, 95% CI: 0.976-0.998, p=0.029).

Conclusions and relevance

We used biobank-scale data to uncover and replicate a novel association betweenNAT2locus variation (and suggestive evidence with several other genes) and better response to simvastatin (and other statins) therapy. The presence ofNAT2*1 versusNAT2*5 may therefore be useful for making clinically informative decisions regarding the potential benefit (e.g., absolute risk reduction) in LDL-C concentration prior to statin treatment.

Subject terms

genetics, genetic association studies, cardiovascular disease
Undetectable=untransmittable (U=U) messaging increases uptake of HIV testing among men: Results from a pilot cluster randomized trial
Authors: Smith Philip , Buttenheim Alison , Schmucker Laura , Bekker Linda-Gail , Thirumurthy Harsha , Davey Dvora L. Joseph
Published: November 2020

HIV testing coverage in sub-Saharan Africa is lower among men than women. We investigated the impact of a peer-delivered U=U (undetectable equals untransmittable) message on men’s HIV testing uptake through a cluster randomized trial with individual mobile clinic days as unit of randomization.

On standard of care (SOC) days, peer promoters’ informed men about the availability of HIV testing at the mobile clinic. On intervention days, peer promoters’ delivered U=U messages. We used logistic regression adjusting for mobile clinic location, clustering by study day, to determine the percentage of invited men who tested for HIV at the mobile clinic.

Peer promoters delivered 1048 invitations over 12 days. In the SOC group, 68 (13%) of 544 men invited tested for HIV (3, 4.4% HIV-positive). In the U=U group, 112 (22%) of 504 men invited tested for HIV (7, 6.3% HIV-positive). Men in the U=U group had greater odds of testing for HIV (adjusted odds ratio=1.59, 95% CI=0.98-2.57).

Tailored, peer-delivered messages that explain the benefits of HIV treatment in reducing HIV transmission can increase men’s HIV testing uptake.
Assessment of effectiveness of a COVID-adapted diagnostic pathway for colorectal cancer to mitigate the adverse impact on investigation and referrals
Authors: Miller Janice , Maeda Yasuko , Au Stephanie , Gunn Frances , Porteous Lorna , Pattenden Rebecca , MacLean Peter , Noble Colin L , Glancy Stephen , Dunlop Malcolm G , Din Farhat V N
Published: November 2020

Objectives

The Coronavirus-19 (COVID-19) pandemic continues to impose formidable challenges on healthcare services. The dramatic curtailment of endoscopy and CT colonography capacity has adversely impacted on timely diagnosis of colorectal cancer (CRC). We describe a COVID-adapted pathway rapidly implemented to mitigate risk and maximise cancer diagnosis in patients referred with symptoms of suspected CRC during the pandemic.

Design

The “COVID-adapted pathway” integrated multiple quantitative faecal immunochemical tests (qFIT), to enrich for significant colorectal disease. CT with oral contrast was used to detect gross pathology. Patients reporting ‘high-risk’ symptoms were triaged to qFIT+CT and the remainder underwent initial qFIT. Prospective data collection comprised referral category, symptoms, blood results, medical history, time to first test, qFIT and CT results.

Setting

Tertiary colorectal unit which manages over 500 cancer patients annually.

Participants

All patients referred as ‘urgent suspicious of cancer’ (USOC) were included. Overall 422 patients (median age 64 years, 220 females) were triaged using this pathway.

Main outcome measures

Outcomes comprised cancer detection frequency.

Results

Compared to the same time period (1stApril – 31stMay) in 2017-2019, we observed a 43% reduction in primary care referrals with suspected CRC (1071 referrals expected reducing to 609). Overall 422 patients (median age 64 years, 220 females) were triaged using this pathway. Most (84·6%) were referred as USOC. Of the 422 patients, 202 (47·9%) were triaged to CT and qFIT, 211 (50·0%) to qFIT only, eight (1·9%) to outpatient clinic, and one to colonoscopy. Fifteen (3·6%) declined investigation and seven (1·7%) were deemed unfit. We detected 13 cancers (3·1%); similar to the mean cancer detection rate from all referrals in 2017-2019 (3·3%).

Conclusions

The response to the COVID-19 pandemic resulted in a marked reduction in referrals and cessation of key diagnostic services. Although this COVID-adapted pathway mitigated the adverse effects on diagnostic capacity, the overall reduction in expected diagnoses is very substantial. It is clear that the adverse impact of measures taken to constrain the pandemic will lead to many undetected cancers due to the decrease in referrals.

Trial registration

Not applicable
Validating the RISE UP score for predicting prognosis in patients with COVID-19 in the emergency department, a retrospective study
Authors: van Dam Paul M.E.L. , Zelis Noortje , Stassen Patricia M. , van Twist Daan J.L. , de Leeuw Peter W. , van Kuijk Sander M.J. , Buijs Jacqueline
Published: November 2020

Objective

To mitigate the burden of COVID-19 on the healthcare system, information on the prognosis of the disease is needed. The recently developed RISE UP score has very good discriminatory value with respect to short-term mortality in older patients in the emergency department (ED). It consists of six items: age, abnormal vital signs, albumin, blood urea nitrogen (BUN), lactate dehydrogenase (LDH), and bilirubin. We hypothesized that the RISE UP score could have discriminatory value with regard to 30-day mortality in ED patients with COVID-19.

Setting

Two EDs of the Zuyderland Medical Centre (MC), secondary care hospital in the Netherlands.

Participants

The study sample consisted of 642 adult ED patients diagnosed with COVID-19 between March 3rd until May 25th 2020. Inclusion criteria were: 1) admission to the hospital with symptoms suggestive of COVID-19, and 2) positive result of the polymerase chain reaction (PCR), or (very) high suspicion of COVID-19 according to the chest computed tomography (CT) scan.

Outcome

Primary outcome was 30-day mortality, secondary outcome was a composite of 30-day mortality and admission to intensive care unit (ICU).

Results

Within 30 days after presentation, 167 patients (26.0%) died and 102 patients (15.9%) were admitted to ICU. The RISE UP score showed good discriminatory value with respect to 30-day mortality (AUC 0.77, 95% CI 0.73-0.81), and to the composite outcome (AUC 0.72, 95% CI 0.68-0.76). Patients with RISE UP scores below 10% (121 patients) had favourable outcome (0% mortality and 5% ICU admissions). Patients with a RISE UP score above 30% (221 patients) were at high risk of adverse outcome (46.6% mortality and 19% ICU admissions).

Conclusion

The RISE UP score is an accurate prognostic model for adverse outcome in ED patients with COVID-19. It can be used to identify patients at risk of short-term adverse outcome, and may help guiding decision-making and allocating healthcare resources.
Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry
Authors: Díez-Manglano Jesús , Marquínez Marta Nataya Solís , García Andrea Álvarez , Alcalá-Rivera Nicolás , Riesco Irene Maderuelo , Aseguinolaza Martín Gericó , Pérez José Luis Beato , Bailon Manuel Mendez , Ruiz Ane Elbire Labirua-Iturburu , Gómez Miriam García , Cilleros Carmen Martinez , Fontan Paula Maria Pesqueira , Vázquez Lucy Abella , Encinar Julio César Blázquez , Boixeda Ramon , Sánchez Ricardo Gil , de la Peña Fernández Andrés , Amigo Jose Loureiro , Sevilla Joaquin Escobar , Garcia Marcos Guzmán , Escalante María Dolores Martín , Gamboa Jeffrey Oskar Magallanes , Gonzalez Angel Luís Martínez , Bermejo Carlos Lumbreras , Santos Juan Miguel Antón ,   for the SEMI-COVID-19 Network
Published: November 2020

Aim

To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW).

Methods

Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality.

Results

As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p=0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.219, 95%CI 0.069-0.693, p=0.01). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001).

Conclusions

Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality.
Blowin’ In The Wind: Long-Term Downwind Exposure to Air Pollution from Power Plants and Adult Mortality
Authors: Tanaka Shinsuke
Published: November 2020

We estimate the causal effects of long-term exposure to air pollution emitted from fossil fuel power plants on adult mortality. We leverage quasi-experimental variation in daily wind patterns, which is further instrumented by the county orientation from the nearest power plant. We find that the county’s fraction of days spent downwind of plants within 20 miles in the last 10 years is associated with increased mortality from COVID-19 through the third peak in mortality in January 2021. This effect is more pronounced in fenceline communities with high poverty rates, low health insurance coverage, and low educational attainment.
A Computational Model to Predict Brain Trauma Outcome in the Intensive Care Unit
Authors: Palepu Anil K. , Murali Aditya , Ballard Jenna L. , Li Robert , Ramesh Samiksha , Nguyen Hieu , Kim Hanbiehn , Sarma Sridevi , Suarez Jose I. , Stevens Robert D.
Published: November 2020

Objectives

To predict short-term outcomes of critically ill patients with traumatic brain injury (TBI) by training machine learning classifiers on two large intensive care databases

Design

Retrospective analysis of observational data.

Patients

Patients in the multicenter Philips eICU and single-center Medical Information Mart for Intensive Care–III (MIMIC-III) databases with a primary admission diagnosis of TBI, who were in intensive care for over 24 hours.

Interventions

None.

Measurements and Main Results

We identified 1,689 and 126 qualifying TBI patients in eICU and MIMIC-III, respectively. Generalized Linear Models were used to predict mortality and neurological function at ICU discharge using features derived from clinical, laboratory, medication and physiological time series data obtained in the first 24 hours after ICU admission. Models were trained, tested and validated in eICU then validated externally in MIMIC-III. Model discrimination determined by area under the receiver operating characteristic curve (AUROC) analysis was 0.903 and 0.874 for mortality and neurological function, respectively. Performance was maintained when the models were tested in the independent MIMIC-III dataset (AUROC 0.958 and 0.878 for mortality and neurological function, respectively).

Conclusions

Computational models trained with data available in the first 24 h after admission accurately predict discharge outcomes in ICU stratum TBI patients.
Loneliness among older adults in the community during COVID-19
Authors: Savage Rachel D. , Wu Wei , Li Joyce , Lawson Andrea , Bronskill Susan E. , Chamberlain Stephanie A. , Grieve Jim , Gruneir Andrea , Reppas-Rindlisbacher Christina , Stall Nathan M. , Rochon Paula A.
Published: November 2020

Objective

Physical distancing and stay-at-home measures implemented to slow transmission of novel coronavirus disease (COVID-19) may intensify feelings of loneliness in older adults, especially those living alone. Our aim was to characterize the extent of loneliness in a sample of older adults living in the community and assess characteristics associated with loneliness.

Design

Online cross-sectional survey between May 6 and May 19, 2020

Setting

Ontario, Canada

Participants

Convenience sample of the members of a national retired educators’ organization.

Primary outcome measures

Self-reported loneliness, including differences between women and men.

Results

4879 respondents (71.0% women; 67.4% 65-79 years) reported that in the preceding week, 43.1% felt lonely at least some of the time, including 8.3% that felt lonely always or often. Women had increased odds of loneliness compared to men, whether living alone (adjusted Odds Ratio (aOR) 1.52 [95% Confidence Interval (CI) 1.13-2.04]) or with others (2.44 [95% CI 2.04-2.92]). Increasing age group decreased the odds of loneliness (aOR 0.69 [95% CI 0.59-0.81] 65-79 years and 0.50 [95% CI 0.39-0.65] 80+ years compared to <65 years). Living alone was associated with loneliness, with a greater association in men (aOR 4.26 [95% CI 3.15-5.76]) than women (aOR 2.65 [95% CI 2.26-3.11]). Other factors associated with loneliness included: fair or poor health (aOR 1.93 [95% CI 1.54-2.41]), being a caregiver (aOR 1.18 [95% CI 1.02-1.37]), receiving care (aOR 1.47 [95% CI 1.19-1.81]), high concern for the pandemic (aOR 1.55 [95% CI 1.31-1.84]), not experiencing positive effects of pandemic distancing measures (aOR 1.94 [95% CI 1.62-2.32]), and changes to daily routine (aOR 2.81 [95% CI 1.96-4.03]).

Conclusions

While many older adults reported feeling lonely during COVID-19, several characteristics – such as being female and living alone – increased the odds of loneliness. These characteristics may help identify priorities for targeting interventions to reduce loneliness.

Strengths and limitations of this study

This survey study leveraged a strong community-based partnership to obtain timely data from a large sample of older Canadians on the impacts of COVID-19.

This study identified several characteristics that increased the odds of loneliness, which may help to identify priorities for targeted interventions to reduce loneliness.

The data were based on a convenience sample of retired, educational staff, who are not fully representative of the Canadian population. The perspectives of vulnerable groups who may be at greater risk for loneliness (e.g. those with severe mental health illness, low income, no home internet access, etc.) are likely underrepresented in this sample.
Reducing travel-related SARS-CoV-2 transmission with layered mitigation measures: Symptom monitoring, quarantine, and testing
Authors: Johansson Michael A. , Wolford Hannah , Paul Prabasaj , Diaz Pamela S. , Chen Tai-Ho , Brown Clive M. , Cetron Martin S. , Alvarado-Ramy Francisco
Published: November 2020

Balancing the control of SARS-CoV-2 transmission with the resumption of travel is a global priority. Current recommendations include mitigation measures before, during, and after travel. Pre- and post-travel strategies including symptom monitoring, testing, and quarantine can be combined in multiple ways considering different trade-offs in feasibility, adherence, effectiveness, cost and adverse consequences. Here we use a mathematical model to analyze the expected effectiveness of symptom monitoring, testing, and quarantine under different estimates of the infectious period, test-positivity relative to time of infection, and test sensitivity to reduce the risk of transmission from infected travelers during and after travel. If infection occurs 0-7 days prior to travel, immediate isolation following symptom onset prior to or during travel reduces risk of transmission while traveling by 26-30%. Pre-departure testing can further reduce risk if testing is close to the time of departure. For example, testing on the day of departure can reduce risk while traveling by 37-61%. For transmission risk after travel with infection time up to 7 days prior to arrival at the destination, isolation based on symptom monitoring reduced introduction risk at the destination by 42-56%. A 14-day quarantine after arrival, without symptom monitoring or testing, can reduce risk by 97-100% on its own. However, a shorter quarantine of 7 days combined with symptom monitoring and a test on day 3-4 after arrival is also effective (95-99%) at reducing introduction risk and is less burdensome, which may improve adherence. To reduce the risk of introduction without quarantine, optimal test timing after arrival is close to the time of arrival; with effective quarantine after arrival, testing a few days later optimizes sensitivity to detect those infected immediately before or while traveling. These measures can complement recommendations such as social distancing, using masks, and hand hygiene, to further reduce risk during and after travel.
Evolution of Human Respiratory Virus Epidemics
Authors: Rochman Nash D. , Wolf Yuri I. , Koonin Eugene V.
Published: November 2020

Background

While pathogens often evolve towards reduced virulence, many counterexamples are evident. When faced with a new pathogen, such as SARS-CoV-2, it is highly desirable to be able to forecast the case fatality rate (CFR) into the future. Considerable effort has been invested towards the development of a mathematical framework for predicting virulence evolution. Although these approaches accurately recapitulate some complex outcomes, most rely on an assumed trade-off between mortality and infectivity. It is often impractical to empirically validate this constraint for human pathogens.

Results

Using a compartment model with parameters tuning the degree to which symptomatic individuals are isolated and the duration of immunity, we reveal kinetic constraints where the variation of multiple parameters in concert leads to decreased virulence and increased pathogen fitness, whereas independent variation of the parameters decreases pathogen fitness. Smallpox, SARS-CoV-2, and Influenza are analyzed as diverse representatives of human respiratory viruses. We show that highly virulent viruses, such as Smallpox, are likely often constrained by host behavior, whereas moderately virulent viruses, such as SARS-CoV-2, appear to be typically constrained by the relationship between the duration of immunity and CFR.

Conclusions

The evolution of human respiratory epidemics appears to be often kinetically constrained and a reduction in virulence should not be assumed. Our findings imply that, without continued public health intervention, SARS-CoV-2 is likely to continue presenting a substantial disease burden. The existence of a parameter regime admitting endemic equilibrium suggests that herd immunity is unachievable. However, we demonstrate that even partial isolation of symptomatic individuals can have a major effect not only by reducing the number of fatalities in the short term but also by potentially changing the evolutionary trajectory of the virus towards reduced virulence.
Predicting heterogeneity in clone-specific therapeutic vulnerabilities using single-cell transcriptomic signatures
Authors: Suphavilai Chayaporn , Chia Shumei , Sharma Ankur , Tu Lorna , Da Silva Rafael Peres , Mongia Aanchal , DasGupta Ramanuj , Nagarajan Niranjan
Published: November 2020

While understanding heterogeneity in molecular signatures across patients underpins precision oncology, there is increasing appreciation for taking intra-tumor heterogeneity into account. Single-cell RNA-seq (scRNA-seq) technologies have facilitated investigations into the role of intra-tumor transcriptomic heterogeneity (ITTH) in tumor biology and evolution, but their application toin silicomodels of drug response has not been explored. Based on large-scale analysis of cancer omics datasets, we highlight the utility of ITTH for predicting clinical outcomes. We then show that heterogeneous gene expression signatures obtained from scRNA-seq data can be accurately analyzed (80%) in a recommender system framework (CaDRReS-Sc) forin silicodrug response prediction. Patient-derived cell lines capturing transcriptomic heterogeneity from primary and metastatic tumors were used asin vitroproxies for validating monotherapy predictions (Pearson r>0.6), as well as optimal drug combinations to target different subclonal populations (>10% improvement). Applying CaDRReS-Sc to the increasing number of publicly available tumor scRNA-seq datasets can serve as anin silicoscreen for furtherin vitroandin vivodrug repurposing studies.

Graphical abstract

Highlights

Large-scale analysis to establish the impact of transcriptomic heterogeneity within tumors on clinical outcomes

Calibrated recommender system for drug response prediction based on single-cell RNA-seq data (CaDRReS-Sc)

Prediction of drug response in patient-derived cell lines with transcriptomic heterogeneity

In silicoidentification of drug combinations that work based on clonal vulnerabilities
LinearTurboFold: Linear-Time Global Prediction of Conserved Structures for RNA Homologs with Applications to SARS-CoV-2
Authors: Li Sizhen , Zhang He , Zhang Liang , Liu Kaibo , Liu Boxiang , Mathews David H. , Huang Liang
Published: November 2020

The constant emergence of COVID-19 variants reduces the effectiveness of existing vaccines and test kits. Therefore, it is critical to identify conserved structures in SARS-CoV-2 genomes as potential targets for variant-proof diagnostics and therapeutics. However, the algorithms to predict these conserved structures, which simultaneously fold and align multiple RNA homologs, scale at best cubically with sequence length, and are thus infeasible for coronaviruses, which possess the longest genomes (∼30,000nt) among RNA viruses. As a result, existing efforts on modeling SARS-CoV-2 structures resort to single sequence folding as well as local folding methods with short window sizes, which inevitably neglect long-range interactions that are crucial in RNA functions. Here we present LinearTurboFold, an efficient algorithm for folding RNA homologs that scaleslinearlywith sequence length, enabling unprecedentedglobalstructural analysis on SARS-CoV-2. Surprisingly, on a group of SARS-CoV-2 and SARS-related genomes, LinearTurbo-Fold’s purelyin silicoprediction not only is close to experimentally-guided models for local structures, but also goes far beyond them by capturing the end-to-end pairs between 5’ and 3’ UTRs (∼29,800ntapart) that match perfectly with a purely experimental work. Furthermore, LinearTurboFold identifies novel conserved structures and conserved accessible regions as potential targets for designing efficient and mutation-insensitive small-molecule drugs, antisense oligonucleotides, siRNAs, CRISPR-Cas13 guide RNAs and RT-PCR primers. LinearTurboFold is a general technique that can also be applied to other RNA viruses and full-length genome studies, and will be a useful tool in fighting the current and future pandemics.

Significance Statement

Conserved RNA structures are critical for designing diagnostic and therapeutic tools for many diseases including COVID-19. However, existing algorithms are much too slow to model the global structures of full-length RNA viral genomes. We present LinearTurboFold, a linear-time algorithm that is orders of magnitude faster, making it the first method to simultaneously fold and align whole genomes of SARS-CoV-2 variants, the longest known RNA virus (∼30 kilobases). Our work enables unprecedented global structural analysis and captures long-range interactions that are out of reach for existing algorithms but crucial for RNA functions. LinearTurboFold is a general technique for full-length genome studies and can help fight the current and future pandemics.
The anti-inflammatory peptide Catestatin blocks chemotaxis
Authors: Muntjewerff Elke M. , Parv Kristel , Mahata Sushil K. , Phillipson Mia , Christoffersson Gustaf , van den Bogaart Geert
Published: November 2020

Increased levels of the anti-inflammatory peptide catestatin (CST), a cleavage product of the pro-hormone chromogranin A, correlates with less severe outcomes in hypertension, colitis and diabetes. However, it is unknown how CST reduces the infiltration of monocytes and macrophages in inflamed tissues. Here, we report that CST blocks leukocyte migration towards inflammatory chemokines. Byin vitroandin vivomigration assays, we show that although CST itself is weakly chemotactic, it blocks migration of monocytes and granulocytes to inflammatory attracting factor CC-chemokine ligand 2 (CCL2) and macrophage inflammatory protein 2 (MIP-2). Moreover, it directs CX3CR1+macrophages away from pancreatic islets. These findings support the emerging notion that CST is a key anti-inflammatory modulator.
Beauty That Moves: Dance for Parkinson’s Effects on Affect, Self-Efficacy, Gait Symmetry and Dual Task Performance
Authors: Fontanesi Cecilia , DeSouza Joseph FX
Published: November 2020

Background

Previous studies have investigated the effects of dance interventions on Parkinson’s motor and non-motor symptoms in an effort to develop an integrated view of dance as a therapeutic intervention. This within-subject study questions whether dance can be simply considered a form of exercise by comparing a Dance for Parkinson’s class with a matched-intensity exercise session lacking dance elements like music, metaphorical language, and social reality of grace and beauty.

Methods

In this repeated-measure design, 7 adults with Parkinson’s were tested four times; (i) before and (ii) after a Dance for Parkinson’s class, as well as (iii) before and (iv) after a matched-intensity exercise session. Physiological measures included heart rate and electrodermal activity. Self-reported affect and body self-efficacy were collected. Gait symmetry and dual task cost were analyzed using the 6-minutes walking test (6MWT) and Timed-Up-and-Go test (TUG), respectively.

Results

Average heart rate was the same for both conditions, while electrodermal activity was higher during Dance for Parkinson’s. Significant differences were found in body self-efficacy, beauty subscale, symmetry of gait, and dual task performance.

Conclusions

Dance, compared to an exercise intervention of matched intensity, yields different outcomes through the means of intrinsic artistic elements, which may influence affective responses, the experience of beauty, self-efficacy, and gait performance.
Rapid shift in microbial community structure in a neutral hydrothermal hot spring from Costa Rica
Authors: Rojas-Gätjens Diego , Arce-Rodríguez Alejandro , Puente-Sánchez Fernando , Avendaño Roberto , Libby Eduardo , Conejo-Barboza Geraldine , Mora-Amador Raul , Rojas Keilor , Pieper Dietmar H. , Chavarría Max
Published: November 2020

In this work, we characterize the geochemistry and microbial community of Bajo las Peñas, a neutral (pH 6.5-7.4), hot spring (T = 62.0-68.0°C) located near Turrialba Volcano, Costa Rica. The microbiota at its two sources belongs mainly to the family Aquificae, comprising OTUs closely related to the generaSulfurihydrogenibium,Thermosulfidibacter,ThermodesulfovibrioandThermocriniswhich is consistent with the presence of moderate levels of sulfate (243-284 mg/L) along the stream. We determined a dramatic shift in the microbial community just a few meters downstream of the sources of the hot spring (15-20 meters), with a change from sulfur related chemoautotrophic (e.g.Sulfurihydrogenibiumand an OTU closely related toThermodesulfovibrio) to chemoheterotrophic prokaryotes (e.g.Meiothermus,Nitrososphaera,Thermoflexus,Thermus). Thus, in this neutral hot spring, the first level of the trophic chain is associated with photosynthesis as well other anaerobic CO2fixing bacteria. Then, thermotolerant chemoheterotrophic bacteria colonize the environment to degrade organic matter and use fermentative products from the first level of the trophic chain. Our data demonstrate how quickly the microbial community of an ecosystem can change in response to environmental variables and sheds light on the microbial ecology of less common circumneutral pH hot springs.
Composition and acquisition of the microbiome in solitary, ground-nesting alkali bees
Authors: Kapheim Karen M. , Johnson Makenna M. , Jolley Maggi
Published: November 2020

Increasing evidence suggests the microbiome plays an important role in bee ecology and health. However, the relationship between bees and their bacterial symbionts has only been explored in a handful of species. We characterized the microbiome across the life cycle of solitary, ground-nesting alkali bees (Nomia melanderi). We find that feeding status is a major determinant of microbiome composition. The microbiome of feeding larvae was similar to that of pollen provisions, but the microbiome of post-feeding larvae (pre-pupae) was similar to that of the brood cell walls and newly-emerged females. Feeding larvae and pollen provisions had the lowest beta diversity, suggesting the composition of larval diet is highly uniform. Comparisons between lab-reared, newly-emerged, and nesting adult females suggest that the hindgut bacterial community is largely shaped by the external environment. However, we also identified taxa that are likely acquired in the nest or which increase or decrease in relative abundance with age. Although Lactobacillus micheneri was highly prevalent in pollen provisions, it was only detected in one lab-reared female, suggesting it is primarily acquired from environmental sources. These results provide the foundation for future research on metagenomic function and development of probiotics for these native pollinators.
Clonal dynamics in early human embryogenesis inferred from somatic mutation
Authors: Park Seongyeol , Mali Nanda Maya , Kim Ryul , Choi Jeong-Woo , Lee Junehawk , Lim Joonoh , Park Jung Min , Park Jung Woo , Kim Donghyun , Kim Taewoo , Yi Kijong , Choi June Hyug , Kwon Seong Gyu , Hong Joo Hee , Youk Jeonghwan , An Yohan , Kim Su Yeon , Kim Moonkyu , Kim Dong Sun , Park Ji Young , Oh Ji Won , Ju Young Seok
Published: November 2020

The trillions of cells that constitute the human body are developed from a fertilized egg through embryogenesis. However, cellular dynamics and developmental outcomes of embryonic cells in humans remain to be largely unknown due to the technical and ethical challenges. Here, we explored whole-genomes of 334 single-cell expanded clones and targeted deep-sequences of 379 bulk tissues obtained from various anatomical locations from seven individuals. Using the discovered 1,688,652 somatic mutations as an intrinsic barcode, we reconstructed cellular phylogenetic trees that provide novel insights into early human embryogenesis. Our findings suggest (1) endogenous mutational rate that is higher in the first cell division of life but decreases to ~1 per cell per cell division later in life, (2) universal unequal contribution of early cells into embryo proper resulting from early cellular bottlenecks that stochastically separate epiblasts from embryonic cells (3) uneven differential outcomes of early cells into three germ layers, left-right and cranio-caudal tissues, (4) emergence of a few ancestral cells that will contribute to the substantial fraction of adult blood cells, and (5) presence of mitochondrial DNA heteroplasmy in the fertilized egg. Our approach additionally provides insights into the age-related mutational processes including UV-mediated mutagenesis and loss of chromosome X or Y in normal somatic cells. Taken together, this study scrutinized somatic mosaicism, clonal architecture, and cellular dynamics in human embryogenesis at an unprecedented level and provides a foundation for future studies to complete cellular phylogenies in human embryogenesis.
Type I and III IFNs produced by the nasal epithelia and dimmed inflammation are key features of alpacas resolving MERS-CoV infection
Authors: Te Nigeer , Rodon Jordi , Ballester Maria , Pérez Mónica , Pailler-García Lola , Segalés Joaquim , Vergara-Alert Júlia , Bensaid Albert
Published: November 2020

While MERS-CoV (Middle East respiratory syndrome Coronavirus) provokes a lethal disease in humans, camelids, the main virus reservoir, are asymptomatic carriers, suggesting a crucial role for innate immune responses in controlling the infection. Experimentally infected camelids clear infectious virus within one week and mount an effective adaptive immune response. Here, transcription of immune response genes was monitored in the respiratory tract of MERS-CoV infected alpacas. Concomitant to the peak of infection, occurring at 2 days post inoculation (dpi), type I and III interferons (IFNs) were maximally transcribed only in the nasal mucosa of alpacas, provoking the induction of interferon stimulated genes (ISGs) along the whole respiratory tract. Simultaneous to mild focal infiltration of leukocytes in nasal mucosa and submucosa, upregulation of the anti-inflammatory cytokine IL10 and dampened transcription of pro-inflammatory genes under NF-κB control were observed. In the lung, early (1 dpi) transcription of chemokines (CCL2 and CCL3) correlated with a transient accumulation of mainly mononuclear leukocytes. A tight regulation of IFNs in lungs with expression of ISGs and controlled inflammatory responses, might contribute to virus clearance without causing tissue damage. Thus, the nasal mucosa, the main target of MERS-CoV in camelids, is central in driving an efficient innate immune response based on triggering ISGs as well as the dual anti-inflammatory effects of type III IFNs and IL10.

IMPORTANCE

Middle East respiratory syndrome coronavirus (MERS-CoV) is the etiological agent of a respiratory disease causing high mortality in humans. In camelids, the main MERS-CoV reservoir host, viral infection leads to subclinical disease. Our study describes transcriptional regulations of innate immunological pathways underlying asymptomatic clinical manifestations of alpacas in response to MERS-CoV. Concomitant to the peak of infection, these animals elicited a strong transient interferon response and induction of the anti-inflammatory cytokine IL10 in the nasal mucosa. This was associated to a dimmed regulation of pro-inflammatory cytokines and induction of interferon stimulated genes along the whole respiratory mucosa, leading to the rapid clearance of the virus. Thus, innate immune responses occurring in the nasal mucosa appear to be the key in controlling MERS-CoV disease by avoiding a cytokine storm. Understanding on how asymptomatic host reservoirs counteract MERS-CoV infection will aid in the development of antiviral drugs and vaccines.