bluuebunny/crossref_metadata_2025 huggingface dataset:
Analysis of community-acquired COVID-19 cases in Taiwan
Authors: Liu Jui-Yao , Chen Tzeng-Ji , Hwang Shinn-Jang
Published: August 2020

Background:

The demographic characteristics and transmission dynamics of the community-acquired coronavirus disease 2019 (COVID-19) cases in Taiwan were analyzed for more effective control and prevention of the community transmission of this novel disease.

Methods:

Open-access data and press releases on COVID-19 in Taiwan were collected on the website of the Taiwan Centers for Disease Control. All 55 community-acquired cases of COVID-19 confirmed from January 28 to April 12, 2020, in Taiwan were included. Basic demographic characteristics, symptom presentation, infection source, route of identification, and transmission dynamics were analyzed.

Results:

Of the 55 cases, 52.7% were female and 74.5% were between 20–59 years of age. One-sixth (16.4%) of community-acquired cases were asymptomatic. More than half (58.2%) of the cases were identified via contact tracing. The median incubation period was 6 days (range 1-13 d) and the median serial interval was 4 days (range −3-24 d). Twenty-six cases (47.3%) were transmitted from presymptomatic cases, 11 cases (20%) from symptomatic cases, and 2 cases (3.6%) from an asymptomatic case. The contagious period of symptomatic cases was from 7 days before to 15 days after the onset of symptoms.

Conclusion:

The high proportion of asymptomatic cases and the transmissibility in the presymptomatic and asymptomatic periods make control of COVID-19 challenging. Protective measures such as social distancing, wearing face masks, and hand washing are mandatory to prevent community transmission.
Job Insecurity, Sickness Presenteeism and the Moderating Effect of Workplace Health Promotion
Authors: Schmidt Kristin , Pförtner Timo-Kolja
Published: August 2020

Objective:

This study examined the relationship between job insecurity and presenteeism, and the role of workplace health promotion as moderator in this association.

Methods:

We used data from 9525 employees from the sixth BIBB/BAuA
∗
Employment Survey 2012 for the working population in Germany. Data analysis was performed with logistic regressions.

Results:

Job insecurity was associated with a higher risk of presenteeism, even after adjustment for control factors (OR = 1.25, CI: 1.01–1.53, P < 0.05). Workplace health promotion moderated this relationship: It no longer existed in companies with health promotion.

Conclusions:

The results suggest that employees with job insecurity are more likely to work despite feeling ill with the aim of securing their jobs. By establishing workplace health promotion, companies can protect their employees from that behavior in order to avoid negative long-term consequences.
Personal Protective Equipment and Mental Health Symptoms Among Nurses During the COVID-19 Pandemic
Authors: Arnetz Judith E. , Goetz Courtney M. , Sudan Sukhesh , Arble Eamonn , Janisse James , Arnetz Bengt B.
Published: August 2020

Objective:

To determine the association between access to adequate personal protective equipment (PPE) and mental health outcomes among a sample of U.S. nurses.

Methods:

An online questionnaire was administered in May 2020 to Michigan nurses via three statewide nursing organizations (n = 695 respondents). Multivariable logistic regression analysis was used to identify factors associated with mental health symptoms.

Results:

Nurses lacking access to adequate PPE (24.9%,n = 163) were more likely to report symptoms of depression (OR 1.96, 95% CI 1.31, 2.94;P = 0.001), anxiety (OR 1.64, 95% CI 1.12, 2.40;P = 0.01) and post-traumatic stress disorder (OR 1.83, 95% CI 1.22, 2.74;P = 0.003).

Conclusions:

Healthcare organizations should be aware of the magnitude of mental health problems among nurses and vigilant in providing them with adequate PPE as the pandemic continues.
Implementing Screening Guidelines for Preeclampsia Prevention in a Birth Center
Authors: Giles Lana Amelia
Published: August 2020

The aim of the project was to identify women at risk for developing preeclampsia who present for birth center care in order to initiate preventative treatment and retain them within the birth center practice. Birth center patients with preeclampsia disqualify for birth center care requiring hospital transfer. The target population consisted of pregnant women choosing birth center care with certified nurse midwives. Quality improvement method was utilized. Over 5-weeks, patients with 12 to 28 weeks' gestation were screened for preeclampsia risk factors; patients with high risk for preeclampsia initiated low-dose aspirin (LDA). All patients were evaluated for preeclampsia diagnosis up to 2 weeks postpartum. Outcomes were evaluated through chart audits. Screening for preeclampsia risk significantly increased LDA use. Preeclampsia screening did not statistically reduce incidences of preeclampsia but did show a moderate reduction. Use of LDA did not statistically reduce preeclampsia diagnoses but had a large reduction effect. Screening for preeclampsia in birth center patients results in increased use of LDA and potentially decreased rates of hospital transfer. Implementing preeclampsia screening is cost-effective and allows for increased patient retention.
Impact of a High Coverage Vaccination Rate on Human Papillomavirus Infection Prevalence in Young Women: A Cross-sectional Study
Authors: Saldanha Conceição , Vieira-Baptista Pedro , Costa Mariana , Silva Ana Rita , Picão Miguel , Sousa Carlos
Published: August 2020

Objective

The aim of the study was to compare the rate of high-risk human papillomavirus (HR-HPV) genotypes in vaccinated (Gardasil [quadrivalent]) and unvaccinated cohorts of young women.

Materials and Methods

This is a retrospective, cross-sectional study, consisting of the comparison of the prevalence of HPV 16, 18, and other HR genotypes in 2183 women younger than 25 years, according to their birth year (born >1994 [mostly vaccinated <13 years]; born 1992–1994 [vaccinated at 17 years]; born <1992 [not vaccinated/vaccinated >17 years]), in a private laboratory.

Results

The rates of HPV 16, 18, 16/18, and others in the cohort born before 1992 (n = 331) were 6.3%, 1.5%, 7.9%, and 31.7%. In those born 1992–1994 (n = 901), the rates were 3.3%, 0.4%, 3.6%, and 32.5%; in the ones born after 1994 (n = 951), the rates were 0.7%, 0.2%, 0.9%, and 33.2%, respectively.

There were no changes in the relative risk (RR) of HR-HPV infection by genotypes other than HPV 16/18 in any cohort.

The RR was significantly reduced in the cohort born after 1994 for HPV 16 (0.12 [0.050–0.270], p < .0001), HPV 18 (0.14 [0.027–0.714], p = .02), and HPV 16/18 (0.12 [0.057–0.254], p < .0001).

In those born 1992–1994, there was a nearly significant reduction in the RR of HPV 18 infection (0.29 [0.079–1.09], p = .07); the reduction was significant for HPV 16 (0.52 [0.305–0.904], p = .02) and HPV 16/18 (0.45 [0.274–0.747], p = .0018).

Conclusions

Young women vaccinated before 13 years had a nearly 90% risk reduction of HPV 16/18, whereas if vaccinated at 17 years, the decrease was of 50%. There was no impact in the nonvaccine genotypes.

Our data highlight the importance of vaccinating at young age and of introducing vaccines covering more HR genotypes.
Current management of superior semicircular canal dehiscence syndrome
Authors: Walsh Erika McCarty
Published: August 2020

Purpose of review

The current article reviews literature on the contemporary management of superior semicircular canal dehiscence syndrome (SSCDS). Approaches to management and surgical techniques are compared along with a discussion of the use of more standardized, objective outcome measures.

Recent findings

Considerable debate still exists as to what approach and technique is most appropriate for patients with SSCDS and how to best measure postoperative outcomes. However, it is increasingly accepted that multiple factors account for outcomes in SSCDS, including presenting symptoms and presence of vestibular comorbidities. Therefore, surgical intervention is best tailored to each individual patient. Data on SSCDS outcomes is heterogenous, and increased emphasis is being placed on validated measures of outcome. Round window approaches remain controversial and their role is still undefined.

The treatment strategies for SSCDS continue to diversify. A patient-specific approach with systematic documentation of outcomes will continue to inform how these patients are best managed.
Rehabilitation Utilization by Cancer Patients with Pathology-Confirmed Leptomeningeal Disease Receiving Intrathecal Chemotherapy
Authors: Fu Jack B. , Ng Amy H. , Molinares Diana M. , Pingenot Edward A. , Morishita Shinichiro , Silver Julie K. , Bruera Eduardo
Published: August 2020

The incidence of leptomeningeal disease (LMD) is believed to be increasing in part because of more effective chemotherapy treatments allowing cancer progression behind the blood-brain barrier. However, little has been published about the rehabilitation of this growing patient population. In this study, impairments and rehabilitation utilization by cytology-proven LMD patients receiving intrathecal chemotherapy at a cancer center are described. A total of 109 consecutive patients with pathology-confirmed LMD who received an intrathecal chemotherapy infusion from January 1, 2017, through October 31, 2017, were retrospectively reviewed. Of the 109 patients, 103 (95%) had impairments described in their medical record that could impact physical function, including 74 of 109 (68%) who had deconditioning or fatigue. Kaplan-Meier median survival from initial LMD diagnosis was 13.1 mos. The median number of hospital admissions and intrathecal chemotherapy administrations was both 8. Of the 109 patients, 43 (39%) had magnetic resonance imaging radiology interpreted LMD. Most LMD patients used rehabilitation services (95/109, 87%) and most were able to forego post–acute inpatient rehabilitation facilities (96/109, 88%). Additional research and education for rehabilitation professionals about this increasingly common syndrome are needed.
Chronic Poststroke Deficits in Gross and Fine Motor Control of the Ipsilesional Upper Limb
Authors: Johnson Brian P. , Westlake Kelly P.
Published: August 2020

Objectives

Individuals with stroke often experience contralesional and ipsilesional arm motor deficits. The aim of this study was to compare fine and gross motor hand dexterity of the ipsilesional hand post-stroke with controls, normative values, and the contralesional hand.

Design

Data were collected from right-handed individuals with chronic stroke (n= 20), age-/sex-matched controls (n= 10), and normative values (n= 20) performing the Nine-Hole Peg Test and the Box and Blocks Test.

Results

Individuals with stroke demonstrated poorer performance with the ipsilesional arm relative to both the control group (mean difference [95% confidence interval]: Nine-Hole Peg Test [seconds], 3.4 [−0.5 to 7.3]; Box and Blocks Test [number of blocks], −12.3 [−20.3 to −4.2]) and normative values (mean difference [95% confidence interval]: Nine-Hole Peg Test [seconds], 6.5 [4.0–9.1]; Box and Blocks Test (number of blocks), −15.3 [−20.1 to −10.5]). Ipsilesional arm performance was significantly better than performance with the contralesional arm (mean difference [95% confidence interval]: Nine-Hole Peg Test [seconds], −9.4 [−20.2 to 1.4]; Box and Blocks Test (number of blocks), 33.2 [20.9–45.5]).

Conclusion

These findings identify residual deficits in fine and gross dexterity of the ipsilesional hand in commonly used outcome measures of hand manipulation among individuals with chronic stroke. Possible underlying mechanisms and clinical relevance are discussed.
Environmental Cleaning and Decontamination to Prevent Clostridioides difficile Infection in Health Care Settings: A Systematic Review
Authors: Schoyer Elizabeth , Hall Kendall
Published: August 2020

Objective

The aim of this systematic review was to examine the most effective and feasible methods for environmental cleaning and decontamination to prevent Clostridioides difficile infection (CDI) in health care settings.

Methods

A systematic search of the databases CINAHL and MEDLINE was conducted from 2008 to 2018 for English language articles with search terms including “Clostridium difficile,” and related medical subject headings, in combination with terms like “disinfection,” “decontamination,” and “no-touch decontamination.”

Results

Twelve studies and 2 systematic reviews were selected for inclusion in this review. The studies were primarily in hospitals (10/12) and used a before-after approach. The studied interventions included cleaning and decontamination with a chlorine-based agent (i.e., bleach; 2 studies), standard cleaning plus the use of hydrogen peroxide decontamination (3 studies), and standard bleach cleaning plus the use of ultraviolet light decontamination (6 studies), and there was 1 study about launderable bed covers. The interventions ranged in frequency, duration, and the area selected for cleaning and decontamination (e.g., all patient rooms versus only CDI patients’ rooms). Studies showed significant reductions in CDI associated with use of bleach (versus quaternary ammonium compound) and hydrogen peroxide decontamination after standard bleach cleaning (versus bleach cleaning alone). Four of 6 studies found significant reductions in CDI after the implementation of ultraviolet light decontamination after standard bleach cleaning.

Conclusions

The studied practices for environmental cleaning and decontamination were associated with significant decreases in facility-level CDI rates in most of the reviewed studies; however, study quality was low. Implementation challenges are worthy of further examination.
Sapovirus: an emerging cause of childhood diarrhea
Authors: Becker-Dreps Sylvia , González Fredman , Bucardo Filemón
Published: August 2020

Purpose of review

Sapovirus, a genus in the Caliciviridae family alongside norovirus, is increasingly recognized as an important cause of childhood diarrhea. Some challenges exist in our ability to better understand sapovirus infections, including the inability to grow sapovirus in cell culture, which has hindered diagnosis and studies of immunity. Another challenge is that individuals with sapovirus infection are commonly coinfected with other enteric pathogens, complicating our ability to attribute the diarrhea episode to a single pathogen.

Recent findings

Development of molecular methods for sapovirus detection has increased our ability to measure disease prevalence. The prevalence of sapovirus varies between 1 and 17% of diarrhea episodes worldwide, with the highest burden in young children and older adults. Further, epidemiological studies have used novel approaches to account for the presence of coinfections with other enteric pathogens; one multisite cohort study of children under two years of age found that sapovirus had the second-highest attributable incidence among all diarrheal pathogens studied.

Especially in settings where rotavirus vaccines have been introduced, efforts to reduce the overall burden of childhood diarrhea should focus on the reduction of sapovirus transmission and disease burden.
A Review of AI and Data Science Support for Cancer Management
Authors: Parimbelli E. , Wilk S. , Cornet R. , Sniatala P. , Sniatala K. , Glaser S.L.C. , Fraterman I. , Boekhout A.H , Ottaviano M. , Peleg M.
Published: August 2020

Introduction

Thanks to improvement of care, cancer has become a chronic condition. But due to the toxicity of treatment, the importance of supporting the quality of life (QoL) of cancer patients increases. Monitoring and managing QoL relies on data collected by the patient in his/her home environment, its integration, and its analysis, which supports personalization of cancer management recommendations. We review the state-of-the-art of computerized systems that employ AI and Data Science methods to monitor the health status and provide support to cancer patients managed at home.

Objective

Our main objective is to analyze the literature to identify open research challenges that a novel decision support system for cancer patients and clinicians will need to address, point to potential solutions, and provide a list of established best-practices to adopt.

Methods

We designed a review study, in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, analyzing studies retrieved from PubMed related to monitoring cancer patients in their home environments via sensors and self-reporting: what data is collected, what are the techniques used to collect data, semantically integrate it, infer the patient’s state from it and deliver coaching/behavior change interventions.

Results

Starting from an initial corpus of 819 unique articles, a total of 180 papers were considered in the full-text analysis and 109 were finally included in the review. Our findings are organized and presented in four main sub-topics consisting of data collection, data integration, predictive modeling and patient coaching.

Conclusion

Development of modern decision support systems for cancer needs to utilize best practices like the use of validated electronic questionnaires for quality-of-life assessment, adoption of appropriate information modeling standards supplemented by terminologies/ontologies, adherence to FAIR data principles, external validation, stratification of patients in subgroups for better predictive modeling, and adoption of formal behavior change theories. Open research challenges include supporting emotional and social dimensions of well-being, including PROs in predictive modeling, and providing better customization of behavioral interventions for the specific population of cancer patients.
Association of 25 hydroxyvitamin D concentration with risk of COVID-19: a Mendelian randomization study
Authors: Liu Di , Tian Qiuyue , Zhang Jie , Hou Haifeng , Wang Wei , Meng Qun , Wang Youxin
Published: August 2020

Background

In observational studies, 25 hydroxyvitamin D (25OHD) concentration has been associated with an increased risk of Coronavirus disease 2019 (COVID-19). However, it remains unclear whether this association is causal.

Methods

We performed a two-sample Mendelian randomization (MR) to explore the causal relationship between 25OHD concentration and COVID-19, using summary data from the genome-wide association studies (GWASs) and using 25OHD concentration-related SNPs as instrumental variables (IVs).

Results

MR analysis did not show any evidence of a causal association of 25OHD concentration with COVID-19 susceptibility and severity (OR=1.168, 95% CI 0.956-1.427; OR=0.889, 95% CI 0.549-1.439). Sensitivity analyses using different instruments and statistical models yielded similar findings, suggesting the robustness of the causal association. No obvious pleiotropy bias and heterogeneity were observed.

Conclusion

The MR analysis showed that there might be no linear causal relationship of 25OHD concentration with COVID-19 susceptibility and severity.
Genomic surveillance, characterisation and intervention of a carbapenem-resistant Acinetobacter baumannii outbreak in critical care
Authors: Roberts Leah W. , Forde Brian M. , Hurst Trish , Ling Weiping , Nimmo Graeme R. , Bergh Haakon , George Narelle , Hajkowicz Krispin , McNamara John F , Lipman Jeffrey , Permana Budi , Schembri Mark A. , Paterson David , Beatson Scott A. , Harris Patrick N. A.
Published: August 2020

Infections caused by carbapenem-resistant Acinetobacter baumannii (CR-Ab) have become increasingly prevalent in clinical settings and often result in significant morbidity and mortality due to their multidrug resistance (MDR). Here we present an integrated whole genome sequencing (WGS) response to a polymicrobial outbreak in a Brisbane hospital between 2016-2018. 28 CR-Ab (and 21 other MDR Gram negative bacilli) were collected from Intensive Care Unit and Burns Unit patients and sent for WGS with a 7-day turn-around-time in clinical reporting. All CR-Ab were sequence type (ST)1050 and within 10 single nucleotide polymorphisms (SNPs) apart, indicative of an ongoing outbreak, and distinct from historical CR-Ab isolates from the same hospital. Possible transmission routes between patients were identified on the basis of CR-Ab and K. pneumoniae SNP profiles. Continued WGS surveillance between 2016 to 2018 enabled suspected outbreak cases to be refuted, but a resurgence of the outbreak CR-Ab mid-2018 in the Burns Unit prompted additional screening. Environmental metagenomic sequencing identified the hospital plumbing as a potential source. Replacement of the plumbing and routine drain maintenance resulted in rapid resolution of the secondary outbreak and significant risk reduction with no discernable transmission in the Burns Unit since. Here we demonstrate implementation of a comprehensive WGS and metagenomics investigation that resolved a persistent CR-Ab outbreak in a critical care setting.
Remedial dosing recommendation for delayed or missed rivaroxaban doses for patients with non-valvular atrial fibrillation based on Monte Carlo simulation
Authors: Liu Xiao-qin , Yin Yi-wei , Wang Chen-yu , Li Zi-ran , Zhu Xiao , Jiao Zheng
Published: August 2020

Background

Rivaroxaban is a non-vitamin K oral anticoagulant used widely for stroke prevention in patients with non-valvular atrial fibrillation (NVAF). During long-term anticoagulant therapy, delayed or missed doses are common. However, a lack of practical instructions on remedial methods has created a barrier for patients to maximise the benefit of their medications. This study aimed to explore appropriate remedial dosing regimens for rivaroxaban-treated patients with NVAF.

Methods

Monte Carlo simulation based on a previously established rivaroxaban population pharmacokinetic/pharmacodynamic model for patients with NVAF was employed to design remedial dosing regimens. Both the European Heart Rhythm Association (EHRA) recommendations and the model were used to establish remedial dosing regimens, which were assessed considering the on-therapy range of drug concentration, factor Xa activity, and prothrombin time under various scenarios of non-adherence.

Results

Recommendations of EHRA guide may not be optimal. Our findings suggested that a missed dose is taken immediately when the delay is less than or equal to 6 h; a half dose is advisable when the delay exceeds 6 h but is less than 4 h before the next dose. It is recommended to skip a dose when there are less than 4 h before the next dose. Age or renal function do not significantly influence the remedial dosing regimen.

Conclusion

A remedial dosing regimen based on model-based Monte Carlo simulation was systematically developed for rivaroxaban-treated patients with NVAF with poor adherence to quickly restore drug concentrations to the on-therapy range and to reduce the risk of bleeding and thromboembolism.

What is known on this topic?

Remedial recommendations for delayed or missed rivaroxaban dose have been mentioned in package inserts and guide, but lack of solid supporting evidence.

Monte Carlo simulation based on population analysis have been proved as an appropriate method to explore the remedial dosing strategy.

What does this paper add?

Remedial recommendations for delayed or missed rivaroxaban in different population are established based on Monte Carlo simulation.

The choice of optimal remedial strategy is related to delay duration.

This paper provides a more time-specific and individualized recommendations compared with previous recommendations.
Emulated Clinical Trials from Longitudinal Real-World Data Efficiently Identify Candidates for Neurological Disease Modification: Examples from Parkinson’s Disease
Authors: Laifenfeld Daphna , Yanover Chen , Ozery-Flato Michal , Shaham Oded , Rozen-Zvi Michal , Lev Nirit , Goldschmidt Yaara , Grossman Iris
Published: August 2020

Real-world healthcare data hold the potential to identify therapeutic solutions for progressive diseases by efficiently pinpointing safe and efficacious repurposing drug candidates. This approach circumvents key early clinical development challenges, particularly relevant for neurological diseases, concordant with the vision of the 21st Century Cures Act. However, to-date, these data have been utilized mainly for confirmatory purposes rather than as drug discovery engines. Here, we demonstrate the usefulness of real-world data in identifying drug repurposing candidates for disease- modifying effects, specifically candidate marketed drugs that exhibit beneficial effects on Parkinson’s disease (PD) progression. We performed an observational study in cohorts of ascertained PD patients extracted from two large medical databases, Explorys SuperMart (N=88,867) and IBM MarketScan Research Databases (N=106,395); and applied two conceptually different, well-established causal inference methods to estimate the effect of hundreds of drugs on delaying dementia onset as a proxy for slowing PD progression. Using this approach, we identified two drugs that manifested significant beneficial effects on PD progression in both datasets: rasagiline, narrowly indicated for PD motor symptoms; and zolpidem, a psycholeptic. Each confers its effects through distinct mechanisms, which we explored via a comparison of estimated effects within the drug classification ontology. We conclude that analysis of observational healthcare data, emulating otherwise costly, large, and lengthy clinical trials, can highlight promising repurposing candidates, to be validated in prospective registration trials, for common, late-onset progressive diseases for which disease-modifying therapeutic solutions are scarce.
Polygenic Risk Score for Gastric Cancer
Authors: Pratinidhi Sharvani Padmaraj , Sayad Saed
Published: August 2020

Background

Gastric Cancer is one of the most predominant types of cancer in the world, and its genomic links are currently being studied at great depth. In this paper, we work towards using Genome Wide Association Studies (GWAS) data for identifying the Single Nucleotide Polymorphisms (SNPs) which have the strongest correlation with the occurrence of gastric cancer through statistical tests and to leverage them to build a predictive model using machine learning algorithms. Polygenic risk scoring (PRS) is a straightforward predictive model for assigning genetic risk to individual outcomes (cancer or healthy).

Method

Genome Wide Association Studies (GWAS) data for Gastric Cancer was subjected to different statistical tests. Chi-square was used for feature selection by determining the degree of association between each probe (SNP) and the target (cancer or control). These results were used to eliminate many probes and proceed with only those that are statistically significant. Naïve Bayes Classifier and Catboost machine learning algorithms were used to build classification models to predict (score) gastric cancer.

Results

Naïve Bayes classifier and Catboost classification algorithms were used for modeling. The features were selected by performing Chi-square test on each of the 319283 SNPs in the data. These values were then ordered according to the negative log of the p-value and the top 5, 100 and 1000 features were used as inputs in the classification models. The Naïve Bayes classifier gave an accuracy in the range of 0.60 to 0.76 for different sets of features. The Catboost algorithm proved to be more suited for this application as it gave an accuracy above 0.90 for all subsets of features.

Conclusions

This paper aims at creating a highly accurate classification model to predict the occurrence of gastric cancer from GWAS genome data. The Catboost model with an input space of 100 SNPs yielded the best results with an accuracy of 0.93 and can be considered as a polygenic risk scoring model to score new patients for gastric cancer.
The Parkinson’s Disease DNA Variant Browser
Authors: Kim Jonggeol J. , Makarious Mary B. , Bandres-Ciga Sara , Gibbs J. Raphael , Ding Jinhui , Hernandez Dena G. , Brooks Janet , Grenn Francis P. , Iwaki Hirotaka , Singleton Andrew B. , Nalls Mike A. , Blauwendraat Cornelis
Published: August 2020

Parkinson’s disease (PD) is a genetically complex neurodegenerative disease with ~20 genes known to contain mutations that cause PD or atypical parkinsonism and 90 common genetic risk factors. Large-scale next-generation sequencing projects have revolutionized genomics research. Applying these data to PD, many genes have been reported to contain putative disease-causing mutations. In most instances, however, the results remain quite limited and rather preliminary, in large part because of an inability of any single group to validate findings in a large independent series of sequenced patients. We present here the Parkinson’s Disease Sequencing Browser: a Shiny-based web application that presents comprehensive summary-level frequency data from multiple large-scale genotyping and sequencing projects. The data is aggregated and involves a total of 102,127 participants, including 30,103 PD cases (including 1,650 proxy cases) and 72,024 controls. Our aim is to assist researchers on their search for PD-risk genes and variant candidates with an easily accessible and open summary-level genomic data browser for the PD research community, https://pdgenetics.shinyapps.io/VariantBrowser/.
Infodemiological study of COVID-19 in Latin America and The Caribbean
Authors: Aragón-Ayala Carlos Jesús , Copa-Uscamayta Julissa , Herrera Luis , Zela-Coila Frank , Quispe-Juli Cender Udai
Published: August 2020

Background

Infodemiology has been widely used to assess epidemics. In light of the recent pandemic, we use Google Search data to explore online interest about COVID-19 and related topics in 20 countries of Latin America and the Caribbean.

Method

Data from Google Trends from 2019/12/30 to 2020/04/25 regarding COVID-19 and other related topics were retrieved and correlated with official data on COVID-19 cases and with national epidemiological indicators.

Results

The Latin American and Caribbean countries with the most interest for COVID19 were Peru (100%) and Panama (98.39%). No correlation was found between this interest and national epidemiological indicators. The global and local response time were 20.2±1.2 days and 16.7±15 days, respectively. The duration of public attention was 64.8±12.5 days. The most popular topics related to COVID-19 were: the country’s situation (100 ± 0) and coronavirus symptoms (36.82±16.16). Most countries showed a strong or moderated (r=0.72) significant correlation between searches related to COVID-19 and daily new cases. In addition, the highest significant lag correlation was found on day 13.35±5.76 (r=0.79).

Conclusions

Interest shown by Latin American and Caribbean countries for COVID-19 was high. The degree of online interest in a country does not clearly reflect the magnitude of their epidemiological indicators. The response time and the lag correlation were greater than in European and Asian countries. Little interest was found for preventive measures. Strong correlation between searches for COVID-19 and daily new cases suggests a predictive utility that should be investigated by further studies.
Network reinforcement driven drug repurposing for COVID-19 by exploiting disease-gene-drug associations
Authors: Nam Yonghyun , Yun Jae-Seung , Lee Seung Mi , Park Ji Won , Chen Ziqi , Lee Brian , Verma Anurag , Ning Xia , Shen Li , Kim Dokyoon
Published: August 2020

Currently, the number of patients with COVID-19 has significantly increased. Thus, there is an urgent need for developing treatments for COVID-19. Drug repurposing, which is the process of reusing already-approved drugs for new medical conditions, can be a good way to solve this problem quickly and broadly. Many clinical trials for COVID-19 patients using treatments for other diseases have already been in place or will be performed at clinical sites in the near future. Additionally, patients with comorbidities such as diabetes mellitus, obesity, liver cirrhosis, kidney diseases, hypertension, and asthma are at higher risk for severe illness from COVID-19. Thus, the relationship of comorbidity disease with COVID-19 may help to find repurposable drugs. To reduce trial and error in finding treatments for COVID-19, we propose building a network-based drug repurposing framework to prioritize repurposable drugs. First, we utilized knowledge of COVID-19 to construct a disease-gene-drug network (DGDr-Net) representing a COVID-19-centric interactome with components for diseases, genes, and drugs. DGDr-Net consisted of 592 diseases, 26,681 human genes and 2,173 drugs, and medical information for 18 common comorbidities. The DGDr-Net recommended candidate repurposable drugs for COVID-19 through network reinforcement driven scoring algorithms. The scoring algorithms determined the priority of recommendations by utilizing graph-based semi-supervised learning. From the predicted scores, we recommended 30 drugs, including dexamethasone, resveratrol, methotrexate, indomethacin, quercetin, etc., as repurposable drugs for COVID-19, and the results were verified with drugs that have been under clinical trials. The list of drugs via a data-driven computational approach could help reduce trial-and-error in finding treatment for COVID-19.
Molluscan dorsal-ventral patterning relying onbmp2/4andchordinprovides insights into spiralian development and bilaterian evolution
Authors: Tan Sujian , Huan Pin , Liu Baozhong
Published: August 2020

Although a conserved mechanism relying onbmp2/4andchordinis suggested in animal dorsal-ventral (DV) patterning, this mechanism has not been reported in spiralians, one of the three major clades of bilaterians. Studies on limited spiralian representatives have suggested markedly diverse DV patterning mechanisms, a considerable amount of which no longer deploy BMP signaling. Here, we showed thatbmp2/4andchordinregulated DV patterning in the molluskLottia goshimai, which was predicted in spiralians but not reported before. In the context of the diverse reports in spiralians, it conversely represents a relatively unusual case. We then showed thatbmp2/4andchordincoordinated to mediate signaling from the D-quadrant organizer to induce the DV axis, among whichchordintransferred breakdown-of-symmetry information. Further investigations on theL. goshimaiembryos with influenced DV patterning suggested roles of BMP signaling in regulating the localization of the blastopore and the organization of the nervous system, indicating a cooption of DV patterning and the transition of these key characteristics at the origin of bilaterians. These findings provide insights into the evolution of animal DV patterning, the unique development mode of spiralians driven by the D-quadrant organizer, and the evolution of bilaterian body plans.
COVID-19 Severity Index: A predictive score for hospitalized patients
Authors: Huespe Iván , Bisso Indalecio Carboni , Gemelli Nicolas Alejandro , Terrasa Sergio , Di Stefano Sabrina , Burgos Valeria , Sinner Jorge , Risk Marcelo , Román Eduardo San , Heras Marcos Las
Published: August 2020

Introduction

Pandemics pose a major challenge for public health preparedness, requiring a coordinated international response and the development of solid containment plans. An early and accurate identification of high-risk patients in the course of the actual COVID-19 pandemic is vital for planning and for making proper use of available resources.

Objective

The purpose of this study was to identify the key variables to create a predictive model that could be used effectively for triage.

Methods

A narrative literature review of 651 articles was conducted to assess clinical, laboratory and imaging findings of COVID-19 confirmed cases. After screening, 10 articles met the inclusion criteria and a list of suggested variables was gathered. A modified Delphi process analysis was performed to consult experts in order to generate a final list of variables for the creation of the predictive model.

Results

The modified Delphi process analysis identified 44 predictive variables that were used for building a severity prediction score, the COVID-19 Severity Index.

Conclusion

Specifically designed for current COVID-19 pandemic, COVID-19 Severity Index could be used as a reliable tool for strategic planning, organization and administration of resources by easily identifying hospitalized patients with higher risk of transfer to Intensive Care Unit (ICU).
Demographic Characteristics, BAV Sievers Types, and Interactions Between BAV-Associated Valvulopathy and Aortopathy Differently Affect BAV Comorbidities and Outcomes of Aortic Valve Replacement
Authors: Li Yijia , Zhao Qiong , Qi Yue , Qu Yichen , Kumar Akshay , Yang Yan , Chen Xiongwen
Published: August 2020

Background

Bicuspid aortic valve (BAV) is a common congenital disorder. The relationship between demographic and clinical characteristics, BAV Sievers types, BAV associated valvulopathy and/or aortopathy and outcomes of aortic valve replacement (AVR) are interwoven and complicate and have not been fully elucidated. We sought to find these interactions in a large cohort of BAV patients.

Methods

We retrospectively reviewed the data of 992 BAV patients and collected the complete demographic and clinical data (baseline characteristic, BAV Sievers types, BAV valvulopathy and aortopathy, and pre-, intra- and postoperative data) to comprehensively analyze these relationships.

Results

In 992 BAV patients, sex differences could be found in demography (body surface area [BSA], age and serum triglyceride), comorbidities, cardiac performance (left ventricular dimension and ejection fraction,), valvulopathy and aortopathy. Sievers types had the same distribution among male and female patients, and had an impact on the incidence of valvulopathy and aortopathy. In the entire cohort, the factors associated with valvulopathy included age, sex, BSA, systolic blood pressure (SBP) and aortopathy, while factors associated with aortopathy were age, sex, BSA and valvulopathy. Aortopathy and valvulopathy promoted the occurrence of each other. Similar risk factors for valvulopathy and aortopathy in male patients were found. For 658 BAV patients underwent AVR, the preoperative demographic characteristics were similar to the whole cohort. More males were required to have simultaneous ascending aortic replacement (AAR). For postoperative early adverse events (EAE) and total ICU hours > 24 hours, the only predict factors were age and aortic cross clamp (ACC) time, while LVEF changes (including postoperative LVEF <50%, LVEF increase or decrease more or less than 5% or 10%) were related to sex, SBP, preoperative LVEF, valvulopathy and aortopathy, AAR, ACC time. Postoperative length of stay > 7 days could be affected by SBP, AAR, aortic stenosis and ACC time.

Conclusion

Our study revealed comprehensive relationships between demographic characteristics, BAV Sievers types, valvulopathy and aortopathy, and the possible risk factors for adverse outcomes after AVR in BAV patients. Sex, SBP, age, Sievers types, subtypes and interactions between aortopathy and valvulopathy differently impact on aortopathy, valvulopathy and the short outcomes of AVR.
Enhanced versus standard outpatient care of asthmatic children in Malawi: study protocol for a pilot randomised controlled trial
Authors: Rylance Sarah , Phiri Joseph , Grigg Jonathan , Jewell Chris , Jambo Kondwani , Mortimer Kevin
Published: August 2020

Background

Asthma is the most common chronic disease in childhood and is a growing global concern. However, there are limited data regarding long-term asthma management in low-income countries (LIC), particularly for children.

This study will assess the feasibility of recruitment and retention, the acceptability of an intervention and data collection methods, and baseline levels of asthma control and exacerbation rates in our target population of Malawian asthmatic children. Furthermore, we plan to; evaluate the effect of a package of enhanced asthma care, appropriate for a LIC, over a 3-month period; to describe clinical and airway inflammatory phenotypes; to identify clinical and laboratory features which might predict response to treatment in this population.

Methods

We will recruit 120 children aged 6-15 years, attending outpatient asthma follow-up at a tertiary government hospital in Malawi. Participants will be randomised, stratified by level of asthma control (Childhood Asthma Control Test (C-ACT) ≤19 or ≥20), to receive standard care in the hospital clinic, or an enhanced care package comprising; detailed clinical assessment (including pre- and post-bronchodilator spirometry, exercise challenge, exhaled nitric oxide (FeNO) measurement and sputum induction), optimisation of inhaled asthma treatment, and asthma education delivered by non-healthcare workers. Feasibility outcomes will include recruitment and retention rates, data completeness for study procedures, and baseline asthma control and exacerbation rates. The primary clinical outcome is asthma control, measured by C-ACT at 3 months, with adjustment for baseline measurement and intervention as covariates in a regression model. Secondary clinical outcomes at 3 months include; asthma exacerbations (requiring emergency health care use, treatment with oral corticosteroids or hospital admission), school absence, lung function and FeNO levels. Participants will be described by clinical and inflammatory phenotypes, with the latter categorised as eosinophilic or non-eosinophilic based on sputum cytology results and FeNO levels.

Discussion

It is important to assess whether global treatment guidelines for long-term asthma management are appropriate for low-income settings. This study will provide key feasibility data, including baseline clinical characteristics of asthmatic Malawian children, to inform assessment of an asthma care package in a low-income setting, which includes task-shifting to non-healthcare workers.

Trial registration

Pan African Clinical Trials Registry: PACTR201807211617031. Registered 09/07/18, https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=3468
Delayed Anxiolytic-Like Effects of Psilocybin in Male Mice Are Supported by Acute Glucocorticoid Release
Authors: Jones Nathan T , Zahid Zarmeen , Grady Sean M , Sultan Ziyad W , Zheng Zhen , Banks Matthew I , Wenthur Cody J
Published: August 2020

Despite observed correlations between acute glucocorticoid release, self-reported anxiety, and long-term treatment outcomes for human studies using psilocybin-assisted psychotherapy approaches, the mechanistic relationship between psychedelic-dependent stress and subsequent behavioral responses remains unclear. Using rodents, direct manipulation of stress-associated hormone responses can be achieved with established pharmacologic models for the assessment of antidepressant and anxiolytic therapeutics. Here, chronic oral corticosterone-induced suppression of the hypothalamic-pituitary-adrenal axis is used to assess the relevance of drug-induced glucocorticoid release on the acute, post-acute, and long-term effects of psilocybin in male C57BL/6J mice. In these studies, psilocybin-induced acute anxiogenesis was found to be correlated to post-acute anxiolysis in a dose-dependent manner. Psilocybin also displayed acute increases in plasma corticosterone, but a post-acute anxiolytic effect in the novelty suppressed feeding test. Both effects were lost when psilocybin was administered in animals pre-exposed to chronic oral corticosterone. A similar long-term interaction between chronic corticosterone and psilocybin administration was observed in an open field test occurring one week after drug administration. Psilocybin administration alone led to more time spent in the center of the arena, but animals spent less time in the center with chronic corticosterone exposure. Intriguingly, these interactive effects were absent in animals exposed to brief isoflurane anesthesia after drug treatment. Overall, these experiments identify acute glucocorticoid release as a relevant biological modifier for the post-acute and long-term behavioral effects of psilocybin in mice. Rodent studies are thus suggested as a tractable means to address neuroendocrine mechanisms supporting context-dependent psychedelic effects in mammalian species.
Attention capture outside the oculomotor range
Authors: Hanning Nina M. , Deubel Heiner
Published: August 2020

Neurophysiological studies demonstrated that attentional orienting is performed by fronto-parietal brain areas which also play an important role in oculomotor control. Accordingly, several studies claimed that exogenous attention can only be allocated to where we can potentially make an eye movement, i.e. within the oculomotor range. We tested this assumption by assessing the disruptive effect of a salient distractor at locations within and beyond participants’ oculomotor range. Participants rotated their heads ~38° leftwards to prevent them from performing large rightward saccades. In this posture, participants fixated the screen center and focused their attention on a location on the left side of the screen, where they had to discriminate the orientation of a visual noise patch. While assessing visual orientation sensitivity – an established proxy of visual attention – at this endogenously attended location, we flashed a salient cue either at the attended location or at various locations inside or outside their oculomotor range. We found that whenever the salient cue occurred at a location other than the endogenously attended location, it withdrew visual attention and significantly disrupted endogenous attentional orienting. Crucially, this effect occurred regardless of whether the cue was presented within or beyond participants’ oculomotor range, demonstrating that exogenous events equally grab our attention both inside and outside the eyes reach. Since spatial exogenous attention was attracted unrestrictedly toward locations to which no saccade could be executed, the coupling of attention and eye movement control is less tight than, for example, the prominent “Premotor Theory of Attention” suggests. Rather, attention can be shifted freely over the entire visual range, independent of pathological and physiological limitations of the eye movement system.