bluuebunny/crossref_metadata_2025 huggingface dataset:
Sexually Transmitted Infection Prevalence Among Women at Risk for HIV Exposure Initiating Safer Conception Care in Rural, Southwestern Uganda
Authors: Chitneni Pooja , Bwana Mwebesa Bosco , Owembabazi Moran , O'Neil Kasey , Kalyebara Paul Kato , Muyindike Winnie , Musinguzi Nicholas , Bangsberg David R. , Marrazzo Jeanne M. , Haberer Jessica E. , Kaida Angela , Matthews Lynn T.
Published: May 2020

Background

Knowledge of sexually transmitted infection (STI) prevalence and risk factors is important to the development of tenofovir-based preexposure prophylaxis (PrEP) and safer conception programming. We introduced STI screening among women at risk for HIV exposure who were participating in a safer conception study in southwestern Uganda.

Methods

We enrolled 131 HIV-uninfected women, planning for pregnancy with a partner living with HIV or of unknown HIV serostatus (2018–2019). Women were offered comprehensive safer conception counseling, including PrEP. Participants completed interviewer-administered questionnaires detailing sociodemographics and sexual history. We integrated laboratory screening for chlamydia, gonorrhea, trichomoniasis, and syphilis as a substudy to assess STI prevalence. Multivariable logistic regression was used to determine correlates.

Results

Ninety-four women completed STI screening (72% of enrolled). Median age was 30 (interquartile range, 26–34) years, and 94% chose PrEP as part of safer conception care. Overall, 24% had STIs: 13% chlamydia, 2% gonorrhea, 6% trichomoniasis, 6% syphilis, and 3% ≥2 STI. Sexually transmitted infection prevalence was associated with younger age (adjusted odds ratio [AOR], 0.87; 95% confidence interval [CI], 0.77–0.99), prior stillbirth (AOR, 5.04; 95% CI, 1.12–22.54), and not feeling vulnerable to HIV (AOR, 16.33; 95% CI, 1.12–237.94).

Conclusions

We describe a 24% curable STI prevalence among women at risk for HIV exposure who were planning for pregnancy. These data highlight the importance of integrating laboratory-based STI screening into safer conception programs to maximize the health of HIV-affected women, children, and families.
Construction and Validation of LEA Hindi Chart: A Multicenter Study
Authors: Datta Sourav , Varadharajan Srinivasa , Mazumdar Deepmala , Narayanan Anuradha , Monira Sirajum , Panda Soumya , Hyvärinen Lea , Satgunam PremNandhini
Published: May 2020

SIGNIFICANCE

This study explains the construction and validation of a chart in Hindi language, one of the commonly spoken languages in the world. The new visual acuity chart is called LEA Hindi chart. The calligraphy construction method described here can help develop other such acuity charts.

PURPOSE

The purpose of this study was to construct and validate a new logMAR Hindi visual acuity chart (LEA Hindi chart) using principles similar to that of LEA symbols acuity chart.

METHODS

A multicenter (three centers) study was conducted in two phases. The first phase consisted of identifying and constructing the Hindi optotypes using calligraphy techniques. The Hindi optotypes were calibrated against the Landolt C optotypes by measuring the threshold distance for visual acuity. In the second phase, the newly constructed LEA Hindi chart was validated against the Early Treatment Diabetic Retinopathy Study (ETDRS) and Landolt C visual acuity charts. Sixty participants were enrolled for the first phase (centers 1 and 2) and for the second phase of the study (centers 1 and 3). Additional 15 participants were enrolled (center 1) for testing repeatability.

RESULTS

Four Hindi optotypes were identified and used for the construction of the chart (first phase). In the second phase, the LEA Hindi chart was found to be comparable with both the Landolt C, (logMAR acuity difference, 0.03 ± 0.13;P> .18) and ETDRS (logMAR acuity difference, −0.02 ± 0.09;P> .25) charts. All the three charts were also found to be repeatable (95% limits of agreement within 0.24 logMAR).

CONCLUSIONS

The newly constructed LEA Hindi visual acuity chart gave comparable levels of visual acuity as that measured in an ETDRS or Landolt C charts. The repeatability was also similar to the standard charts. The LEA Hindi visual acuity chart can be used for patients comfortable with Hindi language and also in studies requiring multiple measurements of visual acuity, to avoid familiarity to a given chart.
Longitudinal Changes in Optical Quality, Spatial Vision, and Depth Vision after Laser Refractive Surgery for Myopia
Authors: Sarkar Samrat , Bharadwaj Shrikant R. , Reddy Jagadesh C. , Vaddavalli Pravin K.
Published: May 2020

SIGNIFICANCE

Laser refractive surgery procedures are efficacious at correcting myopia, but they result in long-term deterioration of optical quality that affects monocular and binocular visual performance. The study shows that the optical quality of the two eyes needs to be similar to optimize binocular visual performance after surgery.

PURPOSE

This study aimed to systematically analyze longitudinal changes in optical quality, high- and low-contrast logMAR acuity and random-dot stereoacuity before and after three refractive surgery procedures for correcting myopia.

METHODS

A total of 106 subjects (laser-assisted in situ keratomileusis, 40; photorefractive keratectomy, 26; small-incision lenticule extraction, 40) with myopia and astigmatism ≤1.5 D participated in this prospective cohort-based study. All aforementioned outcome variables were measured in both eyes pre-operatively and 1 week and 1, 3, and 6 months post-operatively.

RESULTS

Pre-operative myopic spherical equivalent of refraction (median [25th to 75th interquartile range], −6.4 D [−8.0 to −4.2 D] for laser-assisted in situ keratomileusis, −4.3 D [−5.0 to −3.5 D] for photorefractive keratectomy, −5.5 D [−6.5 to −4.3 D] for small-incision lenticule extraction) was corrected to within ±0.75 D of emmetropia in all cohorts up to 6 months post-operatively (P < .001). Higher-order wavefront aberrations, uncorrected high- and low-contrast logMAR acuity, and stereoacuity all worsened and remained so up to 6 months post-operatively, relative to pre-operative values (P < .001). Stereoacuity worsened with both interocular average and difference in the magnitude of higher-order aberrations, whereas logMAR acuities worsened only with interocular average of these aberrations (r
2 ≥ 0.40; P < .01 for all).

CONCLUSIONS

Although the refractive surgery procedures tested here correct myopia, they result in a sustained (up to 6 months) loss of optical quality and spatial and depth-related visual functions post-operatively. Both interocular average and difference in the eye's optical quality seem to impair binocular visual functions after refractive surgery for myopia.
Evaluation of Bivalirudin As an Alternative to Heparin for Systemic Anticoagulation in Pediatric Extracorporeal Membrane Oxygenation*
Authors: Hamzah Mohammed , Jarden Angela M. , Ezetendu Chidiebere , Stewart Robert
Published: May 2020

Objectives:

Heparin is the universal anticoagulant for patients receiving extracorporeal membrane oxygenation support. However, heparin has many disadvantages, especially in young children, who develop heparin resistance. Recently our center has used bivalirudin, a direct thrombin inhibitor, for systemic anticoagulation in pediatric extracorporeal life support. Bivalirudin binds directly to thrombin with no need for antithrombin III and it inhibits both circulating and clot-bound thrombin. In this study, we sought to evaluate our experience with bivalirudin in pediatric extracorporeal life support.

Design:

Retrospective chart review study of patients receiving extracorporeal membrane oxygenation support between October 2014 and May 2018.

Setting:

Tertiary, academic PICU.

Patients:

Sixteen patients receiving heparin and 16 patients receiving bivalirudin on extracorporeal life support were included in the study.

Interventions:

None.

Measurements and Main Results:

Patients in the bivalirudin group had a median age of 31 months versus 59 months in the heparin group (p = 0.41). Recovery and extracorporeal membrane oxygenation decannulation were similar in both groups (56% in the heparin group and 62% in the bivalirudin group; p = 0.62). Time to reach goal therapeutic anticoagulation level was shorter in the bivalirudin group (11 vs 29 hr; p = 0.01). Bleeding events were fewer in the bivalirudin group, and there was no difference in the rate of thrombotic events between the two groups. Comprehensive cost analysis that includes anticoagulant, laboratories, and antithrombin III cost, showed that heparin anticoagulation therapy total cost was significantly higher than bivalirudin (1,184 dollars per day in heparin group vs 494 dollars per day in bivalirudin group; p = 0.03). Bivalirudin dose required to maintain target anticoagulation will increase over time, and this is associated with an increase in creatinine clearance and an increase in fibrinogen serum levels.

Conclusions:

This study showed that the use of bivalirudin in pediatric extracorporeal membrane oxygenation support is feasible, safe, reliable, and cost-effective in comparison to heparin. Further prospective randomized clinical trials are necessary to confirm our observations.
Organizational Interventions to Support Second Victims in Acute Care Settings: A Scoping Study
Authors: Wade Laura , Fitzpatrick Eleanor , Williams Natalie , Parker Robin , Hurley Katrina F.
Published: May 2020

Objectives

Health care providers that experience harm after adverse events have been termed “second victims.” Our objective was to characterize the range and context of interventions to support second victims in acute care settings.

Methods

We performed a scoping study using Arksey and O’Malley’s process. A library scientist searched PubMed, Cumulative Index of Nursing and Allied Health, EMBASE, and Cochrane Central Register of Controlled Trials in September 2017, and updated the search in November 2018. We sought gray literature (Canadian Electronic Library, Proquest and Scopus) and searched reference lists of included studies. Stakeholder organizations and authors of included studies were contacted. Two reviewers independently reviewed titles and abstracts and extracted data. A qualitative approach was used to categorize the context and characteristics of the 22 identified interventions.

Results

After screening 5634 titles and abstracts, 173 articles underwent full-text screening. Twenty-two interventions met the criteria and were categorized as providing peer support (n = 8), proactive education (n = 6), or both (n = 8). Programs came from Canada (n = 2), Spain (n = 2), and the United States (n = 18). A specific traumatic event triggered the development of 5 programs. Some programs used a standard definition of second victims, (n = 6), whereas other programs had a broader scope (n = 12). Confidentiality was explicitly assured in 9 peer support programs. Outcome measures were often not reported.

Conclusions

This is a new area of study with little qualitative data from which to determine whether these programs are effective. Many programs had a similar design, based on the structure proposed by the same small group of experts in this new field. Concerns about potential legal proceedings hinder documentation and study of program effectiveness.
Prediction of Perioperative Cardiovascular Events in Liver Transplantation
Authors: Koshy Anoop N. , Farouque Omar , Cailes Benjamin , Ko Jefferson , Han Hui-Chen , Weinberg Laurence , Testro Adam , Robertson Marcus , Teh Andrew W. , Lim Han S. , Gow Paul J.
Published: May 2020

Background.

Hepatorenal syndrome (HRS) is a serious complication of liver cirrhosis with poor survival in the absence of liver transplantation (LT). HRS represents a state of profound circulatory and cardiac dysfunction. Whether it increases risk of perioperative major adverse cardiovascular events (MACE) following LT remains unclear.

Methods.

We performed a retrospective cohort study of 560 consecutive patients undergoing cardiac workup for LT of whom 319 proceeded to LT. All patients underwent standardized assessment including dobutamine stress echocardiography. HRS was defined according to International Club of Ascites criteria.

Results.

Primary outcome of 30-day MACE occurred in 74 (23.2%) patients. A significantly higher proportion of patients with HRS experienced MACE (31 [41.9%] versus 54 [22.0%]; P = 0.001). After adjusting for age, model for end-stage liver disease score, cardiovascular risk index, history of coronary artery disease, and a positive stress test, HRS remained an independent predictor for MACE (odds ratio [OR], 2.44; 95% confidence interval [CI], 1.13-5.78). Other independent predictors included poor functional status (OR, 3.38; 95% CI, 1.41-8.13), pulmonary hypertension (OR, 3.26; 95% CI, 1.17-5.56), and beta-blocker use (OR, 2.56; 95% CI, 1.10-6.48). Occurrence of perioperative MACE was associated with a trend toward poor age-adjusted survival over 3.6-year follow-up (hazard ratio, 2.0; 95% CI, 0.98-4.10; P = 0.057).

Conclusions.

HRS, beta-blocker use, pulmonary hypertension, and poor functional status were all associated with over a 2-fold higher risk of MACE following LT. Whether inclusion of these variables in routine preoperative assessment can facilitate cardiac risk stratification warrants further study.
The Clinical Conundrum of Cannabis: Current Practices and Recommendations for Transplant Clinicians: An Opinion of the Immunology/Transplantation PRN of the American College of Clinical Pharmacy
Authors: Melaragno Jennifer I. , Bowman Lyndsey J. , Park Jeong M. , Lourenco Laura M. , Doligalski Christina T. , Brady Bethany L. , Descourouez Jillian L. , Chandran Mary M. , Nickels Mark W. , Page Robert L.
Published: May 2020

Cannabis, or marijuana, comprises many compounds with varying effects. It has become a treatment option for chronic diseases and debilitating symptoms, and evidence suggests that it has immunomodulatory and antiinflammatory properties. Transplant centers are more frequently facing issues about cannabis, as indications and legalization expand. As of February 2020, 33 states and the District of Columbia have legalized medical cannabis, and 14 have legalized recreational cannabis. Moreover, 8 states have passed legislation prohibiting the denial of transplant listing solely based on cannabis use. Studies demonstrate the potential for significant pharmacokinetic and pharmacodynamic interactions between cannabis and immunosuppression. Additionally, safety concerns include increased risk of myocardial infarction, ischemic stroke, tachyarrhythmias, malignancy, neurocognitive deficits, psychosis, other neuropsychiatric disorders, cannabis use disorder, respiratory symptoms, and infection. A recent retrospective database study found a negative association between documented cannabis use disorder and graft survival, but little additional evidence exists evaluating this relationship. In the absence of robust clinical data, transplant centers need a clear, reasoned, and systematic approach to cannabis. The results of our national survey, unfortunately, found little consensus among institutions. As both recreational and medicinal cannabis become more ubiquitous nationwide, transplant centers will need to develop comprehensive policies to address its use.
Quality characteristics and retrogradation analysis of sponge cake
added with freeze dried Peucedanum japonicum
powder
Authors: Jung Hee Nam
Published: May 2020

The quality characteristics and retrogradation analysis of sponge cakes added
with different ratios (i.e., 0, 6, 12, 18 and 24 wt%) of freeze dried
Peucedanum japonicum powder (FDPP). The specific gravity of
the batter and the baking-loss rate of the sponge cake were found to increased
significantly upon increasing to amount of FDPP. The lightness (L) and
yellowness (b) values also increased. In addition, the specific volume and
volume index were the highest in 12% FDPP group. Furthermore, in the
presence of FDPP, the symmetry index was good in the range of −0.01–0.15,
and the uniformity index was low, while the hardness and chewiness increased
upon the addition of FDPP. During storage, the inhibition effect of
retrogradation in the sponge cake was ranged from of 6 to 18%, and the
acceptance test indicated that the addition of FDPP in quantities up to
12% did not cause a negative effect on the sensory attributes. The
obtained results therefore suggested that sponge cakes prepared using 12%
FDPP exhibit superior quality characteristics, retrogradation results, and
sensory properties.
Clinical Characteristics, Risk Factors and Outcomes Among the First Consecutive 1,096 Patients Diagnosed with COVID-19: The Kuwait Experience
Authors: Almazeedi Sulaiman , Al Youha Sarah , Jamal Mohammad H , Al-Haddad Mohannad , Al-Muhaini Ali , Al-Ghimlas Fahad , Al-Sabah Salman
Published: May 2020

Background
In Kuwait, prior to the first case of COVID-19 being reported in the country, mass screening of incoming travelers from countries with known outbreaks was performed and resulted in the first identified cases in the country. All COVID-19 cases at the time and subsequently after, were transferred to a single center, Jaber Al-Ahmad Al-Sabah Hospital, where the patients received standardized investigations and treatments. The objective of this study was to characterize the demographics, clinical manifestations and outcomes in this unique patient population.
Methods
This retrospective cohort study was conducted between 24th February 2020 and 20th April 2020. All consecutive patients in the entire State of Kuwait diagnosed with COVID-19 according to WHO guidelines and admitted to Jaber Al-Ahmad Al-Sabah Hospital were recruited. Patients received standardized investigations and treatments. Multivariable analysis was used to determine the associations between risk factors and outcomes.
Findings
Of 1096 patients, the median age was 41 years and 81% of patients were male. Most patients were asymptomatic on admission (49.5%), 69.4% had no signs of infection and 94.6% were afebrile. Only 3.6% of patients required an ICU admission and 1.7% were dead at the study cutoff date. On multivariate analysis, the risk factors found to be significantly associated with admission to intensive care were age above 50 years old, a qSOFA score above 0, smoking, elevated CRP and elevated procalcitonin levels. Asthma, smoking and elevated procalcitonin levels correlated significantly with mortality in our cohort.

Interpretation
To our knowledge, this is the first large retrospective cohort study observing the characteristics of the initial consecutive COVID-19 patients of an entire country. Further, large proportion of asymptomatic patients provides novel insights into the clinical features of patients with milder disease.
Critical levels of mask efficiency and of mask adoption that theoretically extinguish respiratory virus epidemics
Authors: Kot Alan D.
Published: May 2020

Using a respiratory virus epidemiological model we derive equations for the critical levels of mask efficiency (fraction blocked) and of mask adoption (fraction of population wearing masks) that lower the effective reproduction number to unity. The model extends a basic epidemiological model and assumes that a specified fraction of a population dons masks at a given initial number of infections. The model includes a contribution from the ocular (nasolacrimal duct) route, and does not include contributions from contact (fomite) routes. The model accommodates dose-response (probability of infection) functions that are linear or non-linear. Our motivation to study near-population-wide mask wearing arises from the concept that, between two mask wearers, the concentration of particles at inhalation should be the square of the mask penetration fraction. This combination, or team, of masks can provide a strong dose-lowering squaring effect, which enables the use of lower-efficiency, lower-cost, lower pressure-drop (easier breathing) masks.

For an epidemic with basic reproduction number R0 = 2.5 and with a linear dose-response, the critical mask efficiency is calculated to be 0.5 for a mask adoption level of 0.8 of the population. Importantly, this efficiency is well below that of a N95 mask, and well above that of some fabric masks. Numerical solutions of the model at near-critical levels of mask efficiency and mask adoption demonstrate avoidance of epidemics. To be conservative we use mask efficiencies measured with the most-penetrating viral-particle sizes. The critical mask adoption level for surgical masks with an efficiency of 0.58 is computed to be 0.73. With surgical masks (or equally efficient substitutes) and 80% and 90% adoption levels, respiratory epidemics with R0 of about 3 and 4, respectively, would be theoretically extinguished.
Hemogram Data as a Tool for Decision-making in COVID-19 Management: Applications to Resource Scarcity Scenarios
Authors: Dorn Marcio , Avila Eduardo , Alho Clarice Sampaio , Kahmann Alessandro
Published: May 2020

Background: COVID-19 pandemics has challenged emergency response systems worldwide, with widespread reports of essential services breakdown and collapse of health care structure. A critical element involves essential workforce management since current protocols recommend release from duty for symptomatic individuals, including essential personnel. Testing capacity is also problematic in several countries, where diagnosis demand outnumbers available local testing capacity.
Purpose: This work describes a machine learning model derived from hemogram exam data performed in symptomatic patients and how they can be used to predict qRT-PCR test results. Methods: A Naïve-Bayes model for machine learning is proposed for handling different scarcity scenarios, including managing symptomatic essential workforce and absence of diagnostic tests. Hemogram result data was used to predict qRT-PCR results in situations where the latter was not performed, or results are not yet available. Adjusts in assumed prior probabilities allow fine-tuning of the model, according to actual prediction context.
Results: Proposed models can predict COVID-19 qRT-PCR results in symptomatic individuals with high accuracy, sensitivity and specificity. Data assessment can be performed in an individual or simultaneous basis, according to desired outcome. Based on hemogram data and background scarcity context, resource distribution is significantly optimized when model-based patient selection is observed, compared to random choice. The model can help manage testing deficiency and other critical circumstances.
Conclusions: Machine learning models can be derived from widely available, quick, and inexpensive exam data in order to predict qRT-PCR results used in COVID-19 diagnosis. These models can be used to assist strategic decision-making in resource scarcity scenarios, including personnel shortage, lack of medical resources, and testing insufficiency.
COVID-19 research in Wikipedia
Authors: Colavizza Giovanni
Published: May 2020

Wikipedia is one of the main sources of free knowledge on the Web. During the first few months of the pandemic, over 5,200 new Wikipedia pages on COVID-19 have been created and have accumulated over 400M pageviews by mid June 2020.1At the same time, an unprecedented amount of scientific articles on COVID-19 and the ongoing pandemic have been published online. Wikipedia’s contents are based on reliable sources such as scientific literature. Given its public function, it is crucial for Wikipedia to rely on representative and reliable scientific results, especially so in a time of crisis. We assess the coverage of COVID-19-related research in Wikipedia via citations to a corpus of over 160,000 articles. We find that Wikipedia editors are integrating new research at a fast pace, and have cited close to 2% of the COVID-19 literature under consideration. While doing so, they are able to provide a representative coverage of COVID-19-related research. We show that all the main topics discussed in this literature are proportionally represented from Wikipedia, after accounting for article-level effects. We further use regression analyses to model citations from Wikipedia and show that Wikipedia editors on average rely on literature which is highly cited, widely shared on social media, and has been peer-reviewed.
Attributable mortality of vancomycin resistance in ampicillin-resistant Enterococcus faecium bacteremia in Denmark and the Netherlands: a matched cohort study
Authors: Rottier Wouter C. , Pinholt Mette , van der Bij Akke K. , Arpi Magnus , Blank Sybrandus N. , Nabuurs-Franssen Marrigje H. , Ruijs Gijs J.H.M. , Tersmette Matthijs , Ossewaarde Jacobus M. , Groenwold Rolf H. , Westh Henrik , Bonten Marc J.M.
Published: May 2020

Background

In many European hospitals, ampicillin-resistant Enterococcus faecium (ARE) is endemic, while outbreaks of vancomycin-resistant E. faecium (VRE), belonging to the same genetic lineage, are increasingly reported. We studied the attributable mortality due to vancomycin resistance in patients with E. faecium bacteremia and evaluated whether this is mediated by a delay in appropriate antibiotic therapy.

Methods

In a retrospective matched cohort study, patients with VRE bacteremia occurring between 2009 and 2014 in 20 Dutch and Danish hospitals were matched to patients with ARE bacteremia, on hospital, ward, length of hospital stay prior to bacteremia, and age. The risk ratio (RR) for 30-day mortality contrasting VRE with ARE was estimated with further analytic control for confounding factors.

Results

In all, 63 VRE and 234 ARE episodes were matched (36 and 130 for the Netherlands and 27 and 104 for Denmark). Crude 30-day mortality was 27% and 38% for ARE in the Netherlands and Denmark, respectively, and 33% and 48% for VRE in the respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval (CI) 1.06-2.25). Although appropriate therapy was initiated later for VRE than for ARE bacteremia, this did not appear to mediate the increased mortality risk.

Conclusions

Compared to ARE bacteremia, VRE bacteremia was associated with higher 30-day mortality. One explanation for this association would be increased virulence of VRE, although both phenotypes belong to the same well-characterized core genomic lineage. Alternatively, it may be the result of unmeasured confounding.
Modeling the Impact of Nationwide BCG Vaccine Recommendations on COVID-19 Transmission, Severity, and Mortality
Authors: Shah Nita H , Suthar Ankush , Satia Moksha H , Shah Yash , Shukla Nehal , Shukla Jagdish , Shukla Dhairya
Published: May 2020

COVID-19 was declared as pandemic on 11th March 2020 by WHO. There are apparent dissimilarities in incidence and mortality of COVID-19 cases in different parts of world. Developing countries in Asia and Africa with fragile health system have shown lower incidence and mortality compared to developed countries with superior health system in Europe and America. Most countries in Asia and Africa have national BCG vaccination program while Europe and America do not have such program, or have ceased it. At present, there is no known therapy to treat COVID-19 disease. There is no vaccine available currently to prevent COVID- 19 disease. As mathematical modelling is ideal for predicting the rate of disease transmission as well as evaluating efficacy of possible public health prevention measures, we have created a mathematical model with seven compartments to understand nationwide BCG vaccine recommendation on COVID-19 transmission, severity and mortality. We have computed two basic reproduction number, one at vaccine free equilibrium point and other at non-vaccine free equilibrium point and carried out local stability, sensitivity and numerical analysis. Our result showed that individuals with BCG vaccinations have lower risk of getting COVID-19 infection, shorter hospital stays, and increased rate of recovery. Furthermore, countries with long-standing universal BCG vaccination policies have reduced incidence, mortality, and severity of COVID-19. Further research will focus on exploring the immediate benefits of vaccination to healthcare workers and patients as well as benefits of BCG re-vaccination.
The association of cardiovascular disease and other pre-existing comorbidities with COVID-19 mortality: A systematic review and meta-analysis
Authors: Ssentongo Paddy , Ssentongo Anna E. , Heilbrunn Emily S. , Ba Djibril M. , Chinchilli Vernon M.
Published: May 2020

Background

Exploring the association of coronavirus-2019 disease (COVID-19) mortality with chronic pre-existing conditions may promote the importance of targeting these populations during this pandemic to optimize survival. The objective of this systematic review and meta-analysis is to explore the association of pre-existing conditions with COVID-19 mortality.

Methods

We searched MEDLINE, OVID databases, SCOPUS, and medrxiv.org for the period December 1, 2019, to May 1, 2020. The outcome of interest was the risk of COVID-19 mortality in patients with and without pre-existing conditions. Comorbidities explored were cardiovascular diseases (coronary artery disease, hypertension, cardiac arrhythmias, and congestive heart failure), chronic obstructive pulmonary disease, type 2 diabetes, cancer, chronic kidney disease, chronic liver disease, and stroke. Two independent reviewers extracted data and assessed the risk of bias. All analyses were performed using random-effects models and heterogeneity was quantified.

Results

Ten chronic conditions from 19 studies were included in the meta-analysis (n = 61,455 patients with COVID-19; mean age, 61 years; 57% male). Overall the between-study study heterogeneity was medium and studies had low publication bias and high quality. Coronary heart disease, hypertension, congestive heart failure, and cancer significantly increased the risk of mortality from COVID-19. The risk of mortality from COVID-19 in patients with coronary heart disease was 2.4 times as high as those without coronary heart disease (RR= 2.40, 95%CI=1.71-3.37, n=5) and twice as high in patients with hypertension as high as that compared to those without hypertension (RR=1.89, 95%CI= 1.58-2.27, n=9). Patients with cancer also were at twice the risk of mortality from COVID-19 compared to those without cancer (RR=1.93 95%CI 1.15-3.24, n=4), and those with congestive heart failure were at 2.5 times the risk of mortality compared to those without congestive heart failure (RR=2.66, 95%CI 1.58-4.48, n=3).

Conclusions

COVID-19 patients with all any cardiovascular disease, coronary heart disease, hypertension, congestive heart failure, and cancer have an increased risk of mortality. Tailored infection prevention and treatment strategies targeting this high-risk population are warranted to optimize survival.
Lessons from a rapid systematic review of early SARS-CoV-2 serosurveys
Authors: Bobrovitz Niklas , Arora Rahul Krishan , Yan Tingting , Rahim Hannah , Duarte Nathan , Boucher Emily , Van Wyk Jordan , Evans Timothy Grant
Published: May 2020

Background. As the world grapples with the COVID-19 pandemic, there is increasing global interest in the role of serological testing for population monitoring and to inform public policy. However, limitations in serological study designs and test standards raise concerns about the validity of seroprevalence estimates and their utility in decision-making. There is now a critical window of opportunity to learn from early SARS-CoV-2 serology studies. We aimed to synthesize the results of SARS-CoV-2 serosurveillance projects from around the world and provide recommendations to improve the coordination, strategy, and methodology of future serosurveillance efforts.

Methods. This was a rapid systematic review of cross-sectional and cohort studies reporting seroprevalence outcomes for SARS-CoV 2. We included completed, ongoing, and proposed serosurveys. The search included electronic databases (PubMed, MedRXIV, BioRXIV, and WHO ICTPR); five medical journals (NEJM, BMJ, JAMA, The Lancet, Annals of Internal Medicine); reports by governments, NGOs, and health systems; and media reports (Google News) from December 1, 2019 to May 1, 2020. We extracted data on study characteristics and critically appraised prevalence estimates using Joanna Briggs Institute criteria.

Results. Seventy records met inclusion criteria, describing 73 studies. Of these, 23 reported prevalence estimates: eight preprints, 14 news articles, and one government report. These studies had a total sample size of 35,784 and reported 42 prevalence estimates. Seroprevalence estimates ranged from 0.4% to 59.3%. No estimates were found to have a low risk of bias (43% high risk, 21% moderate risk, 36% unclear). Fifty records reported characteristics of ongoing or proposed serosurveys. Overall, twenty countries have completed, ongoing, or proposed serosurveys.

Discussion. Study design, quality, and prevalence estimates of early SARS-CoV2 serosurveys are heterogeneous, suggesting that the urgency to examine seroprevalence may have compromised methodological rigour. Based on the limitations of included studies, future serosurvey investigators and stakeholders should ensure that: i) serological tests used undergo high-quality independent evaluations that include cross-reactivity; ii) all reports of serosurvey results, including media, describe the test used, sample size, and sampling method; and iii) initiatives are coordinated to prevent test fatigue, minimize redundant efforts, and encourage better study methodology.

Other. PROSPERO: CRD42020183634. No third-party funding.
Machine learning model estimating number of COVID-19 infection cases over coming 24 days in every province of South Korea (XGBoost and MultiOutputRegressor)
Authors: Suzuki Yoshiro , Suzuki Ayaka , Nakamura Shun , Ishikawa Toshiko , Kinoshita Akira
Published: May 2020

We built a machine learning model (ML model) which input the number of daily infection cases and the other information related to COVID-19 over the past 24 days in each of 17 provinces in South Korea, and output the total increase in the number of infection cases in each of 17 provinces over the coming 24 days. We employ a combination of XGBoost and MultiOutputRegressor as machine learning model (ML model). For each province, we conduct a binary classification whether our ML model can classify provinces where total infection cases over the coming 24 days is more than 100. The result is Sensitivity = 3/3 = 100%, Specificity = 11/14 = 78.6%, False Positive Rate = 3/11 = 21.4%, Accuracy = 14/17 = 82.4%. Sensitivity = 100% means that we did not overlook the three provinces where the number of COVID-19 infection cases increased by more than100. In addition, as for the provinces where the actual number of new COVID-19 infection cases is less than 100, the ratio (Specificity) that our ML model can correctly estimate was 78.6%, which is relatively high. From the above all, it is demonstrated that there is a sufficient possibility that our ML model can support the following four points. (1) Promotion of behavior modification of residents in dangerous areas, (2) Assistance for decision to resume economic activities in each province, (3) Assistance in determining infectious disease control measures in each province, (4) Search for factors that are highly correlated with the future increase in the number of COVID-19 infection cases.
Evaluation of the Point of Care Molecular Diagnostic Genedrive HCV ID Kit for the detection of HCV RNA in clinical samples.
Authors: Padhi Abhishek , Gupta Ekta , Singh Gaurav , Agarwal Reshu , Sharma Manoj Kumar , Sarin Shiv Kumar
Published: May 2020

BACKGROUND
Despite the availability of an effective treatment for HCV infection, major bottle neck in the HCV care cascade is difficulty in getting the HCV RNA done on serologically positive (antibody to HCV) patients. This is due to the limited availability of HCV RNA test in the periphery. Nucleic acid amplification testing at point of care might revolutionise the HCV care continuum through its increased sensitivity, decreased turn around time and ease of performance in the field. Genedrive is one such assay which has recently got a CE- IVD certification.

OBJECTIVES
The diagnostic accuracy of Genedrive HCV ID kit for the qualitative detection of HCV RNA was evaluated by comparing with Abbott HCV RNA in an Indian demographic setting and across a range of different genotypes commonly found in India.

STUDY DESIGN
For the assay evaluation 150 HCV RNA positive and 170 HCV RNA negative samples as tested by Abbott HCV RNA assay (Abbott, Wiesbaden, Germany) on Automated m2000sp/m2000rt platform, as per the manufacturer instructions, that were retrieved from -80degree Celsius in the Virology repository were included in the study. All the samples were retrieved and re tested for HCV RNA on Genedrive HCV ID kit and compared with Abbott HCV RNA results.

RESULTS
Comparison of the Genedrive HCV ID kit with the Abbott Real Time HCV assay revealed a sensitivity of 100 % (95% CI 97.9 to 100) and a specificity of 100 % (95% CI 97.9 to 100) with a positive predictive value and negative predictive value of 100%. Overall diagnostic accuracy of Genedrive was found to be 100% (95% CI 98.9 to 100).

CONCLUSION
This study demonstrates that Genedrive HCV ID kit can be used for decentralised testing of HCV and ultimately finding the missing million.
REV-ERBα mediates complement expression and circadian regulation of microglial synaptic phagocytosis
Authors: Griffin Percy , Sheehan Patrick W. , Dimitry Julie M. , Guo Chun , Kanan Michael F. , Lee Jiyeon , Zhang Jinsong , Musiek Erik S.
Published: May 2020

The circadian clock has been shown to regulate various aspects of brain health including microglial and astrocyte activation. Here we report that deletion of the master clock protein BMAL1 induces robust increases in the expression of complement genes such asC3, C4bandC1qin the hippocampus. Loss of downstream REV-ERBα-mediated transcriptional repression led to increases inC4bin neurons and astrocytes as well as C3 protein in microglia and astrocytes. REV-ERBα deletion induced complementC3/C4bgene expression and increased microglial phagocytosis of synapses in the CA3 region of the hippocampus. Finally, we observed diurnal variation in the degree of microglial synaptic phagocytosis in wild type mice which was abrogated by REV-ERBα deletion. This work uncovers the BMAL1-REV-ERBα axis as a regulator of complement expression and synaptic phagocytosis in the brain, thereby illuminating a novel mechanism of synaptic regulation by the circadian clock.
Immune landscape of a genetically-engineered murine model of glioma relative to human glioma by single-cell sequencing
Authors: Zamler Daniel B. , Shingu Takashi , Kahn Laura M. , Kassab Cynthia , Ott Martina , Tomczak Katarzyna , Liu Jintan , Li Yating , Lai Ivy , Yee Cassian , Rai Kunal , Watowich Stephanie S. , Heimberger Amy B. , Draetta Giulio F. , Hu Jian
Published: May 2020

Background

This study focuses on the evaluation of intratumoral immune infiltrates of theQk/trp53/Pten(QPP) triple-knockout mouse model of glioblastoma with the purpose of establishing its relevance compared to the human disease. This included an analysis at the single cell level, of immune cells composition in both spontaneous and implanted mouse tumors and of samples obtained from human tumor resections.

Methods

We analyzed a cohort of fifteen spontaneous QPP mice, nine implanted QPP mice and 10 glioma patients by standard immune profiling methods such as IHC. Of those, we analyzed three spontaneous QPP mice, three implanted QPP mice, and 10 glioma patients by single cell RNA sequencing.

Results

In the QPP samples we identified a predominantly myeloid cell population of monocytes, macrophages, and microglia, with minor populations of T, B, and NK cells. When comparing spontaneous and implanted mouse samples, we found that there were more neutrophil, T and NKT cells in the implanted model. In human samples, most of the lymphoid and myeloid compartments were immunosuppressive. While the complexity of the myeloid cell populations is preserved between the QPP model and the human disease, we observed significantly more immune-stimulatory populations in the implanted mouse model.

Conclusions

We found that, despite differences at the subpopulation level, the immunosuppressive nature of the immune system in glioma, is recapitulated in our mouse model. Although we observed differences in the proportions of immune infiltrates derived from the spontaneous and implanted mouse models and in LGG compared to GBM, the major constituents are present in all cases and these differences may be caused by various etiological or pathogenic influences on tumor-immune interactions.

Key Points

New GBM mouse model for immunotherapy

Single cell profiling of the immune systems in human and mouse GBM
Gfral-expressing Neurons Suppress Food Intake via Aversive Pathways
Authors: Sabatini Paul V. , Frikke-Schmidt Henriette , Arthurs Joe , Gordian Desiree , Patel Anita , Adams Jessica M. , Wang Jine , Jørgensen Sebastien Beck , Olson David P. , Palmiter Richard D. , Myers Martin G , Seeley Randy J.
Published: May 2020

To determine the function and mechanisms of action for hindbrain neurons that express GFRAL, the receptor for the anorexigenic peptide, GDF-15, we generatedGfralcreand conditionalGfralCreERTmice. While signals of infection or pathophysiologic states (rather than meal ingestion) stimulate GFRAL neurons, the artificial activation ofGfralCre- expressing neurons inhibited feeding, decreased gastric emptying, and promoted a conditioned taste aversion (CTA). Additionally, activation of the smaller population of GFRAL neurons captured by theGfralCreERTallele decreased gastric emptying and produced a CTA without suppressing food intake, suggesting that GFRAL neurons primarily modulate gastric physiology and stimulate aversive responses. GFRAL neurons most strongly innervated the parabrachial nucleus (PBN), where they targeted CGRP-expressing (CGRPPBN) neurons. Silencing CGRPPBNneurons abrogated the aversive and anorexic effects of GDF-15. These findings suggest that GFRAL neurons link non-meal-associated, pathophysiologic signals to the aversive suppression of nutrient uptake and absorption.
A solvation induced ring puckering effect in fluorinated prolines and its inclusion in classical force-fields
Authors: Muralidharan Ajay , Schmidt J.R. , Yethiraj Arun
Published: May 2020

Strategic incorporation of fluorinated prolines can accelerate folding and increase thermal stability of proteins. It has been suggested that this behavior emerges from puckering effects induced by fluorination of the proline ring. We use electronic structure calculations to characterize the potential energy surface (PES) along puckering coordinates for a simple dipeptide model of proline and its fluorinated derivatives. Comparison of gas phase and implicit solvent calculations shed light on the effect of solvation on electronic structure and conformational preferences of the ring. This effect is unknown in the context of prolines, however, recently reported for furanoses in carbohydrates. The PES based on implicit solvent is then utilized to construct a correction for a classical force-field. The corrected force-field accurately captures the experimental conformational equilibrium including the coupling between ring puckering and cis-trans isomerism in fluorinated prolines. This method can be extended to other rings and substituents besides fluorine.
The scaffold protein IQGAP1 links heat-induced stress signals to alternative splicing regulation in gastric cancer cells
Authors: Birladeanu Andrada , Rogalska Malgorzata , Potiri Myrto , Papadaki Vasiliki , Andreadou Margarita , Kontoyiannis Dimitris , Lewis Joe D. , Erpapazoglou Zoi , Kafasla Panagiota
Published: May 2020

In response to oncogenic signals, Alternative Splicing (AS) regulators such as SR and hnRNP proteins show altered expression levels, subnuclear distribution and/or post-translational modification status, but the link between signals and these changes remains unknown. Here, we report that a cytosolic scaffold protein, IQGAP1, performs this task in response to heat-induced signals. We show that in gastric cancer cells, a nuclear pool of IQGAP1 acts as a tethering module for a group of spliceosome components, including hnRNPM, a splicing factor critical for the response of the spliceosome to heat-shock. IQGAP1 controls hnRNPM’s sumoylation, subnuclear localization and the relevant response of the AS machinery to heat-induced stress. Genome-wide analyses reveal that IQGAP1 and hnRNPM co-regulate the AS of a cell cycle-related RNA regulon in gastric cancer cells, thus favouring the accelerated proliferation phenotype of gastric cancer cells. Overall, we reveal a missing link between stress signals and AS regulation.
Attention Towards Emotions is Modulated by Familiarity with the Expressor. A Comparison Between Bonobos and Humans
Authors: van Berlo Evy , Bionda Thomas , Kret Mariska E.
Published: May 2020

Why can humans be intolerant of, yet also be empathetic towards strangers? This cardinal question has rarely been studied in our closest living relatives, bonobos. Yet, their striking xenophilic tendencies make them an interesting model for reconstructing the socio-emotional capacities of the last common ancestor of hominids. Within a series of dot-probe experiments, we compared bonobos’ and humans’ attention towards scenes depicting familiar (kith and kin) or unfamiliar individuals with emotional or neutral expressions. Results show that attention of bonobos is immediately captured by emotional scenes depicting unfamiliar bonobos, but not by emotional groupmates (Experiment 1) or expressions of humans, irrespective of familiarity (Experiment 2). Using a large community sample, Experiment 3 shows that human attention is mostly captured by emotional rather than neutral expressions of family and friends. On the one hand, our results show that an attentional bias towards emotions is a shared phenomenon between humans and bonobos, but on the other, that both species have their own unique evolutionarily informed bias. These findings support previously proposed adaptive explanations for xenophilia in bonobos which potentially biases them towards emotional expressions of unfamiliar conspecifics, and parochialism in humans, which makes them sensitive to the emotional expressions of close others.
Evaluation of a Loop-Mediated Isothermal Amplification assay to detect carbapenemases fromAcinetobacterspp. directly from bronchoalveolar lavage fluid
Authors: Moreno-Morales J. , Vergara A. , Kostyanev T. , Rodriguez-Baño J. , Goossens H. , Vila J.
Published: May 2020

Carbapenem-resistantAcinetobacterspp. mainlyAcinetobacter baumanniiare frequently causing nosocomial infections with high mortality. In this study, the efficacy of the Eazyplex®SuperBug Complete A system (Amplex Diagnostics GmbH, Gars-Bahnhof, Germany), based on loop-mediated isothermal amplification (LAMP), to detect the presence of carbapenemases inAcinetobacterspp. directly from bronchoalveolar lavage samples was assessed, detecting all tested carbapenemases in less than 30 minutes with a sensitivity of 103CFU/ml.