bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a digital pill and respondent behavioral intervention (PrEPSteps) for HIV pre-exposure prophylaxis adherence among stimulant using men who have sex with men
Authors: Chai Peter R , Mohamed Yassir , Goodman Georgia , Bustamante Maria J , Sullivan Matthew C , Najarro Jesse , Mendez Lizette , Mayer Kenneth H , Boyer Edward W , O’Cleirigh Conall , Rosen Rochelle K
Published: August 2021

The efficacy of pre-exposure prophylaxis (PrEP) for HIV prevention in men who have sex with men (MSM) is contingent upon consistent adherence. Digital pill systems (DPS) provide real-time, objective measurement of ingestions and can inform behavioral adherence interventions. Qualitative feedback was solicited from MSM who use stimulants to optimize a cognitive behavioral therapy (CBT)-based intervention (LifeSteps), used in conjunction with a DPS, to promote PrEP adherence (PrEPSteps). Seven focus groups and one individual qualitative interview were conducted in Boston, MA with cisgender, HIV-negative MSM who reported stimulant use and current PrEP use or interest. Focus groups and interviews explored reactions to the DPS and PrEPSteps messaging components: contingent reinforcement (CR), corrective feedback (CF), LifeSteps, and substance use Screening, Brief Intervention, and Referral to Treatment (SBIRT). Quantitative assessments were administered. Qualitative data were analyzed using applied thematic analysis. Twenty MSM participated. Most were White (N = 12), identified as homosexual or gay (N = 15), and college-educated (N = 15). Ages ranged from 24 to 68 years (median 35.5). Participants were willing to engage with the DPS and viewed it as beneficial for promoting adherence. Confirmatory CR messages were deemed acceptable, and a neutral tone was preferred. CF messages were viewed as most helpful and as promoting individual responsibility. LifeSteps was perceived as useful for contextualizing nonadherence. However, SBIRT was a barrier to DPS use; concerns around potential substance use stigma were reported. MSM who use stimulants were accepting of the DPS and PrEPSteps intervention. CR, CF, and LifeSteps messages were viewed as helpful, with modifications pertaining to tone and content; SBIRT messages were not preferred.
Iodoacetic Acid, a Water Disinfection Byproduct, Disrupts Hypothalamic, and Pituitary Reproductive Regulatory Factors and Induces Toxicity in the Female Pituitary
Authors: Gonzalez Rachel V L , Weis Karen E , Gonsioroski Andressa V , Flaws Jodi A , Raetzman Lori T
Published: August 2021

Iodoacetic acid (IAA) is a water disinfection byproduct (DBP) formed by reactions between oxidizing disinfectants and iodide. In vitro studies have indicated that IAA is one of the most cyto- and genotoxic DBPs. In humans, DBPs have been epidemiologically associated with reproductive dysfunction. In mouse ovarian culture, IAA exposure significantly inhibits antral follicle growth and reduces estradiol production. Despite this evidence, little is known about the effects of IAA on the other components of the reproductive axis: the hypothalamus and pituitary. We tested the hypothesis that IAA disrupts expression of key neuroendocrine factors and directly induces cell damage in the mouse pituitary. We exposed adult female mice to IAA in drinking water in vivo and found 0.5 and 10 mg/l IAA concentrations lead to significantly increased mRNA levels of kisspeptin (Kiss1) in the arcuate nucleus although not affecting Kiss1 in the anteroventral periventricular nucleus. Both 10 mg/l IAA exposure in vivo and 20 μM IAA in vitro reduced follicle stimulating hormone (FSHβ)-positive cell number and Fshb mRNA expression. IAA did not alter luteinizing hormone (LHβ) expression in vivo although exposure to 20 μM IAA decreased expression of Lhb and glycoprotein hormones, alpha subunit (Cga) mRNA in vitro. IAA also had toxic effects in the pituitary, inducing DNA damage and P21/Cdkn1a expression in vitro (20 μM IAA) and DNA damage and Cdkn1a expression in vivo (500 mg/l). These data implicate IAA as a hypothalamic-pituitary-gonadal axis toxicant and suggest the pituitary is directly affected by IAA exposure.
Mast Cells Promote Nitrogen Mustard-Mediated Toxicity in the Lung Associated With Proinflammatory Cytokine and Bioactive Lipid Mediator Production
Authors: Cruz-Hernandez Angela , Mendoza Ryan P , Nguyen Kathleen , Harder Anna , Evans Christopher M , Bauer Alison K , Tewari-Singh Neera , Brown Jared M
Published: August 2021

Sulfur mustard (SM) has been widely used as a chemical warfare agent including most recently in Syria. Mice exposed to SM exhibit an increase in pro-inflammatory cytokines followed by immune cell infiltration in the lung, however, the mechanisms leading to these inflammatory responses has not been completely elucidated. Mast cells are one of the first responding innate immune cells found at the mucosal surfaces of the lung and have been reported to be activated by SM in the skin. Therefore, we hypothesized that nitrogen mustard (NM: a surrogate for SM) exposure promotes activation of mast cells causing chronic respiratory inflammation. To assess the role of mast cells in NM-mediated pulmonary toxicity, we compared the effects of NM exposure between C57BL/6 and B6.Cg-KitW-sh/HNihrJaeBsmJ (KitW-sh; mast cell deficient) mice. Lung injury was observed in C57BL/6J mice following NM exposure (0.125 mg/kg) at 72 h, which was significantly abrogated in KitW-sh mice. Although both strains exhibited damage from NM, C57BL/6J mice had higher inflammatory cell infiltration and more elevated prostaglandin D2 (PGD2) present in bronchoalveolar lavage fluid compared with KitW-sh mice. Additionally, we utilized murine bone marrow-derived mast cells to assess NM-induced early and late activation. Although NM exposure did not result in mast cell degranulation, we observed an upregulation in PGD2 and IL-6 levels following exposure to NM. Results suggest that mast cells play a prominent role in lung injury induced by NM and may contribute to the acute and potentially long-term lung injury observed caused by SM.
Exploring traffic safety climate with driving condition and driving behaviour: a random parameter structural equation model approach
Authors: Xiao Daiquan , Jin Xiaofei , Xu Xuecai , Ma Changxi , Yuan Quan
Published: August 2021

This study aimed to explore traffic safety climate by quantifying driving conditions and driving behaviour. To achieve the objective, the random parameter structural equation model was proposed so that driver action and driving condition can address the safety climate by integrating crash features, vehicle profiles, roadway conditions and environment conditions. The geo-localized crash open data of Las Vegas metropolitan area were collected from 2014 to 2016, including 27 arterials with 16 827 injury samples. By quantifying the driving conditions and driving actions, the random parameter structural equation model was built up with measurement variables and latent variables. Results revealed that the random parameter structural equation model can address traffic safety climate quantitatively, while driving conditions and driving actions were quantified and reflected by vehicles, road environment and crash features correspondingly. The findings provide potential insights for practitioners and policy makers to improve the driving environment and traffic safety culture.
Direct Comparison of Antibody Responses to Four SARS-CoV-2 Vaccines in Mongolia
Authors: Dashdorj Naranjargal J. , Wirz Oliver F. , Röltgen Katharina , Haraguchi Emily , Buzzanco Anthony S. , Sibai Mamdouh , Wang Hannah , Miller Jacob A. , Solis Daniel , Sahoo Malaya K. , Byambabaatar Sumiya , Bat-Ulzii Purevjargal , Enkhbat Anir , Batbold Enkhtuul , Zulkhuu Delgersaikhan , Ochirsum Byambasuren , Khurelsukh Tungalag , Dalantai Ganbold , Burged Natsagdorj , Baatarsuren Uurtsaikh , Ariungerel Nomin , Oidovsambuu Odgerel , Bungert Andreas S. , Genden Zulkhuu , Yagaanbuyant Dahgwahdorj , Mordorj Altankhuu , Jardetzky Theodore , Wilbur James L. , Wohlstadter Jacob N. , Sigal George B. , Pinsky Benjamin A. , Boyd Scott D. , Dashdorj Naranbaatar D.
Published: August 2021

Different vaccines for SARS-CoV-2 are approved in various countries, but few direct comparisons of the antibody responses they stimulate have been reported. We collected plasma specimens in July 2021 from 196 Mongolian participants fully vaccinated with one of four Covid vaccines: Pfizer/BioNTech, AstraZeneca, Sputnik V and Sinopharm. Functional antibody testing with a panel of nine SARS-CoV-2 viral variant RBD proteins reveal marked differences in the vaccine responses, with low antibody levels and RBD-ACE2 blocking activity stimulated by the Sinopharm and Sputnik V vaccines in comparison to the AstraZeneca or Pfizer/BioNTech vaccines. The Alpha variant caused 97% of infections in Mongolia in June and early July 2021. Individuals who recover from SARS-CoV-2 infection after vaccination achieve high antibody titers in most cases. These data suggest that public health interventions such as vaccine boosting, potentially with more potent vaccine types, may be needed to control the COVID-19 pandemic in Mongolia and worldwide.
Cue-Induced Craving and Negative Emotion Disrupt Response Inhibition in Methamphetamine Use Disorder: Behavioral and fMRI Results from a Mixed Go/No-Go Task
Authors: Dakhili Amirhossein , Sangchooli Arshiya , Jafakesh Sara , Bidoki Mehran Zare , Soleimani Ghazaleh , Hossein Batouli Seyed Amir , Kazemi Kamran , Faghiri Ashkan , Oghabian Mohammad Ali , Ekhtiari Hamed
Published: August 2021

Background

Drug-related cue-reactivity, dysfunctional negative emotion processing, and response-disinhibition constitute three core aspects of methamphetamine use disorder (MUD). These phenomena have been studied independently, but the neuroscientific literature on their interaction in addictive disorders remains scant.

Methods

fMRI data were collected from 62 individuals with MUD when responding to the geometric Go or No-Go cues superimposed over blank, neutral, negative-emotional and drug-related background images. Neural correlates of drug and negative-emotional cue-reactivity, response-inhibition, and response-inhibition during drug and negative-emotional blocks were estimated, and methamphetamine cue-reactivity was compared between MUDs and 23 healthy controls (HCs). Relationships between clinical and behavioral characteristics and observed activations were subsequently investigated.

Results

MUDs had longer reaction times and more errors in drug and negative-emotional blocks compared to neutral and blank ones. MUDs showed higher drug cue-reactivity than HCs across prefrontal regions, fusiform gyrus, and visual cortices (Z>3.1, p-corrected<0.05). Response-inhibition was associated with activations in the precuneus, inferior parietal lobule, and anterior cingulate, temporal and inferior frontal gyri (Z>3.1, p-corrected<0.05). Response-inhibition in drug cue blocks coincided with higher activations in the visual cortex and lower activations in the paracentral lobule and superior and inferior frontal gyri, while inhibition during negative-emotional blocks led to higher superior parietal, fusiform, and lateral occipital activations (Z>3.1, p-corrected<0.05).

Conclusion

Higher visual cortical activations and lower parietal and prefrontal activations during drug-related response-inhibition suggest the down-regulation of inhibitory regions and up-regulation of bottom-up drug cue-reactivity. Our results suggest that drug and negative-emotional cue-reactivity influence response-inhibition, and the study of these interactions may aid mechanistic understandings of addiction and biomarker discovery.
Mitochondrial dysfunction compromises ciliary homeostasis in astrocytes
Authors: Ignatenko Olesia , Malinen Satu , Vihinen Helena , Nikkanen Joni , Kononov Aleksandr , Jokitalo Eija , Ince-Dunn Gulayse , Suomalainen Anu
Published: August 2021

Astrocytes, often considered as secondary responders to neurodegenerative processes, are emerging as primary drivers of brain disease. The underlying pathogenic mechanisms are, however, insufficiently understood. Here we show that pathogenesis of mitochondrial spongiotic encephalopathy, a severe manifestation of mitochondrial brain diseases, involves abnormal maintenance of the astrocytic primary cilium, a major signaling organelle of a cell. We show that progressive respiratory chain deficiency in astrocytes activates FOXJ1 and RFX transcription factors and master regulators of motile ciliogenesis. Consequently, a wide aberrant nuclear expression program with FOXJ1 and RFX target genes, encoding motile cilia components, is induced in astrocytes. While the affected astrocytes still retain a single cilium, these organelles elongate and become remarkably distorted. Multiciliated ventricle-lining ependymal cells show no overt cilia morphology defects despite similar mitochondrial dysfunction. We propose that the chronic activation of the integrated mitochondrial stress response (ISRmt), specifically induced in astrocytes, drives anabolic metabolism and promotes ciliary growth. Collectively, our evidence indicate that 1) an active signaling axis exists between astrocyte mitochondria and primary cilia; 2) ciliary signaling is part of ISRmtin astrocytes; 3) metabolic ciliopathy is a novel pathomechanism for mitochondria-related neurodegenerative diseases.
Assessing the impacts of climate change on reproductive phenology in tropical rainforests of Southeast Asia
Authors: Numata Shinya , Yamaguchi Koharu , Shimizu Masaaki , Sakurai Gen , Morimoto Ayaka , Alias Noraliza , Noor Azman Nashatul Zaimah , Hosaka Tetsuro , Satake Akiko
Published: August 2021

In humid forests in Southeast Asia, many species from dozens of plant families flower gregariously and fruit synchronously at irregular multi-year intervals1–4. Little is known about how climate change will impact these community-wide mass reproductive events. Here, we perform a comprehensive analysis of reproductive phenology and its environmental drivers based on a monthly reproductive phenology record from 210 species in 41 families in peninsular Malaysia. We find that the proportion of flowering and fruiting species decreased from 1976 to 2010. Using a phenology model with inputs obtained from general circulation models, we show that low-temperature flowering cues became less available during the monitoring period and will further decrease in the future, leading to decreased flowering opportunities in 57% of species in the Dipterocarpaceae family. Our results highlight the vulnerability of and variability in phenological responses across species in tropical ecosystems that differ from temperate and boreal biomes.
Microbial dark carbon fixation fueled by nitrate enrichment
Authors: Vineis Joseph H. , Bulseco Ashley N. , Bowen Jennifer L.
Published: August 2021

Anthropogenic nitrate amendment to coastal marine sediments can increase rates of heterotrophic mineralization and autotrophic dark carbon fixation (DCF). DCF may be favored in sediments where organic matter is biologically unavailable, leading to a microbial community supported by chemoautotrophy. Niche partitioning among DCF communities and adaptations for nitrate metabolism in coastal marine sediments remain poorly characterized, especially within salt marshes. We used genome-resolved metagenomics, phylogenetics, and comparative genomics to characterize the potential niche space, phylogenetic relationships, and adaptations important to microbial communities within nitrate enriched sediment. We found that nitrate enrichment of sediment from discrete depths between 0-25 cm supported both heterotrophs and chemoautotrophs that use sulfur oxidizing denitrification to drive the Calvin-Benson-Bassham (CBB) or reductive TCA (rTCA) DCF pathways. Phylogenetic reconstruction indicated that the nitrate enriched community represented a small fraction of the phylogenetic diversity contained in coastal marine environmental genomes, while pangenomics revealed close evolutionary and functional relationships with DCF microbes in other oligotrophic environments. These results indicate that DCF can support coastal marine microbial communities and should be carefully considered when estimating the impact of nitrate on carbon cycling in these critical habitats.

Importance

Salt marshes store carbon at one of the fastest rates of any blue carbon system and buffer coastal marine waters from eutrophication. Dark carbon fixation (DCF) conducted by microbes within the sediment can influence the carbon storage capacity, but little is known about the ecology or genomic potential of these organisms. Our study identifies a potential niche space for several functionally distinct groups of chemoautotrophs which primarily use sulfur oxidizing denitrification to fuel DCF under high nitrate concentrations. These findings fill an important gap in our understanding of microbial contributions to carbon storage within salt marsh sediments and how this critical blue carbon system responds to anthropogenic nitrate enrichment.
Effectiveness of vaccination against symptomatic and asymptomatic SARS-CoV-2 infection: a systematic review and meta-analysis
Authors: Meggiolaro A. , Sane Schepisi M. , Nikolaidis G. , Mipatrini D. , Siddu A. , Rezza G.
Published: August 2021

OBJECTIVE

To assess the effectiveness of SARS-CoV-2 vaccines in terms of prevention of disease and transmission. The evaluation was narrowed to two mRNA vaccines and two modified adenovirus vectored vaccines.

METHODS

A frequentist random effects meta-analysis was carried out after data extraction. Risk of bias of the included studies was assessed using New-Castle-Ottawa Scale. The overall risk of SARS-CoV-2 infection confirmed by real time Polymerase Chain Reaction (PCR) was estimated in partially and fully vaccinated individuals. The effect size was expressed as Relative Risk (RR) and RRR (RR reduction) of SARS-CoV-2 infection after vaccination. Potential sources of heterogeneity were investigated through between-study heterogeneity analysis and subgroup meta-analysis.

RESULTS

The systematic review identified 27 studies eligible for the quantitative synthesis. Partially vaccinated individuals presented a RRR=73% (95%CI=59%-83%) for any positive SARS-CoV-2 PCR (RR=0.27) and a RRR=79% (95%CI=30%-93%) for symptomatic SARS-CoV-2 PCR (RR=0.21). Fully vaccinated individuals showed a RRR=94% (95%CI=88%-98%) for any SARS-CoV-2 positive PCR (RR=0.06) compared to unvaccinated. According to the subgroup meta-analysis, full BNT162b2 vaccination protocol achieved a RRR=84%-94% against any SARS-CoV-2 positive PCR and a RRR=68%-84% against symptomatic positive PCR. The RR for any SARS-CoV-2 positive PCR remained higher within elderly groups aged ≥69 years (RR=0.12-0.15) compared to younger individuals (RR=0.05-0.12). The RR against B.1.351 infection approached 0.40 for any positive PCR and 0.36 for symptomatic SARS-COV-2 while the RR of any B.1.1.7 infection was 0.14.

CONCLUSION

The current licensed vaccines may be transmission blocking, especially after full vaccination protocol. Given the substantial heterogeneity, results should be interpreted with caution. Subgroups meta-analyses suggested that the risk of any SARS-CoV-2 infection may be higher for non-B.1.1.7 variants and individuals aged ≥69 years. Further data and longer follow-up are required to investigate additional sources of heterogeneity and the effectiveness of SARS-CoV-2 vaccination within population subgroups.

STRENGTHS

Real-world data suggest that the current licensed vaccines may be transmission blocking, in particular after full vaccination protocol.

The risk of any SARS-CoV-2 infection either symptomatic or asymptomatic, may be higher for non-B.1.1.7 variants and individuals aged ≥69 years.

LIMITATIONS

Given the substantial heterogeneity encountered in this meta-analysis, results should be interpreted with caution

Fur ther evidence on the impact of SARS-CoV-2 variants are vital in order to monitor mutations associated with vaccine escape
Effectiveness of a novel non-intrusive continuous-use air decontamination technology to reduce microbial contamination in clinical settings: A multi-centric study
Authors: Nagaraj Savitha , Chandrasingh Sindhulina , Jose Sanju , B Sofia , Sampath Sriram , Krishna Bhuvana , Menon Indira , Kundu Debosmita , Parekh Sandeepan , Madival Deepak , Nandi Vrinda , Ghatak Arindam
Published: August 2021

Background

Despite rigorous disinfection, fumigation and air treatment, infectious microbial load has been found to circulate and survive for significant durations in health care settings. This raises significant concerns for hospital acquired infections. We have developed a novel, hybrid, trap- and-kill airborne-microbicidal technology called “ZeBox” which is efficient in clearing 99.999% of airborne microbial load under controlled lab conditions. In this study we evaluate the clinical performance of the ZeBox in reducing airborne and surface microbial load in two independent hospital settings.

Methods

The studies were conducted in single bed and multi bed ICU of two hospitals. Airborne and surface microbial loads were collected at pre-determined sampling sites pre- and post-deployment of the ZeBox enabled device. The Normality of data distribution was determined using the Shapiro-Wilk test. Statistical significance was determined using Students’ T test and Mann-Whitney’s U test. Pathogenic and opportunistic organisms were characterized using 16S rDNA sequencing. Furthermore, the antibiotic sensitivity of the isolated organisms was tested against current treatments of choice across major antibiotic classes.

Results

Post-deployment, we found statistically significant reductions in both airborne and surface microbial load within the operating range of the ZeBox enabled technology. Across the both hospital ICUs, there was 90% reduction of airborne microbial load on average, and 75% reduction of surface microbial load on average, providing a low bioburden zone of roughly 10-15 feet diameter around the unit. These reduced microbial levels were maintained during the entire duration of device operation over several weeks. Many of the clinical isolates recovered from one of the hospitals were drug resistant, which highlighted the potential ability of ZeBox to eliminate drug-resistant microbes and thereby reduce the frequency of hospital acquired infections.

Conclusions

ZeBox enabled technology can significantly reduce a broad spectrum of microbial burden in air and on surfaces in clinical settings. It can thereby serve an unmet need in reducing the incidence of hospital acquired infections.
Effect of losartan on hospitalized patients with COVID-19-induced lung injury: A randomized clinical trial
Authors: Puskarich Michael A. , Ingraham Nicholas E. , Merck Lisa H , Driver Brian E , Wacker David A. , Black Lauren Page , Jones Alan E. , Fletcher Courtney V. , South Andrew M. , Nelson Andrew C. , Murray Thomas A , Tignanelli Christopher J. , Lewandowski Christopher , Farhat Joseph , Benoit Justin L. , Byrne Dana , Hall Alex , Reilkoff Ronald A. , Biros Michelle H. , Cherabuddi Kartik , Chipman Jeffrey G. , Schacker Timothy W. , Bold Tyler , Beckman Kenneth , Langlois Ryan , Aliota Matthew T. , Guirgis Faheem W. , Galbriath James , Beyer Margaret , Salmen Chas , Roberts Brian , Wright David , Voelker Helen T. , Koopmeiners Joseph S.
Published: August 2021

Background

SARS-CoV-2 viral entry may disrupt angiotensin II (Ang II) homeostasis in part via ACE2 downregulation, potentially contributing to COVID-19 induced lung injury. Preclinical models of viral pneumonias that utilize ACE2 demonstrate Ang II type 1 receptor (AT1R) blockade mitigates lung injury, though observational COVID-19 data addressing the effect of AT1R blockade remain mixed.

Methods

Multicenter, blinded, placebo-controlled randomized trial of losartan (50 mg PO twice daily for 10 days) versus placebo. Hospitalized patients with COVID-19 and a respiratory sequential organ failure assessment score of at least 1 and not already taking a renin-angiotensin-aldosterone system (RAAS) inhibitor were eligible. The primary outcome was the imputed partial pressure of oxygen to fraction of inspired oxygen (PaO2/FiO2) ratio at 7 days. Secondary outcomes included ordinal COVID-19 severity, oxygen, ventilator, and vasopressor-free days, and mortality. Losartan pharmacokinetics (PK) and RAAS components [Ang II, angiotensin-(1–7) (Ang-(1–7)), ACE, ACE2] were measured in a subgroup of participants.

Findings

From April 2020 - February 2021, 205 participants were randomized, 101 to losartan and 104 to placebo. Compared to placebo, losartan did not significantly affect PaO2/FiO2 ratio at 7 days [difference of -24.8 (95% -55.6 to 6.1; p=0.12)]. Losartan did not improve any secondary clinical outcome, but worsened vasopressor-free days. PK data were consistent with appropriate steady-state concentrations, but we observed no significant effect of losartan on RAAS components.

Interpretation

Initiation of orally administered losartan to hospitalized patients with COVID-19 and acute lung injury does not improve PaO2 / FiO2 ratio at 7 days. These data may have implications for ongoing clinical trials.

Trial Registration

Losartan for Patients With COVID-19 Requiring Hospitalization (NCT04312009), https://clinicaltrials.gov/ct2/show/NCT04312009
History of suicide attempts and COVID-19 infection in Veterans with schizophrenia or schizoaffective disorder: effect modification by age and obesity
Authors: Okusaga Olaoluwa O. , Kember Rachel L. , Peloso Gina M. , Peterson Roseann E. , Vujkovic Mariana , Mitchell Brian G. , Bernard Jared , Walder Annette , Bigdeli Tim B.
Published: August 2021

Importance

As patients with schizophrenia or schizoaffective disorder have a high risk of suicide, and a history of suicide attempt is a strong predictor of suicide, determining whether history of suicide attempt is associated with COVID-19 in patients with schizophrenia or schizoaffective disorder has implications for suicide prevention in this patient population.

Objective

To determine whether a history of suicide attempt is associated with COVID-19 in Veterans with schizophrenia or schizoaffective disorder.

Design

Cross-sectional analyses of nation-wide electronic health records (EHR).

Setting

United States Veterans Health Administration.

Participants

Veterans with a diagnosis of schizophrenia or schizoaffective disorder that received treatment at any United States Veterans Affairs Medical Center from January 1, 2020 to January 31, 2021.

Exposure

History of suicide attempt.

Main Outcome

Adjusted and unadjusted odds ratios (ORs) for COVID-19 positivity in suicide attempters relative to non-attempters. Adjusted analyses included age, sex, race, marital status, BMI, and a medical comorbidity score.

Results

A total of 101,032 Veterans [mean age 56.67 ± 13.13 years; males 91,715 (90.8%)] were included in the analyses. There were 2,703 (2.7%) suicide attempters and 719 (0.7%) patients were positive for COVID-19. There was effect modification by age and BMI in the association of history of suicide attempt with COVID-19 positivity such that the association was only significant in obese (BMI ≥ 30) patients and patients younger than 59 years respectively. In the entire sample, the unadjusted OR for COVID-19 positivity in attempters was 1.42 (95% CI 0.97 to 2.10) and the adjusted odds ratio was 1.90 (95% CI 1.28 to 2.80). In patients younger than 59 years, and in the obese patients respectively, history of suicide attempt was associated with COVID-positive status in unadjusted analyses [OR 3.53 (95% CI 2.10 to 5.94); OR 2.22 (95% CI 1.29 to 3.81)] and adjusted analyses [OR 3.42 (95% CI 2.02 to 5.79); OR 2.85 (95% CI 1.65 to 4.94)].

Conclusions and Relevance

Young or obese suicide attempters with a diagnosis of schizophrenia or schizoaffective disorders have higher rates of COVID-19 diagnosis; due to possible long-term neuropsychiatric sequelae of infection with SARS-CoV-2, such patients should be monitored closely.
The Unequal Burden of the Covid-19 Pandemic: Racial/Ethnic Disparities in US Cause-Specific Mortality
Authors: Luck Anneliese N. , Preston Samuel H. , Elo Irma T. , Stokes Andrew C.
Published: August 2021

Objectives

To quantify changes in all-cause and cause-specific mortality by race and ethnicity between 2019 and 2020.

Methods

Using 2019 and 2020 provisional death counts from the National Center for Health Statistics and population estimates from the US Census Bureau, we estimate age-standardized death rates by race/ethnicity and attribute changes in mortality to various causes of death. We also examine how patterns of change across racial/ethnic groups vary by age and sex.

Results

Covid-19 death rates in 2020 were highest in the Hispanic community whereas Black individuals had the largest increase in all-cause mortality between 2019 and 2020. Increases in mortality from heart disease, diabetes, and external causes of death accounted for the adverse trend in all-cause mortality within the Black population. Percentage increases in all-cause mortality were similar for men and women and for ages 25-64 and 65+ for Black and White populations, but increases were greatest for working-aged men among the Hispanic population.

Conclusions

Examining increases in non-Covid-19 causes of death is essential for fully capturing both the direct and indirect impact of the Covid-19 pandemic on racial/ethnic mortality disparities.
Dietary differences by job type and industry among workers in Japan during the COVID-19 pandemic: A cross-sectional study
Authors: Tanaka Rie , Sakuragi Toshihide , Tsuji Mayumi , Tateishi Seiichiro , Hino Ayako , Ogami Akira , Nagata Masako , Matsuda Shinya , Fujino Yoshihisa ,   for the CORoNaWork Project
Published: August 2021

Background

The COVID-19 pandemic requires people to change their lifestyles. This study aimed to examine the differences in dietary behaviors during the pandemic across job types and industries.

Methods

A cross-sectional study was conducted using data from the Novel-coronavirus and Work Project. Job type and industry were classified into 3 and 22 groups, respectively. Dietary behaviors were assessed using self-reported questionnaires regarding eating breakfast, frequency of meals, and eating fast foods. Changes in eating breakfast during the pandemic were also evaluated. Logistic regression analysis nested in the workplace prefecture was carried out and adjusted for gender, age, body mass index, presence of family members, educational background, and household income.

Results

Workers involved in jobs that require communicating with people were more likely to skip breakfast (OR 1.17, 95%CI 1.10-1.24) and had a lower frequency of meals (OR 1.25, 95%CI 1.17-1.34) than workers engaged in desk work. Manual workers were more likely to eat fast food or meals (OR 1.10, 95%CI 1.03-1.17) than workers engaged in desk work. Workers engaged in newspaper, magazine, television, radio, advertising, and other mass media industries were more likely to skip breakfast (OR 2.43, 95%CI 1.82-3.24) and have a lower frequency of meals (OR 3.90, 95%CI 2.87-5.28) than workers in public offices and organizations.

Conclusion

The tendencies of dietary behaviors across job types/industries during the pandemic were shown, partially consistent with a trend reported before the pandemic. Further studies should clarify the causes of differences in dietary behaviors among workers.
A Reinforcement Learning Framework for Pooled Oligonucleotide Design
Authors: David Benjamin M. , Wyllie Ryan M. , Harouaka Ramdane , Jensen Paul A.
Published: August 2021

The goal of oligonucleotide (oligo) design is to select oligos that optimize a set of design criteria. Oligo design problems are combinatorial in nature and require computationally intensive models to evaluate design criteria. Even relatively small problems can be intractable for brute-force approaches that test every possible combination of oligos, so heuristic approaches must be used to find near-optimal solutions. We present a general reinforcement learning framework, called OligoRL, to solve oligo design problems with complex constraints. OligoRL allows “black-box” design criteria and can be adapted to solve many oligo design problems. We highlight the flexibility of OligoRL by building tools to solve three distinct design problems: 1.) finding pools of random DNA barcodes that lack restriction enzyme recognition sequences (CutFreeRL); 2.) compressing large, non-degenerate oligo pools into smaller degenerate ones (OligoCompressor); and 3.) finding Not-So-Random hexamer primer pools that avoid rRNA and other unwanted transcripts during RNA-seq library preparation (NSR-RL). OligoRL demonstrates how reinforcement learning offers a general solution for complex oligo design problems. OligoRL and its associated software tools are available as a Julia package at http://jensenlab.net/tools.
Large scale function-based genome prospecting for industrial traits applied to 1,3-propanediol production
Authors: Koehorst Jasper J. , Strepis Nikolaos , de Graaf Sanne , Stams Alfons J. M. , Sousa Diana Z. , Schaap Peter J.
Published: August 2021

Due to the success of next-generation sequencing, there has been a vast build-up of microbial genomes in the public repositories. FAIR genome prospecting of this huge genomic potential for biotechnological benefiting, require new efficient and flexible methods. In this study, Semantic Web technologies are applied to develop a function-based genome mining approach that follows a knowledge and discovery in database (KDD) protocol. Focusing on the industrial important trait of 1,3-propanediol (1,3-PD) production 187 new candidate species were identified. Furthermore, the genetic architecture of the particular trait was resolved, and persistent domains identified.
The genome trilogy of Anopheles stephensi, an urban malaria vector, reveals structure of a locus associated with adaptation to environmental heterogeneity
Authors: Thakare Aditi , Ghosh Chaitali , Alalamath Tejashwini , Kumar Naveen , Narang Himani , Whadgar Saurabh , Paul Kiran , Shrotri Shweta , Kumar Sampath , Soumya M , Rao Raksha , Chakraborty Mahul , Choudhary Bibha , Ghosh Susanta K. , Subramani Suresh , Swain Sunita , Srinivasan Subhashini
Published: August 2021

Background

Anopheles stephensi is the most menacing malaria vector to watch for in newly urbanizing parts of the world. The fitness is reported to be a direct consequence of the vector adapting to laying eggs in over-head water tanks with street-side water puddles polluted by oil and sewage. Large frequent inversions of malaria vectors are implicated in adaptation.

Results

We report the assembly of a strain of An. stephensi of the type-form, collected from a construction site from Chennai (IndCh) in 2016. The genome completes the trilogy with respect to a 16 Mbp inversion (2Rb) in An. stephensi associated with adaptation to environmental heterogeneity. Comparative genome analysis revealed breakpoint structure and allowed extraction of 22,650 segregating SNPs for typing this inversion. Using whole genome sequencing of 82 individual mosquitoes, we conclude that one third of both wild and laboratory populations maintain heterozygous genotype of 2Rb. The large number of SNPs are tailored to assign inversion genotype directly from 1740 exonic SNPs 80% of which are expressed in various developmental stages.

Conclusions

The genome trilogy approach accelerates study of fine structure and typing of important inversions in malaria vectors putting the genome resources for the much understudied An. stephensi, on par with the extensively studied malaria vector, Anopheles gambiae. We argue that the IndCh genome is relevant for field translation work compared to those reported earlier by showing that individuals from diverse populations cluster with IndCh pointing to significant commerce between cities, perhaps, allowing for survival of the fittest strain.
CALANGO: a phylogeny-aware comparative genomics tool for discovering quantitative genotype-phenotype associations across species
Authors: Hongo Jorge Augusto , de Castro Giovanni Marques , Albuquerque Menezes Alison Pelri , Rios Picorelli Agnello César , da Silva Thieres Tayroni Martins , Imada Eddie Luidy , Marchionni Luigi , Del-Bem Luiz-Eduardo , Chaves Anderson Vieira , de Freitas Almeida Gabriel Magno , Campelo Felipe , Lobo Francisco Pereira
Published: August 2021

The increasing availability of genomic, annotation, evolutionary and phenotypic data for species contrasts with the lack of studies that adequately integrate these heterogeneous data sources to produce biologically meaningful knowledge. Here, we present CALANGO, a phylogeny-aware comparative genomics tool that uncovers functional molecular convergences and homologous regions associated with quantitative genotypes and phenotypes across species, enabling the fast discovery of novel statistically sound, biologically relevant phenotype-genotype associations. We demonstrate the usefulness of CALANGO in two case studies. The first one unveils potential causal links between prophage density and the pathogenicity phenotype in Escherichia coli, and confidently demonstrates how CALANGO supports the investigation of basic causal relationships by enabling a level of counterfactual investigation of observed associations in the data. As a second case study, we used our tool to search for homologous regions associated with a complex phenotypic trait in a major group of eukaryotes: the evolution of maximum height in angiosperms. We confidently identify a previously unknown association between maximum plant height and the expansion of the self-incompatibility system, a molecular mechanism that prevents inbreeding and increases genetic diversity. Taller species also have lower rates of molecular evolution due to their longer generation times, a critical concern for their long-term viability. The new mechanism we report could counterbalance this fact, and have far-reaching consequences for fields as diverse as conservation biology and agriculture. CALANGO is provided as a fully operational R package that can be freely installed from CRAN.
From Text-based Genome, Population Variations, and Transcriptome Datafiles to SQLite Database and Web Application: A Bioinformatical Study on Alfalfa
Authors: Qiao Shichen , Shen Chen
Published: August 2021

In this study, a web database application with the Flask framework was developed to implement three types of queries and visualize the results over a bioinformatical dataset from Alfalfa (Medicago sativa). A backend SQLite database was constructed from genome FASTA, population variations, transcriptome, and annotation files with extensions “.fasta”, “.gff”, “vcf”, “.annotate”, etc. Further, a supplementary command-line-based Java application was also developed for faster access to the database without direct SQL programming. Overall, Python, Java, and HTML were the main programming languages used in this application. Those scripts and the development procedures are valuable for bioinformaticians to build online databases from similar raw datasets of other species.
Glial Nrf2 signaling mediates the neuroprotection exerted by Gastrodia elata Blume in Lrrk2-G2019S Parkinson’s disease
Authors: Lin Yu-En , Lin Chin-Hsien , Ho En-Peng , Ke Yi-Ci , Petridi Stavroula , Elliott Christopher J. H. , Sheen Lee-Yan , Chien Cheng-Ting
Published: August 2021

The most frequent missense mutations in familial Parkinson’s disease (PD) occur in the highly conserved LRRK2/PARK8 gene with G2019S mutation. We previously established a fly model of PD carrying the LRRK2-G2019S mutation that exhibited the parkinsonism-like phenotypes. An herbal medicine—Gastrodia elata Blume (GE), has been reported to have neuroprotective effects in toxin- induced PD models. However, the underpinning molecular mechanisms of GE beneficiary to G2019S- induced PD remain unclear. Here, we show that these G2019S flies treated with water extracts of GE (WGE) and its bioactive compounds, gastrodin and 4-HBA, displayed locomotion improvement and dopaminergic neuron protection. WGE suppressed the accumulation and hyperactivation of G2019S proteins in dopaminergic neurons, and activated the antioxidation and detoxification factor Nrf2 mostly in the astrocyte-like and ensheathing glia. Glial activation of Nrf2 antagonizes G2019S-induced Mad/Smad signaling. Moreover, we treated LRRK2-G2019S transgenic mice with WGE and found the locomotion declines, the loss of dopaminergic neurons, and the number of hyperactive microglia were restored. WGE also suppressed the hyperactivation of G2019S proteins and regulated the Smad2/3 pathways in the mice brains. We conclude that WGE prevents locomotion defects and the neuronal loss induced by G2019S mutation via glial Nrf2/Mad signaling, unveiling a potential therapeutic avenue for PD.
Anterior thalamic nuclei neurons sustain memory
Authors: Barnett S. C. , Parr-Brownlie L.C. , Perry B. A. L. , Young C. K. , Wicky H. E. , Hughes S. M. , McNaughton N. , Dalrymple-Alford J. C.
Published: August 2021

A hippocampal-diencephalic-cortical network supports memory function. The anterior thalamic nuclei (ATN) form a key anatomical hub within this system. Consistent with this, injury to the mammillary body-ATN axis is associated with examples of clinical amnesia. However, there is only limited and indirect support that the output of ATN neurons actively enhances memory. Here, in rats, we first showed that mammillothalamic tract (MTT) lesions caused a persistent impairment in spatial working memory. MTT lesions also reduced rhythmic electrical activity across the memory system. Next, we introduced 8.5 Hz optogenetic theta-burst stimulation of the ATN glutamatergic neurons. The exogenously-triggered, regular pattern of stimulation produced an acute and substantial improvement of spatial working memory in rats with MTT lesions and enhanced rhythmic electrical activity. Neither behaviour nor rhythmic activity was affected by endogenous stimulation derived from the dorsal hippocampus. Analysis of immediate early gene activity, after the rats foraged for food in an open field, showed that exogenously-triggered ATN stimulation also increased Zif268 expression across memory-related structures. These findings provide clear evidence that increased ATN neuronal activity supports memory. They suggest that ATN-focused gene therapy may be feasible to counter clinical amnesia associated with dysfunction in the mammillary body-ATN axis.

Highlights

The mammillothalamic tract (MTT) supports neural activity in an extended memory system.

Optogenetic activation of neurons in the anterior thalamus acutely improves memory after MTT lesions.

Rescued memory associates with system-wide neuronal activation and enhanced EEG.

Anterior thalamus actively sustains memory and is a feasible therapeutic target.

Abstract Figure

Optostimulation of anterior thalamus restores memory function after MTT lesions

Created with BioRender.com
A local scale evaluation of spatial sampling bias in the Atlas of Australian Birds
Authors: Totterman Stephen L.
Published: August 2021

The reliability of ‘citizen science’ datasets where volunteers are free to choose sampling locations is not clear. This study examined local (‘patch’) scale spatial sampling patterns in the Atlas of Australian Birds and then compared reporting rates, i.e. the proportion of sampling units in which a given species was present, from a sample of atlas points with those from a regular sample. Three sites that have been were surveyed sequentially between January–May 2017: Killawarra Forest, Victoria, Coolah Tops National Park and Pilliga Nature Reserve, New South Wales. Spatial bias in atlas sampling patterns was evident as clusters at tourist areas and special habitat features and linear patterns along roads and creek lines. Atlas samples overestimated reporting rates for species with spatial distributions that were concordant with those sampling patterns and vice versa. At least two-fold differences in atlas/regular sample reporting rate ratios were detected for between 13–15% of non-rare species (with reporting rates ≥ 0.08). Concerns are raised that spatial sampling bias is common in the atlas and affects a variety of species, that popular sites may not be representative of habitat patches and that a large proportion of surveys are being filtered out in data analyses.
Identifying Gene-wise Differences in Latent Space Projections Across Cell Types and Species in Single Cell Data using scProject
Authors: Baraban Asher , Clark Brian S. , Slosberg Jared , Fertig Elana J. , Goff Loyal A. , Stein-O’Brien Genevieve
Published: August 2021

Latent space techniques have emerged as powerful tools to identify genes and gene sets responsible for cell-type and species-specific differences in single-cell data. Transfer learning methods can compare learned latent spaces across biological systems. However, the robustness that comes from leveraging information across multiple genes in transfer learning is often attained at the sacrifice of gene-wise precision. Thus, methods are needed to identify genes, defined as important within a particular latent space, that significantly differ between contexts. To address this challenge, we have developed a new framework, scProject, and a new metric, projectionDrivers, to quantitatively examine latent space usage across single-cell experimental systems while concurrently extracting the genes driving the differential usage of the latent space between defined contrasts. Here, we demonstrate the efficacy, utility, and scalability of scProject with projectionDrivers and provide experimental validation for predicted species-specific differences between the developing mouse and human retina.
The E26 Transformation-Specific-family transcription factor Spi-C is dynamically regulated by external signals in B cells
Authors: Raczkowski Hannah L. , Xu Li S. , Wang Wei Cen , DeKoter Rodney P.
Published: August 2021

Spi-C is an E26 transformation-specific transcription factor closely related to PU.1 and Spi-B. Spi-C has lineage-instructive functions important in antibody-generating responses, B cell development, and red pulp macrophage generation. Spi-C is inducible by heme- and NF-κB-dependent pathways in macrophages. The present research aimed to examine the regulation of Spi-C expression in B cells. RT-qPCR analysis revealed thatSpicexpression was reduced in B cells following addition of lipopolysaccharide, anti-IgM antibodies, CD40L, or cytokines BAFF + IL-4 + IL-5. Cytochalasin treatment partially prevented downregulation ofSpic. Unstimulated B cells upregulatedSpicover time in culture. To determine the mechanism ofSpicregulation, we examined theSpicpromoter and upstream regulatory elements. TheSpicpromoter had unidirectional activity, which was reduced by mutation of an NF-κB binding site.Spicwas repressed by an upstream regulatory region interacting with the heme-binding regulator Bach2. Taken together, these data indicate that Spi-C is dynamically regulated by external signals in B cells and provide insight into the mechanism of regulation.