bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: HIV Infection Does Not Explain Higher Nicotine Metabolism in People Living With HIV
Authors: Arens Yotam , Bilker Warren B. , Han Xiaoyan , Plankey Michael , Ware Deanna , Friedman M. Reuel , D'Souza Gypsyamber , Stosor Valentina , Shoptaw Steven , Schnoll Robert A. , Tyndale Rachel F. , Ashare Rebecca , Gross Robert
Published: September 2022

Background:

Smoking contributes to significant morbidity and mortality in people with HIV. People with HIV have relatively high nicotine metabolism rates, as measured by the nicotine metabolite ratio (NMR, 3-hydroxycotinine/cotinine). A higher NMR is associated with difficulty quitting smoking. We hypothesized that HIV infection might upregulate nicotine metabolism.

Setting:

A retrospective study of male current smokers in the Multicenter AIDS Cohort Study who HIV seroconverted between 1985 and 1993.

Methods:

Eligibility included having plasma stored before and after confirmed HIV seroconversion and current tobacco use. Samples were selected from the closest available visits before (median 3.3 months) and after (median 9.4 months) seroconversion. Antiretroviral therapy use was exclusionary. Cotinine and 3-hydroxycotinine were measured using liquid chromatography–tandem mass spectrometry. We compared NMR from plasma pre-HIV and post-HIV infection using signed-rank tests. We targeted a sample size of 71 pairs to achieve 80% power to detect a 0.1 unit increase in NMR with P = 0.05.

Results:

We analyzed paired samples from 78 participants; the median age was 34.5 years [interquartile range (IQR 29–40 years)]. The median NMR pre-HIV and post-HIV was 0.45 (IQR 0.32–0.54) and 0.46 (IQR 0.34–0.56), respectively. The median change in NMR postseroconversion was +0.01 (IQR −0.05, +0.09), P = 0.25. Stratification of median change in NMR by timing between samples or time since HIV seroconversion did not alter this finding.

Conclusions:

Acquiring HIV had no measurable effect on NMR. We postulate that upregulation of the NMR may be due to direct pharmacologic effects of HIV medications or metabolic changes in response to HIV infection.
Randomized Trial of Individualized Texting for Adherence Building (iTAB) Plus Motivational Interviewing for PrEP Adherence in Transgender Individuals: The iM-PrEPT Study
Authors: Morris Sheldon R. , Jain Sonia , Blumenthal Jill , Bolan Robert , Dubé Michael P. , Henderson Philip , Corado Katya , Sun Shelly , He Feng , Chow Karen , Burke Leah , Anderson Peter L. , Moore David J.
Published: September 2022

Background:

Transgender and nonbinary individuals at risk for HIV may benefit from adherence support for pre-exposure prophylaxis.

Methods:

Between June 2017 and September 2020, 255 transgender and nonbinary individuals received daily oral tenofovir disoproxil fumarate/emtricitabine for 48 weeks randomized 1:1 to receive individualized Texting for Adherence Building (iTAB) or iTAB plus motivational interviewing (iTAB + MI) through phone for nonadherence. The primary end point was dried blood spot tenofovir diphosphate concentrations at weeks 12 and 48 (or last on-drug study visit) ≥1246 fmol/punch consistent with ≥7 doses/week (ie, near-perfect adherence). Secondary outcomes included dried blood spot tenofovir diphosphate concentrations ≥719 fmol/punch consistent with ≥4 doses/week (ie, adequate adherence) and self-reported adherence by daily text messages.

Results:

Adherence for the outcome ≥1246 fmol/punch and ≥719 fmol/punch, respectively, was 49.1% and 57.9% for transgender men, 37.7% and 47.2% for nonbinary individuals, and 31.0% and 44.1% for transgender women. No difference was seen in iTAB + MI compared with iTAB alone by drug levels except where it approached significance in transgender women for the outcome of ≥719 fmol/punch in the iTAB + MI group compared with iTAB only (52% versus 35.7%, P = 0.065). There was a significant difference in self-reported daily dose adherence in the iTAB + MI group compared with iTAB alone (57.9% of days versus 46.4%, P = 0.009). In transgender women, the mean percentage of daily doses taken was 58.5% with iTAB + MI and 37.3% with iTAB alone (P < 0.001).

Conclusions:

In addition to automated approaches to adherence promotion, phone-based MI triggered by repeatedly missing doses may improve pre-exposure prophylaxis adherence among transgender women.
Life Expectancy Among People With HIV in New York City, 2009–2018
Authors: Xia Qiang , Maduro Gil A. , Li Wenhui , Huynh Mary , Torian Lucia V.
Published: September 2022

Objective:

To conduct a population-based analysis and compare life expectancy between people with HIV and the general population in New York City (NYC).

Methods:

We obtained the annual total number and age, sex, and race/ethnicity distributions of people with HIV from the NYC HIV registry and generated comparable numbers for the NYC general population from the Census 2000 and 2010 data using linear interpolation.

Results:

Life expectancy at age 20 among people with HIV increased from 38.5 years [95% confidence interval (CI): 37.4 to 39.5] in 2009 to 50.6 (95% CI: 48.5 to 52.7) in 2018, whereas it increased from 62.0 years (95% CI: 61.8 to 62.1) to 63.6 (95% CI: 63.5 to 63.7) among the NYC general population. The gap between the 2 populations narrowed from 23.5 years (95% CI: 22.4 to 24.6) in 2009 to 13.0 (95% CI: 10.9 to 15.1) in 2018. By sex and race/ethnicity, life expectancy at age 20 among people with HIV increased from 36.7 years in 2009 to 47.9 in 2018 among Black men; 37.5 to 50.5 years among Black women; 38.6 to 48.9 years among Hispanic men; 46.0 to 51.0 years among Hispanic women; 44.7 to 59.7 years among White men; and 38.0 years in 2009–2013 to 50.4 years in 2014–2018 among White women.

Conclusions:

Life expectancy among people with HIV improved greatly in NYC in 2009–2018, but the improvement was not equal across sex and racial/ethnic groups. The gap in life expectancy between people with HIV and the general population narrowed but remained.
Communication, an important link between healthcare providers: a best practice implementation project
Authors: Ifrim Raluca Alexandra , Klugarová Jitka , Măguriță Daniela , Zazu Mariana , Mazilu Doina Carmen , Klugar Miloslav
Published: September 2022

Objectives:

This project aimed to improve communication skills of medical laboratory staff and the quality of health services.

Introduction:

Communication is the basis of all interpersonal actions; optimal and efficient communication needs permanent awareness and training in order to learn these skills. The healthcare industry is a constantly changing field, so communication becomes a very important tool that contributes to change.

Methods:

This project has been conducted following the JBI framework to improve the communication process in a medical laboratory. A baseline audit involved 30 multidisciplinary healthcare providers (HCP). Using audit criteria provided by JBI, data for clinical audits were collected using a completed audit questionnaire based on direct observation and interview of participants, and checking the records. Once the information had been gathered, the team involved in the project implemented a three sessions workshop focused on communication to solve/improve identified barriers. A follow-up audit was conducted to assess the outcomes of the intervention.

Results:

The implementation of the project resulted in the evolution of the participants and the cohesion of the healthcare team. The baseline compliance with best practice for audit criteria shows that only a part of those involved in the study benefited from training communication. Lack of time for team briefings and interactions led to different points of view. In the pandemic context, the implementation of the communication improvement strategy was conducted online, with all 30 HCP participating in training sessions. After the follow-up audit, the evolution was demonstrated by the improvement of the HCP compliance compared with the two audit criteria identified with the insufficient compliance in the basic audit.

Conclusion:

Effective communication is a necessity to meet patient needs and to provide high-quality services. The healthcare team received training for communication focused on interpersonal communication.
Enhancing the evidence-based healthcare principles in clinical practice guidelines development in the Czech Republic: a best practice implementation project
Authors: Vrbová Tereza , Klugarová Jitka , Pokorná Andrea , Dušek Ladislav , Líčeník Radim , Klugar Miloslav
Published: September 2022

Objectives:

The main aim of this project was to enhance compliance with the best available evidence in clinical practice guidelines (CPGs) development based on evidence-based healthcare (EBHC) and GRADE (grading of recommendations, assessment, development and evaluation) principles in healthcare professionals and healthcare providers.

Introduction:

In various healthcare fields, the quality of care provided in different healthcare settings may vary. Guidelines following the EBHC principles should help make the right decisions in healthcare by providing the best healthcare option and be available for all patients. The perspectives of all engaged stakeholders should be respected, however. Within the Czech Republic, there had been no standardized process of CPG development.

Methods:

A baseline audit was conducted to demonstrate the status quo of the EBHC in the Czech Republic, which identified several barriers. Consequently, strategies (educational activities, methodological guidelines) to overcome the barriers were suggested and implemented. Two more audits followed (November 2017, November 2020).

Results:

The baseline audit results showed no or very low compliance to the best available evidence in CPG development. After the implementation, an increased compliance in all audit criteria (national methodology guidelines, trustworthy CPGs, experienced methodologists, clinical summaries) has been reported. The project has helped to establish procedures of CPGs development, enhanced knowledge and skills on EBHC in healthcare professionals, and ignited patients’ involvement in CPG development.

Conclusions:

The implementation project showed an increasing number of national methodology guidelines, CPGs being developed using EBHC and GRADE principles and HC professionals educated in EBHC. A national center for CPGs development within the Ministry of Health is being planned to sustain the project achievements.
The National COVID-19 Epi Model (NCEM): Estimating cases, admissions and deaths in South Africa
Authors: Silal Sheetal Prakash , Pulliam Juliet R.C. , Meyer-Rath Gesine , Jamieson Lise , Nichols Brooke E , Norman Jared , Hounsell Rachel , Mayet Saadiyah , Kagoro Frank , Moultrie Harry
Published: September 2022

Background

In March 2020 the South African COVID-19 Modelling Consortium was formed to support government planning for COVID-19 cases and related healthcare. Models were developed jointly by local disease modelling groups to estimate cases, resource needs and deaths due to COVID-19.

Methods

The National COVID-19 Epi Model (NCEM) while initially developed as a deterministic compartmental model of SARS-Cov-2 transmission in the nine provinces of South Africa, was adapted several times over the course of the first wave of infection in response to emerging local data and changing needs of government. By the end of the first wave, the NCEM had developed into a stochastic, spatially-explicit compartmental transmission model to estimate the total and reported incidence of COVID-19 across the 52 districts of South Africa. The model adopted a generalised Susceptible-Exposed-Infectious-Removed structure that accounted for the clinical profile of SARS-COV-2 (asymptomatic, mild, severe and critical cases) and avenues of treatment access (outpatient, and hospitalisation in non-ICU and ICU wards).

Results

Between end-March and early September 2020, the model was updated several times to generate new sets of projections and scenario analyses to be shared with planners in the national and provincial Departments of Health, the National Treasury and other partners in a variety of formats such as presentations, reports and dashboards. Updates to model structure included finer spatial granularity, limited access to treatment, and the inclusion of behavioural heterogeneity in relation to the adoption of Public Health and Social Measures. These updates were made in response to local data and knowledge and the changing needs of the planners.

Conclusions

The NCEM attempted to incorporate a high level of local data to contextualise the model appropriately to address South Africa’s population and health system characteristics. Origin and contextualisation of data and understanding of the population’s interaction with the health system played a vital role in producing and updating estimates of resource needs, demonstrating the importance of harnessing and developing local modelling capacity.
Automatic approach-avoidance tendency toward physical activity, sedentary, and neutral stimuli as a function of age, explicit affective attitude, and intention to be active
Authors: Farajzadeh Ata , Goubran Miriam , Beehler Alexa , Cherkaoui Noura , Morrison Paula , de Chanaleilles Margaux , Maltagliati Silvio , Cheval Boris , Miller Matthew W. , Sheehy Lisa , Bilodeau Martin , Orsholits Dan , Boisgontier Matthieu P.
Published: September 2022

Using computerized reaction-time tasks assessing automatic attitudes, studies have shown that healthy young adults have faster reaction times when approaching physical activity stimuli than when avoiding them. The opposite has been observed for sedentary stimuli. However, it is unclear whether these results hold across the lifespan and when error rates and a possible generic approach-avoidance tendency are accounted for. Here, reaction times and errors in online approach-avoidance tasks of 130 participants aged 21 to 77 years were analyzed using mixed-effects models. Automatic approach-avoidance tendencies were tested using physical activity, sedentary, and neutral stimuli. Explicit attitudes toward physical activity and intention to be physically active were self-reported. Results accounting for age, sex, gender, level of physical activity, body mass index, and chronic health condition confirmed a main tendency to approach physical activity stimuli (i.e., faster reaction to approach vs. avoid; p = .001) and to avoid sedentary stimuli (i.e., faster reaction to avoid vs. approach; p < .001). Results based on neutral stimuli revealed a generic approach tendency in early adulthood (i.e., faster approach before age 53 and fewer errors before age 36) and a generic avoidance tendency in older adults (i.e., more errors after age 60). When accounting for these generic tendencies, results showed a greater tendency (i.e., fewer errors) to avoid than approach sedentary stimuli after aged 50, but not before (p = .026). Exploratory analyses showed that, irrespective of age, participants were faster at approaching physical activity (p = .028) and avoiding sedentary stimuli (p = .041) when they considered physical activity as pleasant and enjoyable (explicit attitude). However, results showed no evidence of an association between approach-avoidance tendencies and the intention to be physically active. Taken together, these results suggest that both age and explicit attitudes can affect the general tendency to approach physical activity stimuli and to avoid sedentary stimuli.
Early Warning of Atrial Fibrillation Using Deep Learning
Authors: Gavidia Marino , Zhu Hongling , Montanari Arthur N. , Fuentes Jesús , Cheng Cheng , Dubner Sergio , Chames Martin , Maison-Blanche Pierre , Rahman Md Moklesur , Sassi Roberto , Badilini Fabio , Jiang Yinuo , Zhang Shengjun , Zhang Hai-Tao , Du Hao , Teng Basi , Yuan Ye , Wan Guohua , Tang Zhouping , He Xin , Yang Xiaoyun , Goncalves Jorge
Published: September 2022

Abstract

Atrial Fibrillation (AF) is the most common cardiac rhythm disorder. It is associated with increased hospitalization, risk of heart failure, and risk of stroke. Once on AF, it can sometimes be difficult to revert to sinus rhythm (SR), potentially requiring pharmacological or electrical cardioversion. Earlier warning of an imminent switch from SR to AF, even if by only a few minutes, could prompt patients to take actions (e.g., taking oral antiarrhythmic drugs) to avoid AF and its associated complications, thereby easing the workload and costs to the health system. The question is whether there is information, even if subtle, in the minutes prior to AF to indicate an imminent switch from SR. This paper shows that, for the vast majority of patients, the answer is affirmative. We propose a deep-learning model that predicts the onset of AF on average 30.8 minutes before it appears, with an accuracy of 83% and an F1-score of 85% on the test data. Moreover, this performance was obtained from R-to-R interval signals, which can be obtained from common wearable devices such as smartwatches and smart bands. The predictions were performed using a deep convolutional neural network, trained and cross-validated on 24-hour data obtained from Holter electrocardiogram recordings of 280 patients, with an additional 70 patients used as test data. We further tested the model with data from two other external centers with 33 patients. Overall, the proposed method has low computational time and could be embedded in smartphones connected to wearable devices that capture RRI for continuous heart monitoring and early warning of AF onset.
Cutaneous tactile sensation and standing balance in children with autism: A Preliminary Report
Authors: Kukkar Komal , Parikh Pranav J. , Fen-Kao Chyung , Mohapatra Sambit
Published: September 2022

BACKGROUND

Autistic Spectrum Disorder (ASD) presents with a multitude of problems such as physical, social, emotional, psychological, etc. Most common physical problems are impairments in standing balance and posture. It is unknown whether these impairments have any association between tactile sensation or are purely due to deficits in sensory processing and integration. We hypothesized that foot tactile sensation in ASD is positively correlated to performance in standing balance as measured by Pediatric Balance scale.

METHODS

The data collected at Heartshare Human Services of New York was used for secondary analysis. It consisted of 12 participants and included: 1. Muscle and joint ROM testing to rule out any muscle involvement in balance problems. 2. Tactile sensation testing at four sites on sole of foot bilaterally using Semmes Weinstein monofilament. 3. Pediatric Balance Scale (PBS) for balance testing.

RESULTS

We found significant positive correlation between cutaneous tactile sensation (SWF) and Pediatric Balance scale (PBS) measures in our participants i.e., reduced tactile sensation was moderately associated with impaired balance score.

CONCLUSIONS

We propose that during conventional clinical assessment for individuals with ASD, foot tactile sensation should not be overlooked, and included as a part of somato-sensory assessment. In addition, enhancing foot tactile sensation could also be used for targeted interventions to improve balance in children with ASD.
Age-related loss of the Y chromosome is associated with sex hormone binding globulin and selected drivers of clonal hematopoiesis
Authors: Dawoud Ahmed A.Z. , Tapper William J , Cross Nicholas C.P.
Published: September 2022

Mosaic loss of the Y-chromosome (LOY) is the most common somatic alteration in men. We aimed to assess the relationship between LOY and serum biomarkers in UK Biobank and explore the interaction with constitutional and somatic genetics. LOY was strongly associated with levels of sex hormone binding globulin (SHBG, β=0.12, PFDR= P = 7.44×10−36, adjusted for age, age squared, gender, smoking status, smoking intensity and principal genetic components), a key regulator of testosterone bioavailability associated with diverse disorders including cancer and autoimmune diseases. Furthermore, LOY was associated with total testosterone (TT, β=0.09, PFDR=2.23 × 10−20), but not bioavailable testosterone (PFDR=0.46) or free testosterone (PFDR=0.75). These relationships remained significant after sensitivity analysis that included comorbidities and body mass index (SHBG, β = 0.08, PFDR = 4.61×10−21; TT, β = 0.05, PFDR = 4.13 × 10−9). Mendelian randomisation suggested a causal effect of SHBG on LOY in BioBank Japan (P=6.58×10−4) but there was no evidence for an effect of LOY on SHBG (P=0.46). Assessment of cis-eQTLs for 13 genes associated with LOY identified two SNPs that were also associated with levels of SHBG, however only rs7141210 (imprinted DLK1-MEG3 locus) modified the relationship between SHBG and LOY (rs7141210-T/T; Pinteraction=0.04) with low levels of SHBG seen specifically in men without LOY (β=-0.02, P=0.001), but not those with LOY (P=0.41). Age-related clonal hematopoiesis (CH) defined by somatic driver mutations was not associated with sex hormone levels but was associated with LOY at clonal fractions >30% (OR=1.52, P=2.92×10−4). TET2, TP53, and CBL mutations were enriched in high level LOY cases, but not DNMT3A or ASXL1. Our findings thus identify independent relationships between LOY, sex hormones and CH.
Wastewater Surveillance for Monkeypox Virus in Nine California Communities
Authors: Wolfe Marlene K. , Yu Alexander T. , Duong Dorothea , Rane Madhura S. , Hughes Bridgette , Chan-Herur Vikram , Donnelly Marisa , Chai Shua , White Bradley J. , Vugia Duc J. , Boehm Alexandria B.
Published: September 2022

Background

Wastewater represents a composite biological sample from the entire contributing population. People infected with monkeypox virus (MPXV)1 may excrete viral DNA into wastewater via multiple ways such as in feces, urine, skin lesions, and/or saliva. We describe results from rapid establishment of wastewater surveillance in selected regions in California within a month of the first reported case of monkeypox in the United States.

Methods

PCR assays targeting genomic DNA from MPXV were deployed in an ongoing wastewater surveillance program in California. MPXV DNA concentrations were measured daily in settled solids samples from nine wastewater plants. Results over a four-week period were validated across different MPXV assays, compared using influent and solids samples, and correlated using non-parametric methods (Kendall’s tau) with the number of monkeypox cases reported from each sewershed.

Results

MPXV DNA was detected at all nine sites between June 19 and August 1, 2022; 5 of 9 sites detected MPXV DNA prior to or within a day of the first case identified in the source sewershed. At the four sites with >10 positive detections, we observed a positive, statistically significant correlation (p <0.001) between MPXV DNA in wastewater solids and incidence rate of reported cases.

Conclusions

Our findings suggest wastewater can be used to effectively detect the introduction of MPXV and monitor its circulation in the community to inform public health and clinical response. This flexible wastewater surveillance infrastructure may be rapidly leveraged to monitor other pathogens of public health importance that are shed into wastewater.
Selective whole-genome amplification reveals population genetics ofLeishmania braziliensisdirectly from patient skin biopsies
Authors: Pilling Olivia A. , Grace Cooper A. , Reis-Cunha João L. , Berry Alexander S. F. , Mitchell Matthew W. , Yu Jane A. , Malekshahi Clara , Krespan Elise , Go Christina K. , Lombana Cláudia , Song Yun S. , Amorim Camila F. , Lago Alexsandro S. , Carvalho Lucas P. , Carvalho Edgar M. , Brisson Dustin , Scott Phillip , Jeffares Daniel C. , Beiting Daniel P.
Published: September 2022

In Brazil,Leishmania braziliensisis the main causative agent of the neglected tropical disease, cutaneous leishmaniasis (CL). CL presents on a spectrum of disease severity with a high rate of treatment failure. Yet the parasite factors that contribute to disease presentation and treatment outcome are not well understood, in part because successfully isolating and culturing parasites from patient lesions remains a major technical challenge. Here we describe the development of selective whole genome amplification (SWGA) forLeishmaniaand show that this method enables culture-independent analysis of parasite genomes obtained directly from primary patient skin samples, allowing us to circumvent artifacts associated with adaptation to culture. We show that SWGA can be applied to multipleLeishmaniaspecies residing in different host species, suggesting that this method is broadly useful in both experimental infection models and clinical studies. SWGA carried out directly on skin biopsies collected from patients in Corte de Pedra, Bahia, Brazil, showed extensive genomic diversity. Finally, as a proof-of-concept, we demonstrated that SWGA data can be integrated with published whole genome data from cultured parasite isolates to identify variants unique to specific geographic regions in Brazil where treatment failure rates are known to be high. SWGA provides a relatively simple method to generateLeishmaniagenomes directly from patient samples, unlocking the potential to link parasite genetics with host clinical phenotypes.

AUTHOR SUMMARY

Leishmania braziliensisis the main cause of cutaneous leishmaniasis in Brazil. Due to limitations in culturing, it is important to study the parasite in a culture-independent manner. We use selective whole genome amplification (SWGA) to explore parasite genomic diversity directly from patient biopsies. This method is inexpensive and can be broadly used to generate parasite genome sequence data sampled from differentLeishmaniaspecies infecting different mammalian hosts. We found high diversity among theL. braziliensisgenomes from Bahia, Brazil, which correlated with geographic location. By integrating these data with publicly available genome sequences from other studies spanning four countries in South America, we identified variants unique to Northeast Brazil that may be linked to high regional rates of treatment failure.
Sequencing of 19,219 exomes identifies a low-frequency variant inFKBP5promoter predisposing to high myopia in a Han Chinese population
Authors: Su Jianzhong , Yuan Jian , Xu Liangde , Xing Shilai , Sun Mengru , Yao Yinghao , Ma Yunlong , Chen Fukun , Jiang Longda , Li Kai , Yu Xiangyi , Xue Zhengbo , Zhang Yaru , Fan Dandan , Zhang Ji , Liu Hui , Liu Xinting , Zhang Guosi , Wang Hong , Zhou Meng , Lyu Fan , An Gang , Yu Xiaoguang ,   Myopia Associated Genetics and Intervention Consortium, Xue Yuanchao , Yang Jian , Qu Jia
Published: September 2022

High myopia (HM) is one of the leading causes of visual impairment and blindness worldwide. Here, we report a whole-exome sequencing (WES) study in 9,613 HM cases and 9,606 controls of Han Chinese ancestry to pinpoint HM-associated risk variants. Single-variant association analysis identified three novel genetic loci associated with HM, including an East Asian ancestry-specific low-frequency variant (rs533280354) inFKBP5. Multi-ancestry meta-analysis with WES data of 2,696 HM cases and 7,186 controls of European ancestry from the UK Biobank discerned a novel European ancestry-specific rare variant inFOLH1. Functional experiments revealed a mechanism whereby a single G to A transition at rs533280354 disrupted the binding of transcription activator KLF15 to the promoter ofFKBP5, resulting in decreased transcription ofFKBP5. Furthermore, burden tests showed a significant excess of rare protein-truncating variants among HM cases involved in retinal blood vessel morphogenesis and neurotransmitter transport.
Using genome-wide association results to identify drug repurposing candidates
Authors: Bell Nathaniel , Uffelmann Emil , van Walree Eva , de Leeuw Christiaan , Posthuma Danielle
Published: September 2022

Drug repurposing may provide a solution to the substantial challenges facingde novodrug development. Given that 66% of FDA-approved drugs in 2021 were supported by human genetic evidence, drug repurposing methods based on genome wide association studies (GWAS), such as drug gene-set analysis, may prove an efficient way to identify new treatments. However, to our knowledge, drug gene-set analysis has not been tested in non-psychiatric phenotypes, and previous implementations may have contained statistical biases when testing groups of drugs. Here, 1201 drugs were tested for association with hypercholesterolemia, type 2 diabetes, coronary artery disease, asthma, schizophrenia, bipolar disorder, Alzheimer’s disease, and Parkinson’s disease. We show that drug gene-set analysis can identify clinically relevant drugs (e.g., simvastatin for hypercholesterolemia [p= 2.82E-06]; mitiglinide for type 2 diabetes [p= 2.66E-07]) and drug groups (e.g., C10A for coronary artery disease [p =2.31E-05]; insulin secretagogues for type 2 diabetes [p= 1.09E-11]) for non-psychiatric phenotypes. Additionally, we demonstrate that when the overlap of genes between drug-gene sets is considered we find no groups containing approved drugs for the psychiatric phenotypes tested. However, several drug groups were identified for psychiatric phenotypes that may contain possible repurposing candidates, such as ATC codes J02A (p= 2.99E-09) and N07B (p= 0.0001) for schizophrenia. Our results demonstrate that clinically relevant drugs and groups of drugs can be identified using drug gene-set analysis for a number of phenotypes. These findings have implications for quickly identifying novel treatments based on the genetic mechanisms underlying diseases.
Racial/ethnic disparities in cardiovascular disease mortality attributable to long-term PM2.5exposure in the United States from 2001 to 2016
Authors: Ma Yiqun , Zang Emma , Opara Ijeoma , Lu Yuan , Krumholz Harlan M. , Chen Kai
Published: September 2022

Background

The average concentration of fine particulate matter (PM2.5) has decreased in the U.S. in recent years. However, the health benefits of this improvement among different racial/ethnic groups are not known. This study aimed to estimate the associations between long-term exposure to ambient PM2.5and cause-specific cardiovascular disease (CVD) mortality rate and assess the PM2.5-attributable CVD deaths in non-Hispanic White, non-Hispanic Black, and Hispanic people across all counties in the contiguous U.S. from 2001 to 2016.

Methods

Using nationwide CVD mortality data for all ages obtained from National Center for Health Statistics, this study applied interactive fixed effects models to estimate the associations between 12-month moving average of PM2.5concentrations and monthly age-adjusted CVD mortality rates by race/ethnicity, controlling for both measured and unmeasured spatiotemporal confounders. Mortality from major types of CVD (ischemic heart disease [IHD], myocardial infarction [MI], stroke, hypertensive disease, and hypertensive heart disease) was also studied. We then calculated the burden of PM2.5-attributable CVD deaths in different race/ethnicity groups and examined the magnitude of racial/ethnic disparity and its changes over time.

Results

A total of 13,289,147 CVD deaths were included in the study. Each 1-µg/m3increase in 12-month moving average of PM2.5concentration was associated with increases of 7.16 (95% confidence interval [CI]: 3.81, 10.51) CVD deaths per 1,000,000 Black people per month, significantly higher than the estimates for non-Hispanic White people (Pvalue: 0.002). The higher vulnerability in non-Hispanic Black people was also observed for mortality from IHD, MI, and stroke. Long-term PM2.5exposure contributed to approximately 75.47 (95% CI: 40.14, 110.80) CVD deaths per 1,000,000 non-Hispanic Black people annually, over 3 times higher than the estimated rate in non-Hispanic White people (16.89, 95% CI:13.17, 20.62). From 2001 to 2016, the difference in attributable CVD mortality rate between Black and White people reduced by 44.04% (from 75.80 to 42.42 per 1,000,000 people), but the burden in Black people was still over 3 times higher compared to White people.

Conclusions

Non-Hispanic Black people have the highest PM2.5-attributable CVD mortality burden. Although the racial/ethnic disparity in this burden was narrowed over time, the gap between racial/ethnic minorities and non-Hispanic White people remains substantial.
An Early and Preliminary Assessment of the Clinical Severity of the Emerging SARS-CoV-2 Omicron Variants in Maharashtra, India
Authors: Karyakarte Rajesh , Das Rashmita , Taji Nyabom , Yanamandra Sushma , Shende Smriti , Joshi Suvarna , Karekar Bhagyashree , Bawale Reshma , Tiwari Rahul , Jadhav Madhuri , Sakalkar Shivani , Chaudhari Geetanjali , Rane Srushti , Agarasen Jeanne , Pillai Praveena , Dudhate Sonali , Chandankhede Priyanka , Labhshetwar Rutika , Gadiyal Yogita , Rajmane Mansi , Mukade Savita , Kulkarni Preeti
Published: September 2022

Background

The SARS-CoV-2 Omicron variants BA.2.74, BA.2.75 and BA.2.76 have appeared recently in India and have already spread to over 40 countries. They have acquired additional mutations in their spike protein compared to BA.2, branching away on the SARS-CoV-2 phylogenetic tree. These added mutations, over and above those of the parental BA.2 variant, have raised concerns about the impact on viral pathogenicity, transmissibility, and immune evasion properties of the new variants.

Material and Methods

A total of 990 RT-PCR positive SARS-CoV-2 samples, with a cycle threshold value (Ct) less than 25, were processed for SARS-CoV-2 whole genome sequencing between 3rd June 2022 to 7th August 2022. All corresponding demographic and clinical data were recorded and analyzed using Microsoft® Excel.

Results

Out of 990 samples sequenced, BA.2.75 (23.03%) was the predominant Omicron sublineage, followed by BA.2.38 (21.01%), BA.5 (9.70%), BA.2 (9.09%), BA.2.74 (8.89%) and BA.2.76 (5.56%). A total of 228 cases of BA.2.74, BA.2.75 and BA.2.76 were contacted by telephone, of which 215 (94.30%) were symptomatic with mild symptoms, and 13 (5.70%) had no symptoms. Fever (82.02%) was the most common symptom, followed by cough (49.12%), cold (35.97%), fatigue (27.19%), headache (21.05%) and myalgia (20.61%). Of the 228 cases, 195 (85.53%) cases recovered at home, and 33 (14.47%) required institutional quarantine. Recovery with conservative treatment was observed in 92.98% of cases, while 4.83% required additional oxygen therapy. Only 03 (1.32%) cases had poor outcomes resulting in death, and the remaining 225 (98.68%) had a good outcome. Among the 228 cases, 219 (96.05%) cases were vaccinated with COVID-19 vaccine; of these 72.60% had received both doses, 26.03% had also received the precautionary booster dose, while 1.37% were incompletely vaccinated with a single dose of vaccine.

Conclusion

The current study indicates that the three BA.2 sublineages are causing mild disease in India. However, BA.2.75 has key mutations that are notable for accelerated growth and transmission and require close and effective monitoring.
SARS-CoV-2 seroprevalence on the north coast of Peru: A cross-sectional study after the first wave
Authors: Moyano Luz M. , Toledo Angie K. , Chirinos Jenny , Vilchez Barreto Percy Mc Quen , Cavalcanti Sofia , Gamboa Ricardo , Ypanaque Jhon , Meza Mauro , Noriega Sheila , Herrera Victor , Bazan Edgar , Requena Alexandra , Silva Henry , Burgos Harold , León-Jimenez Franco ,   Group of Neuroepidemiology and Science of Life of Peru
Published: September 2022

Background

The devastating repercussions of COVID-19 were felt in developing nations like Peru. However, few studies have been conducted in these countries. To make good decisions about public health, it is important to understand how the disease is spread in our area.

Methodology/Principal findings

An observational, cross-sectional study was performed between November 11th and November 30th, 2020. In Puerto Pizarro, one out of every four homes was invited to participate in a systematic randomized sampling. Individuals were screened for the qualitative detection of anti-SARS-CoV-2 nucleocapsid (N) protein antibodies and anti-SARS-CoV-2 spike RBD with a rapid chromatographic immunoassay. An adult of legal age was selected, and an additional molecular test (RT-PCR) was taken to look for active COVID-19 cases.

Conclusions/Significance

This study shows an adjusted seroprevalence of 24.72% posterior to the first wave of COVID-19 in Tumbes. When adjusted by participant characteristics, women had higher adjusted seroprevalence compared to men (213/356 vs 143/356 [28.01 % vs 21.18 %], p=0.005). More than 20% of IgG seropositive cases belong to the age group under 16 years old. Asymptomatic individuals with recent infections were 66.3% (IgM and IgM/IgG) across all age groups. No association between positive seroprevalence and water supply, water resources, or sanitation services was found. The information is relevant to the Ministry of Health’s establishment of a regional program of COVID-19 control and strategic interventions, targeting vulnerable groups and improving vaccination campaigns.

Author summary

COVID-19 had devastating effects on developing countries such as Peru. It’s crucial to understand the disease’s underlying distribution in our region to create useful dynamics that engage the population in prevention measures. We performed an observational, cross-sectional study between November 11th and November 30th, 2020, in Puerto Pizarro. One out of every four houses was invited to participate, and individuals were screened for the qualitative detection of anti-SARS-CoV-2 antibodies (IgG and IgM) with a rapid test. This study shows an adjusted seroprevalence of 24.72% posterior to the first wave of COVID-19 in Tumbes. Women had a higher adjusted seroprevalence compared to men (213/356 vs 143/356 [28.01 % vs 21.18 %], p=0.005). More than 20% of IgG seropositive cases belong to the age group under 16 years old. Asymptomatic individuals with recent infections were 66.3% (IgM and IgM/IgG) across all age groups. Community participation in epidemiological surveillance strategies is crucial to establish a future follow-up cohort and evaluate the medium-term sequelae of this disease.
Psychological factors associated with reporting side effects following COVID-19 vaccination: a prospective cohort study (CoVAccS – wave 3)
Authors: Smith Louise E. , Sim Julius , Sherman Susan M. , Amlôt Richard , Cutts Megan , Dasch Hannah , Sevdalis Nick , Rubin G James
Published: September 2022

Objective

To investigate symptom reporting following the first and second COVID-19 vaccine doses, attribution of symptoms to the vaccine, and factors associated with symptom reporting.

Methods

Prospective cohort study (T1: 13-15 January 2021, T2: 4-15 October 2021). Participants were aged 18 years or older, living in the UK. Personal, clinical, and psychological factors were investigated at T1. Symptoms were reported at T2. We used logistic regression analyses to investigate associations.

Results

After the first COVID-19 vaccine dose, 74.1% (95% CI 71.4% to 76.7%, n=762/1028) of participants reported at least one injection-site symptom, while 65.0% (95% CI 62.0% to 67.9%, n=669/1029) reported at least one other (non-injection-site) symptom. Symptom reporting was associated with being a woman and younger. After the second dose, 52.9% (95% CI 49.8% to 56.0%, n=532/1005) of participants reported at least one injection-site symptom and 43.7% (95% CI 40.7% to 46.8%, n=440/1006) reported at least one other (non-injection-site) symptom. Symptom reporting was associated with having reported symptoms after the first dose, having an illness that put one at higher risk of COVID-19 (non-injection-site symptoms only), and not believing that one had enough information about COVID-19 to make an informed decision about vaccination (injection-site symptoms only).

Conclusions

Women and younger people were more likely to report symptoms from vaccination. People who had reported symptoms from previous doses were also more likely to report symptoms subsequently, although symptom reporting following the second vaccine was lower than following the first vaccine. Few psychological factors were associated with symptom reporting.

Highlights

We measured symptom reporting and attributions from the COVID-19 vaccines.

A prospective cohort study was used (T1: January 2021, T2: October 2021).

Women and younger people were more likely to report side effects.

Side effects reporting after the first and second dose was strongly associated.
Single and 2-dose vaccinations with MVA-BN® induce durable B cell memory responses in healthy volunteers that are comparable to older generation replicating smallpox vaccines
Authors: Ilchmann Heiko , Samy Nathaly , Reichhardt Daniela , Schmidt Darja , Powell Jacqueline D , Meyer Thomas PH , Silbernagl Günter , Nichols Rick , Weidenthaler Heinz , De Moerlooze Laurence , Chen Liddy , Chaplin Paul
Published: September 2022

While the MVA-BN vaccine has been proven protective against smallpox and monkeypox, the long-term immunological persistence or booster effect has not been described. In this set of clinical studies, participants who had never been immunized against smallpox were randomized to receive, 4 weeks apart: 2 placebo vaccinations (PBO group, N =181); 1 MVA-BN vaccination followed by placebo(1×MVA group, N =181); or 2 MVA-BN vaccinations (2×MVA group, N = 183). In addition, participants with a history of smallpox vaccination received 1 MVA-BN booster (HSPX+ group, N = 200). The 1×MVA and 2×MVA groups responded with increases in neutralizing antibody (nAb) GMTs at Week 2 (5.1 and 4.8, respectively) that further increased at Week 4 (7.2 and 7.5). Two weeks after the second primary vaccination in the 2×MVA group (at Week 6), nAb GMT peaked (45.6) before stabilizing 2 weeks thereafter (at Week 8) (34.0). In the HSPX+ group, a rapid anamnestic response was observed with a peak nAb GMT at Week 2 (175.1) that was much larger than the peak responses in either of the primary vaccination (1× or 2×MVA) dose groups of smallpox vaccine-naïve subjects. Persistence of nAbs relative to baseline was observed at 6 months in all groups (highest in HSPX+), with a return to near baseline nAb levels 2 years later. Subsets of ∼75 participants each, who received primary vaccinations in the 1×MVA and 2×MVA groups, were administered an MVA-BN booster 2 years later. Both booster dose (BD) groups exhibited rapid anamnestic responses with nAb GMTs that peaked 2 weeks post-booster (80.7 and 125.3). These post-booster titers in the 1×MVA and 2×MVA groups were higher than those observed at any timepoint following primary vaccination, were comparable to HSPX+ subjects who had been administered a booster, and remained elevated at 6 months post-booster (25.6 and 49.3). The observed anamnestic responses, in the absence of sustained detectable nAbs, support the presence of durable immunological memory following MVA-BN immunization. No safety concerns were identified, and the most common adverse event following the 2-year MVA-BN booster was injection site erythema in 82.2% of participants.

Clinical Trial Registry Numbers

NCT00316524 and NCT00686582

Highlights

MVA-BN booster-induced anamnestic responses support durable immune memory

One or two primary MVA-BN vaccinations induce similar durable B cell memory responses

Anamnestic responses were observed in those immunized with MVA-BN 2 years earlier

No safety concerns were revealed following a 2-year MVA-BN booster
Improved Robustness of SARS-CoV-2 Whole-Genome Sequencing from Wastewater with a Nonselective Virus Concentration Method
Authors: Segelhurst Emily , Bard Jonathan E. , Pillsbury Annemarie N. , Alam Md Mahbubul , Lamb Natalie A. , Zhu Chonglin , Pohlman Alyssa , Boccolucci Amanda , Emerson Jamaal , Marzullo Brandon J. , Yergeau Donald A. , Nowak Norma J. , Bradley Ian M. , Surtees Jennifer A. , Ye Yinyin
Published: September 2022

The sequencing of human virus genomes from wastewater samples is an efficient method for tracking viral transmission and evolution at the community level. However, this requires the recovery of viral nucleic acids of high quality. We developed a reusable tangential-flow filtration system to concentrate and purify viruses from wastewater for whole-genome sequencing. A pilot study was conducted with 94 wastewater samples from four local sewersheds, from which viral nucleic acids were extracted, and the whole genome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was sequenced using the ARTIC V4.0 primers. Our method yielded a high probability (0.9) of recovering complete or near-complete SARS-CoV-2 genomes (>90% coverage at 10× depth) from wastewater when the COVID-19 incidence rate exceeded 33 cases per 100 000 people. The relative abundances of sequenced SARS-CoV-2 variants followed the trends observed from patient-derived samples. We also identified SARS-CoV-2 lineages in wastewater that were underrepresented or not present in the clinical whole-genome sequencing data. The developed tangential-flow filtration system can be easily adopted for the sequencing of other viruses in wastewater, particularly those at low concentrations.

SYNOPSIS

The tangential-flow filtration method extracts viral nucleic acids of high enough quality from wastewater for robust and successful whole-genome sequencing.

GRAPHIC FOR TABLE OF CONTENTS (TOC)
Statistical Evaluation of the Test Threshold for the Alzheimer’s Disease EEG Coherence Marker
Authors: Radinski Crystal , Perez Grace
Published: September 2022

A progressive reduction in synaptic connections between neurons is one neurophysiological indicator of brain ageing and was linked to the severity of dementia. In our study, we hypothesized that if synaptic disconnection as the neuropathology of Alzheimer’s disease (AD) is responsible for the brain’s inability to integrate diverse regions into efficient networks, then electroencephalographic data may be utilized to identify Alzheimer’s dementia. The study explored EEG coherence, reflecting connectivity between regions, as a potential AD indicator and identified four promising EEG coherence markers. As the pattern of degeneration follows the temporal-parietal-frontal axis, the temporal gamma marker was chosen for further evaluation. We utilize conventional analysis, producing paired results such as sensitivity and specificity and the receiver operating characteristic (ROC) curve to evaluate the accuracy of the temporal gamma marker. The optimal cut-off point of 0.950 was confirmed by both methods and provided 95% correct classification indicating an almost perfect differentiation between control and impaired cognitive status. This evaluation will be used in a blinded diagnostic test accuracy study to determine the TG_marker validity in detecting AD and excluding pseudo-dementias.