bluuebunny/crossref_metadata_2025 huggingface dataset:
Over-the-Counter Pain Medication Use During Pregnancy
Authors: Vignato Julie , Mehner Brooke , Negrete Alondra , Segre Lisa S.
Published: June 2023

Purpose:

To examine over-the-counter pain medication use in pregnancy.

Study Design and Methods:

Secondary analysis of a weighted surveillance survey using the 2019 Iowa Pregnancy Risk Assessment Monitoring System (PRAMS) data. A sample of 759 pregnant women of childbearing age from Iowa was weighted to represent 31,728 Iowa mothers. The weighted sample represents 80% non-Hispanic White mothers, with smaller percentages of Hispanic (10%) mothers and non-Hispanic Black (7%) mothers, consistent with the population of Iowa. Approximately two-thirds of women had commercial insurance (66%), some college or greater education (62%), and were from urban areas (59%).

Analysis:

Descriptive statistics were calculated. Variables include over-the-counter pain reliever usage among all respondents and by race/ethnicity and education level.

Results:

Seventy-six percent of women reported taking over-the-counter pain relievers during pregnancy. Of these, 71% reported taking acetaminophen, 11% reported taking ibuprofen, 8% aspirin, and 3% naproxen. Nearly 80% of non-Hispanic White mothers reported taking an over-the-counter pain reliever during pregnancy compared to just 64% of mothers reported as Hispanic. Iowa mothers with a college education or greater were more likely to report over-the-counter pain reliever use during pregnancy (84%) than their counterparts with a high school education or less (64%).

Clinical Implications:

Some medications may cause harm to the fetus if taken at specific time during pregnancy. Reinforcement of current pain medication education, including risks to fetus throughout pregnancy may be needed.
The Oral Microbiome Throughout Pregnancy
Authors: Koerner Rebecca , Prescott Stephanie , Alman Amy , Duffy Allyson , Groer Maureen
Published: June 2023

Introduction:

Oral health is associated with systemic health, including adverse pregnancy outcomes. Understanding the oral microbiome during pregnancy may lead to targeted interventions for prevention of adverse outcomes. The purpose of this review is to examine the literature on the oral microbiome throughout pregnancy.

Methods:

We conducted a literature search with four electronic databases for original research conducted between 2012 and 2022 that examined the oral microbiome longitudinally using 16s rRNA sequencing during pregnancy.

Results:

We identified six studies that examined the oral microbiome longitudinally throughout pregnancy, though comparisons of oral niches, oral microbiome measures, and findings between studies were not consistent. Three studies identified alterations in alpha diversity throughout pregnancy and two studies identified increased pathogenic bacteria during pregnancy. Three studies reported no changes in the oral microbiome throughout pregnancy, and one study identified differences in the composition of the microbiome based on socioeconomic status and antibiotic exposure. Two studies examined adverse pregnancy outcomes in association with the oral microbiome, one reporting no associations and one reported difference in community gene composition in those diagnosed with preeclampsia.

Clinical Implications:

There is limited research on the composition of the oral microbiome throughout pregnancy. There may be alterations in the oral microbiome during pregnancy such as increased relative abundance of pathogenic bacteria. Socioeconomic status, antibiotic use, and education may contribute to differences in the microbiome composition over time. Clinicians should evaluate oral health and educate on the importance of oral health care during the prenatal and perinatal time period.
Accommodation in Children after 4.7 Years of Multifocal Contact Lens Wear in the BLINK Study Randomized Clinical Trial
Authors: Chandler Moriah A. , Robich Matthew L. , Jordan Lisa A. , Mutti Donald O. , Berntsen David A. , Fenton Rachel , Day Elizabeth , Walline Jeffrey J. ,   for the BLINK2 Study Group
Published: June 2023

Significance

When worn for myopia control in children, soft multifocal contact lenses with a + 2.50 D add reduced the accommodative response over a three-year period, but wearing them for over four years did not affect accommodative amplitudes, lag, or facility.

Purpose

To compare the accommodative response to a 3 D stimulus between single vision, +1.50 D add, and + 2.50 D add multifocal contact lens wearers during three years of contact lens wear, then to compare accommodative amplitude, lag, and facility between the three groups after an average of 4.7 years of wear.

Methods

Seven- to 11-year-old BLINK Study participants were randomly assigned to wear single vision, +1.50 D add, or + 2.50 D add soft contact lenses (CooperVision, Pleasanton, CA). The accommodative response to a 3 D stimulus was measured at baseline and annually for three years. After 4.7 years, we measured objective accommodative amplitudes, lead/lag, and binocular facility with ±2.00 D flippers. We compared the three accommodative measures using multivariate analysis of variance, adjusting for clinic site, sex, and age group (7-9 or 10-11 years).

Results

The +2.50 D add contact lens wearers exhibited lower accommodative response than the single vision contact lens wearers for three years, but the +1.50 D add contact lens wearers only exhibited lower accommodative response than the single vision contact lens wearers for two years. After adjustment for clinic site, sex, and age group, there were no statistically significant or clinically meaningful differences between the three treatment groups for accommodative amplitude (MANOVA, P = .49), accommodative lag (MANOVA, P = .41), or accommodative facility (MANOVA, P = .87) after an average of 4.7 years of contact lens wear.

Conclusions

Almost five years of multifocal contact lens wear did not affect the accommodative amplitude, lag, or facility of children.
Trends in COVID-19 Vaccine Hesitancy and Uptake Among Persons Living With HIV in Washington, DC
Authors: Castel Amanda D. , Barth Shannon , Wilbourn Brittany C. , Horberg Michael , Monroe Anne K. , Greenberg Alan E. ,   On behalf of the DC Cohort Executive Committee
Published: June 2023

Objective:

The COVID-19 pandemic has disproportionately affected older people, people with underlying health conditions, racial and ethnic minorities, socioeconomically disadvantaged, and people living with HIV (PWH). We sought to describe vaccine hesitancy and associated factors, reasons for vaccine hesitancy, and vaccine uptake over time in PWH in Washington, DC.

Methods:

We conducted a cross-sectional survey between October 2020 and December 2021 among PWH enrolled in a prospective longitudinal cohort in DC. Survey data were linked to electronic health record data and descriptively analyzed. Multivariable logistic regression was performed to identify factors associated with vaccine hesitancy. The most common reasons for vaccine hesitancy and uptake were assessed.

Results:

Among 1029 participants (66% men, 74% Black, median age 54 years), 13% were vaccine hesitant and 9% refused. Women were 2.6–3.5 times, non-Hispanic Blacks were 2.2 times, Hispanics and those of other race/ethnicities were 3.5–8.8 times, and younger PWH were significantly more likely to express hesitancy or refusal than men, non-Hispanic Whites, and older PWH, respectively. The most reported reasons for vaccine hesitancy were side effect concerns (76%), plans to use other precautions/masks (73%), and speed of vaccine development (70%). Vaccine hesitancy and refusal declined over time (33% in October 2020 vs. 4% in December 2021, P < 0.0001).

Conclusions:

This study is one of the largest analyses of vaccine hesitancy among PWH in a US urban area highly affected by HIV and COVID-19. Multilevel culturally appropriate approaches are needed to effectively address COVID-19 vaccine concerns raised among PWH.
The Effect of Various Temperatures on the Inflammatory Profile of Fat Graft Storage: An Experimental Study
Authors: Yuan Xihang , Lu Haibin , Hu Yuling , Yang Zhenyu , Jin XiaoLei , Qi Zuoliang
Published: June 2023

Fat tissue has been widely used as a filler material during plastic surgery, but unpredictable fat retention remains a significant concern. Fat tissue is vulnerable to ischemia and hypoxia, but it always has waiting time before injection in the operation theater. Apart from transferring fat tissue as quickly as possible after harvesting, washing the aspirate with cool normal saline is often used. However, the mechanisms of cool temperature acting on adipose tissue have yet to be fully elucidated. Herein, this study aims to explore the effect of preservation at different temperatures on the inflammatory profile of adipose tissue. Inguinal adipose tissue of rats was collected and cultured in vitro under 4°C, 10°C, and room temperature for 2 hours. The proportion of damaged adipocytes and an array of cytokines were determined. We observed that the damage rate of the adipocyte membrane was slightly higher at room temperature, but there was no significant difference, while we noticed increased IL-6 and MCP-1 levels in adipose tissue at room temperature (P＜0.01). The 4°C and 10°C cool temperatures may offer protection against proinflammatory states during the adipose tissue preserved in vitro.
Defining Biliary Hyperkinesia and the Role of Cholecystectomy
Authors: Kartik Akash , Jorge Irving A , Webb Christopher , Lim Elisabeth S , Chang Yu-Hui , Madura James
Published: June 2023

BACKGROUND:

Functional gallbladder disorder is most commonly defined by biliary colic and low ejection fraction (EF) on cholescintigraphy. Biliary hyperkinesia is a controversial type of functional gallbladder disorder, and its definition and the role of cholecystectomy in treating functional gallbladder disorder remains unclear.

STUDY DESIGN:

We conducted a retrospective review of patients who underwent cholecystokinin-stimulated cholescintigraphy and cholecystectomy at 3 Mayo Clinic sites between 2007 and 2020. Eligible patients were 18 years or older, presented with symptoms of biliary disease, had an EF greater than 50%, underwent cholecystectomy, and had no evidence of acute cholecystitis or cholelithiasis on imaging. We used receiver operating characteristics curve analysis to identify the optimal cutoff value that predicted symptom resolution within 30 days of cholecystectomy.

RESULTS:

A total of 2,929 cholecystokinin-stimulated cholescintigraphy scans were performed during the study period; the average EF was 67.5% and the median EF was 77%. Analyzing those with EFs greater than or equal to 50% yielded 1,596 patients with 141 (8.8%) going on to have cholecystectomy. No significant differences were found in age, sex, BMI, final pathology between patients with and without pain resolution. Using a cutoff EF of 81% was significantly associated with pain resolution after cholecystectomy (78.2% for EF greater than or equal to 81% vs 60.0% for EF less than 81%, p = 0.03). Chronic cholecystitis was found in 61.7% of the patients on final pathology.

CONCLUSIONS:

We determined that an EF cutoff of 81% is a reasonable upper limit of normal gallbladder EF. Patients with biliary symptoms and an EF greater than 81% but no evidence of biliary disease on ultrasound or scintigraphy can be classified as having biliary hyperkinesia. Based on our findings, we recommend cholecystectomy for this patient population.
Pigment-dispersing factor is present in circadian clock neurons of pea aphids and may mediate photoperiodic signalling to insulin-producing cells
Authors: Colizzi Francesca Sara , Veenstra Jan A. , Rezende Gustavo L. , Helfrich-Förster Charlotte , Martínez-Torres David
Published: June 2023

The neuropeptide pigment-dispersing factor (PDF) plays a pivotal role in the circadian clock of most Ecdysozoa and is additionally involved in the timing of seasonal responses of several photoperiodic species. The pea aphid,Acyrthosiphon pisum,is a paradigmatic photoperiodic species with an annual life cycle tightly coupled to the seasonal changes in day length. Nevertheless, PDF could not be identified inA. pisumso far.In the present study, we identified a PDF-coding gene that has undergone significant changes in the otherwise highly conserved insect C-terminal amino acid sequence. A newly generated aphid-specific PDF antibody stained four neurons in each hemisphere of the aphid brain that co-express the clock protein Period and have projections to thepars lateralisthat are highly plastic and change their appearance in a daily and seasonal manner, resembling those of the fruit fly PDF neurons. Most intriguingly, the PDF terminals overlap with dendrites of the insulin-like peptide (ILP) positive neurosecretory cells in thepars intercerebralisand with putative terminals of Cryptochrome (CRY) positive clock neurons. Since ILP has been previously shown to be crucial for seasonal adaptations and CRY might serve as a circadian photoreceptor vital for measuring day length, our results suggest that PDF plays a critical role in aphid seasonal timing.
How to be a good partner and father? The role of adult males in pair bond maintenance and parental care in Javan gibbons
Authors: Yi Yoonjung , Mardiastuti Ani , Choe Jae C.
Published: June 2023

In pair-living species, female and male pairs may maintain stable social bonds by adjusting spatial and social associations. Nevertheless, each sex invests differently to maintain the pair bond, and the investment can depend on the presence of paternal care or ‘male services.’ While most species live in pairs, the sex responsible for pair bond maintenance in gibbons is still controversial. We investigated pair bond maintenance and parental care in three pairs of wild Javan gibbons in Gunung Halimun-Salak National Park, Indonesia, for over 21 months. We found that Javan gibbon fathers groomed their offspring more than adult females, especially as offspring got older. While both parents increased playing time with offspring when offspring became older and more independent, fathers played with offspring 20 times more than mothers on average. Grooming within Javan gibbon pairs was male-biased, suggesting that pair bond maintenance was heavily the job of males. However, offspring age as a proxy for paternal care did not affect the pair bond maintenance. Our study highlights that adult male Javan gibbons may have an important role in pair bond maintenance and the care of juveniles.
Osteoarticular tuberculosis of the ankle, a rare localization: a case report
Authors: Malihy Zakaria , Benaissa Elmostafa , Ben Lahlou Yassine , Maleb Adil , Elouennass Mostafa
Published: June 2023

Tuberculosis is a real scourge, posing a real public health problem in countries where the disease is endemic. Osteoarticular tuberculosis represents 2% to 5% of all tuberculosis cases and 11% to 15% of extra-pulmonary tuberculosis cases. Involvement of the foot and ankle is rarer. We report the case of osteoarticular tuberculosis of the ankle in a 71-year-old patient with type 2 diabetes and hypertension who presented to the trauma department of the Mohammed V Military Hospital with a painful swelling of the ankle. Standard X-rays and CT scan of the ankle showed inflammatory involvement of the bone and joints. Antitubercular antibiotic therapy was instituted for nine months. Given the context of endemicity, any atypical presentation of lingering bone lesions should raise the suspicion of osteoarticular tuberculosis in order to ensure early therapeutic management.
Combining a prioritization strategy and functional studies nominates 5’UTR variants underlying inherited retinal disease
Authors: Rey Alfredo Dueñas , del Pozo Valero Marta , Bouckaert Manon , Van Den Broeck Filip , Varela Malena Daich , Van Heetvelde Mattias , De Bruyne Marieke , Van de Sompele Stijn , Bauwens Miriam , Ellingford Jamie , Lenaerts Hanne , Mahieu Quinten , Josifova Dragana ,   Genomics England Research Consortium, Rivolta Carlo , Webster Andrew , Arno Gavin , Ayuso Carmen , De Zaeytijd Julie , Leroy Bart P. , De Baere Elfride , Coppieters Frauke
Published: June 2023

Background

5’ untranslated regions (5’UTRs) are essential modulators of protein translation. Predicting the impact of 5’UTR variants is challenging and typically not performed in routine diagnostics. Here, we present a combined approach of a comprehensive prioritization strategy and subsequent functional assays to evaluate 5’UTR variation in two large cohorts of patients with inherited retinal diseases (IRDs).

Methods

We performed an isoform-level re-analysis of retinal RNA-seq data to identify the protein-coding transcripts of 378 IRD genes with highest expression in retina. We evaluated the coverage of these 5’UTRs by different whole exome sequencing (WES) capture kits. The selected 5’UTRs were analyzed in whole genome sequencing (WGS) and WES data from IRD sub-cohorts from the 100,000 Genomes Project (n = 2,417 WGS) and an in-house database (n = 1,682 WES), respectively. Identified variants were annotated for 5’UTR-relevant features and classified into 7 distinct categories based on their predicted functional consequence. We developed a variant prioritization strategy by integrating population frequency, specific criteria for each category, and family and phenotypic data. A selection of candidate variants underwent functional validation using diverse experimental approaches.

Results

Isoform-level re-quantification of retinal gene expression revealed 76 IRD genes with a non-canonical retina-enriched isoform, of which 20 display a fully distinct 5’UTR compared to that of their canonical isoform. Depending on the probe-design 3-20% of IRD genes have 5’UTRs fully captured by WES. After analyzing these regions in both IRD cohorts we prioritized 11 (likely) pathogenic variants in 10 genes (ARL3,MERTK,NDP,NMNAT1,NPHP4,PAX6,PRPF31,PRPF4,RDH12,RD3), of which 8 were novel. Functional analyses further supported the pathogenicity of 2 variants. TheMERTK:c.-125G>A variant, overlapping a transcriptional start site, was shown to significantly reduce both luciferase mRNA levels and activity. TheRDH12:c.-123C>T variant was foundin ciswith the reported hypomorphicRDH12:c.701G>A (p.Arg234His) variant in 11 patients. This 5’UTR variant, predicted to introduce an upstream open reading frame, was shown to result in reduced RDH12 protein but unaltered mRNA levels.

Conclusions

This study demonstrates the importance of 5’UTR variants implicated in IRDs and provides a systematic approach for 5’UTR annotation and validation that is applicable to other inherited diseases.
Biallelic loss of function variants inWBP4, encoding a spliceosome protein, result in a variable neurodevelopmental delay syndrome
Authors: Engal Eden , Oja Kaisa Teele , Maroofian Reza , Geminder Ophir , Le Thuy-Linh , Mor Evyatar , Tzvi Naama , Elefant Naama , Zaki Maha S. , Gleeson Joseph G. , Muru Kai , Pajusalu Sander , Wojcik Monica H. , Pachat Divya , Elmaksoud Marwa Abd , Jeong Won Chan , Lee Hane , Bauer Peter , Zifarelli Giovanni , Houlden Henry , Elpeleg Orly , Gordon Chris , Harel Tamar , Õunap Katrin , Salton Maayan , Mor-Shaked Hagar
Published: June 2023

Over two dozen spliceosome proteins are involved in human diseases, also referred to as spliceosomopathies. WBP4 (WW Domain Binding Protein 4) is part of the early spliceosomal complex, and was not described before in the context of human pathologies. Ascertained through GeneMatcher we identified eleven patients from eight families, with a severe neurodevelopmental syndrome with variable manifestations. Clinical manifestations included hypotonia, global developmental delay, severe intellectual disability, brain abnormalities, musculoskeletal and gastrointestinal abnormalities. Genetic analysis revealed overall five different homozygous loss-of-function variants inWBP4. Immunoblotting on fibroblasts from two affected individuals with different genetic variants demonstrated complete loss of protein, and RNA sequencing analysis uncovered shared abnormal splicing patterns, including enrichment for abnormalities of the nervous system and musculoskeletal system genes, suggesting that the overlapping differentially spliced genes are related to the common phenotypes of the probands. We conclude that biallelic variants inWBP4cause a spliceosomopathy. Further functional studies are called for better understanding of the mechanism of pathogenicity.
The dynamically neurodiverse human brain: Measuring excitatory-inhibitory dynamics and identifying homeostatic differences in autistic and non-autistic people
Authors: Ellis C. L. , Ahmad J. , Zoumpoulaki A. , Dimitrov M. , Velthuis H. E. , Pereira A. C. , Wong N. M. L. , Ponteduro M. F. , Kowalewski L. , Leonard A. , Garces P. , Huang Q. , Daly E. , Murphy D. , McAlonan G.
Published: June 2023

Brain function is the dynamic output of coordinated excitatory and inhibitory (E-I) activity. E-I alterations, arising from differences in excitatory glutamate and inhibitory GABA pathways, are implicated in the development and heterogeneity of multiple neurodevelopmental conditions, such as autism; and are consequently targets for pharmacological support options. Yet, E-I measures of neurotransmitter levels or receptors in the living human brain (such as Magnetic Resonance Spectroscopy or Positron Emission Tomography) are expensive and/or invasive and do not capture dynamics. The determine if a candidate metric captures a neurosignalling system, the system must be challenged and changes observed objectively. This is basis of animal study designs. The aperiodic 1/f exponent of the EEG power spectrum is sensitive to E-I perturbations in animals but, more work is needed to translate to humans. Therefore, we tested the hypotheses that i) the aperiodic 1/f exponent of resting-state EEG in humans changes following a pharmacological E-I challenge with arbaclofen, a GABABreceptor agonist; and ii) dynamic responsivity to GABAergic challenge is different in a neurodevelopmental condition associated with E-I differences, namely autism. As predicted, in both groups the aperiodic 1/f exponent significantly increased following a high (30mg) dose of arbaclofen. However, an aperiodic exponent increase was also elicited at a lower (15mg) dose of arbaclofen in autistic but not non-autistic individuals. Hence, in humans, the aperiodic 1/f exponent captures E-I dynamics and autistic brains are dynamically different compared to non-autistic brains. We suggest that our results can be explained by homeostatic differences E-I regulation between groups.
PanelCAT: an Open-Source Comparative Analysis Tool for Next-Generation Sequencing Panel Target Regions
Authors: Oszwald André , Zisser Lucia , Compérat Eva , Müllauer Leonhard
Published: June 2023

Multi-gene next-generation sequencing (NGS) panels have become a routine diagnostic method in the contemporary practice of personalised medicine. To avoid inadequate test choice or interpretation, a detailed understanding of the precise panel target regions is required. However, the necessary bioinformatic expertise is not always available, and publicly accessible and easily interpretable analyses of target regions are scarce. To address this critical knowledge gap, we present the Panel Comparative Analysis Tool (PanelCAT) an open-source application to analyze, visualize and compare NGS panel DNA target regions. PanelCat uses RefSeq, ClinVar and COSMIC cancer mutation census databases to quantify the exon and mutation coverage of target regions and provides interactive graphical representations and search functions to inspect the results. We demonstrate the utility of PanelCAT by analyzing two large NGS panels (Illumina TSO500 and Qiagen pan-cancer panel) to validate the advertized target genes, quantify targeted exons and mutations, and identify differences between panels. PanelCat will enable institutions and researchers to catalogue and visualize NGS panel target regions independent of the manufacturer, promote transparency of panel limitations, and share this information with employees and requisitioners.
Status of Magnetic Resonance Imaging Systems and Quality Control Programs in Nigeria
Authors: Adewole Maruf , Ige Taofeeq A. , Irurhe Nicholas , Adewole Philip , Akpochafor Michael , Ibitoye Ayo , Adeneye Samuel
Published: June 2023

Magnetic Resonance Imaging (MRI) employs the use of magnetic field and radio waves to produce images of the body. Quality Control (QC) is essential for ensuring optimal performance of MRI systems, as recommended by American College of Radiology (ACR), American Association of Physicists in Medicine (AAPM), and the International Society of Magnetic Resonance in Medicine (ISMRM). This survey examines the status of MRI systems and QC in Nigeria. Questionnaires were administered through google form to Radiologists, Radiographers, Medical Physicists, and biomedical engineers working in various MRI centers across the country, with a total of 44 responses received from 24 centers. The professional bodies of the professionals involved facilitated the questionnaire administration. The survey results indicate that 1.5T is the most common field strength of MRI systems in the country. 83% of the imaging centers rely solely on the service engineer to keep the MRI operational. Although 71% of the centers have Radiation Safety Advisors (RSA), their services do not include MRI. Moreover, 45% of the centers lack an understanding of the composition and importance of MRI QC. This is due to factors such as the absence of regulatory requirements, high patient workload, no trained personnel, and the unavailability of QC equipment. The findings of this survey highlight the need for improved QC programs in the country to improve image quality and longevity of MRI systems. It also underscores the need for the establishment of a regulatory framework and national policy to ensure the safe use of MRI in Nigeria.
History of tuberculosis disease is associated with genetic regulatory variation in Peruvians
Authors: Suliman Sara , Nieto-Caballero Victor E. , Asgari Samira , Lopez Kattya , Iwany Sarah K. , Luo Yang , Nathan Aparna , Fernandez-Salinas Daniela , Chiñas Marcos , Huang Chuan-Chin , Zhang Zibiao , León Segundo R , Calderon Roger I , Lecca Leonid , Murray Megan , Van Rhijn Ildiko , Raychaudhuri Soumya , Moody D. Branch , Gutierrez-Arcelus Maria
Published: June 2023

A quarter of humanity is estimated to be latently infected withMycobacterium tuberculosis(Mtb) with a 5-10% risk of developing tuberculosis (TB) disease. Variability in responses toMtbinfection could be due to host or pathogen heterogeneity. Here, we focused on host genetic variation in a Peruvian population and its associations with gene regulation in monocyte-derived macrophages and dendritic cells (DCs). We recruited former household contacts of TB patients who previously progressed to TB (cases, n=63) or did not progress to TB (controls, n=63). Transcriptomic profiling of monocyte-derived dendritic cells (DCs) and macrophages measured the impact of genetic variants on gene expression by identifying expression quantitative trait loci (eQTL). We identified 330 and 257 eQTL genes in DCs and macrophages (False Discovery Rate (FDR) < 0.05), respectively. Five genes in DCs showed interaction between eQTL variants and TB progression status. The top eQTL interaction for a protein-coding gene was withFAH, the gene encoding fumarylacetoacetate hydrolase, which mediates the last step in mammalian tyrosine catabolism.FAHexpression was associated with genetic regulatory variation in cases but not controls. Using public transcriptomic and epigenomic data ofMtb-infected monocyte-derived dendritic cells, we found thatMtbinfection results inFAHdownregulation and DNA methylation changes in the locus. Overall, this study demonstrates effects of genetic variation on gene expression levels that are dependent on history of infectious disease and highlights a candidate pathogenic mechanism through pathogen-response genes. Furthermore, our results point to tyrosine metabolism and related candidate TB progression pathways for further investigation.
The Finger Dexterity Test: validation study of a smartphone-based manual dexterity assessment
Authors: Van Laethem Delphine , Denissen Stijn , Costers Lars , Descamps Annabel , Baijot Johan , Van Remoortel Ann , Van Merhaegen-Wieleman Annick , D’hooghe Marie B , D’Haeseleer Miguel , Smeets Dirk , Sima Diana M , Van Schependom Jeroen , Nagels Guy
Published: June 2023

Background

The Nine-Hole Peg Test (9HPT) is the golden standard in clinical practice to measure manual dexterity in people with multiple sclerosis (MS). However, administration requires trained personnel and dedicated time during a clinical visit.

Objective

To validate a smartphone-based test for remote manual dexterity assessment, the icompanion Finger Dexterity Test (FDT), to be included into the icompanion application.

Methods

65 MS and 81 healthy subjects performed a first testing session, and 21 healthy subjects performed a second session approximately two weeks later.

Results

The FDT significantly correlated with the 9HPT (dominant: Spearman’s ρ=0.62, p<0.001; non-dominant: ρ=0.52, p<0.001). FDT scores showed a significant difference between the MS and healthy subjects (dominant: Cohen’s d=0.24, p=0.015; non-dominant: Cohen’s d=0.18, p=0.013), which was not the case for the 9HPT. A significant correlation with age (dominant: ρ=0.46, p<.001; non-dominant: ρ=0.40, p=0.002), Expanded Disability Status Scale (EDSS, dominant: ρ=0.37, p=0.004; non-dominant: ρ=0.33, p=0.017), and disease duration for the non-dominant hand (ρ=0.31, p=0.016) was observed.

Conclusion

The icompanion Finger Dexterity Test shows a moderate-to-good concurrent validity, ecological validity and test-retest reliability, and differentiates between the MS subjects and healthy controls. This test can be implemented into routine MS care for remote follow-up of manual dexterity.
SR-TWAS: Leveraging Multiple Reference Panels to Improve TWAS Power by Ensemble Machine Learning
Authors: Parrish Randy L. , Buchman Aron S. , Tasaki Shinya , Wang Yanling , Avey Denis , Xu Jishu , De Jager Philip L. , Bennett David A. , Epstein Michael P. , Yang Jingjing
Published: June 2023

Multiple reference panels of a given tissue or multiple tissues often exist, and multiple regression methods could be used for training gene expression imputation models for TWAS. To leverage expression imputation models (i.e., base models) trained with multiple reference panels, regression methods, and tissues, we develop a Stacked Regression based TWAS (SR-TWAS) tool which can obtain optimal linear combinations of base models for a given validation transcriptomic dataset. Both simulation and real studies showed that SR-TWAS improved power, due to increased effective training sample sizes and borrowed strength across multiple regression methods and tissues. Leveraging base models across multiple reference panels, tissues, and regression methods, our real application studies identified 6 independent significant risk genes for Alzheimer’s disease (AD) dementia for supplementary motor area tissue and 9 independent significant risk genes for Parkinson’s disease (PD) for substantia nigra tissue. Relevant biological interpretations were found for these significant risk genes.
Restrictions on top speed and nighttime usage substantially decrease the incidence of electric scooter injuries
Authors: Pakarinen Oskari , Kobylin Arja , Harjola Veli-Pekka , Castrén Maaret , Vasara Henri
Published: June 2023

Objective

To investigate the effectiveness of restrictions on top speed and nighttime usage on the incidence of e-scooter-related injuries.

Design

A retrospective comparative study. We compared shared e-scooter injuries from two periods: Unrestricted period (1.1-31.8.2021), and Restricted period (1.1.-31.8.2022).

Setting

General population of Helsinki, Finland. We collected the data from the electric patient database from three trauma hospitals representing all public hospitals treating acute trauma patients in Helsinki.

Participants

All patients with an injury related to shared e-scooter riding sustained in Helsinki

Interventions

The restrictions established for shared e-scooters during the restricted period were: 1) The daytime top speed of 20km/h, as opposed to the previous 25km/h, 2) the use of shared e-scooters was prohibited on Friday and Saturday nights between 12 p.m. and 5 a.m, and 3) the nighttime top speed was lowered to 15 km/h from Sunday to Thursday between 12 p.m. and 5 a.m., as opposed to 25 km/h.

Main outcome measure

Proportional incidence of e-scooter injuries compared to the total trips made by e-scooters.

Results

There were 528 e-scooter injuries requiring hospital care during the unrestricted period (1.1.-31.8.2021) and 318 injuries during the restricted period of similar length (1.1.-31.8.2022). The proportional incidence of e-scooter injuries was 19 (95% CI 17-20) for every 100 000 rides during the unrestricted period and 9 (95% 8-10) per 100 000 rides during the restricted period. In the risk analysis, the odds ratio (OR) for shared e-scooter accidents was 0.5 (95% CI 0.4-0.6) for the restricted period when adjusted for hourly temperature, rain amount, wind speed, and visibility. After introducing the restrictions, the number of e-scooter injuries decreased significantly between 11 p.m. and 5 a.m.

Conclusions

Restrictions on the top speed and nighttime usage of e-scooters decreased the amount of e-scooter injuries. We recommend similar restrictions in cities with shared e-scooter services.
Surveying Argentine healthcare providers’ knowledge, attitude, and practice about diagnosis and management of sports-related concussions
Authors: Russo María Julieta , Salvat Fernando , Kañevsky Agostina , Saco Marcelo , Hidalgo Ignacio Alonso , Vedova Franco Della , Allegri Ricardo Francisco , Sevlever Gustavo
Published: June 2023

Background

A better understanding of the healthcare providers’ knowledge, attitude, and practice (KAP) level would help athletes, trainers, and athletic administrators, implement more effective concussion-management recommendations and guidelines. This survey aims to understand healthcare providers’ KAP dimensions regarding the diagnosis and management of sports-related concussions.

Methods

Cross-sectional study. An online-based KAP survey was carried out on a convenience sample of healthcare providers, coaches, parents, and athletes (n=626) in partnership with sports concussion clinics, rugby union, and rugby league in Argentina. The questionnaire incorporated 25 questions. Descriptive analysis was estimated as means, SD, and proportion. Chi-square tests, two-sample t-tests, and regression analysis were utilized for the response analysis.

Results

Seventy-four percent of the respondents reported having concussion training. Respondents correctly answered on average 6.23 ± 2.16 (out of 10) knowledge questions. The largest gaps were related to the clinical interpretation of symptom severity and neuroimaging. The smallest gaps were identified in young athletes’ management. There was a significant difference in mean survey respondents’ knowledge scores [F (1,622) =109.479, p<0.001] between those who had received formal concussion training and those who had not.

Conclusions

This study reveals that healthcare providers have appropriate knowledge and attitude regarding sport-related concussions but there are important knowledge gaps and practices that are often wanting. Our findings confirm the need for training and education on sport-related concussions. It would be advisable to implement educational campaigns specifically focused on the diagnosis and management of sports concussions, to raise awareness about this topic in schools, leagues, and sports associations.
Exposome Epidemiology for Suspect Environmental Chemical Exposures during Pregnancy Linked to Subsequent Breast Cancer Diagnosis
Authors: Go Young-Mi , Weinberg Jaclyn , Teeny Sami , Cirillo Piera , Krigbaum Nickilou , Singer Grant , Ly ViLinh , Cohn Barbara , Jones Dean P.
Published: June 2023

Breast cancer is now the most common cancer globally, accounting for 12% of all new annual cancer cases worldwide. Despite epidemiologic studies having established a number of risk factors, knowledge of chemical exposure risks is limited to a relatively small number of chemicals. In this exposome research study, we used non-targeted, high-resolution mass spectrometry (HRMS) of pregnancy cohort biospecimens in the Child Health and Development Studies (CHDS) to test for associations with breast cancer identified via the California Cancer Registry. Second (T2) and third (T3) trimester archival samples were analyzed from 182 women who subsequently developed breast cancer and 384 randomly selected women who did not develop breast cancer. Environmental chemicals were annotated with the Toxin and Toxin-Target Database (T3DB) for chemical signals that were higher in breast cancer cases and used with an exposome epidemiology analytic framework to identify suspect chemicals and associated metabolic networks. Network and pathway enrichment analyses showed consistent linkage in both T2 and T3 to inflammation pathways, including linoleate, arachidonic acid and prostaglandins, and identified new suspect environmental chemicals associated with breast cancer, i.e., an N-substituted piperidine insecticide and a common commercial product, 2,4-dinitrophenol (DNP), linked to variations in amino acid and nucleotide pathways in T2 and benzo[a]carbazole and a benzoate derivative linked to glycan and amino sugar metabolism in T3. The results identify new suspect environmental chemical risk factors for breast cancer and provide an exposome epidemiology framework for discovery of suspect environmental chemicals and potential mechanistic associations with breast cancer.
Trajectories of atherosclerotic cardiovascular disease risk scores as a predictor for incident chronic kidney disease
Authors: Lee Hye Sun , Lim Hong Il , Moon Tae Ju , Lee So Young , Lee Jun-Hyuk
Published: June 2023

Background

The relationship between atherosclerosis and renal function is well established. Atherosclerotic cardiovascular disease (ASCVD) risk scores reflect atherosclerotic burden, which changes over time. We investigated the association between ASCVD risk trajectories and incident chronic kidney disease (CKD) using data from a large community-based Korean cohort with up to 16 years of follow-up.

Methods

We analyzed data from 5032 participants without CKD from the baseline survey of the Korean Genome and Epidemiology Study Ansan-Ansung cohort. Participants were categorized into stable or increasing ASCVD risk groups based on the revised ASCVD risk pooled cohort equation over a median period of exposure of 5.8 years. Incident CKD was defined as two consecutive events of an estimated glomerular filtration rate <60 mL/min/1.73 m2.

Results

During a median 9.9 years of event accrual period, 449 (8.92%) new-onset CKD cases were identified. Multiple Cox proportional regression analyses showed that the hazard ratio (95% confidence interval) for incident CKD in the increasing group, compared to the stable group, was 2.13 (1.74–2.62) in the unadjusted model and 1.35 (1.02–1.78) in the fully-adjusted model. Significant relationships were maintained in subgroups of individuals in their 50s, without diabetes mellitus or hypertension. The prevalence of proteinuria was consistently higher in the increasing group than that in the stable group.

Conclusions

An increasing trend in ASCVD risk scores independently predicted adverse renal outcomes. Continuous monitoring of ASCVD risk is not only important for predicting cardiovascular disease but also for predicting CKD.
Integrative metabolomics differentiate coronary artery disease, peripheral artery disease, and venous thromboembolism risks
Authors: Lee Jiwoo , Gilliland Thomas , Koyama Satoshi , Nakao Tetsushi , Dron Jacqueline , Lannery Kim , Wong Megan , Peloso Gina M. , Hornsby Whitney , Natarajan Pradeep
Published: June 2023

Rationale

Arterial and venous cardiovascular conditions, such as coronary artery disease (CAD), peripheral artery disease (PAD), and venous thromboembolism (VTE), are genetically correlated. Interrogating distinct and overlapping mechanisms may shed new light on disease mechanisms.

Objective

In this study, we aimed to: identify and compare (1) epidemiologic and (2) causal, genetic relationships between metabolites and CAD, PAD, and VTE.

Methods

We used metabolomic data from 95,402 individuals in the UK Biobank, excluding individuals with prevalent cardiovascular disease. Logistic regression models adjusted for age, sex, genotyping array, first five principal components of ancestry, and statin use estimated the epidemiologic associations of 249 metabolites with incident CAD, PAD, or VTE. Bidirectional two-sample Mendelian randomization (MR) estimated the causal effects between metabolites and cardiovascular phenotypes using genome-wide association summary statistics for metabolites (N = 118,466 from UK Biobank), CAD (N = 184,305 from CARDIoGRAMplusC4D 2015), PAD (N = 243,060 from Million Veterans Project) and VTE (N = 650,119 from Million Veterans Project). Multivariable MR (MVMR) was performed in subsequent analyses.

Results

We found that 194, 111, and 69 metabolites were epidemiologically associated (P < 0.001) with CAD, PAD, and VTE, respectively. Metabolomic profiles exhibited variable similarity between disease pairs: CAD and PAD (N = 100 shared associations, R2= 0.499), CAD and VTE (N = 68, R2= 0.455), and PAD and VTE (N = 54, R2= 0.752). MR revealed 28 metabolites that increased risk for both CAD and PAD and 2 metabolites that increased risk for CAD but decreased risk for VTE. Despite strong epidemiologic overlap, no metabolites had a shared genetic relationship between PAD and VTE. MVMR revealed several metabolites with shared causal effects on CAD and PAD related to cholesterol content within very-low-density lipoprotein particles.

Conclusions

While common arterial and venous conditions are associated with overlapping metabolomic profiles, MR prioritized the role of remnant cholesterol in arterial diseases but not venous thrombosis.
Spatial and temporal clustering of anti-SARS-CoV-2 antibodies in Illinois household cats, 2021-2023
Authors: Chen Chi , Martins Mathias , Nooruzzaman Mohammed , Yettapu Dipankar , Diel Diego G. , Reinhart Jennifer M. , Urbasic Ashlee , Robinson Hannah , Varga Csaba , Fang Ying
Published: June 2023

This study evaluated the seroprevalence of SARS-CoV-2 antibodies in Illinois household cats from October 2021 to May 2023. Among 1,715 samples tested by serological assays, 244 samples (14%) tested positive. High-rate temporal, spatial, and space-time clusters of SARS-CoV-2 cases were assessed within 63 counties in Illinois. Three space-time clusters with higher than expected seroprevalence rates were identified in the northeastern, central-east, and southwest regions of Illinois, occurring between June and October 2022. Young cats had a higher seropositivity than older cats, and the third quarter of the year had the highest odds of seropositivity . This study provides an in-depth analysis of SARS-CoV-2 epidemiology in Illinois household cats, which will aid in COVID-19 control and prevention.

Article summary line

SARS-CoV-2 antibody seroprevalence was assessed in Illinois domestic cats, in which a higher seropositivity rate was clustered in the northern, central, and southern Illinois regions with peak periods occurring between June and October 2022.
Characterizing personalized neuropathology in dementia and mild cognitive impairment with explainable artificial intelligence
Authors: Leonardsen Esten H. , Persson Karin , Grødem Edvard , Dinsdale Nicola , Schellhorn Till , Roe James M. , Vidal-Piñeiro Didac , Sørensen Øystein , Kaufmann Tobias , Westman Eric , Marquand Andre , Selbæk Geir , Andreassen Ole A. , Wolfers Thomas , Westlye Lars T. , Wang Yunpeng ,   the Alzheimer’s Disease Neuroimaging,   the Australian Imaging Biomarkers and Lifestyle flagship study of ageing
Published: June 2023

Deep learning approaches for clinical predictions based on magnetic resonance imaging data have shown great promise as a translational technology for diagnosis and prognosis in neurological disorders, but its clinical impact has been limited. This is partially attributed to the opaqueness of deep learning models, causing insufficient understanding of what underlies their decisions. To overcome this, we trained convolutional neural networks on brain scans to differentiate dementia patients from healthy controls, and applied layerwise relevance propagation to procure individual-level explanations of the model predictions. Through extensive validations we demonstrate that deviations recognized by the model corroborate existing knowledge of neuropathology in dementia. By employing the explainable dementia classifier in a longitudinal dataset of patients with mild cognitive impairment, we show that the spatially rich explanations complement the model prediction when forecasting transition to dementia and help characterize the biological manifestation of disease in the individual brain. Overall, our work exemplifies the clinical potential of explainable artificial intelligence in precision medicine.
Uncovering a stability signature of brain dynamics associated with meditation experience using massive time-series feature extraction
Authors: Bailey Neil W , Fulcher Ben D. , Caldwell Bridget , Hill Aron T , Fitzgibbon Bernadette , van Dijk Hanneke , Fitzgerald Paul B
Published: June 2023

Previous research has examined resting electroencephalographic (EEG) data to explore brain activity related to meditation. However, previous research has mostly examined power in different frequency bands. Here we compared >7000 time-series features of the EEG signal to comprehensively characterize brain activity differences in meditators, using many measures that are novel in meditation research. Eyes-closed resting-state EEG data from 49 meditators and 46 non-meditators was decomposed into the top eight principal components (PCs). We extracted 7381 time-series features from each PC and each participant and used them to train classification algorithms to identify meditators. Highly differentiating individual features from successful classifiers were analysed in detail. Only the third PC (which had a central-parietal maximum) showed above-chance classification accuracy (67%,pFDR= 0.007), for which 405 features significantly distinguished meditators (allpFDR< 0.05). Top-performing features indicated that meditators exhibited more consistent statistical properties across shorter subsegments of their EEG time-series (higher stationarity) and displayed an altered distributional shape of values about the mean. By contrast, classifiers trained with traditional band-power measures did not distinguish the groups (pFDR> 0.05). Our novel analysis approach suggests the key signatures of meditators’ brain activity are higher temporal stability and a distribution of time-series values suggestive of longer, larger, or more frequent non-outlying voltage deviations from the mean within the third PC of their EEG data. The higher temporal stability observed in this EEG component might underpin the higher attentional stability associated with meditation. The novel time-series properties identified here have considerable potential for future exploration in meditation research and the analysis of neural dynamics more broadly.