bluuebunny/crossref_metadata_2025 huggingface dataset:
Multifaceted, Brief Intensive Home-Based Exposure Treatment in Patients with Obsessive-Compulsive Disorder Who are Nonresponsive to Regular Cognitive Behavior Therapy: An Uncontrolled Pilot Study
Authors: Remmerswaal Karin C.P. , Batelaan Neeltje M. , van Oppen Patricia , Scholten Willemijn D. , van Balkom Anton J.L.M.
Published: July 2024

Objective:

To test a multifaceted treatment program for patients with obsessive-compulsive disorder (OCD) who did not respond to regular cognitive behavior therapy (CBT). The treatment addresses several factors that may play a role in maintaining OCD.

Methods:

We designed a treatment consisting of a 6-day intensive, individual exposure in vivo with response prevention (ERP) format, with 24 therapist-assisted treatment hours at the patient’s home and 12 self-controlled ERP hours, including behavioral activation and family interventions. Next, we investigated the effect (obsessive-compulsive symptoms, comorbidity, functioning, quality of life, OCD-related interaction patterns) and feasibility (dropout, treatment satisfaction, and organization) of this program using pre-post-tests, pre-follow-up tests, and qualitative data from patients, family members, and therapists.

Results:

In a sample of 22 participants, obsessive-compulsive symptoms (Y-BOCS pre: 28.7, post: 15.9; Wilcoxon S-R tests P<0.01) improved significantly, as did most other effect measures. Results were largely, but not completely, preserved at 3-month follow-up. There was only 1 dropout. Patients, family members, and therapists were satisfied with the treatment. Implementation of the treatment did not pose difficulties.

Conclusions:

In nonresponders with OCD, a multifaceted, brief, intensive home-based ERP program targeting factors maintaining OCD is promising and feasible. Extra care is needed to maintain improvement.
Assessing the Effectiveness of Simulation-Based Education in Emerging Infectious Disease Management
Authors: Yoon Sol , Kim Su Hyun
Published: July 2024

Summary Statement

This systematic review and meta-analysis aimed to thoroughly examine the effectiveness of simulation-based education in the management of emerging infectious diseases, focusing on educational content and methods. Studies published between 2000 and 2022 were identified, and a meta-analysis was conducted using a random-effects model. The findings revealed that simulation-based education significantly enhances various competencies related to managing emerging infectious diseases, encompassing cognitive, negative-affective, positive-affective, and psychomotor outcomes. Subgroup analysis indicated that methods effective in improving competencies include the use of equipment with limited or full patient interaction, simulated or in situ settings, and scenarios involving some interruptions by educators or independent participation of trainees. This review underscores the importance of appropriate methodological considerations in simulation-based education, including equipment, settings, and scenario designs, to optimize educational outcomes in the management of emerging infectious diseases.
Associations of Resilience, Perceived Control of Health, and Depression with Geriatric Outcomes after Surgery
Authors: Miller Matthew J. , Cenzer Irena , Covinsky Kenneth E. , Finlayson Emily , Raue Patrick J. , Tang Vicky L.
Published: July 2024

Objective:

To identify if depression, resilience, and perceived control of health are related to 2.5-year mortality and instrumental activities of daily living (IADL) decline among older adults after surgery

Summary Background Data:

The relationships of psychosocial factors with postoperative mortality and IADL decline among older adults are understudied.

Methods:

We identified 3778 community-dwelling older adults in the Health and Retirement Study (HRS) with Medicare claims for surgery (mean [SD] age: 75.4 [7.8] years, 53.9% women, and 86.0% non-Hispanic White). We assessed associations of depression, resilience, and perceived control of health with 2.5-year postoperative mortality and IADL decline using cox and modified Poisson regression analyses, adjusting for sociodemographic and health variables.

Results:

The incidence of 2.5-year postoperative mortality was 18.5% and IADL decline was 9.4%. Depression was associated with a higher incidence and adjusted hazard [95% CI] of mortality (26% vs. 16%, aHR:1.2[0.9, 1.5]), but high resilience was associated with a lower incidence and adjusted hazard of mortality (9% vs. 21%, aHR:0.6[0.5, 0.8]). Those with depression had higher incidence and adjusted relative risk [95% CI] of IADL decline (17% vs. 7%, aRR:1.6[1.2, 2.2]), but lower incidence and adjusted relative risk of IADL decline was identified for those with high resilience (4% vs. 11%, aRR:0.6[0.4, 1.0]) and high perceived control of health (7% vs. 10%, aRR:0.6[0.4, 1.0]).

Conclusion:

While depression confers greater risk of mortality and IADL decline, higher resilience and perceived control of health may be protective. Addressing psychosocial factors in the peri-operative period may improve outcomes among older adults.
Aspergillus esophagitis in a patient with solid tumors: a case report
Authors: Abi Rached Vanessa , Azar Karine , Gerges Sarah , Hallit Souheil , Akoury Elie , Chahine Georges , Hallit Rabih , Akiki Bassem , Rizk Rita
Published: July 2024

Esophageal aspergillosis is a rare occurrence primarily documented in hematologic malignancies, and only rarely occurring among patients with solid tumors. In this case report, we present the unique case of an 81-year-old Lebanese man who had a remarkable medical history, including four solid tumors. The patient sought medical attention due to dysphagia and weight loss, prompting a gastroscopic examination that revealed a necrotic abscess at the esophagogastric junction. Initial treatment with fluconazole and esomeprazole was administered, but the recurrence of similar symptoms led to a repeat gastroscopy, unveiling a diagnosis of Aspergillus esophagitis. Intravenous voriconazole was promptly initiated; however, the patient developed a significant pericardial effusion and expired, with Aspergillus species identified in the pericardial fluid prior to patient expiring. This exceptional case emphasizes the importance of considering esophageal aspergillosis in cancer patients who present with refractory symptoms such as epigastric pain, dysphagia, nausea, and vomiting, despite symptomatic treatment. Our findings underscore the need for increased awareness and the inclusion of gastrointestinal endoscopy as part of the diagnostic approach for this rare but potentially life-threatening condition.
The Genetic Architecture of the Human Corpus Callosum and its Subregions
Authors: Bhatt Ravi R. , Gadewar Shruti P. , Shetty Ankush , Ba Gari Iyad , Haddad Elizabeth , Javid Shayan , Ramesh Abhinaav , Nourollahimoghadam Elnaz , Zhu Alyssa H. , de Leeuw Christiaan , Thompson Paul M. , Medland Sarah E. , Jahanshad Neda
Published: July 2024

The corpus callosum (CC) is the largest set of white matter fibers connecting the two hemispheres of the brain. In humans, it is essential for coordinating sensorimotor responses, performing associative/executive functions, and representing information in multiple dimensions. Understanding which genetic variants underpin corpus callosum morphometry, and their shared influence on cortical structure and susceptibility to neuropsychiatric disorders, can provide molecular insights into the CC’s role in mediating cortical development and its contribution to neuropsychiatric disease. To characterize the morphometry of the midsagittal corpus callosum, we developed a publicly available artificial intelligence based tool to extract, parcellate, and calculate its total and regional area and thickness. Using the UK Biobank (UKB) and the Adolescent Brain Cognitive Development study (ABCD), we extracted measures of midsagittal corpus callosum morphometry and performed a genome-wide association study (GWAS) meta-analysis of European participants (combinedN= 46,685). We then examined evidence for generalization to the non-European participants of the UKB and ABCD cohorts (combinedN= 7,040). Post-GWAS analyses implicate prenatal intracellular organization and cell growth patterns, and high heritability in regions of open chromatin, suggesting transcriptional activity regulation in early development. Results suggest programmed cell death mediated by the immune system drives the thinning of the posterior body and isthmus. Global and local genetic overlap, along with causal genetic liability, between the corpus callosum, cerebral cortex, and neuropsychiatric disorders such as attention-deficit/hyperactivity and bipolar disorders were identified. These results provide insight into variability of corpus callosum development, its genetic influence on the cerebral cortex, and biological mechanisms related to neuropsychiatric dysfunction.
Ongoing local adaptation to climate change in yarrow (Achillea millefoliumL.)
Authors: Losapio Gianalberto , Doussot Baptiste , Araniti Fabrizio , Bruno Leonardo , Guevara Roger , Dirzo Rodolfo
Published: July 2024

Climate change threatens biodiversity as populations can persist if they migrate or adapt to the rapidly changing conditions of the Anthropocene. However, little is known about the persistence of plant populations under the long-term trends of increasing temperature and drought. We explore whether historical populations of yarrow (Achillea millefoliumL.) surveyed in the 1920s have persisted locally or undergone local extinction after 100 years. We resurveyed historical sites spanning a broad climatic gradient (from 1 m to 3,200 m a.s.l.), examined to what extent plant growth signature (height) has changed over time, and analyzed metabolic diversity. Nine out of ten populations persisted locally and showed phenotypic and metabolic differentiation. The only population potentially extirpated is that of the hottest and driest site. Populations from warm sites in coastal and mountain regions had grown taller than 100 years ago. In contrast, populations from dry sites in lowlands and foothills became shorter. Furthermore, we document differentiation in metabolic diversity involving plant defenses and signaling. Ongoing local adaptation is constrained by changing both temperature and precipitation as well as by biotic interactions. Preserving locally adapted populations and metabolic diversity is key for conservation efforts.
Genomic Epidemiology of Monkeypox Virus During the 2022 Outbreak in New York City
Authors: Akther Saymon , Su Michelle , Wang Jade C. , Amin Helly , Taki Faten , De La Cruz Nelson , Chowdhury Moinuddin , Clabby Tyler , Kopping Erik , Ruiz Victoria E. , Leelawong Mindy , Latash Julia , Johnson Kimberly , Baumgartner Jennifer , Wong Marcia , Olsen Aaron , Fowler Randal C. , Pekar Jonathan C. , Havens Jennifer L. , Vasylyeva Tetyana I. , Wertheim Joel O. , Hughes Scott , Omoregie Enoma
Published: July 2024

New York City (NYC) was one of the hotspots of monkeypox virus (MPXV) infections in the United States during the multi-country mpox outbreak in 2022. This study used the most comprehensive dataset to date to investigate the genomic characteristics of MPXV in NYC. We performed Nextclade lineage assignment, phylogenetic and mutational analyses on 1,138 specimens from 748 individuals at the NYC Public Health Lab in the context of 2,968 MPXV sequences sampled globally. Nextclade lineage assignment showed B.1.12 as a NYC specific lineage and phylogenetic analysis showed NYC and North America specific clades. The majority of mutations showed signatures of APOBEC3 activity. When looking at the intra-host genomic diversity for MPXV, distinct MPXV genomic profiles were observed in 6.4% of individuals with multiple sampled specimens, with at least 4.2% of NYC cases due to multiple MPXV infections from distinct viral strains. Further, 13% of the sequences in infected patients had a lack of concordance between epidemiologic and genetic linkages. This study identified NYC-specific MPXV genomic profiles and provided a conservative estimate of simultaneous infections with multiple MPXV variants, likely due to behavioral risk factors during the peak of the outbreak in July 2022. Improving concordance between genomic and epidemiological clusters for mpox investigations may require expanding partnerships with testing labs, clinics, and community groups to enhance the representativeness of MPXV samples that are available for sequencing.
Genomic prediction of metabolic content in rice grain in response to warmer night conditions
Authors: Bi Ye , Walia Harkamal , Obata Toshihiro , Morota Gota
Published: July 2024

It has been argued that metabolic content can be used as a selection marker to accelerate crop improvement because metabolic profiles in crops are often under genetic control. Evaluating the role of genetics in metabolic variation is a long-standing challenge. Rice, one of the world’s most important staple crops, is known to be sensitive to recent increases in nighttime temperatures. Quantification of metabolic levels can help measure rice responses to high night temperature (HNT) stress. However, the extent of metabolic variation that can be explained by regression on whole-genome molecular markers remains to be evaluated. In the current study, we generated metabolic profiles for mature grains from a subset of rice diversity panel accessions grown under optimal and HNT conditions. Metabolite accumulation was low to moderately heritable, and genomic prediction accuracies of metabolite accumulation were within the expected upper limit set by their genomic heritability estimates. Genomic heritability estimates were slightly higher in the control group than in the HNT group. Genomic correlation estimates for the same metabolite accumulation between the control and HNT conditions indicated the presence of genotype-by-environment interactions. Reproducing kernel Hilbert spaces regression and image-based deep learning improved prediction accuracy, suggesting that some metabolite levels are under non-additive genetic control. Joint analysis of multiple metabolite accumulation simultaneously was effective in improving prediction accuracy by exploiting correlations among metabolites. The current study serves as an important first step in evaluating the cumulative effect of markers in influencing metabolic variation under control and HNT conditions.

Core ideas

Rice is sensitive to increases in nighttime and daytime temperatures

Metabolite accumulation from rice grains was low to moderately heritable

Non-additive genomic prediction models improved prediction accuracy for some metabolites

Results shed new light on the utility of genomic predictions for metabolite accumulation from rice grains
Reduced perceptual error monitoring in autism
Authors: Zuk Nathaniel J. , Weiss Yarden , Akrami Athena , Ahissar Merav
Published: July 2024

Individuals with autism spectrum disorder (ASD) exhibit both slower updating of perceptual priors and reduced online error correction in motor tasks, leading to diminished behavioral flexibility. We hypothesized that these difficulties may be related to atypical activation of anterior cingulate cortex (ACC), known to produce a feedback-related negativity (FRN), measurable with EEG, following erred motor responses. We reasoned that ACC might also monitor perceptual performance and produce FRN following “incorrect” perceptual feedback. Participants performed a two-tone pitch discrimination task. Overall behavioral performance and EEG responses to stimuli did not differ between individuals with and without autism. However, almost all (33/35) non-autistics produced a clear perceptual FRN, while less than half (13/30) of autistic participants did. Behaviorally, non-autistics showed response slowing following incorrect trials, improved accuracy after difficult correct trials, and greater influence of perceptual priors following easy successful trials. In contrast, ASD participants did not exhibit these patterns. By examining FRN in a perceptual decision-making task involving feedback dependent choice updates, we demonstrated that FRN differs between ASD and non-autistic individuals and is associated with distinct behavioral differences. This study is the first to measure FRN in such a task, revealing significant disparities. Our findings suggest atypical ACC activation and insensitivity to feedback contribute to reduced behavioral flexibility in ASD, particularly when feedback is essential for performance update.

Significance statement

A characteristic of autism is cognitive “slowness” in updating expectations in new contexts. Our study shows that this cognitive difference is related to a reduced use of feedback, linked to atypical activity in a brain area involved in error detection and behavioral adjustment. Using EEG, we found that autistic individuals have weaker feedback-related signals and do not adjust their behavior as effectively as non-autistic individuals. This effect was significant enough to serve as a potential biomarker for autism. This is the first time such brain responses have been measured in a perceptual task requiring continuous adjustments. Understanding these brain mechanisms can inform strategies to enhance learning and adaptability in autism, providing new insights into the neural basis of behavioral flexibility.
Causal Estimands for Analyses of Averted and Avertible Outcomes due to Infectious Disease Interventions
Authors: Jia Katherine M , Boyer Christopher B , Wallinga Jacco , Lipsitch Marc
Published: July 2024

During the coronavirus disease (COVID-19) pandemic, researchers attempted to estimate the number of averted and avertible outcomes due to non-pharmaceutical interventions or vaccination campaigns to quantify public health impact. However, the estimands used in these analyses have not been previously formalized. It is also unclear how these analyses relate to the broader framework of direct, indirect, total, and overall causal effects of an intervention under interference. In this study, using potential outcome notation, we adjust the direct and overall effects to accommodate analyses of averted and avertible outcomes. We use this framework to interrogate the commonly-held assumption in empirical studies that vaccine-averted outcomes via direct impact among vaccinated individuals (or vaccine-avertible outcomes via direct impact among unvaccinated individuals) is a lower bound on vaccine-averted (or -avertible) outcomes overall. To do so, we describe a susceptible-infected-recovered-death model stratified by vaccination status. When vaccine efficacies wane, the lower bound fails for vaccine-avertible outcomes. When transmission or fatality parameters increase over time, the lower bound fails for both vaccine-averted and -avertible outcomes. Only in the simplest scenario where vaccine efficacies, transmission, and fatality parameters are constant over time, outcomes averted via direct impact among vaccinated individuals (or outcomes avertible via direct impact among unvaccinated individuals) is shown to be a lower bound on overall impact on vaccine-averted (or -avertible) outcomes. In conclusion, the lower bound can fail under common violations to assumptions on constant vaccine efficacy, pathogen properties, or behavioral parameters over time. In real data analyses, estimating what seems like a lower bound on overall impact through estimating direct impact may be inadvisable without examining the directions of indirect effects. By classifying estimands for averted and avertible outcomes and examining their relations, this study improves conduct and interpretation of research evaluating impact of infectious disease interventions.
Peer victimization in adolescence alters gene expression and cytokine profiles during transition to adulthood
Authors: Heumann Jens , Cole Steve W. , Eisner Manuel , Ribeaud Denis , Grünblatt Edna , Shanahan Michael J.
Published: July 2024

Social adversity downregulates antiviral genes and upregulates inflammatory genes, altering cytokine levels. This study investigated the effects of peer victimization (PV) during adolescence on gene expression, cellular dynamics, and cytokine profiles in young adulthood. Data from the Zurich Brain and Immune Gene Study (z-GIG,n= 200; 47% female) captured PV between ages 11 and 20, with mRNA and plasma cytokines analyzed in 144 participants at age 22. A counterfactual design with genetically informed inverse probability weighting adjusted for baseline confounders in individual and environmental characteristics.In silicodeconvolution revealed altered leukocyte composition in victims, including an M2-like monocyte–skewed profile. Differentially expressed genes in victims were enriched in preselected Reactome pathways, includingInterferon signaling, MetabolismandSignal transduction. Exploratory Reactome-wide queries confirmed pathways in theImmune SystemandMetabolism, highlighted their downregulation, and identified additional pathways, such as those involved inChromatin organizationandMetabolism of proteins. Transcription factors STAT2, IRF2, and NF-κB emerged as key regulators in victims, with target genes prominently mapped to Interferon signaling and Chromatin organization pathways. Victims exhibited altered cytokine levels, including pro-inflammatory CCL4, TNF, CXCL9, and CXCL10. These findings suggest that adolescent PV can lead to changes in gene regulation and cytokine levels, potentially altering the immune profile into young adulthood. The results underscore the importance of health policies aimed at prevention, building resilience, and mitigating the long-term effects of PV.
The valine-arginine dipeptide repeat protein encoded by mammalian telomeric RNA appears highly expressed in mitosis and may repress global translation
Authors: Al-Turki Taghreed M. , Mantri Venkata , Willcox Smaranda , Mills C. Allie , Herring Laura E. , Cho Su-Ji , Lee Hannah , Meyer Cailyn , Anton E. S. , Griffith Jack D.
Published: July 2024

Translation of mammalian telomeric G-rich RNA via the Repeat Associated non-AUG translation mechanism can produce two dipeptide repeat proteins: repeating valine-arginine (VR) and repeating glycine-leucine (GL). Their potentially toxic nature suggests that one or both must play a needed role in the cell. Using light microscopy combined with antibody staining we discovered that cultured human cells stain brightly for VR during mitosis with VR staining co-localizing with ribosomes.In vitro, VR protein represses translation in a firefly luciferase assay. Affinity purification combined with mass spectrometry identified ribosomal proteins as the major class of VR interacting proteins. Extension to mouse embryonic cerebral cortical development showed strong staining in the ventricular zone where high mitotic index neural progenitor cells proliferate and in the cortical plate where new neurons settle. These observations point to VR playing a key role in mitosis very possibly depressing global translation, a role mediated by the telomere.

Teaser

The telomeric valine-arginine dipeptide repeat protein is highly expressed in mitotic cells in culture and in mouse embryonic neural tissue.
ThunderBolt: An interactive data sharing and analysis platform for large-omics experiments
Authors: Geddes Thomas Andrew , Chaudhuri Rima , Parker Benjamin L. , Yang Pengyi , Burchfield James G.
Published: July 2024

Mass-spectrometry (MS) datasets present a unique set of challenges that make in-depth bioinformatics analysis non-trivial, with analysis requiring both expertise and time. Often these datasets have unique structures that need to be dealt with on an individual basis. Currently, tools providing a fast, interactive and guided way of exploring and analysing these data sets are not readily available. To this end, we have developed ThunderBolt: a highly interactive, point-and-click web-based application providing both bioinformaticians and biologists with a platform for i) searching and comparing multiple omics datasets, ii) fast data exploration and quality control, iii) interactive visualization, iv) pre-processing, v) statistical analysis and vi) functional and network enrichment analysis of large proteomics datasets using the Shiny framework.

Availability

ThunderBolt is a shiny-application accessible athttps://thunderbolt.sydney.edu.au/

Contact

james.burchfield@sydney.edu.au

Supplementary information
Endoglin regulates the integrity of the bone marrow vasculature
Authors: Rodriguez Diego , Jaykar Mangesh , Watts Deepika , Sinha Anupam , Gaete Diana , Krüger Anja , Mirtschink Peter , Rauner Martina , Chavakis Triantafyllos , Arthur Helen M. , Wielockx Ben
Published: July 2024

Endoglin (Eng) is an accessory receptor for transforming growth factor-β (TGF-β) that is critical for maintaining vascular integrity. Mutations in Eng cause hereditary hemorrhagic telangiectasia (HHT), resulting in arteriovenous malformations (AVMs) and blood abnormalities. Despite the known association between Eng deficiency and AVMs, the underlying mechanisms are unclear. In addition, the role of the bone marrow (BM), a major source of immune and blood cells, in endothelial Eng (EC-Eng) deficiency is unexplored. We show that BM blood vessels conditionally deficient in Eng (cKO) undergo a structured remodeling process over four weeks, with distinct proliferative and resolution phases. These phases involve angiogenic set points, the involvement of integrins, and the modulation of vascular integrity. In addition, we observe changes in hematopoietic stem and progenitor cells (HSPC) and circulating granulocytes, along with reduced red blood cells and platelets due to splenic sequestration. Using a conditional heterozygous EC-Eng deficient mouse model, reflecting the genetics of HHT patients, we identify vascular changes similar to those in the cKO model. Taken together, using multiplein vivoapproaches, we suggest that reduced Eng expression in the endothelium drives significant BM vascular remodeling, sharing mechanisms with early vascular processes associated with AVM formation.

Explanation of Novelty

Our findings reveal that BM blood vessels deficient in endoglin undergo an orchestrated remodeling process with distinct proliferative and resolution phases over several weeks. We identify specific angiogenic set points and profound alterations in vascular integrity, along with hematopoietic changes starting at the level of hematopoietic stem and progenitor cells. These findings advance our understanding of the role of Eng in vascular remodeling and may provide novel therapeutic targets for HHT.

Key Points

Conditional EC-Eng deficiency leads to vascular remodeling in the BM of mice in a temporally orchestrated manner.

EC-Eng facilitates vascular integrity, hematopoietic homeostasis, and immune cell mobilization.
Postnatal xanthine metabolism regulates cardiac regeneration in mammals
Authors: Saito Yuichi , Sugiura Yuki , Sakaguchi Akane , Sada Tai , Nishiyama Chihiro , Maeda Rae , Kaneko Mari , Kiyonari Hiroshi , Kimura Wataru
Published: July 2024

Postnatal cardiomyocyte cell cycle withdrawal is a critical step wherein the mammalian heart loses regenerative potential after birth. Here, we conducted interspecies multi-omic comparisons between the mouse heart and that of the opossum, which have different postnatal time-windows for cardiomyocyte cell cycle withdrawal. Xanthine metabolism was activated in both postnatal hearts in parallel with cardiomyocyte cell cycle arrest. The pentose phosphate pathway (PPP) which produces NADPH was found to decrease simultaneously. Postnatal myocardial tissues became oxidized accordingly, and administration of antioxidants to neonatal mice altered the PPP and suppressed the postnatal activation of cardiac xanthine metabolism. These results suggest a redox-dependent postnatal switch from purine synthesis to degradation in the heart. Inhibition of xanthine metabolism in the postnatal heart extended postnatal duration of cardiomyocyte proliferation and maintained postnatal heart regeneration potential in mice. These findings highlight a novel role of xanthine metabolism as a metabolic regulator of cardiac regeneration potential.
The impact of antibiotics on the presence of the protozoan anaerobeBlastocystisand the surrounding microbiome: a case study
Authors: Newton Jamie M. , Edwards William JS. , Thompson Gary , Gentekaki Eleni , Tsaousis Anastasios D.
Published: July 2024

Background

Blastocystis, the most prevalent eukaryotic gut microbe in humans, has a global distribution. Studies have linked its presence with distinct gut microbiome and metabolome profiles compared to those where the organism is absent. However, the in vivo effect of antibiotics onBlastocystisand the surrounding gut microbiome remains understudied. This case study aimed to explore how antibiotic consumption influences the presence ofBlastocystisand the subsequent changes in the gut microbiome and metabolome of an individual with irritable bowel syndrome (IBS).

Methods

Stool samples from an IBS patient, collected at various time points, were tested forBlastocystispresence using RT-PCR targeting theSSUrRNAgene, followed by sequencing of positive samples. Illumina sequencing determined the gut microbiome composition, while one-dimensional proton NMR spectroscopy analysed the metabolome composition. Statistical analyses were conducted to identify relationships between antibiotic consumption, bacterial diversity, metabolome composition, andBlastocystispresence.

Results

Antibiotics significantly impacted the gut microbiome, with diversity declining early in the antibiotic course, then recovering later and post-course.Blastocystiswas detected early, late, and post-course but not mid-course, coinciding with the decline in bacterial diversity. No significant differences were observed betweenBlastocystis-positive andBlastocystis-negative samples. However, bacterial composition significantly differed between samples collected before, early, and after the antibiotic course compared to those collected mid-course. Metabolite groups, including short-chain fatty acids, amino acids, and succinate, exhibited changes throughout the antibiotic course, indicating that gut metabolite composition is affected by antibiotic consumption.

Discussion/Conclusion

While antibiotics did not significantly impactBlastocystiscolonisation, they did cause a mid-course decline in microbial diversity andBlastocystispresence. The study also revealed significant alterations in important metabolites such as SCFAs and amino acids throughout the antibiotic course, with an altered metabolome observed post-course. This case study underscores the complex interactions between antibiotics, gut microbiota, and metabolites, highlighting the resilience ofBlastocystisin the gut ecosystem.
Trends in syphilis prevalence by race and ethnicity among people who are pregnant in the United States 2016–2023
Authors: Liang Yizhi , Menzies Nicolas A , Rönn Minttu M
Published: July 2024

Background

This study aimed to estimate syphilis prevalence among people who are pregnant with live births by race and ethnicity 2016–2023.

Methods

We analyzed data on syphilis infection from U.S. birth certificates using a Bayesian mathematical model, adjusting for test sensitivity, specificity, and screening coverage. We calibrated the model under two scenarios: (1) assuming screening coverage is as estimated in Medicaid claims data and (2) assuming higher screening coverage than observed in Medicaid claims data. We compared the estimates to stillbirths attributable to syphilis reported through routine surveillance. We examined racial and ethnic disparities using the index of disparity.

Results

In Scenario 1, syphilis prevalence among people who are pregnant with live births increased from 101.1 (95% uncertainty interval [UI]: 87.5–120.5) per 100,000 live births in 2016 to 533.4 (95% UI: 496.6–581.0) per 100,000 live births in 202. In Scenario 2, prevalence increased from 73.9 (95% UI: 51.2–130.0) per 100,000 live births to 378.1 (95% UI: 295.5–592.0) per 100,000 live births over the same period. With rising prevalence, relative racial and ethnic disparities narrowed over time. Prevalence was estimated to be higher among women with stillbirths compared to women with live births.

Conclusions

In the United States, improved estimates of screening coverage are needed to understand the gaps in congenital syphilis prevention and to inform estimates of syphilis prevalence among pregnant persons.

One sentence summary line

In the United States, we estimated an increasing syphilis prevalence among people who are pregnant, reaching 533 per 100,000 live births in 2023, with notable racial and ethnic disparities.
Impact of active case finding for tuberculosis with mass chest X-ray screening in Glasgow, Scotland, 1950-1963: an epidemiological analysis of historical data
Authors: MacPherson Peter , Stagg Helen R , Schwalb Alvaro , Henderson Hazel , Taylor Alice E , Burke Rachael M , Rickman Hannah M , Miller Cecily , Houben Rein MGJ , Dodd Peter J , Corbett Elizabeth L
Published: July 2024

Background

Community active case finding for tuberculosis was widely implemented in Europe and North America between 1940-1970, when incidence was comparable to many present-day high-burden countries. Using an interrupted time series analysis, we analysed the effect of the 1957 Glasgow mass chest X-ray campaign to inform contemporary approaches to screening.

Methods and findings

Case notifications for 1950-1963 were extracted from public health records and linked to demographic data. We fitted Bayesian multilevel regression models to estimate annual relative case notification rates (CNR) during and after a mass screening intervention implemented over five weeks in 1957 compared to the counterfactual scenario where the intervention had not occurred. We additionally estimated case detection ratios and incidence. From 11/3/1957-12/4/1957, 714,915 people (622,349 of 819,301 [76.0%] resident adults ≥15 years) were screened with miniature chest X-ray; 2,369 (0.4%) were diagnosed with tuberculosis. Pre-intervention (1950-1956), pulmonary CNRs were declining at 2.3% per year from a CNR of 222/100,000 in 1950. With the intervention in 1957, there was a doubling in the pulmonary CNR (RR: 1.95, 95% uncertainty interval [UI]: 1.80-2.11), and 36% decline in the year after (RR: 0.64, 95%UI: 0.59-0.71). Post-intervention (1958-1963) annual rates of decline (5.4% per year) were greater (RR: 0.77, 95%UI: 0.69-0.85), and there were an estimated 4,656 (95%UI: 3,670-5,725) pulmonary case notifications averted due to the intervention. Effects were consistent across all city wards and notifications declined substantially in young children (0-5 years) with the intervention.

Conclusions

A single, rapid round of mass screening with chest X-ray (probably the largest ever conducted) resulted in a major and sustained reduction in tuberculosis case notifications. Contemporary high-burden settings may achieve similar benefits with high-intensity screening.
Protein signatures associated with loneliness and social isolation: plasma proteome analyses in the English Longitudinal Study of Ageing, with causal evidence from Mendelian randomization
Authors: Gong Jessica , Preminger Zohar , Steptoe Andrew , Fancourt Daisy
Published: July 2024

The understanding of biological pathways related to loneliness and social isolation remains incomplete. Cutting-edge population-based proteomics offers opportunities to uncover novel biological pathways linked to social deficits. This study employed a proteome-wide and data-driven approach to estimate the cross-sectional associations between objective measures of social connections (i.e., social isolation) and subjective measures (i.e., loneliness) with protein abundance, using the English Longitudinal Study of Ageing. Greater social isolation was associated with higher levels of 11 proteins (TNFRSF10A, MMP12, TRAIL-R2, SKR3, TNFRSF11A, VSIG2, PRSS8, FGFR2, KIM1, REN, and NEFL) after minimal adjustments; and three proteins were significantly associated after full adjustments (TNFRSF10A, TNFRSF11A, and HAOX1). Findings from two-sample Mendelian randomization indicated that a lower frequency of in-person social contact with friends or family causally increased levels of TNFRSF10A, TRAIL-R2, TNFRSF11A, and KIM1, and decreased the level of NEFL. The study also highlighted several enriched biological pathways, including necrosis and cell death regulation, dimerization of procaspase-8, and inhibition of caspase-8 pathways, which have previously not been linked to social deficits. These findings could help explain the relationship between social deficits and disease, confirming the importance of continuing to explore novel biological pathways associated with social deficits.
Long-term neurological and gastrointestinal sequelae of SARS-CoV-2, influenza, and other neurotropic infections with and without vaccination
Authors: Konings Bo , Villatoro Luisa , Burns Robert , Barahona Guillermo , McKnight Megan , Hui Ken , Tack Jan , Pasricha Pankaj Jay
Published: July 2024

COVID-19 increases the risk of neurological and gastrointestinal sequelae, but it is unclear if it does so more than other infections. Using a multicenter record network, we matched 649,478 COVID-19 patients to negative controls (NCs) and patients infected with influenza, human herpesvirusses, and lyme’s disease (LD) to compare new-onset gastrointestinal (GISx), autonomic (ANSx), sensory (SNSx), and motor (MNSx) symptoms 3-12 months after infection. ANSx showed significant increases compared to NCs (odds ratio (OR) 1.34; confidence interval (CI) 1.31-1.36) and most other investigated infections (LD, influenza, infectious mononucleosis, and herpes zoster; OR 1.40, 1.13, 1.11, and 1.05, respectively). SNSx (OR 1.35; CI 1.31-1.39), MNSx (OR 1.32; CI 1.28-1.36) and GISx (OR 1.36; CI 1.33-1.38) were increased but varied more compared with other infections. COVID-19 vaccination reduced the risk of GISx, ANSx, and SNSx. Sequelae frequently ascribed to COVID-19 may manifest with similar or higher frequency after other infections, except ANSx.
Understanding Opportunities for Prescribing Pre-exposure Prophylaxis (PrEP) at Two Academic Medical Centers in a High Priority Jurisdiction for Ending the HIV Epidemic
Authors: McNulty Moira C. , McGuckin Katherine , Friedman Eleanor E. , Caputo Matthew , Mason Joseph A. , Devlin Samantha A. , Giurcanu Mihai , Hazra Anu , Ridgway Jessica P. , Achenbach Chad J.
Published: July 2024

Introduction

Pre-exposure prophylaxis (PrEP) is an effective, yet underutilized tool for HIV prevention. We sought to understand practice patterns and opportunities for prescribing PrEP across two large, urban, academic healthcare institutions in Chicago, Illinois.

Methods

We analyzed electronic medical record data from two institutions including encounters for persons ≥18 years of age with ≥1 negative HIV test between 1/1/2015-12/31/2021 who had indications for PrEP. Eligible encounters were those within a six-month window after STI diagnosis, or as long as injection drug use (IDU) was documented. We categorized encounters as inpatient, emergency department (ED), primary care, infectious disease (ID), obstetrics and gynecology/women’s health (OBGYN) and other outpatient settings. We performed bivariable and multivariable mixed effects regression models to examine associations, reporting odds ratios (or adjusted odds ratios) and 95% confidence intervals (OR, aOR, 95% CI).

Results

In total, 9644 persons contributed 53031 encounters that resulted in 4653 PrEP prescriptions. The two healthcare institutions had differing patient demographics; institution A had more 18–24 year-olds (58.3% vs 31.3%), more African Americans (83.8% vs 27.9%), and more women (65.7% vs 46.3%). Institution B had more White (40.6% vs 7.1%) and Hispanic persons (14.0% vs 4.2%), and more men who have sex with men (MSM) (15.2% vs 3.3%). Institution A had more eligible encounters in the ED (30.8% vs 7.3%) as well as in infectious disease, inpatient, OBYGN, and primary care settings. Institution B accounted for the majority of PrEP prescriptions (97.0%).

Adjusted models found lower odds of PrEP prescriptions in non-Hispanic Black (aOR 0.23 [0.16, 0.32]) and Latino (aOR 0.62 [0.44, 0.89]) patients, those with injection drug use (aOR 0.01 [0.00, 0.09]), men who have sex with women (aOR 0.36 [0.23, 0.56]), women who have sex with men (aOR 0.11 [0.06, 0.19]), and in the ED (ref) or OBGYN (0.11 [0.04, 0.27]) settings; while increased odds of PrEP prescription were associated with non-Hispanic White (ref) and MSM (aOR 24.87 [15.79, 39.15]) patients, and encounters at Institution B (aOR 1.78 [1.25, 2.53]) and in infectious disease (aOR [11.92 [7.65, 18.58]), primary care (aOR 2.76 [1.90, 4.01]), and other outpatient subspecialty settings (aOR 2.67 [1.84, 3.87]).

Conclusions

Institution A contained persons historically underrepresented in PrEP prescriptions, while institution B accounted for most PrEP prescriptions. Opportunities exist to improve equity in PrEP prescribing and across ED and OBGYN settings.
LDAK-KVIK performs fast and powerful mixed-model association analysis of quantitative and binary phenotypes
Authors: Hof Jasper P. , Speed Doug
Published: July 2024

Mixed-model association analysis (MMAA) is the preferred tool for performing a genome-wide association study, because it enables robust control of type 1 error and increased statistical power to detect trait-associated loci. However, existing MMAA tools often suffer from long runtimes and high memory requirements. We present LDAK-KVIK, a novel MMAA tool for analyzing quantitative and binary phenotypes. Using simulated phenotypes, we show that LDAK-KVIK produces well-calibrated test statistics, both for homogeneous and heterogeneous datasets. LDAK-KVIK is computationally-efficient, requiring less than 20 CPU hours and 8Gb memory to analyse genome-wide data for 350k individuals. These demands are similar to those of REGENIE, one of the most efficient existing MMAA tools, and up to 30 times less than those of BOLT-LMM, currently the most powerful MMAA tool. When applied to real phenotypes, LDAK-KVIK has the highest power of all tools considered. For example, across 40 quantitative phenotypes from the UK Biobank (average sample size 349k), LDAK-KVIK finds 16% more significant loci than classical linear regression, whereas BOLT-LMM and REGENIE find 15% and 11% more, respectively. LDAK-KVIK can also perform gene-based tests; across the 40 quantitative UK Biobank phenotypes, LDAK-KVIK finds 18% more significant genes than the leading existing tool.
Seroprevalence of HumanBrucellaAntibodies and associated Among Patients Seeking Medical Attention at Community Hospitals in Selected Districts of Western Province in Zambia
Authors: Mambote Armand Mayindu , Muma John Bwalya , Mubiana Mary , Mudenda Steward , Daka Victor , Mubanga Melai , Bumbangi Flavien Nsoni , Chitalu Chanda , Mfune Ruth Lindizyani
Published: July 2024

Introduction

Brucellosis is a neglected zoonotic disease that affects humans and animals and can lead to severe illness in humans and financial losses for households that rear livestock. The study aimed to investigate the seroprevalence of humanBrucellaantibodies and associated risk factors among patients seeking medical attention at community hospitals.

Methods

A cross-sectional seroepidemiological study was conducted from 21stApril 2021 to 21stApril 2024 among patients seeking medical attention at community hospitals in selected districts of Western province in Zambia. 225 blood samples were collected from consenting participants. Sera were separated and analysed for anti-Brucellaantibodies using the Rose Bengal Test (RBT) and Competitive enzyme-linked immunosorbent assay (c-ELISA) in parallel. A questionnaire was administered to obtain epidemiological data related to exposure to theBrucellapathogen. The data obtained were coded and entered in the Micro-Soft Excel 2013® and analysed using STATA version 15®.

Results

197 sera samples were found acceptable for testing and analysis for this study, out of these, the seroprevalence ofBrucellaantibodies was 18.3% (n=36, 95% CI=0.13-0.24) and 4.57% (n=9, 95% CI=-0.68-0.28) on RBT and c-ELISA respectively.Among the risk factors considered, the number of animals was statistically significantly associated withBrucellaseropositivity (OR 6.49, 95% CI=1.10-38.13, p-value = 0.039).

Conclusions

Brucellaantibodies are prevalent among patients attending health facilities in the Western province of Zambia. The number of animals were significantly associated with theBrucellaseropositivity.
An optimised approach to evaluate variability in gut health markers in healthy adults
Authors: Krüger Kirsten , Myeonghyun Yoou , van der Wielen Nicky , Kok Dieuwertje , Hooiveld Guido J. , Keshtkar Shohreh , Diepeveen-de Bruin Marlies , Balvers Michiel G.J. , Grootte-Bromhaar Mechteld , Mudde Karin , Ly Nhien T.H.N , Vermeiren Yannick , de Groot Lisette C.P.G.M , de Vos Ric C.H. , Gonzales Gerard Bryan , Steegenga Wilma T. , van Trijp Mara P.H.
Published: July 2024

Despite advances in gut health research, the variability of important gut markers within individuals over time remains underexplored. We investigated the intra-individual variation of various faecal gut health markers using an optimised processing protocol aimed at reducing variability. Faecal samples from ten healthy adults over three consecutive days demonstrated marker-specific intra-individual coefficients of variation (CV%), namely: stool consistency (16.5%), water content (5.7%), pH (3.9%), total SCFAs (17.2%), total BCFAs (27.4%), total bacteria and fungi copies (40.6% and 66.7%), calprotectin and myeloperoxidase (63.8% and 106.5%), and untargeted metabolites (on average 40%). For thirteen microbiota genera, includingBifidobacteriumandAkkermansia, variability exceeded 30%, whereas microbiota diversity was less variable (Phylogenetic Diversity 3.3%, Inverse Simpson 17.2%). Mill-homogenisation of frozen faeces significantly reduced the replicates CV% for total SCFAs (20.4% to 7.5%) and total BCFAs (15.9% to 7.8%), and untargeted metabolites compared to only faecal hammering, without altering mean concentrations. Our results show the potential need for repeated sampling to accurately represent specific gut health markers. We also demonstrated the effectiveness of optimised preprocessing of stool samples in reducing overall analytical variability.
Endothelial TRPV4/Cx43 Signaling Complex Regulates Vasomotor Tone in Resistance Arteries
Authors: Burboa Pía C. , Gaete Pablo S. , Shu Ping , Araujo Priscila A. , Beuve Annie V. , Durán Walter N. , Contreras Jorge E. , Lillo Mauricio A.
Published: July 2024

S-nitrosylation of Cx43 gap junction channels critically regulates communication between smooth muscle cells and endothelial cells. This posttranslational modification also induces the opening of undocked Cx43 hemichannels. However, its specific impact on vasomotor regulation remains unclear. Considering the role of endothelial TRPV4 channel activation in promoting vasodilation through nitric oxide (NO) production, we investigated the direct modulation of endothelial Cx43 hemichannels by TRPV4 channel activation. Using the proximity ligation assay, we identify that Cx43 and TRPV4 are found in close proximity in the endothelium of resistance arteries. In primary endothelial cell cultures from resistance arteries (ECs), GSK-induced TRPV4 activation enhances eNOS activity, increases NO production, and opens Cx43 hemichannels via direct S-nitrosylation. Notably, the elevated intracellular Ca2+levels caused by TRPV4 activation were reduced by blocking Cx43 hemichannels. In ex vivo mesenteric arteries, inhibiting Cx43 hemichannels reduced endothelial hyperpolarization without affecting NO production in ECs, underscoring a critical role of TRPV4/Cx43 signaling in endothelial electrical behavior. We perturbed the proximity of Cx43/TRPV4 by disrupting lipid rafts in ECs using β-cyclodextrin. Under these conditions, hemichannel activity, Ca2+influx, and endothelial hyperpolarization were blunted upon GSK stimulation. Intravital microscopy of mesenteric arteriolesin vivofurther demonstrated that inhibiting Cx43 hemichannels activity, NO production and disrupting endothelial integrity reduce TRPV4-induced relaxation. These findings underscore a new pivotal role of Cx43 hemichannel associated with TRPV4 signaling pathway in modulating endothelial electrical behavior and vasomotor tone regulation.