bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of Chronic Hepatitis B Virus Infection, Alameda County, California, 2017-2021
Authors: Yette Emily , Marusinec Rachel , Conlon Craig , Pham Thi T. Hang , Toy Mehlika , So Samuel , Wong Robert J. , Chitnis Amit S. 
Published: September 2024

Context
In the United States, chronic hepatitis B (CHB) virus infection predominantly affects ethnic minorities and vulnerable populations.

Objective
We analyzed surveillance data to describe CHB epidemiology to guide hepatitis B virus (HBV) elimination efforts in Alameda County.

Design
Persons with CHB during 2017-2021 were identified by ≥2 positive HBV tests (ie, HBsAg, HbeAg, and HBV DNA) ≥180 days apart using data from California Reportable Disease Information Exchange. Persons with CHB were stratified by age, race/ethnicity, zip code-based Healthy Places Index (HPI), and federally designated Medically Underserved Areas (MUA). Comparisons of reported CHB prevalence between groups utilized z test; comparisons between MUA regions utilized chi-square testing.

Results
A total of 8122 persons with CHB were identified; reported 5-year CHB prevalence was 0.53% (95% confidence interval: 0.52%–0.54%). Reported CHB 5-year prevalence was significantly higher among persons aged 50 to 69 years old than persons aged 30 to 49 years old (0.99%, 0.78%; P < .001) and Asians, Native Hawaiian/Pacific Islanders, African Americans compared to Whites (1.22%, 0.56%, 0.18%, 0.06%; P < .001). Reported CHB 5-year prevalence in the 2 lowest and most disadvantaged HPI quartiles was significantly higher than the 2 highest quartiles (0.55%, 0.68%, 0.37%, 0.42%; P < .001). The 1918 persons with CHB in MUA, compared to 5859 non-MUA persons, were significantly more likely to be African American (7%, 3%; P < .001) and from the lowest HPI quartile (79%, 19%; P < .001).

Conclusions
Reported CHB 5-year prevalence in Alameda County was 1.5 times the national prevalence estimates, and reported prevalence was highest among Asians and persons in more disadvantaged areas. Analysis of local CHB surveillance data can guide public health efforts toward HBV elimination.
Decompressive nerve surgery associated with low diabetic foot ulcer rate and high-risk bias: A systematic review and meta-analysis
Authors: Louca Milton , Meares Charles , Dusseldorp Joseph R. 
Published: September 2024

Background:
Diabetic sensorimotor polyneuropathy (DSPN) occurs in 50% of diabetes mellitus (DM) patients. Up to 70% of DM patients incur diabetic foot ulcer(s) (DFU). Of those with DSPN, 20% develop DFU and medical therapy remains challenging. Decompression nerve surgery (DNS) purportedly improves DSPN and DFU. Currently, there is no accurate, pooled DFU incidence post-DNS. Thus, this systematic review meta-analyses DFU incidence post-DNS. Given the 60% global DFU incidence, we hypothesised a lower, pooled DFU incidence following DNS.

Methods:
Two authors searched six databases (MEDLINE/PubMed/Web of Science/Embase/Scopus/Cochrane/Google Scholar) to July 2023 for DNS clinical studies. Primary tracked outcomes were new and recurrent DFU incidence post-DNS. Inclusion criteria: clinical studies, adult DM patients, DNS of tibial nerve(s) at minimum, three-month minimum follow-up, and reported new/recurrent DFU incidence post-DNS. Exclusion criteria: non-clinical, non-human studies. GRADE and MINORS instrument(s) evaluated evidence. With random-effects model, DFU incidence was meta-analysed.

Results:
For inclusion, 1074 studies were identified and 208 screened. Thirteen studies yielded 2466 and 540 new and recurrent patients with DFU incidence(s) of 1% and 5%, respectively. Primary studies had low-level evidence and high-risk bias, including selection bias using Cochrane Collaboration Bias Risk Tool. A sub-analysis of sample size (new:0% and recurrent:2%) and follow-up length (new:1% and recurrent:7%) produced similar results. Additional analyses based on further co-variables was precluded because of incomplete primary study data.

Conclusions:
Overall, despite low DFU incidence post-DNS, clinical studies provide too low-level evidence and high-risk bias for any recommendations. Future randomized, control trials may validate DNS for DFU management.
Association of cardiovascular disease risk with liver steatosis and fibrosis in people with HIV in low- and middle-income countries
Authors: Kuniholm Mark H. , Murenzi Gad , Shumbusho Fabienne , Brazier Ellen , Plaisy Marie K. , Mensah Ephrem , Wandeler Gilles , Riebensahm Carlotta , Chihota Belinda V. , Samala Niharika , Diero Lameck , Semeere Aggrey S. , Chanyachukul Thida , Borse Rohidas , Nguyen Dung T.H. , Perazzo Hugo , Lopez-Iniguez Alvaro , Castilho Jessica L. , Maruri Fernanda , Jaquet Antoine 
Published: September 2024

Objective:
The aim of this study was to understand the relationship between cardiovascular disease (CVD) risk and liver steatosis and fibrosis among people with HIV (PLWH) at least 40 years of age on antiretroviral therapy (ART) in low and middle-income countries (LMIC).

Design:
We used cross-sectional behavioral and clinical data collected during study enrollment visits in 2020–2022 for the Sentinel Research Network of International epidemiology Databases to Evaluate AIDS (SRN of IeDEA).

Methods:
Ten-year CVD risk was calculated using 2019 WHO nonlaboratory and laboratory models. Transient elastography was used to assess liver disease. Presence of steatosis and significant fibrosis were defined by controlled attenuation parameter (CAP) at least 248 dB/m and liver stiffness measurement (LSM) at least 7.1 kPa, respectively. Participants with viral hepatitis, hazardous alcohol consumption, and unsuppressed HIV viral load were excluded from the analysis. Logistic regression was used to estimate odds ratios, adjusting for study site, CD4+ T cell count, stavudine and didanosine exposure, and in models stratified by sex and geographic region.

Results:
There were 1750 participants from nine LMIC. Median CVD risk was 3% for both nonlaboratory and laboratory-based models. Adjusted odds ratios (ORs) for steatosis and significant fibrosis associated with laboratory CVD risk (≥10 vs. <5%) were OR = 1.83 [95% confidence interval (95% CI) = 1.21–2.76; P = 0.004] and OR = 1.62 (95% CI = 0.85–3.07; P = 0.14), respectively. Associations of CVD risk with steatosis were stronger in men and among participants at study sites outside Africa.

Conclusion:
Higher CVD risk was associated with steatosis but not with significant fibrosis in PWH in our LMIC cohort.
To PE or Not to PE
Authors: Ali Aamir , Gopal Akilan , Lu Yang 
Published: September 2024

Abstract
A 41-year-old woman with metastatic breast cancer presented with dyspnea, hypoxia, and elevated d-dimer. Perfusion planar imaging followed by SPECT/CT of the chest was performed due to the patient’s iodinated contrast allergy. Planar images showed multiple pleural-based wedge-shaped defects concerning for bilateral pulmonary embolism (PE). Perfusion SPECT/CT of the chest confirmed multiple areas of perfusion defects but was considered negative for PE and attributed the perfusion defects to the compressing of pulmonary vasculature from metastatic lymph nodes and pulmonary masses. Given the high pretest probability of PE, a CT pulmonary angiogram was performed after premedication for contrast allergy confirming absence of PE.
The first comparative metagenomic analysis of diarrheal and non-diarrheal gut microbiome leading to the identification of prospective prognostic markers and probiotics to protect from diarrhea: A Brief Report
Authors: De Rituparna , Kanungo Suman , Mukhopadhyay Asish K. , Dutta Shanta 
Published: September 2024

Introduction: Diarrhea is a leading contributor of mortality. Its disease burden can be assuaged using enhanced prognostics and therapeutics. A cross-sectional gut microbiome analysis of non-diarrheal and diarrheal fecal samples was conducted to meet the goals of the Global Action Plan for Pneumonia and Diarrhea.
Hypothesis: Next-generation Sequencing as a tool for epidemiological surveillance helps in the comparison of structural diversity of the gut microbiome of diarrheal and non-diarrheal samples and can identify prognostic and therapeutic candidates. Aim: The pilot study was designed to identify taxa that are enriched in non-diarrheal samples and to predict gut microbial interactions. Methodology: 16SrRNA amplicon sequencing and analysis were deployed for taxonomic profiling and abundance interpretation of OTUs (Operational Taxonomic Units). Results: The findings suggested significant differences in structural composition between the two groups. Firmicutes was the most abundant phylum in most samples. B/F ratio was consistently <1 in all diarrheal samples. Proteobacteria was more abundant in diarrheal samples. Prevotellaceae was the most abundant family in non-diarrheal samples. Streptococcaceae was the most abundant family in 60% diarrheal samples.Where Streptococcaceae was suppressed, Bacteroideaceae and Nocardeaceae were the most abundant. In non-diarrheal samples where Bifidobacteriaceae was the most abundant other families were significantly low. A negative correlation was observed between Prevotellaceae and Bacteroideaceae in non-diarrheal samples. Prevotella copri was the most abundant species in 70% non-diarrheal samples and was significantly suppressed in diarrheal samples. Proteus mirabilis was identified in all the non-diarrheal samples and were absent in diarrheal samples. Conclusion: The OTUs associated with diarrheal dysbiosis can serve as prognostic markers. This is the first report on the comparative analysis of diarrheal and non-diarrheal microbiome. The study addressed gut microbiome dysbiosis from the context that can lead to the development of prognostic markers and probiotics for protecting the endemic population from diarrhea and help in reaching Sustainable Development Goals 2 and 3.
Geographic characterization of RPE structure and lipid changes in the PEX1-p.Gly844Asp mouse model for Zellweger spectrum disorder
Authors: Omri Samy , Argyriou Catherine , Pryce Rachel , Di Pietro Erminia , Chaurand Pierre , Braverman Nancy 
Published: September 2024

AbstractPeroxisome Biogenesis Disorders-Zellweger Spectrum (PBD-ZSD) are a heterogenous group of autosomal recessive disorders caused by defects inPEXgenes whose proteins are required for peroxisome assembly and function. Peroxisomes are ubiquitous organelles that play a critical role in complex lipid metabolism. Dysfunctional peroxisomes in ZSD cause multisystem effects, with progressive retinal degeneration (RD) leading to childhood blindness being one of the most frequent clinical findings. Despite progress in understanding the role of peroxisomes in normal cellular functions, much remains unknown about how their deficiency causes RD, and there is no treatment. To study RD pathophysiology in this disease, we used the knock-in PEX1-p.GlyG844Asp (G844D) mouse model of milder ZSD, which represents the common human PEX1-p.Gly843Asp allele. We previously reported diminished retinal function, functional vision, and neural retina structural defects in this model. Beyond the neural retina, structural defects in retinal pigment epithelium (RPE) have been reported in ZSD patients and murine models with single peroxisome enzyme deficiency, suggesting that RPE degeneration may contribute to overall RD progression in this disease. Here, we investigate the RPE phenotype in our PEX1-G844D mouse model, observing morphological, inflammatory, and lipid changes at 1, 3, and 6 months of age. We report that RPE cell degeneration appears at 3 months of age and worsens with time, starts in the dorsal pole, and is accompanied by subretinal inflammatory cell infiltration. We match these events with lipid remodelling using imaging mass spectrometry which allowed regional analysis specific to the RPE cell layer. We identified 47 lipid alterations that precede structural changes, 10 of which are localized to the dorsal pole. 32 of these lipid alterations persist to 3 months, with remodelling of the lipid signature at the dorsal pole. 14 new alterations occur concurrent with histological changes. Changes in peroxisome-dependent lipids detected by liquid chromatography tandem mass spectrometry (reduced docosahexanoic acid and increased very long chain lysophosphatidylcholines) are exacerbated over time. This study represents the first characterization of RPE in any animal model of ZSD, and the firstin situlipid analysis in any peroxisome-deficient tissue. Our findings reveal candidate lipid drivers that could be targeted to alleviate RD progression in ZSD, as well as candidate biomarkers that could be used to evaluate retinopathy progression and response to therapy.
Association between maternal depressive symptoms and hair cortisol concentration during pregnancy with corpus callosum integrity in newborns
Authors: Mariani Wigley Isabella L.C , Mustonen Paula , Karlsson Linnea , Nolvi Saara , Scheinin Noora M , Kortesluoma Susanna , Pastore Massimiliano , Tervahartiala Katja , Coimbra Bárbara , Rodrigues Ana João , Sousa Nuno , Karlsson Hasse , Tuulari Jetro J 
Published: September 2024

AbstractBackgroundMaternal prenatal depressive symptoms are linked to neurodevelopmental impairments in offspring. Maternal cortisol levels are hypothesized to moderate this association, but its relationship with depressive symptoms is inconsistent. This study examined how maternal prenatal depressive symptoms and cortisol levels predict infant brain development, focusing on neonatal corpus callosum (CC) integrity.MethodsUsing data from the FinnBrain Birth Cohort Study, we analyzed 37 mother-infant dyads. MRI data were collected from 2 to 5 weeks old infants, and DTI imaging estimated fractional anisotropy (FA) in CC regions (Genu, Body, and Splenium). Maternal cortisol levels were assessed through hair cortisol concentration (HCC) from a 5cm hair segment, reflecting cortisol over the last five months of pregnancy. A factor score of maternal depressive symptoms was computed from EPDS questionnaire data collected at gestational weeks 14, 24, and 34. We employed multivariate regression models with a Bayesian approach for statistical testing, controlling for maternal and infant attributes.ResultsResults indicated that maternal prenatal depressive symptoms and HCC interact negatively in predicting infants’ FA across all CC regions. Infants exposed to high prenatal depressive symptoms and low HCC (1 SD below the mean) showed higher FA in all CC regions.ConclusionsThese findings highlight the complex dynamics between maternal prenatal cortisol levels and depressive symptoms, revealing a nuanced impact of those factors on the structural integrity of infants’ CC.
Synaptic inhibition in the accessory olfactory bulb regulates pheromone location learning and memory
Authors: Marathe Shruti D. , Abraham Nixon M. 
Published: September 2024

AbstractPheromone signaling is pivotal in driving social and reproductive behaviors of rodents. Learning and memorizing the pheromone locations involve olfactory subsystems. To study the neural basis of this behavior, we trained female heterozygous knockouts of GluA2 (AMPAR subunit) and NR1 (NMDAR subunit), targeting GAD65 interneuron population, in a pheromone place preference learning assay. We observed memory loss of pheromone locations on early and late recall periods, pointing towards the possible role of ionotropic glutamate receptors (iGluRs), and thereby the synaptic inhibition in pheromone location learning. Correlated changes were observed in the expression levels of activity-regulated cytoskeletal (Arc)protein, which is critical for memory consolidation, in the associated brain areas. Further, to probe the involvement of main olfactory bulb (MOB) and accessory olfactory bulb (AOB) in pheromone location learning, we knocked out NR1 and GluA2 from MOB and/or AOB neuronal circuits by stereotaxic injection of Cre-dependent AAV5 viral particles. Perturbing the inhibitory circuits of MOB and AOB & AOB-alone resulted in the loss of pheromone location memory. These results confirm the role of iGluRs and the synaptic inhibition exerted by the interneuron network of AOB in regulating learning and memory of pheromone locations.
Quantification of electron transport-related oxidative signals by time and wavelength-resolved redox biosensors and chlorophyll fluorescence
Authors: Hipsch Matanel , Lampl Nardy , Lev Raz , Rosenwasser Shilo 
Published: September 2024

AbstractReductive and oxidative signals transmitted from the photosynthetic electron chain to target proteins through the redox signaling network are key regulators of carbon assimilation and downstream metabolism. However, despite their crucial role in activating and inhibiting photosynthetic activity, their relation to photosynthetic efficiency is hardly quantified due to the methodological gap between traditional spectroscopic approaches for investigating photosynthesis and biochemical analyses used in the redox regulation field. Here, we simultaneously quantified redox signals and photosynthetic activity by exploring time and wavelength-resolved fluorescence spectra that capture biosensor and chlorophyll fluorescence signals. Using a set of potato plants expressing genetically encoded redox biosensors, we demonstrated how reductive and oxidative signals are amplified with elevated light intensities and revealed the tight connection between electron transport rate (ETR) and the generation of peroxiredoxin-related oxidative signals. These results demonstrate how full spectrum analysis can pave the way for the integration of genetically encoded biosensors in photosynthesis research and demonstrate light-dependent activation of inhibitory oxidative signals in major crop plants.
Widespread naturally variable human exons aid genetic interpretation
Authors: Jacobs Hannah , Gorissen Bram L. , Guez Jeremy , Kanai Masahiro , Finucane Hilary K. , Karczewski Konrad J. , Burge Christopher B. 
Published: September 2024

AbstractMost mammalian genes undergo alternative splicing. The splicing of some exons has been acquired or lost in specific mammalian lineages, but differences in splicing within the human population are poorly characterized. Using GTEx tissue transcriptomes from 838 individuals, we identified 56,415 exons which are included in mRNAs in some individuals but entirely excluded from others, which we term “naturally variable exons” (NVEs). NVEs impact three quarters of protein-coding genes, occur at all population frequencies, and are often absent from reference annotations. NVEs are more abundant in genes depleted of genetic loss-of-function mutations and aid in the interpretation of causal genetic variants. Genetic variants modulate the splicing of many NVEs, and 5’UTR and coding-region NVEs are often associated with increased and decreased gene expression, respectively. Together, our findings characterize abundant splicing variation in the human population, with implications for a range of human genetic analyses.
Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration
Authors: Lane Alicia R. , Scher Noah E. , Bhattacharjee Shatabdi , Zlatic Stephanie A. , Roberts Anne M. , Gokhale Avanti , Singleton Kaela S. , Duong Duc M. , McKenna Mike , Liu William L. , Baiju Alina , Moctezuma Felix G Rivera , Tran Tommy , Patel Atit A. , Clayton Lauren B. , Petris Michael J. , Wood Levi B. , Patgiri Anupam , Vrailas-Mortimer Alysia D. , Cox Daniel N. , Roberts Blaine R. , Werner Erica , Faundez Victor 
Published: September 2024

AbstractRare inherited diseases caused by mutations in the copper transportersSLC31A1(CTR1) orATP7Ainduce copper deficiency in the brain, causing seizures and neurodegeneration in infancy through poorly understood mechanisms. Here, we used multiple model systems to characterize the molecular mechanisms by which neuronal cells respond to copper deficiency. Targeted deletion of CTR1 in neuroblastoma cells produced copper deficiency that was associated with a metabolic shift favoring glycolysis over oxidative phosphorylation. Proteomic and transcriptomic analysis of CTR1 KO cells revealed simultaneous upregulation of mTORC1 and S6K signaling and reduced PERK signaling. Patterns of gene and protein expression and pharmacogenomics show increased activation of the mTORC1-S6K pathway as a pro-survival mechanism, ultimately resulting in increased protein synthesis. Spatial transcriptomic profiling ofAtp7aflx/Y:: Vil1Cre/+mice identified upregulated protein synthesis machinery and mTORC1-S6K pathway genes in copper-deficient Purkinje neurons in the cerebellum. Genetic epistasis experiments inDrosophilademonstrated that copper deficiency dendritic phenotypes in class IV neurons are partially rescued by increased S6k expression or 4E-BP1 (Thor) RNAi, while epidermis phenotypes are exacerbated by Akt, S6k, or raptor RNAi. Overall, we demonstrate that increased mTORC1-S6K pathway activation and protein synthesis is an adaptive mechanism by which neuronal cells respond to copper deficiency.SignificanceCopper deficiency is present in rare conditions such as Menkes disease and CTR1 deficiency and in more common diseases like Alzheimer’s. The mechanisms of resilience and ultimate susceptibility to copper deficiency and associated pathology in the brain remain unknown.We demonstrate that in a human cell line,Drosophila, and the mouse cerebellum, copper-deficient neuronal cells exhibit increased protein synthesis through mTORC1 activation and decreased PERK (EIF2AK3) activity.Upregulation of protein synthesis facilitates resilience of neuronal cells to copper deficiency, including partial restoration of dendritic arborization. Our findings offer a new framework for understanding copper deficiency-related pathology in neurological disorders.
Dynamic HIV risk differentiation among youth: Validation of a tool for prioritization of prevention in East Zimbabwe
Authors: Moorhouse Louisa R , Gregson Simon , Imai-Eaton Jeffrey W , Mayini Justin , Dadirai Tawanda , Magoge-Mandizvidza Phyllis , Maswera Rufurwokuda , Mabaya Simbarashe , Baggaley Rachel , Low-Beer Daniel , Nyamukapa Constance , Dalal Shona 
Published: September 2024

AbstractBackgroundDifferentiating risk for HIV infection is important for providing focussed prevention options to individuals. We conducted a longitudinal study to validate a risk-differentiation tool for predicting HIV or HSV-2 acquisition among HIV-negative youth.SettingPopulation-based household survey in east Zimbabwe.MethodsHIV and HSV-2 status and HIV behavioural risk factors were assessed in two surveys conducted 12 months apart among young people. Associations between risk-behaviours and combined HIV/HSV-2 incident infection were estimated using proportional hazards models. We calculated the sensitivity and specificity of risk-differentiation questions in predicting HIV/HSV-2 acquisition and quantified changes between surveys among low, medium, and high-risk categories.ResultsIn total, 44 HIV/HSV-2 seroconversions were observed in 1812 person-years of follow up (2.43/100PY, 95%CI: 1.71-3.15); 50% of incident cases reported never having had sex at baseline. Risk of HIV/HSV-2 acquisition was higher for those reporting non-regular partners (women: HR=2.71, 95% CI:1.12-6.54, men: HR=1.37, 95%CI: 0.29-6.38) and those reporting having a partner with a sexually transmitted infection (STI) (HR=7.62 (1.22-47.51). Adding a question on non-regular partnerships increased tool sensitivity from 18.2% to 38.6%, and further to 77.3% when restricted to those who had ever had sex. Individual risk category increased for 28% of men and 17% of women over 12-months.ConclusionThe refined risk differentiation tool identified a high proportion of youth at risk of HIV acquisition. Despite this, half of incident infections were among individuals who reported no prior sexual activity. The shifting patterns of risk behaviours underscore the need for dynamic prevention engagement strategies in high HIV prevalence or incidence settings.