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The bile acid pool, which is synthesized collaboratively by the host and its microbiome, impacts metabolism, immunity, and disease risk. Targeted microbiome interventions could in principle reshape the bile acid pool for therapeutic benefit, but practical strategies remain elusive. In the course of screening a complex defined community for metabolic phenotypes by dropping out individual strains, we observed that several of the single-strain dropout communities had markedly increased deoxycholic and lithocholic acid levels and a larger bile acid pool. In each of these communities, a second strain- Lactobacillus plantarum- had bloomed. The bile salt hydrolase activity of L. plantarum was necessary and sufficient to expand the size of the bile acid pool. An engineered community in which the bsh gene is overexpressed in multiple Lactobacillus strains confers on mice increased levels of secondary bile acid levels and a larger pool size. By overexpressing a different pair of bile acid metabolic genes in multiple strains of Lactobacillus -7α- and 7β-hydroxysteroid dehydrogenase-we changed the composition of the bile acid pool, enlarging it and redirecting it toward ursodeoxycholic acid. Together, these results demonstrate that fine details of the microbiome's strain composition can have a substantial effect on bile acid metabolism, and that rational manipulation of the microbiome can alter the size and composition of the bile acid pool.

Tick-borne pathogens (TBPs) pose a significant threat to livestock production in Kerman Province, Iran. Despite the high prevalence of TBPs, our understanding of specific pathogens circulating within local tick populations remains limited. Furthermore, the potential for co-infections with multiple microorganisms complicates the diagnosis and disease management. This study aimed to investigate the prevalence of TBPs in ticks collected from domestic animals in Kerman province using real-time quantitative PCR (qPCR). Tick collection was conducted between April and June 2022 from 199 domestic animals (63 cattle, 63 sheep, 63 goats, and 10 dogs) across 65 villages in three counties of Kerman Province, Iran. Collected ticks were subjected to qPCR assays targeting Coxiella burnetii, Bartonella spp., Rickettsia spp., Francisella spp., Borrelia spp., and Ehrlichia spp. Phylogenetic analysis of the amplified DNA sequences was performed to elucidate the genetic relationships among the detected pathogens. In this study, 707 ixodid ticks was collected included Hyalomma marginatum marginatum (70.7%, 108 pools) and Rhipicephalus linnaei (29.2%, 27 pools). Based on molecular analysis, Rickettsia spp., Ehrlichia spp, C. burnetii and Bartonella spp. were detected in 55.5%, 9.6%, 8.1% and 0.7%, respectively. Rickettsia aeschlimannii, R. sibirica, R. conorii subsp. israelensis and R. africae were identified based on sequencing and phylogenetical analysis.Co-infections were also observed: 5.9% of the pools (8 pools) were co-infected with Ehrlichia spp. and Rickettsia spp., 3.7% (5 pools) with Rickettsia spp. and C. burnetii, and 0.7% (1 pool) with Rickettsia spp. and Bartonella spp. No infections with Francisella spp. or Borrelia spp. were detected. This study demonstrates the presence of multiple tick-borne pathogens of veterinary and public health significance in ruminants from Kerman Province, highlighting the need for further research on tick-borne diseases affecting both animal and human populations in this and surrounding regions.

Anemia is an established marker of cardiovascular disease severity and risk which leads to elevations in resting myocardial blood flow (MBF) and impaired myocardial flow reserve (MFR) in patients without obstructive coronary artery disease (CAD). Anemia can potentially be detected opportunistically from blood pool density changes on computed tomography (CT) imaging. We evaluated relationships between chamber density measurements with hemoglobin, positron emission tomography (PET) findings, and cardiovascular events. We included 33460 patients from 13 sites in the REFINE-PET who underwent PET and 24368 patients undergoing lung cancer screening chest CT. A deep learning model segmented cardiac chambers from CT images, then quantified chamber density. We evaluated the relationship between chamber density measures with resting MBF and MFR, as well as associations with death or myocardial infarction (MI). We included a total of 57,828 patients. A higher density in myocardium compared to left ventricle blood pool was associated with reduced MFR (adjusted odds ratio 3.02 per SD increase, 95% confidence interval[CI] 2.72 - 3.38) and an increased risk of death or MI in (adjusted hazard ratio[HR] 1.38 per SD increase, 95% CI 1.26-1.51). Having myocardial density higher than blood pool density was also associated with cardiovascular death in patients undergoing low-dose chest CT (adjusted HR 1.73, 95% CI 1.20-2.52). In a large multimodality dataset, lower cardiac chamber density is associated with impaired MFR and independently associated with cardiovascular events. These biomarkers can be automatically extracted from CT to provide physiologic insights and potentially guide patient care. Anemia is an important marker of cardiovascular disease severity and predictor of cardiovascular events. We utilized deep learning to measure cardiac chamber density on computed tomography imaging as a surrogate for anemia in 57,828 patients from two large multicenter studies. A higher density in myocardium compared to left ventricle blood pool was associated with reduced MFR and an increased risk of death or MI in patients undergoing positron emission tomography, and an increased risk of cardiovascular death in patients undergoing low-dose computed tomography. These biomarkers can provide additionally physiologic insights which could be used to guide patient care.

α-Lipoic acid (LA) is widely included in "mitochondrial cocktails" recommended to patients with primary mitochondrial disorders, yet its mechanism of action remains unclear. Here, we define the intracellular availability and functional utilization of LA in mammalian cells. We show that LA exists in two functionally distinct cellular pools: a low-abundance free pool and a protein-bound pool generated through mitochondrial fatty acid synthesis (mtFAS). Disruption of the mtFAS pathway abolishes protein lipoylation and impairs oxidative phosphorylation without altering free LA levels. Conversely, supplementation with exogenous LA markedly increases free intracellular LA without restoring protein lipoylation, mitochondrial respiration, or cell proliferation. Instead, the cellular effects of LA supplementation resemble those of the antioxidant N-acetylcysteine. These findings clarify the mechanism of action of a widely used mitochondrial supplement and identify a fundamental disconnect between cellular LA abundance and mitochondrial utilization, challenging the rationale for using LA supplementation to restore mitochondrial function.

Adolescent depressive disorder is a clinically heterogeneous condition with poorly understood molecular mechanisms. Protein N-glycosylation, a key post-translational modification involved in immune regulation and neuronal communication, has not been systematically investigated across depressive subtypes in youth. Understanding glycosylation alterations may reveal novel biochemical pathways underlying disease heterogeneity and pathophysiology. We applied a site-specific glycoproteomic approach integrating liquid chromatography-tandem mass spectrometry (LC-MS/MS) and StrucGP to profile serum N-glycosylation in adolescents with major depressive disorder (MDD), MDD with non-suicidal self-injury (NSSI), and MDD with suicide attempts (SA), compared with healthy controls. Serum samples were pooled by group (10 individuals per pool), and glycan alterations were identified using predefined fold-change thresholds. This approach is classified as an exploratory research strategy, which does not support statistical inference. All depressive subtypes displayed shared alterations, characterized by reduced bi-antennary glycans and LacNAc/Lewis structures, alongside elevated tetra-antennary sialylation, particularly N6H7S4. Candidate subtype-associated patterns were also observed: increased tri-antennary sialylation in NSSI, and selective upregulation of N6H7S4 on ORM2 in SA. Differentially glycosylated proteins, including SERPING1 and A2M, were enriched in immune, complement, and coagulation pathways. Notably, protein-level changes were minimal in label-free quantification, suggesting glycan-specific dysregulation. This exploratory study identifies candidate subtype-dependent alterations in N-glycosylation in adolescent depression, which may implicate glycan-mediated immune and neuroinflammatory mechanisms in its molecular heterogeneity. This study provides a preliminary, pooled-sample based catalog of candidate site-specific N-glycosylation alterations for adolescent depression, warranting validation in larger, individual-level cohorts.

Cell adhesion molecules of the immunoglobulin superfamily (IgCAMs) coordinate adhesive interactions with intracellular organization during tissue morphogenesis. In the Drosophila follicular epithelium, epithelial maintenance depends on reintegration, a process in which mitotically displaced cells reincorporate into the epithelial monolayer. Previous work identified the IgCAMs Fasciclin 2 (Fas2) and Neuroglian (Nrg) as parallel, partially redundant regulators of reintegration, but the intracellular mechanisms linking adhesion to reintegration remained unclear. Here, we show that Fas2 supports reintegration through two mechanistically distinct modes: a transmembrane mode and a GPI-linked mode. Although both contribute to reintegration, the transmembrane mechanism is more effective and depends on stabilization of a cortical Fas2 pool through intracellular coupling. Using yeast two-hybrid screening, genetics, and fluorescence recovery after photobleaching (FRAP), we identify the scaffold protein Discs large (Dlg1) as a functional intracellular partner of transmembrane Fas2. Partial disruption of Dlg1 preferentially sensitizes epithelia in which the parallel Nrg-dependent reintegration mechanism is compromised, consistent with Dlg1 functioning primarily within the Fas2-dependent reintegration arm. While Dlg1 is not required for Fas2 membrane localization, Dlg1 disruption increases the mobile fraction of transmembrane Fas2, indicating that Dlg1 promotes retention of a stabilized cortical Fas2 pool. Together, these findings support a model in which epithelial reintegration depends on coordinated adhesion-scaffold coupling and reveal mechanistic parallels between epithelial reintegration and IgCAM-dependent processes in the developing nervous system.

Microglia are the resident hematopoietic cells of the central nervous system 1 . In mice, microglia seed the brain during embryogenesis and can be maintained throughout life with minimal input from adult hematopoiesis 2-4 . The origins of human microglia are less clear, but recent evidence suggests that marrow-derived cells may be able to supplement the human microglial pool in certain individuals 5,6 . Here, to investigate the ontogeny of human microglia, we develop a method that uses the collection of accumulated somatic mutations which uniquely labels each clone of cells to track the infiltration of marrow-derived cells into the human brain. Applying this method to 20 aged individuals, we find evidence of an influx of marrow-derived cells into the brain in all examined individuals. Single cell analysis, including single cell lineage tracing using mitochondrial DNA variants, demonstrates that these infiltrating cells are nearly identical to microglia and can comprise a large fraction of the microglial pool. Analysis of large-scale sequencing cohorts demonstrates a protective association between most types of clonal hematopoiesis and Alzheimer's disease. In sum, this work uncovers a widespread influx of myeloid cells into the healthy human brain which serves to reinforce the pool of human microglia and becomes common with aging.

Non-transitive environments complicate the notion of a single "best" strategy: performance depends on the opponent population, and rankings are meaningful only relative to a specified opponent pool and protocol. We present a reproducible multi-agent benchmark for iterated rock-paper-scissors and evaluate 54 agents from 18 archetypes-deep recurrent and transformer sequence models, actor-critic reinforcement learners, Bayesian/Markov predictors, classical classifiers, and rule-based baselines-in 500-round double round-robin tournaments across 10 random seeds. To support auditability, we define a simple regret certificate: a Lipschitz-type inequality that upper-bounds a best-response payoff gap using the [Formula: see text] discrepancy between an agent's predicted action distribution and an empirical estimate of the opponent's action distribution, computable online from logged predictions. Our experiments indicate that (i) recurrent predictors tend to achieve the highest and most stable scores, with gains that are largest against predictable opponents; (ii) rankings shift notably with the opponent pool (Spearman [Formula: see text] between two evaluation rosters), with the top-ranked method changing across configurations; and (iii) the induced meta-game exhibits substantial non-transitivity, including 134 detected three-cycles in the pairwise payoff matrix. Under our 500-round online update budget and short-context design, transformer agents are competitive but do not outperform tuned recurrent baselines, which may reflect an inductive-bias mismatch in short-horizon adversarial play. Our code and analysis pipeline provide an extensible testbed for studying population-dependent evaluation and learning dynamics in canonical non-transitive games.

Constructed-response situational judgement tests (CR-SJTs) are used internationally to assess personal and professional attributes in health professions admissions, with over one million applicants to more than 500 programs having used them in the last decade. Despite this, a synthesis of their validity is lacking. This study aimed to quantify the association between CR-SJT scores and measures of personal, interpersonal and professional performance in health professions education and to determine how moderating factors influence this relationship. MEDLINE, EMBASE, CINAHL, ERIC, SCOPUS, Web of Science and grey literature sources (ProQuest Dissertations & Theses, EThOS and OpenGrey) were searched from inception to 7 April 2025. Search was supplemented by contacting experts and admissions directors to include unpublished quality assurance studies. Eligible studies evaluated a CR-SJT for applicants or trainees in health professions programmes and reported a quantitative relationship with a non-academic outcome (e.g., professionalism and communication). Of 463 full-texts reviewed, 27 met inclusion criteria. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, two reviewers independently extracted data and assessed risk of bias using the Quality In Prognosis Studies (QUIPS) tool. A multilevel random-effects meta-analysis was used to pool Fisher z-transformed correlation coefficients. Meta-regressions tested moderator effects, and sensitivity analyses examined bias impact. The primary outcome was the correlation between CR-SJT scores and measures of interpersonal or professional skills. Moderators included the construct congruence between the CR-SJT and the outcome measure, outcome type, publication type, and outcome assessment stage. The 27 studies yielded 100 unique effect sizes and were judged, in total, to be at moderate risk of bias. The pooled correlation between CR-SJT scores and outcomes was z&#x2009;=&#x2009;0.22 (95% CI, 0.16-0.28; p&#x2009;<&#x2009;0.001). Construct congruence was the only significant moderator; more congruent outcomes showed z&#x2009;=&#x2009;0.32 (95% CI, 0.25-0.37), compared to that of less congruent outcomes (z&#x2009;=&#x2009;0.17; 95% CI, 0.12-0.18). Publication bias was insignificant (Egger's test, p&#x2009;=&#x2009;0.73). The use of CR-SJTs in health professions selection is supported by the evidence. Validity depends substantially on construct congruence between the CR-SJT and the outcome measure. Programs should consider CR-SJTs within their operational context and with deliberate attention to downstream evaluation alignment.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used for type II diabetes and obesity because of their cardiometabolic benefits. However, concerns regarding potential ocular adverse effects, particularly diabetic macular edema (DME), have prompted the need to clarify their retinal safety. A systematic review and meta-analysis study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and Meta-analysis of Observational Studies in Epidemiology statements (PROSPERO registration: CRD420251176164). MEDLINE (Ovid), EMBASE (Ovid), CENTRAL (Ovid), Web of Science, and PubMed were searched from inception to October 24, 2025. Randomized trials and observational cohort or case-control studies, including individuals with diabetes without baseline DME and exposed to GLP-1RAs were eligible. Two reviewers independently screened studies, extracted data, and assessed risk of bias using ROBINS-I. Certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development, and Evaluation. Random-effects models were used to pool incidence proportions and hazard ratios (HRs). Thirteen retrospective cohort studies (2021-2025) using large real-world databases were included. Across 6 studies, the pooled proportion of incident DME among GLP-1RA users was 0.14 (95% CI: 0.07-0.23; I&#xb2;&#x202f;=&#x202f;99.8%). Compared with mixed antihyperglycemic therapies, GLP-1RA use was not associated with increased DME risk (pooled HR: 0.81, 95% CI: 0.52-1.26). GLP-1RAs were associated with a higher relative risk of DME compared with sodium-glucose cotransporter-2 inhibitors (HR: 1.50, 95% CI: 1.17-1.94) but not compared with dipeptidyl peptidase-4 inhibitors (HR: 0.90, 95% CI: 0.69-1.19). Evidence certainty was very low. Current low-certainty observational evidence does not support an overall increased risk of DME with GLP-1RA use. Prospective studies are needed to clarify comparative retinal safety.

Enterococcus species are part of normal microbiota but can cause severe infections, especially among hospital-adapted strains. In Ghana, data on their dynamics, including prevalence and resistance patterns, remain limited. This systematic review and meta-analysis is the first to assess the current scope and identify gaps in One-Health research on Enterococcus. We searched PubMed/MEDLINE, Scopus, and Web of Science following PRISMA 2020 guidelines for studies published up to October 24, 2024 (search conducted October 12-24, 2024). A random-effects model with restricted maximum likelihood was used to pool prevalence and antimicrobial resistance. Sixty-nine studies met the inclusion criteria with nineteen eligible for meta-analysis. The pooled prevalence of Enterococcus was 6.76% (CI: 1.19-16.39, I2 = 99.3%, p < 0.0001) while adjusted vancomycin-resistance isolates was 0.06% (CI: 0.00-27.86; I2 = 99.4%, p < 0.0001). Antibiotic resistance rates were comparable across human and animal studies, often higher in animals. Ciprofloxacin showed the lowest resistance (1.30%), while cloxacillin had the highest (17.46%). This review underscores the one-sided focus on humans, limiting understanding of transmission within the One-Health spectrum. We advocate integrating genomic approaches, particularly environmental genomics, into One-Health frameworks to resolve transmission pathways, inform policy, and strengthen antimicrobial resistance control in Ghana. Enterococcus bacteria usually live harmlessly in humans and animals but can cause serious infections and drug resistance. We reviewed studies from Ghana and found limited, human-focused data. Our results show similar resistance across humans and animals, highlighting the need for environmental and genomic approaches within One Health surveillance.

The continual advancement of genetic tools has been critical to our modern understanding of bacteria, with transposons, plasmids, and homologous recombination becoming workhorses of molecular microbiology. However, precisely specified reverse genetic approaches remain painstakingly slow and inaccessible, particularly in non-model strains. This reality is exemplified by the opportunistic pathogen, Pseudomonas aeruginosa (Pa), where conventional allelic exchange remains the dominant reverse genetic method. Here, we adapt a rapid genetic toolkit for use in Pa, relying directly on commercially available oligonucleotides (120 bases) to create precise genomic mutations through homologous recombination (i.e. oligo recombineering). Oligo Recombineering followed by Bxb-1 Integrase Targeting (ORBIT) uses a short attachment site for an integrating plasmid, which provides traditional antibiotic selection and can also carry flexible cargo. We establish Pa ORBIT works effectively for gene deletion without off target mutations, optimize protocol parameters (e.g. oligo length, electroporation), and demonstrate markerless and clean deletions. Importantly, our toolkit works well in clinical Pa strains as demonstrated by constructing efflux pump deletions in three different isolates. To test the high throughput capabilities of Pa ORBIT, we created over 160 degron-based hypomorphs (i.e. knockdowns) across 43 essential proteins in a pooled mutant library. Upon screening this library with and without antibiotics, we identify highly vulnerable essential proteins and hypomorphs that display synergy with clinical drugs. Therefore, ORBIT can be used for cutting edge low and high throughput investigations in this priority pathogen, setting the stage for answering critical basic and clinical science questions. To understand bacterial genomes, researchers need access to rapid, flexible, precise and high throughput genetic perturbation tools. Here we present an oligonucleotide-based method that satisfies these requirements for use in the opportunistic pathogen, Pseudomonas aeruginosa . By relying on oligos to encode genomic homology arms, no molecular cloning is required - making these tools rapid, robust, and scalable. We benchmark gene deletions in both lab and clinical strains, opening the possibility of rapid genetic studies across the P. aeruginosa pangenomic space. At high throughput, we use an oligo pool to create a mutant library of degron tagged essential proteins. These knockdowns (i.e. hypomorphs) show certain essential genes are highly vulnerable and others are synergistic with clinical drugs, providing insight into future antibiotic and co-therapy development.

Understanding dissolved organic nitrogen (DON) transformation is critical for estuarine nitrogen dynamics, yet microbial contribution and mechanism remain poorly constrained under high terrestrial input. This study reveals that DON in Pearl River Estuary (PRE) exhibits non-conservative mixing jointly regulated by terrestrial inputs, autochthonous production and microbial processes. By integrating field observations, model simulations, and incubation experiments, this study identifies the mid-salinity mixing zone (10-25 PSU) as a transformation hotspot. Based on dark in vitro incubations, the microbial transformation rate was approximately 0.67&#xb1;0.23 &#x3bc;mol&#xb7;L-1&#xb7;h-1. This process accounted for 77-87% of the total potential DON pool (defined as the sum of measured concentration and transformed DON) in mixing zone. Molecular analysis indicates that while physical dilution primarily drives the decline in bulk aromaticity (AImod, DBE), microbial processing qualitatively reshapes the DON pool. Specifically, microbial metabolism promotes the relative accumulation of recalcitrant lignin-like compounds by selectively consuming labile components. Microbial metabolism (particularly Candidate_Actinomarina) is the core driver of DON transformation. FAPROTAX analysis suggests a functional transition from methyl-oxidation-associated N transformations (heterotrophic nitrification and denitrification) to sulfur-oxidation-associated N transformations underlies the DON molecular variations along the salinity gradient. Terrestrial input accelerates biochemical reactions such as demethylation and deamination through the priming effect. Furthermore, mineralization of labile terrestrial DON potentially supplies key substrates that are closely linked to N2O production. These findings highlight the pivotal role of microbial transformation in regulating DON fate, providing new insights into estuarine nitrogen cycling under strong terrestrial inputs.

Sleep is essential for healthy bodily functioning in many aspects, including physiology, psychology and cognition. Due to the reverse causation, it remains inconclusive whether sleep disturbances contribute to Alzheimer's disease (AD). The purpose of this meta-analysis was to investigate the association between sleep disturbances and AD risk. PubMed, Embase, and Web of Science were searched for longitudinal cohort studies until May 2025. Random-effects models were employed to pool risk ratios (RRs) with 95% confidence intervals (CIs). Of the 2106 records, 31 studies from East Asia (23%), Europe (32%), and North America (45%) were eligible for inclusion, involving 13,109,323 participants. The pooled effect size showed that sleep disturbances were linked to higher risk of AD (RR 1.40, 95% CI 1.29 to 1.51), with the magnitude attenuated but still significant through multivariate adjustment (adj-RR 1.29, 95% CI 1.18 to 1.42). Similar effects persisted even after reducing effects of reverse causation, as implemented by stratified analysis on mid-life cohorts and longer follow-ups (5-15: RR 1.35, 95% CI 1.01 to 1.81;&#x2009;&#x2265;&#x2009;15&#xa0;years: RR 1.26, 95% CI 1.02 to 1.57). Dose-response analysis revealed a U-shaped correlation, with sleep duration&#x2009;<&#x2009;6 or&#x2009;>&#x2009;8&#xa0;h associated with AD risk elevation. Neither baseline age, follow-up length, nor study quality significantly diluted the observed association. This study adds to evidence that sleep disturbances are relevant to incident AD, even in mid-life cohorts and longer follow-ups, supporting sleep disturbances as a mid-life risk factor of AD.

To systematically evaluate the association between fear of falling (FOF) and functional impairment in patients with osteoporosis and to explore potential moderators using meta-regression analysis. A systematic review and meta-regression analysis was conducted. Data sources PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to June 2025. Eligibility criteria observational studies involving adults with osteoporosis that quantitatively assessed fear of falling and functional impairment were included. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Random-effects meta-analysis was conducted to pool effect estimates. Heterogeneity was quantified using the I2 statistic. Meta-regression analyses were performed to identify potential sources of heterogeneity. A total of 18 studies comprising 6243 participants were included. Higher levels of fear of falling were significantly associated with increased odds of functional impairment (pooled OR 2.12, 95% CI 1.72 to 2.61; I2&#x2009;=&#x2009;68%). Meta-regression suggested that mean age, proportion of female participants, and history of osteoporotic fracture significantly moderated the association. Fear of falling is strongly associated with functional impairment in patients with osteoporosis. These findings highlight the importance of incorporating psychological assessment and targeted interventions for fear of falling into osteoporosis management.

Quality sleep is vital for women's health during reproductive years, affecting both physical and mental well-being. In Ethiopia, socio-economic and cultural factors worsen sleep issues, but data on this demographic are scarce. This systematic review and meta-analysis assesses the prevalence of poor sleep quality among Ethiopian women and identifies contributing factors, aiming to inform interventions and policies to improve sleep health in low-resource settings. This systematic review followed PRISMA guidelines and searched PubMed, Scopus, and Web of Science for observational studies. We included studies utilizing the Pittsburgh Sleep Quality Index (PSQI), as it is the most widely validated tool for assessing subjective sleep quality across diverse populations. Reviewers independently screened articles using Rayyan and assessed study quality with the Joanna Briggs Institute tools. Data were analyzed using Stata version 17. To account for potential clinical and methodological variability across studies, a random-effects model was employed to pool results, with heterogeneity assessed using statistics and the Cochrane's Q test. Publication bias and sensitivity analyses were also performed. Nine studies involving 4,376 women of reproductive age (15-49 years) in Ethiopia were included. The pooled prevalence of poor sleep quality was 49.17% (95% CI: 35.29, 63.08). Significant predictors of poor sleep quality included intimate partner violence (OR: 3.24), depression (OR: 3.37), unplanned pregnancy (OR: 2.71), multigravidity (OR: 2.61), and substance use (OR: 2.24). A systematic review indicates that nearly half of Ethiopian women of reproductive age experience poor sleep quality. Key factors include unplanned pregnancies, substance use history, intimate partner violence, previous depression, stress, being in the third trimester, and comorbidities; these need urgent attention and the implementation of screening and preventive measures. Future research should focus on effective interventions to improve sleep quality in these populations. https://www.crd.york.ac.uk/prospero/, identifier CRD42023455867.

The optimal transcatheter aortic valve replacement strategy in patients with a small aortic annulus (SAA) remains unclear. We performed a systematic review and meta-analysis comparing self-expanding valves (SEVs) to balloon-expandable valves (BEVs) in SAA patients. We searched PubMed, Embase, Web of Science, and Scopus for studies comparing SEVs and BEVs in patients with SAA defined by computed tomography. A random-effects model using the Der Simonian and Laird estimator was used to pool odds ratios (ORs) and mean differences (MDs). We identified 25 studies encompassing 13,846 patients (5633 BEV; 8213 SEV). SEVs demonstrated superior hemodynamics, including a larger indexed effective orifice area (MD: 0.20&#x2009;cm2/m2; P < 0.00001), a lower mean transvalvular gradient (MD: -4.11&#x2009;mm Hg; P < 0.00001), and a lower risk of severe patient-prosthesis mismatch (OR: 0.37; P < 0.00001). However, SEVs were associated with a higher risk of permanent pacemaker implantation (PPI) (OR: 1.63; P = 0.0008) and moderate or severe paravalvular leak (PVL) (OR: 2.26; P < 0.00001). There was no significant difference in all-cause mortality at 1 year (OR: 0.96; P = 0.55) or stroke at 30 days (OR: 1.34; P = 0.18). Notably, in a subgroup analysis restricted to patients with extra-small annuli (area <400&#x2009;mm2 or diameter <23&#x2009;mm), the hemodynamic advantages of SEVs persisted while the elevated risks of PPI and PVL were no longer statistically significant. In patients with SAA, SEVs provide better hemodynamics but carry safety concerns including higher risks of PVL and PPI in the overall population. These risks were not observed in the extra-small annulus subgroup. Valve selection should be individualized based on patient anatomy and procedural risk profile.

ObjectiveStudies on the clinical and lifestyle characteristics of tuberculosis patients with diabetes mellitus in Bangladesh remain limited. This study compared the demographic, clinical, and lifestyle characteristics between older and younger tuberculosis patients with diabetes mellitus.MethodsThis multicenter analytical cross-sectional study was conducted from January to December 2024 in 18 centers of the Diabetic Association of Bangladesh. Adult patients with a history of completed tuberculosis treatment and diabetes diagnosed >2 weeks after initiation of tuberculosis treatment were considered eligible. Among 393 eligible participants, all 80 patients aged&#x2009;&#x2265;50 years were included. For balanced comparison, 80 participants&#x2009;aged <50 years were selected from the remaining eligible pool. Data were collected through face-to-face interviews using a pretested semistructured questionnaire and checklist. Categorical variables were compared using the chi-square test or Fisher's exact test. Multivariable binary logistic regression was used to identify characteristics independently associated with older age. Written informed consent was obtained, and ethical issues were maintained.ResultsMale patients were predominant in both older (80.0%) and younger (93.8%) tuberculosis patients with diabetes mellitus. Pulmonary tuberculosis was more common in younger patients (97.5%), while family history of diabetes (46.3%) and comorbidity (47.5%) were more common in older patients with diabetes mellitus. Moreover, occupation, body mass index category, physical inactivity, family history of diabetes, comorbidity, and type of tuberculosis were found to be significant (p&#x2009;<&#x2009;0.05) between older and younger patients. In multivariable analysis, family history of diabetes (adjusted odds ratio&#x2009;=&#x2009;3.873, p&#x2009;=&#x2009;0.001) and pulmonary tuberculosis classification (adjusted odds ratio&#x2009;=&#x2009;12.820, p&#x2009;=&#x2009;0.003) remained independently associated with older age.ConclusionFamily history of diabetes and type of tuberculosis were found to be independently associated with older tuberculosis patients with diabetes mellitus. These findings may help inform age-sensitive screening, referral, and follow-up strategies for integrated tuberculosis-diabetes mellitus care; however, larger and more representative studies are warranted.

The establishment of lifelong nephron endowment depends on the tightly coordinated regulation of nephron progenitor cell (NPC) self-renewal, lineage specification, and differentiation during kidney development. Conrad H. Waddington's developmental landscape provides a powerful conceptual framework for understanding how NPCs navigate sequential fate decisions toward mature renal epithelial identities. Within this paradigm, the topology of the landscape is actively shaped by epigenetic mechanisms, including DNA methylation, histone post-translational modifications, non-coding RNA-mediated gene regulation, and higher-order chromatin organization, which collectively control the timing, location, duration, and strength of gene expression programs that direct nephrogenesis. Under normal conditions, these epigenetic programs preserve progenitor competence while progressively stabilizing lineage commitment and nephron patterning. When disrupted, however, they impair progenitor plasticity, accelerate NPC pool depletion, and ultimately reduce nephron number. Such maladaptive epigenetic reprogramming establishes a mechanistic link between adverse intrauterine environments and lifelong susceptibility to hypertension and chronic kidney disease. In this review, we revisit Waddington's landscape in the context of renal development and integrate emerging insights from developmental biology, cell metabolism, and epigenomics to examine how early-life environmental perturbations durably reshape the nephrogenic program and increase the risk of adult-onset kidney disease.