Aquaculture

The distribution of fat-soluble compounds (including antioxidants) in follicular fluid (FF) remains sparsely documented in relation to in vitro fertilization (IVF) outcomes and existing studies have reported diverging associations. This study aimed to describe plasma and FF concentrations of fat-soluble micronutrients in women undergoing IVF and to analyze their adjusted associations with ovarian function, embryo development and pregnancy outcomes. In 2021-2022, plasma and FF samples were collected from 82 women (first IVF cycle) at oocyte puncture, along with lifestyle data covering the three preceding months. Eleven compounds (two tocopherols, three xanthophylls, five carotenes and retinol) were quantified. All compounds were detected in both compartments (lowest in FF) except phytoene, undetectable in FF. Plasma and FF -tocopherol concentrations were positively associated with plasma estradiol levels before oocyte puncture (both p<0.01) while FF -carotene and lycopene were inversely associated with plasma progesterone concentrations (p=0.01 and 0.02, respectively). Plasma phytofluene and phytoene were positively associated with mature oocyte rate (p=0.03 and p=0.01, respectively), while FF retinol was negatively associated (p=0.03). Carotenes, tocopherols and retinol were inversely associated with later IVF outcomes: fertilization rate (p<0.001 for plasma g-tocopherol, 0.02 for FF retinol), top-quality embryo (p=0.02 for plasma phytofluene), biochemical pregnancy at day 7 post-embryo transfer (p=0.05 for plasma -tocopherol, 0.02 for plasma -carotene), clinical pregnancy (p=0.03 for plasma -tocopherol, 0.01 for plasma phytoene) and live birth (p=0.04 for plasma -tocopherol, 0.02 for plasma phytoene). Plasma and FF g-tocopherol were positively associated with embryo fragmentation (both p<0.05). Finally, among xanthophylls, only plasma {beta}-cryptoxanthin was positively associated with plasma progesterone concentrations (p=0.02). Our findings of heterogeneous associations between tocopherols, carotenes, retinol and IVF outcomes across the stages of IVF suggest a beneficial effect limited to early outcomes and support a complex and context-dependent role of these compounds in female reproduction. This manuscript has been submitted to PlosOne on August 19, 2026.

Nitrogenous waste excretion is essential for all developmental stages of fish. Embryonic fish excrete urea, transitioning to cutaneous and later branchial ammonia excretion. In zebrafish, ammonia excretion involves rhesus glycoproteins Rhbg and Rhcgb in keratinocytes and ionocytes, but the developmental moment they appear in the gill remains unclear. Potential redundancy between Rhbg and Rhcgb in ammonia excretion is also not fully investigated, nor is the difference in response to low pH. We hypothesized that rhesus glycoproteins are partially redundant, and that they differ in their response to low pH as ammonia excretion enables ionocytes to exchange Na+ and H+ (Rh-NHE-metabolon). We predicted that a loss of rhbg or rhcgb induces compensatory responses. We characterized the transition from urea to branchial ammonia excretion from 0 to 8 days-post fertilization (dpf) and the response to pH 5.0 on the expression and localization of rhesus glycoproteins in control zebrafish and rhbg or rhcgb-crispants. Effects of high external ammonia (HEA, 500 M NH4Cl) and 10 mM HEPES-buffering were further characterized in rhcgb-crispants. Rhag and Rhbg appeared in the gill at 5 dpf, while Rhcgb appeared at 6 dpf. A loss of rhbg or rhcgb did not impact baseline N-excretion, illustrating that zebrafish can maintain ammonia excretion without the full complement of rhesus glycoproteins. We observed no compensatory increase in rhesus glycoproteins, but expression of the transporter hippocampus-abundant transcript 1b increased. HEA-exposed rhcgb-crispants switched to urea as primary nitrogen waste. Together, these findings underline the plasticity of the larval in dealing with nitrogenous waste.

Diatoms are major contributors to marine primary production, yet current approaches for monitoring their abundance and function rely on coarse satellite chlorophyll estimates or sparse cell count and carbon fixation measurements. Molecular markers are a promising approach for high-resolution measurement of both abundance and metabolic activity through analysis of environmental DNA (eDNA) and RNA (eRNA). We present an isothermal quantitative recombinase polymerase amplification (qRPA) assay targeting rbcL gene copies and transcripts of marine diatoms, operating at low temperature and producing results in less than 15 min. We demonstrate specificity and calibration across diverse diatom taxa, then apply the assay to eDNA and eRNA samples from the Mare Chiara Long-Term Ecological Research site in the Bay of Naples, Italy, alongside microscopy, chlorophyll, physicochemical, and carbon-fixation data. Diatom rbcL DNA tracked abundance across five orders of magnitude despite seasonal shifts in community composition. Combining molecular and optical data revealed increased cellular rbcL copies and chlorophyll in low-light winter populations, suggesting enhanced photosynthetic capacity despite lower abundance. Furthermore, rbcL RNA reflected total carbon fixation rates and identified populations with differing carbon fixation activity. These results support rapid, RPA-based rbcL quantification as a robust approach for biomolecular ocean observing.

The exponential increase in the number of genotyped animals, combined with the availability of high-density SNP chips has introduced computational challenges for routine genomic evaluations, particularly during the construction of the genomic relationship matrix. Although higher-density SNP panels can facilitate the identification of causal mutations, their use substantially increases computational requirements without a proportional gain in genomic prediction performance. To optimize computational efficiency while maintaining accuracy of genomic predictions, this study compared five SNP selection strategies (i.e., random sampling, random sampling with inclusion of informative SNPs, linkage disequilibrium (LD)-based pruning, a Shannon entropy-based machine learning approach, and [[EQUATION]]-based prioritization) to develop reduced-density panels for Nellore cattle. Using high-density (HD) genotype data comprising 437,650 SNPs from 304,782 animals (after quality control) as reference, three reduced-density panels (25K, 45K, and 65K SNPs) panels were tested across five traits (i.e., Age at first calving, Stayability, Weaning weight, Yearling weight, Muscling) with diverse genetic architectures. Genomic estimated breeding values (GEBVs) derived from these reduced panels were compared to those obtained from the HD reference panel using Pearsons correlations, under both genomic best linear unbiased prediction (GBLUP) and single-step GBLUP (ssGBLUP) methods. In the GBLUP model, prediction accuracy generally improved with increased marker density. Random selection with and without the informative SNPs consistently yielded the highest accuracies, whereas the [[EQUATION]]-based approach showed the lowest agreement with the HD reference across all densities. In contrast, ssGBLUP demonstrated strong robustness to marker reduction, producing uniformly high correlations {approx}1.00) across all SNP densities and selection strategies. These findings indicate that optimized low-density SNP panels maintain prediction accuracy comparable to HD panels, offering a cost-effective tool for large-scale genomic evaluations.

Hydrozoa is a group of relatively simple animals with a well-developed nervous system. The nervous system in all hydrozoan medusae is highly conserved and includes outer and inner nerve rings at the bell margin, a neural network in the manubrium, and radial neural pathways that connect them. However, one element of the nervous system shows substantial variability among species: the subumbrella neural network. We examined the structure of the nervous and muscular systems in the subumbrella of 14 species of hydrozoan medusae. The main conclusion of this study is that the distribution of neural networks in the subumbrella strongly correlates with the distribution of smooth radial muscles. This correlation suggests that smooth radial muscles are the primary target of the subumbrella nervous system. Most species in the order Anthoathecata show a trend toward secondary loss of the neural networks and radial smooth muscle fibers in the subumbrella region, concentrating neural elements and smooth muscles only in the radial pathways along the radial canals. By contrast, all studied species in the order Leptothecata have neural networks in the subumbrella area, as well as radial smooth muscle fibers spread throughout the entire subumbrella region. The correlation between radial smooth muscles and the nervous system is also observed in the radial pathways along the radial canals. All species with thick bundles of smooth radial muscles along the radial canals have clearly defined, dense neural pathways running along or even embedded within the smooth muscle bundles.

Edible mushrooms have been reported to have antimicrobial properties and other health benefits. This study aims to test the antimicrobial activities of several edible mushrooms from markets and test if co-culturing them with bacteria could induce stronger anti-bacterial properties. Commercial mushrooms, Hericium erinaceus (lions mane), Pleurotus ostreatus (oyster mushroom), Lentinula edodes (Shiitake) and Agaricus bisporus (button mushroom), were grown from strictly controlled/sterile substrates. Ethanol and water extracts from the mushrooms were prepared and tested against the bacteria Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Bacillus subtilis, and the fungus Candida albicans for antimicrobial activities. Shiitake water extract (SWE) showed strong antibacterial effects against all tested bacterial species, inhibitory effects on their biofilms, and antifungal activity. The antimicrobials in SWE seem to damage the cell wall and cell membrane of the bacteria, prefer weak acidic conditions, and are heat labile. Some antimicrobials are likely proteins and polysaccharides. In contrast, 3 other mushrooms displayed only weak antimicrobial effects. The fast-growing lions mane and oyster mushroom were co-cultured with different bacteria. The co-cultivation promoted the fruiting body development of lions mane. Co-culturing with S. aureus increased the anti-bacterial effects of lions mane against S. aureus, E. coli and particularly B. subtilis. Co-culturing the oyster mushroom with bacteria, especially B. subtilis and P. aeruginosa, boosted the mushroom growth. All tested bacteria, especially S. aureus, increased oyster mushroom anti-bacterial effect against E. coli and B. subtilis. The findings indicate that mushroom-bacteria co-culturing could have benefits both agriculturally and medicinally.

Background Trypanosoma cruzi, the causative agent of Chagas disease, is subdivided into distinct genetic groups known as Discrete Typing Units (DTUs), each with distinct genetic traits that influence epidemiology and transmission dynamics. Several triatomine species serve as potential vectors of T. cruzi in the United States. However, despite the growing number of Chagas disease cases in the country, little is known about the genetic diversity and population structure of T. cruzi in natural vector populations. Methodology/Principal Findings We applied a multilocus metabarcoding approach to improve DTU resolution and characterize the genetic diversity and structure of T. cruzi in triatomines collected across five states of the southern United States. Five single-copy nuclear markers and one mitochondrial marker were amplified and processed by high-throughput sequencing to assess genetic diversity. We recovered 35 nuclear and 15 mitochondrial haplotypes from 70 infected specimens. Overall, genetic diversity was low ({pi} < 0.01 at all nuclear loci), with DTUs TcI and the North American lineage of TcIV detected, TcI being the most prevalent. Geographic structuring was particularly evident in TcI strains, which exhibited a distinctive haplotype profile in Florida populations, potentially linked to the recently revalidated vector species Triatoma ambigua. Mitochondrial introgression from TcIV into TcI suggests inter-DTU genetic exchange in these populations. Multiple haplotypes within individual insects detected across single-copy nuclear markers, support multiclonal infection as common feature of T. cruzi in natural vectors. Conclusions/Significance These findings provide new insights into the genetic landscape and evolution of T. cruzi in the United States. Evolutionary connectivity through mitochondrial introgression and frequent multiclonality highlights the importance of deep sequencing approaches for resolving T. cruzi genetic diversity, with direct implications for understanding for transmission dynamics, disease monitoring and control.

Objective: The Brief-cope questionnaire explore coping behavior. However, the underlying factor structure remains a subject of ongoing debate. Exploratory factor analyses (EFA) conducted across different populations have identified factor solutions ranging from two to fourteen factors. As of yet, the underlying factor structure of the Brief-cope has not been investigated in patients with seropositive rheumatoid arthritis (RA). Therefore, the aim of this study was to explore the underlying factor structure of the Brief-cope in a German population of seropositive RA. Methods: 216 outpatients with seropositive RA completed the Brief-cope. An EFA with principal axis factoring and Promax rotation was conducted. Results: EFA indicated a five-factor solution. The five-factor solution explained 51.95% of variance. The identified factors were: (1) problem-focused coping (Cronbach's = .851), (2) emotion-focused coping ( = .754), (3) maladaptive coping ( = .747), (4) religious coping ( = .851), and (5) substance-use coping ( = .869). Conclusion: A five-factor solution provided the most appropriate representation of the underlying factor structure of the Brief-cope in patients with seropositive RA. This factor structure may serve as a suitable basis for future analyses of Brief-cope data in comparable RA populations.

Background: Adult congenital heart disease (ACHD) patients are prone to HLA-antibody formation from multiple surgeries, transfusions, and prosthetic surgical material. Females with ACHD may accrue additional, non-surgical alloantigen exposure. Whether sex modifies the impact of allosensitization on heart transplant (HT) access and outcomes in ACHD remains unknown. Methods: We retrospectively analyzed the OPTN/UNOS registry of adults with ACHD listed for first-time HT (2018-2025). Sensitization was defined by calculated panel reactive antibodies (cPRA) at listing. We tested the sex x sensitization (highly sensitized, cPRA >50%) interaction on transplant access using Fine-Gray competing-risks regression, treating transplantation as the event of interest and death or removal from the waitlist as competing events, and on post-transplant survival using multivariable Cox proportional-hazards regression, both adjusted for age at listing, mechanical support at listing, and the number of distinct prior cardiac surgery categories. Results: Among 856 candidates (38% female), females were more often highly sensitized than males (23% vs 14%; age-adjusted OR 1.81, 95% CI 1.26-2.61), even after adjusting for surgical burden. Sensitization reduced transplant access in females (84% to 71%; median wait 60 to 110 days, p < 0.001) but not males (79% vs 79%, median wait 88 vs 98 days). In adjusted Fine-Gray models, the subdistribution hazard for transplant was reduced in sensitized females (sHR 0.54, 95% CI 0.41-0.72) with no effect in males (sHR 0.96, 95% CI 0.73-1.26), and the sex x sensitization interaction was significant (interaction sHR 0.64, 95% CI 0.44-0.94, p = 0.02). Post-transplant mortality was numerically higher in sensitized than non-sensitized candidates in both sexes and the sex x sensitization interaction on 1-year mortality was not significant. The sex-asymmetric effect persisted and was more pronounced in the multiorgan candidates. Conclusions: Allosensitization is not a sex-neutral barrier to transplant in HT candidates with ACHD. Females are more sensitized and have reduced transplant access without differences in 1-year mortality. The female excess in sensitization is not accounted for by surgical burden, and the exposures responsible remain to be defined. These findings warrant a sex-aware listing strategy and further studies.

Background: Sickle cell anaemia (SCA) is characterised by chronic haemolysis, inflammation, platelet activation, and recurrent vaso-occlusive complications. Mean platelet volume (MPV) is a readily available platelet index, but evidence regarding its relationship with disease severity in paediatric SCA remains limited and inconsistent, particularly in African populations. Objective: To evaluate the relationship between MPV and disease severity among children with SCA in Kwara State, North-Central Nigeria. Methods: This hospital-based cross-sectional study included 51 clinically stable children with confirmed SCA consecutively recruited from the paediatric haematology clinic of Children Emergency Specialist Hospital, Ilorin. Complete blood count, including MPV, was performed using a Rayto RT-7600 automated haematology analyser. Disease severity was assessed using a composite clinical and laboratory scoring system based on a previously described method. Pearson's correlation, Spearman's rank correlation, simple linear regression, and the Kruskal-Wallis test were used as appropriate. Statistical significance was set at p < 0.05. Results: Of 51 participants, 14 (27.5%) had mild, 33 (64.7%) moderate, and 4 (7.8%) severe disease. Mean MPV was 9.34 +/- 0.76 fL (range, 8.0-11.2). Pearson's correlation showed a weak positive, non-significant linear relationship with severity score (r = 0.231, p = 0.103), whereas Spearman's analysis showed a weak positive monotonic association (rho = 0.286, p = 0.042). Regression explained 5.3% of severity-score variation (R2 = 0.053, p = 0.103). MPV did not differ significantly across severity categories (H = 2.163, p = 0.339). MPV correlated inversely with haemoglobin (r = -0.556, p < 0.001) and positively with platelet count (r = 0.307, p = 0.029). Conclusion: MPV showed a weak relationship with disease severity but inconsistent statistical evidence across analyses. The limited explained variance and absence of significant differences between severity categories do not support MPV as a standalone severity marker. Larger longitudinal studies are warranted. Keywords: Sickle cell anaemia; Mean platelet volume; Disease severity; Platelet indices; Paediatric haematology; Cross-sectional study; Nigeria.

Background: Consumer use of AI chatbots for health advice is rising, yet triage safety relative to established services remains unclear. Australia's Healthdirect, a government-backed symptom checker with 2.4 million uses in FY2024-25, remains unevaluated against frontier large language models (LLMs), and whether premium subscriptions improve triage safety remains unexplored. This study compared the triage accuracy and safety of Healthdirect against six LLM configurations across ChatGPT, Claude, and Gemini, assessed whether paid subscriptions improve triage safety, and characterised each system's error patterns. Methods: Forty-five clinical vignettes from the Semigran et al. benchmark spanning emergency, non-emergent, and self-care categories (15 each) were evaluated across seven systems. Healthdirect was tested following a seven-rule interaction protocol. LLMs were evaluated using first-person patient-language prompts under free-tier and paid-tier conditions. Outcomes were triage accuracy, emergency sensitivity, under-triage, and critical misses, analysed using Cochran's Q, Bonferroni-corrected McNemar tests, Cohen's kappa, and Wilson intervals. Findings: Triage accuracy differed significantly (Cochran's Q = 36.79, p < 0.001). Healthdirect achieved 48.9% accuracy (95% CI 35.0% to 63.0%; kappa = 0.233) versus 73.3% to 86.7% for LLMs (kappa = 0.600 to 0.800). Healthdirect operated under conservative interactive defaults while LLMs received complete information in a single prompt, which may have disadvantaged Healthdirect. Emergency sensitivity was 46.7% versus 80.0% to 86.7% for LLMs. Healthdirect produced two critical misses; no LLM produced any across 270 evaluations (95% CI 0% to 1.4%). When LLMs undertriaged, they recommended GP care rather than self-care. No tier differences were significant (all p > 0.05), and most systems over-triaged self-care cases. Interpretation: Frontier LLMs demonstrated higher triage accuracy and safer error profiles than Healthdirect. All LLMs avoided critical misses; Healthdirect did not. Premium subscriptions did not significantly improve triage safety. These findings support clinical governance decisions about whether LLMs warrant formal evaluation alongside government-backed symptom checkers.

Artificial intelligence applied to routine electrocardiograms (ECGs) has largely focused on detecting existing disease or predicting individual cardiovascular outcomes. Whether ECGs can support prediction of multiple future diseases across organ systems remains unclear. We developed ECG-RISK, a multitask survival model for 67 incident three-character ICD-10 endpoints using ECG waveforms, demographic characteristics and routinely collected laboratory data from 86,673 MIMIC-IV patients. Discrimination was highest for heart, brain, kidney and lung endpoints, with organ-level C-indices ranging from 0.796 to 0.825, whereas liver and pancreatic endpoints showed lower discrimination. The ECG-only model achieved strong discrimination across most endpoints, whereas the incremental improvement gained by incorporating ECG and laboratory inputs beyond demographic information varied substantially across endpoints. Across the nine exploratory aggregated outcomes, Kaplan Meier curves showed clear separation among model-score tertiles. Discrimination was highest for dementia (C-index, 0.891) and heart failure (C-index, 0.857). These findings support the feasibility of ECG-based longitudinal risk prediction across multiple diseases. External validation and competing-risk analyses are required to assess generalisability and clinical utility.

Rationale: Pulmonary hypertension is defined by pulmonary hemodynamics, but diagnostic and prognostic biomarkers remain limited. Nuclear magnetic resonance (NMR) spectroscopy provides detailed insights, particularly in the lipid metabolism. Objectives: To explore circulating NMR-derived metabolites and lipoprotein-related parameters for their association with pulmonary hemodynamics and to analyse their prognostic properties in pulmonary arterial hypertension (PAH). Methods: Retrospective analysis of a PAH cohort with complete diagnostic workup including right heart catheterization and baseline serum samples, from the prospective GRaz Pulmonary Hypertension-Metabolism (GRAPH-M) registry. Measurements: NMR-derived metabolites and lipoprotein-related parameters were analyzed for their association with clinically relevant parameters of PAH. We defined PHIHDL, a score derived from high-density lipoprotein (HDL) related measures based on their strong association with pulmonary hemodynamics, and evaluated its prognostic value. Results: We included 100 patients with PAH treated at the PH clinic of LKH University Hospital, Medical University of Graz, between 2011 and 2021. Age was 61{+/-}15 years, female/male ratio 2.5, BMI 26 {+/-}7 kg/m2, mPAP 41{+/-}16 mmHg, PAWP 8.8{+/-}3.2 mmHg, PVR 8.0{+/-}4.9 WU, and median survival was 8.0 years. During follow-up, 46 patients died. We identified a cluster of 12 HDL-related measures that showed significant inverse association to pulmonary hemodynamics and derived PHIHDL from the reversed scaled average of these particles. PHIHDL was associated with all-cause mortality after adjustment for age and sex (HR 2.96, 95% CI 1.52-5.70), independent of the clinical risk scores COMPERA 2.0 and REVEAL Lite2. Conclusion: PHIHDL, a pulmonary hemodynamics-based metabolomic score, provides independent prognostic information beyond established risk scores in PAH.

Objectives To evaluate whether access to a certified large language model (LLM)-based clinical decision support system improves physician diagnostic performance in rheumatology compared with conventional diagnostic resources alone. Methods In this multicentre, open-label, randomised controlled trial, 82 physicians from seven hospitals in two countries were randomised 1:1 to conventional diagnostic resources plus Prof. Valmed or conventional resources alone. Participants assessed three rheumatology vignettes before and after assistance. The primary outcome was top-1 diagnostic accuracy. Secondary outcomes included top-3 accuracy, diagnostic reasoning, confidence, case-processing time and perceived support quality. Results Top-1 accuracy increased from 22.2% to 33.3% in the intervention group and from 23.3% to 35.0% in the control group, with no between-group difference in improvement (adjusted OR 0.99, 95% CI 0.45 to 2.19; p=0.979). Differences in top-3 accuracy, diagnostic reasoning and confidence were also not significant. Assisted case-processing time was substantially shorter with LLM support (94 vs 206 s; adjusted mean difference -112 s, 95% CI -141 to -83; p<0.001). Information timeliness and perceived diagnostic support quality were rated significantly higher in the intervention group. Exploratory analyses showed persistent overconfidence and substantial AI over-reliance. Conclusions Certified LLM-based diagnostic support did not improve diagnostic accuracy compared with conventional resources, but substantially reduced case-processing time and improved perceived support quality. These findings suggest potential workflow benefits while highlighting overconfidence and over-reliance as important safety considerations.

Purpose: To evaluate the safety, procedural performance, sample recovery, and surgeon preference of an ophthalmic needle designed specifically for anterior chamber (AC) paracentesis. Methods: In this multicenter study, AC paracentesis was performed in clinic and operating-room settings using a 32-gauge x 4-mm needle with low dead space. The procedure was evaluated using a standardized physician survey. Prespecified outcomes included procedure-related adverse events (primary outcome), needle entry and handling, aspiration and sample recovery, comparative performance versus a 30-gauge needle, and physician preference for future use. Results: A total of 110 needle uses by eight surgeons were included. No ocular complications occurred, including lens or iris injury, hyphema, AC collapse, wound leak, hypotony, infection, or retinal complication, and no procedure required needle exchange or conversion to another device. Two technical events without ocular sequelae were noted, in which needle entry was partial thickness and did not reach the AC (1.8%; exact 95% CI, 0.2%-6.4%). Physicians rated needle entry, handling and sample recovery as good or excellent. Compared with a 30-gauge needle, the study needle was rated as at least comparable across all assessed domains. All surgeons rated it better or much better for intra-procedural safety and preferred it for future AC taps. Conclusions and Relevance: This short, 32-gauge low-dead-space ophthalmic needle demonstrated a favorable safety profile and was preferred over a 30-gauge needle by all surgeons. As aqueous humor liquid biopsy expands in clinical diagnostics and trials, an ophthalmic-specific needle design may help improve the consistency and safety of aqueous humor collection for molecular analysis and broader clinical use. Keywords: Anterior chamber paracentesis; Aqueous humor; Liquid biopsy; Low dead space; Ophthalmic needle

Introduction: Polyendocrine metabolic ovarian syndrome (PMOS), formerly known as polycystic ovary syndrome (PCOS), is a common endocrine disorder affecting women of reproductive age. Besides reproductive and metabolic disturbances, PMOS negatively impacts psychological well-being and quality of life. Despite available treatment options, there remains a need for safe and effective therapies that improve both clinical symptoms and fertility outcomes. Aim: To compare the efficacy of VAMHA and MYRHA tablet combination therapy with standard non-hormonal therapy in restoring regular menstruation. Secondary objectives included assessment of ovulation, menstrual symptoms, polycystic ovarian morphology, hormonal and metabolic parameters, anthropometric measures, and skin manifestations. Study Design: Open-label, randomized, multicentre, prospective comparative clinical study. Methods: Seventy-one women with PMOS were randomized to Group A (n=37) or Group B (n=34). Group A received VAMHA and MYRHA tablets (2 tablets each), while Group B received Metformin 500 mg plus Myoinositol 600 mg (1 tablet), twice daily for 180 days. Data were recorded in Case Report Forms. Statistical Analysis: Continuous variables were summarized using mean and standard deviation, while categorical variables were expressed as frequencies and percentages. Appropriate statistical tests, including Chi-square, were used. A p-value [&le;]0.05 was considered significant. Results: Significantly more participants in Group A achieved regular menstrual cycles than Group B (31 vs. 22; p<0.05). Ovulation occurred in 16 participants in Group A compared with 6 in Group B (p<0.05). Both groups showed significant improvement in menstrual irregularity and related symptoms. Significant reductions in Anti-Mullerian Hormone (AMH), fasting insulin, and body mass index (BMI) were observed in both groups (p<0.05). Resolution of polycystic ovarian morphology occurred in 13 participants (38.23%) in Group A and 10 (33.33%) in Group B. Both treatments were well tolerated with no major safety concerns. Conclusions: VAMHA and MYRHA combination therapy was superior to standard non-hormonal therapy in improving menstrual regularity and ovulation. It also produced favourable metabolic, hormonal, and ultrasonographic outcomes, suggesting its potential as a safe and effective option for comprehensive PMOS management and fertility enhancement.

Introduction Acute lower respiratory tract disease (aLRTD) is a leading cause of hospitalisation and death, particularly in older adults and adults with comorbidities, with acute lower respiratory tract infection (aLRTI; pneumonia and non-pneumonic LRTI) being a major component. Non-pulmonary complications and functional decline after aLRTI are recognised, but their pathogen-specific burden is poorly described. We aimed to quantify renal, hepatic, thromboembolic and functional complications, and mortality, after aLRTI hospitalisation, by clinical phenotype and pathogen. Methods We conducted a cohort study of adults (>18 years) admitted with aLRTD to two hospitals in Bristol, UK (01 August 2022-31 July 2024). aLRTD was classified as pneumonia, non-pneumonic LRTI (NP-LRTI) or no diagnosis of aLRTI. Pathogens were identified from standard-of-care and research microbiology. Outcomes were acute kidney injury (AKI), acute liver dysfunction, venous thromboembolism (VTE), in-hospital falls, reduced mobility at discharge, increased care requirements, and 30-day and 1-year mortality. Analyses were descriptive. Results Among 246,797 adult admissions, 21,456 aLRTD hospitalisations were included: 10,239 (47.7%) pneumonia, 7,742 (36.1%) NP-LRTI and 3,475 (16.2%) with no evidence of aLRTI. Of 19,152 tested aLRTD admissions, 8,503 (44.4%) had a positive microbiological/virological test, yielding 9,204 pathogen detections; 1,194 (6.2%) had co-infections, and SARS-CoV-2 was most frequent, with influenza the second most common in pneumonia and NP-LRTI. Pneumonia had greater severity than NP-LRTI and no diagnosis of aLRTI (median length of stay 6 vs 4 vs 4 days; ICU admission 3.4% vs 0.7% vs 0.5%, respectively). Overall, 22.2% developed AKI, 6.1% acute liver dysfunction, 0.6% DVT and 2.4% PE; 1.8% had a fall, 11.5% reduced mobility, and 16.6% required increased care at discharge. 30-day and 1-year mortality were highest for pneumonia (14.0% and 32.0%, respectively). Pathogen-specific analyses showed longer stays and higher complications and mortality rates for SARS-CoV-2 and Streptococcus pneumoniae, and shorter stays with lower complication and mortality rates for influenza and Haemophilus influenzae. Conclusions Non-cardiovascular complications and functional decline after aLRTI were common, particularly in pneumonic and SARS-CoV-2 or pneumococcal disease. These findings support routine surveillance for renal, hepatic, thromboembolic events, early mobilisation and rehabilitation, and consideration of multi-system outcomes when evaluating public health and economic value of vaccines and therapies.

Background & Aims: Fatigue is a central symptom of chronic liver disease (CLD), substantially impacting health-related quality of life (HRQoL). This study aimed to further understand CLD symptomatology, including fatigue, and its impact on HRQoL from a patient perspective. Methods: Abbott Global Assessment of Patients unmet needs (aGAP) was a multinational, cross-sectional survey in adults with compensated CLD in China, India and Mexico, conducted between July and November 2024. Adult participants who self-reported that they had physician-diagnosed CLD and were experiencing fatigue completed a quantitative survey to assess symptom burden and included three HRQoL patient-reported outcome (PRO) questionnaires (Patient-Reported Outcomes Measurement Information System [PROMIS]-29+2, Work Productivity and Activity Impairment - Specific Health Problem version 2.0 [WPAI: SHP], Multidimensional Fatigue Inventory [MFI]). Results: Overall, 505 participants (China: 200; Mexico: 105; India: 200) completed the study. Participants reported that their CLD-related fatigue sometimes, often or always affected their self-esteem/confidence (45.1%) and ability to maintain or acquire new employment (38.6%). Most participants reported moderate (51.3%) or serious (26.9%) fatigue, with 33.5% experiencing fatigue every day or almost every day. Many participants felt their social life was negatively impacted by their fatigue (47.3%) and that there were related financial difficulties (53.9%). Use of validated PRO tools demonstrated severe fatigue (MFI: overall mean [SD] 13.9 [3.4] general fatigue and 13.4 [3.6] physical fatigue) as well as substantial levels of work and activity impairment (WPAI: SHP overall mean [SD] 53.0 [26.4]) and high levels of anxiety, pain interference, depression and sleep interference (PROMIS T-scores [&ge;]54). Conclusions: Fatigue has a substantial impact on HRQoL among adults with CLD across several countries, highlighting a global unmet need for targeted interventions to effectively identify and manage the condition.

Importance: Evidence on GLP-1/GIP therapies is largely derived from trials enrolling selected populations or medical records that miss utilization outside healthcare channels. No nationally representative cohort has characterized real-world uptake, indications, and access. Objective: To characterize GLP-1/GIP prevalence, indication, clinical profile, and access. Design: Prospective cohort study with three GLP-1/GIP surveillance waves (March 2024, December 2024, October 2025). Setting: The Understanding America Study, an address-based, nationally representative panel of approximately 15,000 US adults aged 18+ years initiated in 2014. Participants: UAS participants responding to at least one surveillance wave (n=9150). Exposures: GLP-1/GIP use status (never vs any use, comprising current and former use), self-reported primary indication (diabetes, weight loss, or other), and access pathway (traditional vs non-traditional). Main Outcomes and Measures: Survey-weighted prevalence of GLP-1/GIP use, overall and by indication and access pathway; sociodemographic, cardiometabolic, treatment, and access characteristics; and smartwatch-derived resting heart rate, heart rate variability, maximum activity heart rate, step count, and sleep duration and variability. Results: Among n=9150 adults (1274 with any use; 60.9% female; median age 53 years), weighted prevalence increased 46%, from 8.2% (March 2024) to 12.0% (October 2025) representing 32 million. Weight-loss indications grew, reaching nearly half of use (4.1% to 5.6%); diabetes-indicated use was stable (5.3% to 5.4%). Users carried high cardiometabolic burden (obesity, 68.2%; diabetes, 53.6%) but diverged by indication: diabetes-indicated users were older (median, 59 vs 49 years), whereas weight-loss-indicated users were more often female (69.9% vs 51.3%) and healthier. One in three users (~9 million) had non-traditional access, especially in weight-loss-indicated users, of whom 33% had no conventional prescription; 41% used compounding, online, or foreign pharmacies; and, 43% lacked coverage. Non-traditional users were five times as likely to report an unlisted, likely compounded formulation (19.8% vs 4.1%). All p<0.05. Conclusions and Relevance: Real-world GLP-1/GIP use has grown rapidly and diversified substantially in indication, access, and population profile. One in 3 users obtained treatment through nontraditional channels largely invisible to claims data, raising long-term safety, efficacy, and coverage questions. GLIMMER provides a public, nationally representative longitudinal evidence base for future payer and provider decisions.

Background. Videolaryngoscopy still requires adjuncts or hyperangulated rescue in a clinically important minority, and bedside screening discriminates modestly. Point-of-care ultrasound (POCUS) of the anterior airway is a promising alternative, but existing prediction models are opaque or assume a pre-specified functional form. We developed and internally validated a parsimonious, fully disclosed POCUS risk equation whose form is recovered from data and whose structural properties are machine-checked by formal proof - to our knowledge the first formally verified clinical risk predictor - following TRIPOD+AI 2024. Methods. In a prospective single-centre, single-operator cohort of 259 adults undergoing elective videolaryngoscopy (no-Easy airway 68/259, 26.3%), Sequentially Thresholded Least Squares with bootstrap stability selection (B=300) screened a 71-term library of nine POCUS features and retained a seven-term logistic equation; a two-term bootstrap-stable model was pre-specified as robustness analysis. Internal validation used 5x10 repeated cross-validation plus temporal and device hold-outs, with pre-specified overfitting and optimism assessments. Five behavioural properties of the deployed equation were machine-checked in Lean 4. Results. Two interactions met the |c|/sigma_c>2 stability criterion: skin-to-epiglottis x skin-to-hyoid-bone distance and tongue volume x sagittal tongue area. The seven-term equation reached a 5x10 cross-validated C-statistic of 0.966 (optimism-corrected 0.968) and held across temporal and device hold-outs (0.94-0.97). Calibration-in-the-large matched prevalence, with cross-validated slope 0.90 attenuating to 0.625 out-of-time; standard recalibration restored 0.92 without loss of discrimination. The pre-specified two-term robustness model reproduced this performance (C-statistic 0.964-0.968; events-per-parameter 34; shrinkage 0.99), confirming the result is not an artefact of the screening stage. Net benefit over a clinical baseline was positive across 10-50% thresholds. All five Lean 4 theorems compiled without sorry. Conclusions. A sparse, formally verified POCUS equation predicts difficult videolaryngoscopy with high internally validated discrimination and quantified, modest overfitting. Because the equation was developed in a single-operator cohort and its inputs are operator-dependent, external validation requires prior harmonisation of the measurement protocol and operator credentialing.