Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Peripheral Nervous System Diseases”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

839 records · Page 9Linked to original sources
PubMed2026

A Pilot Study: Developing a Lactating Dairy Goat Model to Study Staphylococcus aureus Mastitis in Women.

INTRODUCTION: Lactational mastitis is common in lactating women, with Staphylococcus aureus as the most commonly isolated agent associated with infectious lactational mastitis. Currently, there are no evidence-based guidelines for antimicrobial treatment due to barriers in obtaining pharmacokinetic data from lactating women. To overcome this barrier, a suitable large animal model is needed. Goats are an ideal translational model for human mastitis due to their anatomical and physiological similarity to humans. The objective of this pilot study was to assess if goats would develop clinical mastitis following intramammary inoculation with a clinical human isolate of S. aureus with the goal of establishing an alternative in vivo model for future research. The hypothesis was that the infected mammary gland half would show similar clinical signs to women with mastitis and demonstrate a similar local immune response when compared to the control mammary gland half. METHODS: One half of the mammary gland of two healthy lactating does was inoculated with a clinical human isolate of S. aureus. The other half of the mammary gland was sham inoculated with sterile buffered saline. Physical examinations, mammary gland assessments, and sterile milk samples were collected every 12 hours post inoculation. At 96 hours post inoculation, the goats were euthanized, and the mammary glands were examined for pathological changes. RESULTS: Goats did not develop systemic signs of disease following inoculation. Focal infected mammary gland changes included warmth, swelling, redness, discoloration, and reduced milk production; the other mammary gland half remained normal throughout the study period. S. aureus was enumerated from only the infected mammary gland half. The microscopic findings of the infected half showed neutrophilic inflammation and cell necrosis consistent with acute mastitis. DISCUSSION: This pilot study demonstrated lactating does can develop clinical signs like those observed in women. Goats have the potential to be a promising animal model to study infectious lactational mastitis.

Animals↗
PubMed2026

Effects of Sacubitril Valsartan Combined With Vericiguat on NT-proBNP and CK-MB Levels in Patients With Chronic Heart Failure.

This study aims to probe the influence of sacubitril valsartan sodium tablets combined with vericiguat on N-terminal pro-B-type natriuretic peptide (NT-proBNP) and creatine kinase isoenzyme (CK-MB) levels in patients with chronic heart failure (CHF). One hundred and twenty CHF patients were enrolled and stratified into a control group (sacubitril valsartan sodium tablets) and a combination group (sacubitril valsartan sodium tablets + vericiguat). Outcome measures included New York Heart Association (NYHA) functional class shifts, echocardiographic indices, cardiac injury markers, 6-min walk distance (6MWD), endothelial function parameters, inflammatory mediator levels, and adverse clinical events. Following a 6-month treatment period, patients in the combination group exhibited superior functional improvement, as reflected by greater advancement in NYHA class. Echocardiographic evaluation revealed more favorable ventricular remodeling in this group, with reduced left ventricular end-diastolic and end-systolic diameters and an elevated ejection fraction. The combination group had a higher 6MWD. Biomarker analysis showed lower NT-proBNP and CK-MB levels in the combination group. Furthermore, improvements in endothelial function were noted, with decreased endothelin and elevated NO, NOS, and CGRP levels in the combination group. Markers of systemic inflammation, including CRP and IL-6, were also attenuated in the combination group. The incidence of adverse reactions and cardiovascular events did not differ significantly between the groups. Co-administration of sacubitril/valsartan and vericiguat enhances cardiac performance, optimizes vascular endothelial responsiveness, modulates heart failure-related biomarkers, and mitigates inflammatory activity in patients with CHF without increasing the risk of adverse events.

Humans↗
PubMed2026

Safety and Immunogenicity of Varicella Vaccination in Children and Adolescents Living With HIV: A Systematic Review.

INTRODUCTION: Preventing varicella-zoster virus infection is important in the management of human immunodeficiency virus (HIV)-positive persons. Varicella remains endemic worldwide, and HIV-positive persons can experience greater morbidity than the general population. We summarized the global literature on the safety and immunogenicity of the varicella vaccine in HIV-positive children. METHODS: Systematic review of original reports on varicella vaccination of HIV-positive children, published through December 31, 2024, including assessment of safety, immunologic responses and effectiveness after vaccination. RESULTS: Eighteen articles were analyzed. Local reactions were the most common adverse events, albeit infrequent (<21% and <10% of vaccinees after dose 1 and 2, respectively). Systemic reactions were also infrequent, consisting mostly of low-grade fever. A vaccine-related rash, reported in <5% of vaccinees, had fewer lesions and a shorter duration than typical varicella. Serious adverse events were reported only when the vaccine was inadvertently administered to children with severe HIV immunosuppression. Varicella vaccination had no clinically significant impact on plasma HIV RNA or CD4+ T-cell count after either dose. An antibody response was reported in 60%-79% of HIV-positive vaccinees after dose 2 and often declined more rapidly than in uninfected children. Cell-mediated immunity was detected in 67%-83% after dose 2. No significant differences in adverse events or short-term immune response after vaccination correlated with past or current CD4+ T-cell status. CONCLUSIONS: The varicella vaccine had a favorable safety profile and induced specific immune responses in most nonseverely immunocompromised HIV-positive children. The vaccine remains contraindicated for persons with severe HIV infection. Robust data on the durability of immune response and long-term effectiveness are needed.

Humans↗
PubMed2026

Herd-level heterogeneity of antimicrobial resistance in commensal Escherichia coli: A nationwide high-throughput survey of Australian pig herds.

Antimicrobial resistance in commensal Escherichia coli provides a useful indicator for overall antimicrobial resistance burden. We applied this approach to assess antimicrobial resistance within and between commercial pig herds across Australia. A high-throughput robotic workflow was used to isolate 2730 E. coli colonies from rectal contents collected in 2022 from healthy slaughter pigs (n&#x202f;=&#x202f;300) representing 30 herds (&#x223c;70% of national production). Up to 94 isolates per herd underwent antimicrobial susceptibility testing using the Robotic Antimicrobial Susceptibility Platform. Isolate- and herd-level antimicrobial resistance indices were calculated, weighting antimicrobials by their human health importance. Resistance to first-line agents was widespread: ampicillin 77% and tetracycline 79%. By contrast, resistance to critically important antimicrobials was rare (ciprofloxacin 0.11%; extended-spectrum cephalosporins 0.04%), and no clinical resistance to carbapenems or colistin was detected. Overall, 56.9% of isolates were multi-class resistant. Herd-level antimicrobial resistance within indices ranged from 1.51 to 5.76, revealing substantial between-herd heterogeneity. Three herds carried critically important antimicrobials-resistant isolates that would likely have been missed using conventional, lower-density sampling approaches. Whole-genome sequencing identified fluoroquinolone-resistant isolates belonging to ST10 and ST69 (both qnrS1), and ST744 (Quinolone Resistance Determining Region mutations plus blaCTX-M-27). By testing approximately tenfold more isolates than conventional surveys, we uncovered considerable antimicrobial resistance with heterogeneity within and between animals and herds, including farm-specific variability. This expanded sampling also enabled detection of critically important antimicrobial resistance at very low prevalence. In conclusion, high-throughput, high-density testing offers a practical early-warning system and herd-level benchmark to inform surveillance and targeted interventions.

Animals↗
PubMed2026

Community-tailored One Health educational intervention to enhance knowledge and practices for zoonotic disease prevention in rural Thailand: A protocol for a prospective cluster randomised controlled Trial in Chanthaburi, Thailand (Saan Suk trial).

BACKGROUND: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailand's established Village Health Volunteer (VHV) system. METHODS: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. DISCUSSION: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. TRIAL REGISTRATION: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Zoonoses↗
PubMed2026

[Study of a patient with azoospermia due to variant of MOV10L1 gene].

OBJECTIVE: To explore the clinical and genotypic characteristics of a patient with Sertoli cell-only syndrome (SCOS) due to variants of MOV10L1 gene. METHODS: A 27-year-old patient with Non-obstructive azoospermia (NOA) underwent routine semen analysis. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), prolactin (PRL), and testosterone (T) were determined by chemiluminescence assays. Peripheral blood samples were collected for G-banded karyotyping analysis. Multiplex PCR fluorescence detection was used to screen for AZF gene microdeletions. Whole exome sequencing (WES) and Sanger sequencing were performed simultaneously. Testicular biopsy tissues were subjected to Hematoxylin-Eosin (HE) staining to assess seminiferous tubule cell composition, and MOV10L1 protein expression was detected by immunohistochemical staining. Bioinformatics tools were employed to predict the pathogenicity of variants and their impact on protein structure and function. This study was approved by the Medical Ethics Committee of the Guangdong Institute of Reproductive Sciences [Ethics No.: 2023(01)]. RESULTS: The patient's two semen analyses had failed to detect any sperm. Hormone tests indicated elevated FSH (22.32 mIU/mL) and PRL (397.6 mIU/mL), while T (3.68 nmol/L) and E2 (38.32 pmol/L) were reduced. Chromosomal karyotyping revealed 46,XY, and no AZF gene deletion was detected. WES and Sanger sequencing detected compound heterozygous variants of the MOV10L1 gene, including a c.345C>A (p.C115X) nonsense variant and a c.3323C>T (p.T1108I) missense variant, with the former being unreported previously. HE staining showed only Sertoli cells in the seminiferous tubules, confirming the diagnosis of SCOS. Immunohistochemical staining revealed absent MOV10L1 protein expression in the testicular tissue. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the c.345C>A (p.C115X) was classified as a pathogenic variant (PVS1+PM2_Supporting+PP4), while the c.3323C>T (p.T1108I) was deemed variant of uncertain significance (PM2_Supporting+PP3_Supporting+PP4). Bioinformatics analysis demonstrated that c.345C>A (p.C115X) may cause premature termination of protein translation, while c.3323C>T (p.T1108I) may disrupt the hydrophobicity of the RNA helicase domain, reducing the active pocket volume and decreasing its affinity for MILI protein. CONCLUSION: This study has diagnosed a case of SCOS due to compound heterozygous variants of the MOV10L1 gene, which also enriched its mutational spectrum.

Humans↗
PubMed2026

Nephropathies Associated with Sickle Cell Trait and How to Study Them.

Sickle cell trait (SCT), which carries a single point mutation in the hemoglobin-&#x3b2; (HBB) gene, has long been considered a benign condition. However, epidemiological evidence challenges this assumption, revealing that individuals with SCT face an elevated risk of renal dysfunction. However, this field of study remains ill-defined as it has focused on sickle cell disease (SCD), where renal complications are severe. As SCT is more prevalent than SCD, consequences of nephropathies in this group translate into a substantial and largely unaddressed public health burden. Clinical data, primarily observational, implicate age and sex in the development of SCT-associated nephropathies. These manifestations span glomerular hyperfiltration, tubular damage, hematuria, renal papillary necrosis, renal medullary carcinoma, and progression to chronic kidney disease, all complications that cluster disproportionately in older male individuals. Despite this, the mechanistic basis of SCT nephropathy, the thresholds at which renal injury becomes clinically significant, and the optimal strategies for early identification and prevention remain inadequately defined. In vitro studies have primarily focused on SCD blood cell biology, with SCT receiving comparatively little attention. Humanized murine models (i.e., Berkeley and Townes) have recapitulated some SCT-associated renal phenotypes but need to be more fully characterized. This review aims to provide an overview of the biology of sickle cell trait nephropathies, the gaps in our knowledge, and the model systems we can use to fill those gaps.

Journal Article↗
PubMed2026

Multi-omics reveals that burdock seed aglycone alleviates renal fibrosis by restoring mitochondrial oxidative phosphorylation function.

Renal fibrosis (RF), a common pathological process driving chronic kidney disease (CKD) progression to end-stage renal failure, is closely associated with oxidative phosphorylation (OXPHOS). Arctigenin (ATG), the main active component of burdock seed, exhibits anti-inflammatory and anti-fibrotic activities, but its mechanisms in RF treatment remain unclear. Here, we performed integrated transcriptomic and proteomic analyses to identify key targets and pathways of ATG in a unilateral ureteral obstruction-induced rat RF model. Multi-omics enrichment analysis revealed that NDUFS8 and NDUFS2 were the core targets of ATG, with the OXPHOS pathway as the central intersecting pathway. Our results suggest that ATG exerts anti-renal fibrosis effects by targeting the OXPHOS pathway to inhibit excessive reactive oxygen species production and oxidative stress. SIGNIFICANCE: Chronic kidney disease (CKD) continues to impose an escalating global health and socioeconomic burden, while renal fibrosis (RF), as the convergent pathological endpoint of virtually all progressive nephropathies, remains the principal determinant of irreversible renal failure and adverse clinical outcomes. Despite extensive efforts to develop antifibrotic therapies, effective clinical interventions remain elusive, largely due to the complex and multifactorial nature of RF pathogenesis. In this study, we employed an integrated multi-omics framework encompassing transcriptomics, proteomics, and metabolomics to systematically decipher the antifibrotic mechanism of arctigenin (ATG), a bioactive natural compound derived from traditional Chinese medicine. Our findings identify mitochondrial oxidative phosphorylation as the pivotal regulatory axis underlying the renoprotective effects of ATG and further establish key catalytic subunits of mitochondrial complex I as its direct molecular targets. Mechanistically, ATG not only restores complex I activity and reprograms mitochondrial energy metabolism but also preserves the intracellular stability and localization of these subunits, thereby preventing their aberrant release-mediated inflammatory activation and disrupting the self-perpetuating cycle linking metabolic dysfunction, inflammation, and fibrosis progression. Beyond revealing a previously unrecognized dual mechanism integrating metabolic and inflammatory regulation, this study provides compelling evidence that mitochondrial dysfunction is not merely a secondary consequence of tissue injury but a fundamental driver of fibrotic remodeling. Importantly, our work highlights the translational potential of natural product-based mitochondrial interventions for CKD treatment and supports a broader conceptual shift toward metabolism-centered therapeutic strategies for chronic fibrotic diseases. Given the central role of mitochondrial dysfunction across multiple organs, these findings may also have far-reaching implications for the treatment of systemic fibrosis-related disorders beyond the kidney.

Animals↗
PubMed2026

Nutrition and Diet-Related Training and Curriculum in the US Predoctoral Dental Programs.

PURPOSE: Nutrition and diet are vital for oral and systemic health. It is unclear how well US predoctoral dental programs prepare students in nutrition screening and counseling. This study analyzed US dental school curricula on these topics. METHODS: A cross-sectional online survey was sent to the publicly available email addresses of 67 of 72 academic dental deans at US Commission on Dental Accreditation-accredited dental schools. Items assessed availability, modes and hours of instruction, curricular topics, clinical integration, and instructors. Descriptive statistics summarized responses. RESULTS: A total of 21 academic deans responded, for an overall response rate of 29%. Most (85%) of responding academic dental deans reported that nutrition and diet education was mandatory, with none treating it as optional. Of these schools, 83% offered both classroom and clinical training, while 17% provided only didactic teaching. Didactic hours varied; 42% reported 10 or fewer hours. Foundational nutrition topics were common, although dietary guidelines such as MyPlate were reported less often (66%). Oral health-related nutrition content was broadly covered, with all respondents reporting instruction related to caries, erosion, periodontal disease, and oral dysfunction. Counseling content was less consistent, particularly public health nutrition (67%) and the impact of oral dysfunction on diet and nutrition (72%). CONCLUSION(S): Most responding academic dental deans report including nutrition and diet education in their curricula. However, it remains uncertain whether these topics are incorporated at schools that did not participate in the survey. Variability in curricular time, counseling, and teaching highlights the need for clearer competencies and more clinical training. Improving this could better prepare future dentists for common dietary risks affecting oral and systemic health.

dental caries↗
PubMed2026

Early Analgesia for the Management of Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: We aimed to evaluate the efficacy and safety of early analgesic interventions, particularly NSAIDs versus opioids, in reducing pain and improving clinical outcomes among adults with AP. METHODS: A systematic literature search was conducted across PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, Scopus, and ClinicalTrials.gov from database/registry inception to December 2025 to obtain relevant data. Randomized controlled trials involving adults aged 18 years or older diagnosed with AP, irrespective of the etiology and severity, who were administered analgesics (opioids, nonsteroidal anti-inflammatory drugs, cyclooxygenase-2 inhibitors, epidural anesthesia, local anesthesia, and paracetamol) and compared with placebo, conventional treatment, or another analgesic modality were included in this review. The primary outcome assessed was pain reduction. The secondary outcomes assessed were the need for rescue analgesia, length of hospital stay, complications (local and/or systemic), mortality, and adverse drug effects. Risk of bias was assessed using the Cochrane Risk of Bias tool 2.0. Effect estimates were pooled using a random-effects meta-analysis (DerSimonian-Laird approach), while nonpooled outcomes were summarized narratively. RESULTS: A total of 13 studies were included in the analysis. NSAIDs provided pain relief comparable to opioids, with a lower incidence of local complications (RR: 0.59, 95% CI: 0.37-0.94). No significant differences in the need for rescue analgesia (OR: 0.88, 95% CI: 0.33-2.35), length of hospital stay (MD: -2.68&#xa0;d, 95% CI: -6.27 to 0.91), mortality (RR: 0.76, 95% CI: 0.19-3.05), and adverse drug effects (RR: 0.55, 95% CI: 0.17-1.76) were observed. However, the findings are limited by study bias and heterogeneity. CONCLUSION: Early analgesia with NSAIDs has efficacy and safety comparable to opioids in adults with AP, with the advantage of reducing local complications.

Humans↗
PubMed2026

Efficacy and Safety of Bimagrumab in Adults With Obesity and Metabolic Dysfunction: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

AIMS: This study aims to systematically evaluate the efficacy of bimagrumab on body composition and glucose parameters in adults with obesity and metabolic dysfunction and its safety profile. METHODS: We searched MEDLINE, PubMed, Embase, and the Cochrane Library on April 20, 2026, for randomized controlled trials (RCTs) assessing bimagrumab treatment in adults with obesity, insulin resistance, or type 2 diabetes mellitus (T2DM). The risk of bias was assessed using the Cochrane Risk of Bias tool (RoB 2), and meta-analyses of efficacy and safety data were conducted using R software. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) system was used to assess the strength of evidence. The study was registered with PROSPERO (CRD420261377110). RESULTS: Of the 134 retrieved records, 4 RCTs (enrolling 268 participants) were included. The included population represented a broad spectrum of metabolic dysfunction, from obesity and nondiabetic insulin resistance to established T2DM. Compared with placebo, bimagrumab treatment significantly reduced total weight (mean difference [MD] -4.85&#x2009;kg, 95% confidence interval [CI] -6.82 to -2.88), fat mass (-4.72&#x2009;kg [-8.05 to -1.40]), and glycated haemoglobin (HbA1c) (-0.13% [-0.23 to -0.03]) and significantly increased total lean mass (1.66&#x2009;kg [0.81 to 2.51]). However, bimagrumab led to an increase in low-density lipoprotein (LDL) concentrations of 0.47&#x2009;mmol/L [0.03 to 0.91] and significantly increased incidences of discontinuation (risk ratio [RR] 5.75 [1.61 to 20.46]), muscle spasms (RR 10.44 [4.23 to 25.75]), and diarrhoea (RR 4.91 [2.38 to 10.11]). CONCLUSION: Bimagrumab effectively reversed adverse effects on body composition in obese individuals, resulting in significant fat reduction, increased skeletal muscle mass, and improved glycemic control, suggesting that bimagrumab is a promising new target for personalized metabolic therapy.

Humans↗
PubMed2026

Premeal insulin administration lowers postprandial blood glucose and increases myocardial microvascular blood flow in people with type 1 diabetes: a randomised, crossover clinical trial.

AIMS/HYPOTHESIS: We aimed to evaluate whether prandial insulin timing affects vascular function in people with type 1 diabetes. Our hypothesis was that premeal insulin administration would lead to greater myocardial microvascular blood flow (MBF) via blunting postprandial hyperglycaemia. METHODS: People with type 1 diabetes between 18 and 35 years of age with BMI <30 kg/m2 underwent two protocols with a 1:1 randomised crossover design wherein prandial insulin was injected either 15 min before or 15 min after meal intake began. To provide a physiological comparison, age-, sex- and BMI-matched control participants completed one study where they consumed the same meal but received no exogenous insulin. Glucose, insulin, vascular function (including ultrasound measures of myocardial and skeletal muscle microvascular perfusion, aortic stiffness, brachial artery endothelial function) and biomarkers of systemic inflammation and endothelial dysfunction were assessed at baseline and then 2 h after meal ingestion within each protocol. The primary outcome was change in myocardial MBF within each protocol. Study personnel assessing outcomes were masked to group assignment. RESULTS: Eighteen people with type 1 diabetes and 18 matched control participants were analysed within each protocol. Glucose area under the curve was significantly greater (p=0.015) in the postmeal insulin study compared with the premeal insulin study in participants with type 1 diabetes. Myocardial microvascular flow velocity significantly increased (p=0.031) with premeal insulin administration in people with type 1 diabetes and this consequently led to greater myocardial MBF (p=0.044). There were no changes in myocardial MBF within the other protocols. Changes in vital signs were similar between all protocols. CONCLUSIONS/INTERPRETATION: Appropriately timed premeal insulin led to lower postprandial blood glucose along with increased myocardial MBF in people with type 1 diabetes. Further work is needed to determine the underlying aetiology of these changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT04730882.

Humans↗
PubMed2026

An AI-assisted Clinical Decision Support System for Green Classification of Cystocele on Dynamic Transperineal Ultrasound.

Green classification of cystocele on dynamic transperineal ultrasound (TPUS) remains operator-dependent because it requires manual frame selection and landmark-based assessment of the Valsalva maneuver. We developed a workflow-oriented AI-assisted clinical decision support system for automated urethrovesical junction localization and dynamic Green classification and prospectively evaluated its standalone and reader-support performance. This diagnostic accuracy and reader study included 881 patients from a tertiary referral hospital, comprising a retrospective development cohort (n&#x2009;=&#x2009;688) and an independent prospective test cohort (n&#x2009;=&#x2009;193). A nested subset of 67 prospective patients was used for a reader study involving two junior and two intermediate radiologists under unaided and AI-assisted conditions. In the complete prospective test cohort, Green-AttGRU achieved a macro-averaged AUC of 0.939 (95% CI, 0.897-0.971) and an overall accuracy of 0.902 (95% CI, 0.860-0.943). In the reader study, overall accuracy increased from 0.761 to 0.821 without AI to 0.851-0.881 with AI, while macro-F1 increased from 0.660 to 0.777 to 0.820-0.860. Overall inter-reader agreement increased from a Fleiss' &#x3ba; of 0.453 to 0.786, and pooled median interpretation time decreased from 26.7&#xa0;s to 9.9&#xa0;s. These findings support the preliminary feasibility of the system as a workflow-oriented decision-support tool for dynamic TPUS interpretation.

Humans↗
PubMed2026

Improving insurance deduction identification: a hybrid artificial intelligence model using machine learning and expert systems.

PURPOSE: Financial challenges in healthcare systems worldwide, especially in low- and middle-income countries like Iran, have increased hospitals' reliance on insurance reimbursements. Unrecognized insurance deductions often cause severe financial shortages, making efficient deduction management crucial. This study aimed to design a hybrid intelligent system for identifying and predicting insurance deductions by combining machine learning and expert system frameworks. DESIGN/METHODOLOGY/APPROACH: A mixed-methods design was applied in four stages. First, a scoping review identified the causes and patterns of insurance deductions. Second, interviews with 15 insurance experts produced a validated checklist and a dataset from inpatient billing records. Third, using the CRISP-DM methodology, machine learning algorithms were developed and tested in SPSS Modeler alongside a fuzzy expert system developed in MATLAB. Finally, the model was validated using the holdout method. FINDINGS: Four categories of deduction drivers were identified: service provision, registration errors, document submission issues, and revenue conversion processes. The CHAID decision tree outperformed other algorithms with a 99% precision rate and the lowest Mean Absolute Error (9.43). A brief assessment of potential overfitting was conducted to ensure that the CHAID model's high accuracy was interpreted cautiously and supported by the validation results. The fuzzy expert system with validated rules was adaptable for deduction classification, especially for cases unsuitable for quantitative modeling. ORIGINALITY/VALUE: The hybrid model improves detection and prevention of deductions, offering actionable insights for hospital administrators, insurers, and policymakers. Its implementation can enhance hospital information systems, streamline claims processing, and optimize revenue management amid financial constraints.

Machine Learning↗
PubMed2026

The glucagon and GLP-1 receptor dual agonist DD01 for metabolic dysfunction-associated steatotic liver disease and steatohepatitis (DD01-DN-02): 12-week results from a randomised, double-blind, multicentre, placebo-controlled, phase 2 trial.

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH) is a major public health problem arising in the context of metabolic syndrome and obesity. DD01 is a liver-targeted GLP-1 receptor and glucagon dual agonist being investigated for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASH. The DD01-DN-02 trial aimed to evaluate the efficacy and safety of DD01 in adults with MASLD or MASH; this initial analysis reports prespecified 12-week outcomes to assess early hepatic effects. METHODS: DD01-DN-02 is an ongoing, randomised, double-blind, multicentre, placebo-controlled, phase 2 trial conducted at 12 outpatient clinical sites in the USA. Adults aged 18-70 years with obesity or who were overweight (BMI &#x2265;25 kg/m2) were included in the study. Patients with MASLD or MASH underwent liver biopsy and MRI-proton density fat fraction (PDFF) and were eligible if liver fat content was 10% or higher with metabolic risk factors, or if the biopsy confirmed MASH with a non-alcoholic fatty liver disease activity score of at least 4. Participants were randomly assigned (1:1) to receive once-weekly subcutaneous DD01 40 mg or matched placebo over 48 weeks, dose-escalated over 2 weeks, using a centrally administered interactive response technology system. The randomisation sequence was computer-generated by an independent statistician. Participants, investigators, study staff, outcome assessors, and the sponsor were masked to treatment assignment. The primary endpoint was the proportion of participants having at least a 30% relative reduction in liver fat by MRI-PDFF at week 12, which was analysed in all randomly assigned participants receiving at least one dose of study drug or placebo. Safety analyses included all participants who received at least one dose of study drug. Missing primary endpoint data were handled using multiple imputation under a missing-at-random assumption. This trial is registered with ClinicalTrials.gov (NCT06410924) and is ongoing but closed to new participants. FINDINGS: Between June 13, 2024, and Jan 30, 2025, 67 eligible participants were enrolled, of whom 33 were randomly assigned to DD01 and 34 to placebo. The mean age of participants was 48&#xb7;4 years (SD 10&#xb7;6), 42 (63%) were female, 25 (37%) were male, 57 (85%) were White, and 52 (78%) participants had biopsy-confirmed MASH. At week 12, 25 (76%) of 33 participants receiving DD01 had a 30% or higher reduction in liver fat versus four (12%) of 34 participants receiving placebo (adjusted common odds ratio 28&#xb7;8 [95% CI 7&#xb7;2-115&#xb7;2]; adjusted relative risk 6&#xb7;3 [95% CI 2&#xb7;5-15&#xb7;9]; p<0&#xb7;0001). Treatment-emergent adverse events occurred in 28 (85%) of 33 participants receiving DD01 and 23 (68%) of 34 participants receiving placebo. The most common adverse events were nausea (18 [55%] of 33 participants assigned DD01; six [18%] of 34 participants assigned placebo), diarrhoea (nine [27%] of 33; six [18%] of 34), and vomiting (ten [30%] of 33; four [12%] of 34). Treatment-emergent adverse events led to treatment discontinuation in four (12%) of 33 participants in the DD01 group and one (3%) of 34 participants in the placebo group. Two (6%) treatment-emergent serious adverse events occurred in the DD01 group (abdominal pain and acute cholecystitis) and zero in the placebo group. No deaths occurred. INTERPRETATION: In this prespecified 12-week primary analysis, DD01 produced rapid reductions in liver fat compared with placebo, supporting further evaluation in long-term studies. FUNDING: D&D Pharmatech, Neuraly.

Humans↗
PubMed2026

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health↗
PubMed2026

Development of a new recombineering system for Edwardsiella species.

Edwardsiella species are important aquaculture pathogens that also cause opportunistic infections in humans, necessitating efficient genome editing tools to study their pathogenesis and develop control strategies. In this study, we identified and characterized six endogenous recombinases pairs from Edwardsiella and its phages. Among these, the BAS_MS17 system exhibited the highest recombination efficiency in E. piscicida EIB202&#x394;p. Extending homology arms from 150 bp to 200 bp improved editing efficiency by 2-fold, while the addition of Redg or Plug further enhanced recombination by 3-fold and 2.5-fold, respectively, without compromising accuracy (100%). More importantly, when applied to E. piscicida sdu12S, Redg or Plug improved the editing efficiency by 8-fold and 7-fold, respectively. Deletion of the phage-derived single-strand binding protein (SSB) reduced efficiency to 25% of the BAS_MS17 level, whereas expression of the endogenous RecA-family SSB (rSSB) increased recombinant yield by 5-fold, highlighting functional conservation. Furthermore, SSB proteins from heterologous hosts failed to enhance recombination efficiency. Using the optimized system, we successfully knocked out ten distinct genes, including virulence-associated loci, with editing accuracy exceeding 85%. Phenotypic analysis revealed that luxR, but not the other tested genes, contributes to biofilm formation. Virulence evaluation results showed that aroA, fur, and hfq are critical virulence-associated factors. Collectively, this streamlined recombineering system provides a simple, rapid, and efficient genetic tool for Edwardsiella, supporting mechanistic studies of virulence and the development of live attenuated vaccine candidates.

Edwardsiella piscicida↗