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PubMed2026

Effects of digital health-based exercise interventions on older adults with sarcopenia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Sarcopenia, the progressive loss of muscle mass and function, impairs independence in older adults. Digital health exercise interventions are scalable solutions for older adults with sarcopenia. This systematic review and meta-analysis aimed to synthesize the evidence on their efficacy in populations with clinically diagnosed sarcopenia and identify influential intervention characteristics associated with treatment outcomes. METHODS: We systematically searched PubMed, EMBASE, Web of Science, Cochrane Library, CINAHL, CNKI, and Wanfang on May 20, 2026, with no date restrictions. We included randomized controlled trials involving adults aged ≥60 with sarcopenia receiving digital exercise interventions. Two reviewers independently screened studies, extracted data, and assessed risk of bias; analyses were performed using R and Review Manager. RESULTS: Fourteen trials (n = 927) were included. Digital interventions showed potential improvements in muscle mass (MD = 0.25, 95%CI:0.03-0.46, 95% PI:-0.36 to 0.85), muscle strength (MD = 2.14, 95% CI:1.18-3.11, P < 0.001), balance ability (SMD = 0.31, 95% CI:0.12-0.51, P = 0.001), walking performance (SMD = 0.55, 95% CI:0.21-0.89, 95% PI:-0.70 to 1.79), and physical function (SMD = 0.89, 95% CI:0.08-1.71, 95% PI:-2.33 to 4.12), but not quality of life (SMD = 0.08, 95% CI:-0.19 to 0.35, P = 0.53). Exploratory subgroup analyses suggested that factors such as supervision, program duration, and measurement tools may influence outcomes; however, formal tests for subgroup differences were generally non-significant, and consistent patterns across all metrics were not observed. CONCLUSION: Digital exercise interventions show potential for managing sarcopenia in older adults, though the very low to moderate certainty of evidence indicates that true effects may differ substantially from observed estimates. This review explores potential roles of intervention design, supervision, and multimodal delivery. Future research should adopt rigorous designs and longer follow-up to validate results and enhance clinical application. TRIAL REGISTRATION: PROSPERO CRD420251135174.

Humans↗

PubMed2026

Preoperative Carbohydrate Supplementation Reduces Thirst and Improves Patient Satisfaction Before Elective Cesarean Delivery: A Randomized Controlled Trial.

BACKGROUND & AIMS: Prolonged preoperative fasting is a major source of patient discomfort, particularly thirst, before elective cesarean delivery. This study aimed to evaluate whether preoperative carbohydrate (CHO) supplementation could alleviate these discomforts and improve patient satisfaction without compromising safety. METHODS: In this single-center randomized controlled trial, 262 women scheduled for elective cesarean delivery under neuraxial anesthesia were randomly allocated to either the CHO group (Group CHO, n = 131), which received 355 mL of an oral carbohydrate solution on the night before and the morning of surgery, or the control group (Group C, n = 131), which followed conventional fasting. The primary outcome was the thirst Numeric Rating Scale (NRS, 0-10) score measured immediately before surgery. Secondary outcomes included hunger NRS, satisfaction NRS, and maternal and neonatal safety parameters. RESULTS: Baseline characteristics were comparable between groups. Despite a longer preoperative fasting duration in Group CHO (9.25 ± 1.05 vs. 8.74 ± 0.97 h, P < 0.001), this group exhibited significantly lower thirst NRS scores (1.69 ± 0.90 vs. 4.02 ± 0.99, P < 0.001) and hunger NRS scores (1.25 ± 0.94 vs. 2.09 ± 0.82, P < 0.001), as well as higher satisfaction NRS scores (7.70 ± 0.69 vs. 5.69 ± 1.17, P < 0.001). Subgroup analyses confirmed consistent benefits of CHO supplementation across most patient characteristics. Further analyses suggested that the maximum effect on thirst reduction occurred at approximately 9.2 h of solid fasting; however, the interaction between fasting duration and treatment group was not statistically significant (P = 0.187). CONCLUSION: Preoperative carbohydrate supplementation effectively reduces thirst and hunger and improves patient satisfaction before elective cesarean delivery without increasing maternal or neonatal risk. The beneficial effects were consistent across varying fasting durations, with exploratory spline analyses suggested a potential peak effect around 9.2 h, though this was not statistically significant and should be interpreted cautiously. These findings support the incorporation of carbohydrate loading into enhanced recovery protocols. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2500097956.

Humans↗

PubMed2026

Older adults with resectable gastric cancer undergoing perioperative chemotherapy or preoperative chemoradiotherapy plus perioperative chemotherapy: A secondary analysis of the AGITG TOPGEAR phase III trial.

PURPOSE: To evaluate treatment adherence, adverse events, and survival in older (≥70 years) adults undergoing perioperative treatment for gastric cancer. METHODS: Patients with resectable gastric/gastro-esophageal junction adenocarcinoma (ECOG 0-1) enrolled in the phase III TOPGEAR trial were randomized to perioperative chemotherapy (ECF/ECX or FLOT) alone or perioperative chemotherapy plus preoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent fluoropyrimidine). In this exploratory analysis, treatment completion, grade ≥ 3 adverse events (CTCAE v3.0), surgical outcomes, overall survival (OS) and progression-free survival (PFS) were compared between older and younger adults. RESULTS: Of the 574 patients enrolled, 135 (24%) were ≥ 70 years. Older adults more frequently required preoperative chemotherapy dose reductions, omissions, or delays (chemoradiotherapy: 55% vs 35%, p = 0.004; chemotherapy: 60% vs 48%, p = 0.087). Rates of grade ≥ 3 adverse events were comparable between older and younger patients (chemoradiotherapy: 66% vs 67%, p = 0.874; chemotherapy: 68% vs 59%, p = 0.220), but older adults more often had hematologic toxicity and grade ≥ 3 diarrhea in the chemotherapy group (56% vs 37%, p = 0.006; 21% vs 6%, p < 0.001). Resection rates, grade 3/4 surgical complications, number of removed lymph nodes, and 30-/90-day mortality were similar by age. OS and PFS were comparable across age groups, with numerically favorable outcomes for older adults (OS: HR 0.86, 95% CI 0.58-1.26 [chemoradiotherapy]; HR 0.75, 95% CI 0.51-1.11 [chemotherapy]; PFS: HR 0.78, 95% CI 0.53-1.15 [chemoradiotherapy]; HR 0.70, 95% CI 0.47-1.03 [chemotherapy]). CONCLUSIONS: Older adults with gastric cancer achieved comparable oncologic outcomes to younger patients, despite more frequent treatment modifications and higher hematologic toxicity.

Humans↗

PubMed2026

King's Mill anterior-posterior and transverse versus paracervical block in operative outpatient hysteroscopy: a randomised trial.

BACKGROUND: Pain control during operative outpatient hysteroscopy remains a clinical challenge, with the paracervical block (PCB) showing inconsistent efficacy. The King's Mill Anterior-Posterior and Transverse (KAPT) block targets the Lee-Frankenhauser plexus within the uterosacral ligament complex, where the highest density of uterine and cervical sensory fibres lies. We compared the KAPT block with the PCB in operative outpatient hysteroscopy. METHODS: Single-centre, participant- and outcome assessor-blinded randomised controlled trial in a UK district general hospital. Forty-eight women undergoing operative outpatient hysteroscopy were randomised 1:1 to the KAPT block or the PCB, each delivered with 10 ml of prilocaine. Pain was measured on a 10-point Visual Analogue Scale (VAS) during the procedure and 10 minutes post-procedure (co-primary endpoints), and during cervical dilatation (exploratory). Analyses used the Mann-Whitney U test on an intention-to-treat basis, with Hodges-Lehmann median differences, percentile bootstrap 95% confidence intervals, and a hierarchical fixed-sequence testing strategy. RESULTS: Median intra-procedural VAS was 1 (IQR 0 to 3) with the KAPT block versus 2 (IQR 1 to 6) with the PCB (Hodges-Lehmann median difference -1.00, 95% CI -3.00 to 0.00; p = 0.040). At 10 minutes post-procedure, median VAS was 0 (IQR 0 to 1.25) versus 2 (IQR 0 to 3.25) (median difference -1.00, 95% CI -2.00 to 0.00; p = 0.011). Both co-primary endpoints reached significance under hierarchical testing. Cervical dilatation pain did not differ significantly (p = 0.146). Satisfaction was 100% in both arms; willingness to recommend was 100% (KAPT) versus 95.8% (PCB). No serious adverse events occurred. CONCLUSIONS: The KAPT block was associated with lower intra-procedural and post-procedural pain than the PCB, with effect sizes consistent with a clinically meaningful difference. These findings support the KAPT block as a superior, anatomically targeted alternative to the PCB and justify evaluation in a larger multicentre trial.Trial registration: ISRCTN15619382.

Humans↗

PubMed2026

Multiscale Modeling Primer: Focus on Chromatin and Epigenetics.

A central challenge in modern biology is to understand how molecular interactions produce cellular and organismal functions across vast spatiotemporal scales. Nowhere is this challenge more apparent than in the study of chromatin, where meters of DNA compact into a micron-sized nucleus. How this polymer folds is a dynamic process, regulated by epigenetic modifications-chemical changes to DNA and histones that involve only a handful of atoms. These small changes cooperate to produce emergent, higher-order structures that define cellular identity and function. To explain this system, we must integrate static, high-resolution snapshots from techniques like cryo-EM with dynamic, lower-resolution data from microscopy and genomics. Multiscale computational models are essential tools that bridge these experimental gaps and reveal the mechanisms of emergent behavior. However, the communication divide between experimental biologists and quantitative modelers often hampers progress. This primer addresses that gap. It first introduces the fundamental biology of chromatin and epigenetics at an introductory level for non-biologists audiences. We then survey the landscape of computational approaches, from atomistic to systems-level models, and connect them to the experimental data that inform and validate them at an introductory level for non-computationalists. We argue that the next frontier will require us to build integrative models that can predict how molecular perturbations mechanistically alter cellular phenotypes, which will open a new era of chromatin-targeted therapeutics.

Chromatin Dynamics↗

PubMed2026

Transcriptomic analysis reveals the molecular mechanisms underlying the inhibition of Mytilus edulis attachment by biofouling control agents.

This study combined acute toxicity assays, phenotypic quantification, and transcriptomic profiling to systematically investigate the inhibitory effects and molecular regulatory mechanisms of a novel alkylamine-based antifouling agent on survival, byssus secretion, and attachment behavior of juvenile Mytilus edulis. The 96 h-LC50 of the agent to juvenile M. edulis was 8.84 mg/L, and 10 mg/L of the agent completely inhibited mussel attachment within 24 h, significantly reducing byssal thread number, length, and diameter while increasing detachment frequency, resulting in irreversible attachment failure. Transcriptomic analysis identified 2746 differentially expressed genes, which were mainly enriched in pathways including signal transduction, immune defense, stress response, cytoskeleton organization, and protein binding. KEGG and GSEA enrichment revealed that the antifouling agent activated the MAPK stress signaling pathway, disturbed transcriptional regulation, and impaired intracellular homeostasis and cytoskeletal stability, thereby synergistically suppressing the expression of key byssal protein genes including mfp-1 and mfp-3 and ultimately blocking byssus synthesis and adhesion. This study clarifies the multi-pathway molecular mechanism underlying antifouling agent-induced attachment inhibition in M. edulis, and provides core molecular targets and theoretical support for developing efficient, specific antifouling activity, and potentially applicable marine antifouling technologies.

Animals↗

PubMed2026

TWIST2-dependent transcriptional activation of TPI1 mediates TGF-β1-driven fibroblast activation in pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by aberrant profibrotic signaling and excessive extracellular matrix deposition, accompanied by fibroblast-to-myofibroblast transition. Despite extensive investigation, the molecular mechanisms underlying IPF pathogenesis remain incompletely understood. Here, we investigated the role of triosephosphate isomerase 1 (TPI1) in IPF progression and its regulation by transforming growth factor-β (TGF-β) signaling. Loss-of-function analyses identified TPI1 as a downstream effector of TGF-β1, as its knockdown markedly suppressed fibrotic marker expression, fibroblast proliferation, and migration. Mechanistically, TWIST2 was shown to function as a direct transcriptional regulator of TPI1, binding to its promoter and promoting transcriptional activation. Rescue experiments further confirmed that the TWIST2-TPI1 axis is central to the progression of pulmonary fibrosis. Notably, knockdown of either TPI1 or TWIST2 effectively attenuated TGF-β1-induced fibrotic phenotypes. Collectively, these findings define the TGF-β1/TWIST2/TPI1 signaling axis as an important regulator of pathogenic fibroblast behavior and pro-fibrotic responses through transcriptional control of TPI1, highlighting its potential as a therapeutic target for IPF.

Twist-Related Protein 1↗

PubMed2026

Ameliorating Effects and Autonomic Mechanisms of Transcutaneous Auricular Vagus Nerve Stimulation on Abdominal Pain in Patients With Functional Dyspepsia and Irritable Bowel Syndrome.

BACKGROUND: Patients with functional dyspepsia (FD) and irritable bowel syndrome (IBS) often experience abdominal pain and reduced quality of life and need effective treatments. This exploratory study aimed to evaluate whether transcutaneous auricular vagus nerve stimulation (taVNS) could improve abdominal pain and quality of life in patients with FD and IBS, and whether the effects were mediated via the autonomic mechanisms. METHODS: A total of 64 patients with abdominal pain (43 FD and 21 IBS) with a pain score of 3 out of 10 or higher were randomized to receive 2 weeks of taVNS or sham-taVNS treatment. The primary outcome was numeric rating scale (NRS) for abdominal pain. The dyspeptic symptom scales (DSS), IBS symptom severity scale score (IBS-SSS), anxiety and depression scores, and the SF36 quality of life scale were assessed before and after the treatment. The electrocardiogram was also recorded for the assessment of autonomic function at baseline and after the treatment. KEY RESULTS: (1) taVNS reduced the abdominal pain score (p < 0.001 for both FD and IBS), the frequency of abdominal pain (p < 0.001 for both FD and IBS), and overall symptom scores in both FD patients and IBS patients (p < 0.001 for FD and IBS). There was no significant difference in the effect of taVNS on abdominal pain between FD and IBS patients. (2) taVNS improved quality of life compared with baseline in both FD and IBS patients. (3) taVNS decreased anxiety (p < 0.001) and depression (p < 0.001). (4) taVNS increased vagal activity. At the end of the taVNS treatment, the vagal activity was negatively correlated with the pain score (r = -0.491, p = 0.004). CONCLUSIONS: Non-invasive taVNS improves abdominal pain, quality of life, and anxiety and depression in patients with FD and patients with IBS, possibly attributed to the enhancement of vagal activity. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR2400085697.

Humans↗

PubMed2026

Formation of environmental persistent free radicals in soil of ammunition demolition site: Roles of 2,4,6-trinitrotoluene and heavy metals.

Environmental Persistent Free Radicals (EPFRs) are a particular type of contaminant present in soil. This study investigated the formation process, environmental behavior, and main influencing variables of EPFRs in soils contaminated with heavy metals and 2,4,6-trinitrotoluene (TNT) from an ammunition demolition site. The results showed that the concentration of total organic carbon (TOC) in the soil was negatively correlated with EPFRs (r = -0.29). In contrast, the content of TNT and copper was significantly positively correlated with EPFRs (r = 0.90 and 0.78, respectively), indicating that TNT acts as a precursor macromolecule in the formation of EPFRs in this type of contaminated soil. Transition metal Cu may be an essential carrier in EPFR production. In order to explore the possible formation mechanism of EPFRs, a simulation experiment was carried out under different temperature and light conditions. The results showed that the photolysis process of TNT was impacted by external energy sources such as heat and light. TNT was firstly adsorbed onto the surface of a transition metal (Cu), and then EPFRs were formed through further electron transfer. This is the first study to detect significant levels of EPFRs in the soil at ammunition demolition sites.

Trinitrotoluene↗

PubMed2026

Functional neuroimaging subtypes of obsessive-compulsive disorder: A systematic review and meta-analysis.

Obsessive-compulsive disorder (OCD) exhibits substantial clinical heterogeneity that may reflect underlying neurobiological diversity. Neuroimaging-based subtyping may advance precision psychiatry by identifying biologically distinct subgroups with differential treatment responses. This study systematically synthesized evidence from functional neuroimaging subtyping studies in OCD to identify reproducible neurobiological subtypes, characterize their clinical profiles, and establish a consensus-based classification framework. We reviewed 40 original studies employing machine learning, clustering, normative modeling, or classification approaches, encompassing approximately 8,150 patients. Consensus clustering identified three reproducible neurobiological subtypes. The Limbic-Hyperactive subtype, comprising approximately 40% of patients, exhibited amygdala and insula hyperconnectivity, elevated anxiety levels, predominant contamination and washing symptoms, and favorable response to cognitive-behavioral therapy. The Fronto-Striatal-Hypoconnected subtype, comprising approximately 35% of patients, demonstrated reduced orbitofrontal-striatal connectivity, cognitive inflexibility, predominant checking and ordering symptoms, and a favorable response to selective serotonin reuptake inhibitors. The Global-Disrupted subtype, comprising approximately 25% of patients, exhibited widespread connectivity disruption, greater symptom severity, and poor treatment response. Support vector machine classification achieved 81.5% accuracy for subtype assignment, though classification of OCD versus healthy controls showed limited generalizability in multisite settings (AUC 0.567-0.673). These findings support a neuroimaging-based framework for personalized treatment selection but require prospective validation.

Humans↗

PubMed2026

Alarms and alarm management with automated versus conventional ventilation in neurocritical care patients.

INTRODUCTION: False or clinically irrelevant alarms are a major driver of ICU alarm fatigue and nursing workload. Ventilator alarms make up a large share, and although automated ventilation modes can reduce manual adjustments, their effect on alarm burden is still unclear. This issue can be particularly relevant in neurocritical care patients, where precise ventilator and alarm management is imperative for patient safety. OBJECTIVES: This explorative post hoc analysis of a randomized clinical trial compared alarm frequency and management between automated ventilation and conventional ventilation in neurocritical care patients. METHODS: Ventilator alarms and manual ventilator changes were captured continuously from the ventilator for up to 24 h per patient. The primary endpoint was a composite of workload-relevant alarms; with alarm management interventions at the ventilator as a key secondary outcome. Additional endpoints included redundant alarms, alarm duration and ventilator management. RESULTS: 13 patients received automated ventilation and 24 received conventional ventilation. No difference was observed in workload-relevant alarm frequency between automated and conventional ventilation (3.28 [2.87 to 4.30] vs 3.73 [1.66 to 7.33] alarms per hour; P = 0.81), while alarm management interventions at the ventilator were lower with automated ventilation (0.14 [0.10 to 0.15] vs 0.21 [0.17 to 0.31] interventions per hour; P = 0.01). Other alarm frequencies, duration of alarms and ventilator management were similar. CONCLUSIONS: In this exploratory post hoc analysis of a randomized clinical trial in neurocritical care patients during the early phase of mechanical ventilation, automated ventilation did not reduce the frequency of total or workload-relevant alarms, nor their duration, but was associated with fewer alarm management interventions compared to conventional ventilation. IMPLICATIONS FOR CLINICAL PRACTICE: Automated ventilation may not reduce alarm frequency in neurocritical care patients, but the observed reduction in alarm-related bedside interventions suggests a potential benefit for nursing workload.

Humans↗

PubMed2026

Angiography-Based Index of Microcirculatory Resistance in Assessing the MVO and Infarct Size in STEMI Patients.

OBJECTIVES: To evaluate angiography-based index of microcirculatory resistance (angio-IMR) in assessing microvascular obstruction (MVO) and infarct size (IS) in ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The effect of thrombolysis on post-percutaneous coronary intervention (PCI) angio-IMR, and its associations with MVO and IS remains unclear. METHODS: One hundred twenty-three STEMI patients randomized to receive 5 mg intravenous bolus of recombinant staphylokinase (r-SAK) or normal saline (NS) before PCI were recruited. Angio-IMR was computed in infarct-related arteries. MVO and IS were detected by cardiac magnetic resonance imaging. RESULTS: Compared with NS group, r-SAK group exhibited numerically lower post-PCI angio-IMR (39.12 U vs. 42.57 U; p = 0.567), MVO (54.0% vs. 70.9%; p = 0.059), MVO extent (0.70% vs. 1.90%; p = 0.101) and IS (21.30% vs. 24.50%; p = 0.079). Post-PCI angio-IMR was positively correlated with MVO extent (ρ = 0.347; p < 0.001) and IS (ρ = 0.324; p < 0.001). Receiver operating characteristic analyses showed moderate diagnostic performance of angio-IMR for MVO (area under the curve [AUC] = 0.750; p < 0.001), MVO > 2.6% (AUC = 0.735; p < 0.001) and IS > 25% (AUC = 0.712; p < 0.001). The exploratory optimal cut-off values for these endpoints were approximately 40 U. CONCLUSIONS: In STEMI patients, a single bolus of r-SAK before PCI was associated with numeric reductions in post-PCI angio-IMR, MVO, MVO extent and IS. Additionally, angio-IMR exhibited a significantly positive correlation with both MVO extent and IS, demonstrating the diagnostic value of this wire-free method for assessing microvascular injury.

Humans↗

PubMed2026

CanDo (Canadian Donor Milk) randomised controlled trial: pasteurised human donor milk supplementation in the well-baby unit - protocol.

INTRODUCTION: Mother's milk is the gold standard for feeding newborns. Despite lactation support while in hospital, supplementation rates remain high in Canadian well-baby units at 35-50%. When supplementation is needed, the choice between formula milk and pasteurised human donor milk (donor milk) remains uncertain with a lack of clinical trials to inform this practice. This study aims to compare the effect of supplementing mother's milk with donor milk versus formula in infants at higher risk for supplementation (infants of diabetic mothers, infants born small for gestational age or with a birth weight less than 2.5 kg and late preterm infants born between 350/7 and 366/7 weeks gestation). METHODS AND ANALYSIS: This is an ongoing, open-label, single-centre, randomised controlled trial conducted at Mount Sinai Hospital, Toronto, Canada. A total of 112 infants (56 per group) will be randomised to receive donor milk or infant formula as a supplement to mother's milk during their initial hospital stay, when supplementation is deemed necessary by the family and/or healthcare team. The primary outcome is exclusive human milk feeding at 4 months of age. Secondary outcomes include any or exclusive human milk feeding at 1, 2 and 3 months; infant growth and health indicators and breastfeeding self-efficacy. Exploratory outcomes encompass infant temperament; parental mental health (assessed using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale); milk cortisol concentrations; and informal milk sharing comparing donor milk and formula supplementation. Follow-up includes monthly telephone assessments and a virtual or in-person visit at 4 months post partum. Data will be analysed using intention-to-treat principles. ETHICS AND DISSEMINATION: The CanDo trial has received ethics approval from the Mount Sinai Hospital Research Ethics Board and the University of Toronto. Results will be disseminated through peer-reviewed journals, conference presentations and stakeholder engagement with hospital and public health decision-makers. Findings will address a critical evidence gap regarding the use of donor milk supplementation in well-baby units and may inform future clinical practice and policy in newborn feeding. TRIAL REGISTRATION NUMBER: NCT06315127.

Humans↗

PubMed2026

UNCX/SIN3A-Mediated H4K8 decrotonylation suppresses FOXO3 to drive TNBC progression and docetaxel resistance.

Triple-negative breast cancer (TNBC) remains a clinically challenging subtype characterized by aggressive behavior and limited treatment options. Though docetaxel remains a cornerstone chemotherapy for TNBC, the frequent emergence of resistance highlights the urgent need to identify novel therapeutic targets. In this study, we report that uncoordinated homeobox (UNCX) is upregulated in docetaxel-resistant breast cancer cells, genomically amplified in breast cancer, and associated with poor survival in breast carcinoma patients. Functional studies revealed that UNCX promotes breast cancer cell proliferation, migration and reduces the docetaxel sensitivity. Mechanistically, UNCX functions as a transcriptional repressor by recruiting the SIN3A complex. Genome-wide profiling indicated that the UNCX/SIN3A complex directly binds to the promoters of tumor-suppressor genes including FOXO3, and represses their transcription by removing histone H4K8 crotonylation (H4K8cr). Additionally, the UNCX/SIN3A complex enhances FOXO3 phosphorylation and inhibits its nuclear translocation, further inhibiting its activity. Notably, SIN3A knockdown, FOXO3 overexpression, or crotonylation restoration effectively reverses UNCX-induced malignant phenotypes. These findings collectively establish the UNCX/SIN3A-H4K8cr-FOXO3 axis as a pivotal epigenetic regulator of TNBC progression and chemoresistance, revealing new avenues for targeted therapeutic development against this aggressive breast cancer subtype.

Humans↗

PubMed2026

Influenza A virus in Swiss pig herds with respiratory disease: Seasonality and age dependence.

Influenza A virus (IAV) is an important respiratory pathogen in pigs and poses a zoonotic risk to humans in close contact. While IAV epidemiology has been extensively studied in large-scale production systems, data from Switzerland - characterized by small herds and limited live pig imports - remain scarce. This exploratory nationwide cross-sectional study aimed to assess the association between herd-level IAV detection and reported respiratory disease in pig herds, and to explore associations with husbandry-, animal-, and human health-related factors. Between November 2023 and April 2025, 25 Swiss pig herds with caretaker-suspected respiratory symptoms were investigated. In each herd, five nasal swabs were collected and analyzed by quantitative PCR. Herd managers completed an interview, and clinical examinations were performed. Overall, 56 % (95 % CI: 37,1 - 73,3) of herds tested positive for IAV, comparable to reports from other European countries. The estimated intra-herd detection rate was 49,6 % (95 % CI: 31,2 - 68,0). Respiratory disease outbreaks associated with IAV detection showed indications of seasonal variation, with no positive herds identified during summer. Across age groups, pigs aged 11-14 weeks had a higher likelihood of IAV detection, with 15,79-fold increased odds (95 % CI: 1,50 - 860,4), although with considerable uncertainty. The interpretation is limited by the small sample size, heterogeneous data, and reliance on single time-point qPCR detection. The results suggest that IAV detection in clinically apparent respiratory outbreaks may follow seasonal patterns in Swiss pig herds. Weaners and newly introduced fattening pigs may play a role in such respiratory outbreaks and could represent relevant targets for IAV surveillance in Switzerland. Continued monitoring and the implemen tation of appropriate control measures remain important given the virus's zoonotic potential and impact on pig health.

Animals↗

PubMed2026

Simulating the effects of an alcohol minimum unit price policy on distilled spirits sales in 28 states of the USA.

BACKGROUND AND AIMS: Excessive alcohol use is a leading preventable chronic disease risk factor. Alcohol minimum unit pricing (MUP) policies are not used in the United States despite evidence of associations with reduced drinking and alcohol-related harms. To inform potential population-level chronic disease prevention strategies, we estimated effects of various hypothetical MUPs on alcohol sales. METHOD: Simulation based on observational time-series data. We used weekly off-premises product-specific alcohol retail sales and prices in 28 states of the United States for November 2022-November 2023 from NielsenIQ to estimate the own-price elasticity of spirits and cross-price elasticities of wine, beer and ready-to-drinks with respect to spirits. Using estimated elasticities, we simulated changes in total alcohol sales associated with hypothetical spirits MUPs ranging from $0.10 to $1.10 per standard drink (0.6 fluid ounces of alcohol). RESULTS: A hypothetical MUP of $0.80 per standard drink on spirits yielded the largest estimated decrease in alcohol sales (-1.7%) and would affect 5374 of 26 249 spirits products. To reach the $0.80 MUP, the sales-weighted average price increase among affected products was $0.24 per drink. CONCLUSIONS: Minimum unit pricing policies on distilled spirits in the United States could shift purchasing behavior and help reduce alcohol-related harms.

alcohol policy↗

PubMed2026

Differential contributions of mt-Tr and Cs variants to developmental cochlear defects and mitochondrial dysfunction in A/J mice.

A/J mice exhibit early-onset hearing loss linked to Cdh23, mitochondrial tRNA-Arg (mt-Tr), and citrate synthase (Cs) variants. Although developmental cochlear defects have been identified in juvenile A/J mice, the hierarchical contributions of mt-Tr versus Cs remain unclear. Using reciprocal intercross-derived strains to decouple mitochondrial haplotypes from nuclear factors, we demonstrate that the mitochondrial background is the primary determinant of auditory dysfunction. Mice with A/J mtDNA (AXB strains) displayed significantly higher ABR thresholds, accelerated hair cell attrition, and severe stereocilia dysmorphology compared to those with B6 mtDNA (BXA strains), occurring largely independently of the Cs genotype. While the Cs mutation exacerbated hearing loss, its impact was secondary to that of the dominant mitochondrial background. Systemic behavioral assessments and mitochondrial assays confirmed that A/J mitochondria exert a more profound metabolic impact than the Cs mutation. Our findings establish that the mitochondrial genomic background, with the mt-Tr locus as a prominent candidate variant, serves as the principal driver of developmental cochlear defects and early-onset hearing loss in A/J mice, while the nuclear Cs mutation acts as a synergistic modifier. This study underscores the critical role of mitonuclear crosstalk in inner ear maturation and provides new insights into the etiology of hereditary hearing loss.

Animals↗

PubMed2026

A Meta-analysis of the intervention effects of ball sports on children with autism Spectrum disorder.

PURPOSE: To evaluate the overall efficacy of ball sports interventions for children with autism spectrum disorder (ASD) and to explore potential moderators that may influence intervention outcomes. METHODS: Randomized controlled trials were retrieved from nine databases (e.g., CNKI, PubMed) from 2000 to April 2025. Meta-analysis was conducted using RevMan 5.4 and Stata 18.0, with subgroup analyses by age, duration, frequency, session length, and ball sport type. RESULTS: A total of 14 randomized controlled trials involving 406 children were ultimately included. Meta-analysis results indicated that ball sports had a significant overall intervention effect on children with ASD (SMD = -1.12, 95% CI: -1.56, -0.68, P < 0.05), with significant improvements observed in social skills (SMD = -0.55), verbal communication (SMD = -0.85), and behavioral problems (SMD = -1.10). Subgroup analysis indicated that interventions involving mini-basketball or other ball sports with simple rules-conducted over a 12-week period, 3-5 times per week, for 30-60 min per session-yielded better outcomes, with children aged 3-6 years showing more consistent benefits. CONCLUSION: Ball-based interventions effectively alleviate core ASD symptoms. Structured moderate-intensity programs are recommended as adjunct therapies. Future studies should standardize protocols and examine long-term benefits.

Humans↗