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PubMed2026

Neonatal outcomes following antenatal corticosteroid administration before planned caesarean birth at late preterm or early term (36-38 weeks' gestation): a retrospective cohort study.

OBJECTIVE: To investigate the benefits and harms associated with antenatal corticosteroids (ACS) prior to planned caesarean birth at late preterm or early term. DESIGN: Retrospective cohort study. SETTING: South Australia, Australia, 2005-2018. PATIENTS: Women with singleton pregnancies undergoing planned caesarean birth between 36+0 and 38+6 weeks' gestation. METHODS: We used routinely collected electronic maternity and neonatal data. Adjusted risk differences (aRD) with 95% CIs were calculated for neonatal and maternal outcomes. OUTCOME MEASURES: Neonatal outcomes included respiratory distress requiring oxygen, hypoglycaemia requiring glucose, neonatal unit (NNU) admission and prolonged NNU admission (≥48 hours). RESULTS: Among the cohort of 4049 women, the proportion receiving ACS was 54.8%, 48.4% and 5.6% at 36, 37 and 38 completed weeks' gestation, respectively. ACS administration was associated with a significant reduction in respiratory distress across all gestations, with the greatest reduction seen at 36 weeks' gestation (aRD -12.5%; 95% CI -21.4% to -3.6%). At 38 weeks' gestation, ACS administration was associated with an increased risk of neonatal hypoglycaemia (aRD 5.7%; 95% CI 1.1% to 10.2%), NNU admission (aRD 5.4%; 95% CI 0.1% to 10.7%) and prolonged NNU admission (aRD 4.6%; 95% CI 0.2% to 8.9%). CONCLUSIONS: ACS administration prior to late preterm and early term planned caesarean birth was associated with reduced risk of respiratory distress. The net benefit of ACS administration before planned caesarean birth remains unclear; however, there was evidence of potential neonatal harm when birth occurred after 37 weeks' gestation.

Epidemiology↗

PubMed2026

A systematic review and network meta-analysis of single nucleotide polymorphisms associated with oral submucous fibrosis risk.

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic and insidious oral disease characterized by hyalinization of the subepithelial connective tissue and progressive fibrosis of the oral submucosa. It is a precancerous condition of oral squamous cell carcinoma. Studies have demonstrated that single nucleotide polymorphisms (SNPs) are closely associated with susceptibility to OSF. This study aims to comprehensively evaluate the association between SNPs and OSF risk and to rank the strength of the association between different genetic models and OSF susceptibility. METHODS: Literature related to OSF was comprehensively searched from PubMed, Web of Science, Embase, Cochrane Library, CNKI, and Wangfang databases up to July 2025. Full-text case-control studies with patients diagnosed with OSF were included. Quality assessment was performed to evaluate the risk of bias. RevMan 5.4, GeMTC 0.14.3, and STATA 17.0 were used for the pairwise and Bayesian network meta-analysis. RESULTS: A total of 24 studies with 2545 cases and 3772 controls, covering 13 SNPs in 11 genes, were included in our meta-analysis. We found that CYP1A1 rs4646903:T>C, CYP1A1 rs1048943:A>G, GSTT1 null genotype, GSTM1 null genotype, and XRCC3 rs861539:C>T were associated with an increased risk of OSF, while MMP2 rs243865:C>T and MMP3 rs3025058: 5A>6A were associated with a decreased risk of OSF. Further Bayesian network meta-analysis indicated the top 5 genetic models with the highest association with OSF risk in network group 1 were the dominant model, homozygous model, allelic model, and recessive model of CYP1A1 rs1048943:A>G (ranked 1-4), and the heterozygous/dominant model of CYP1A1 rs4646903:T>C (both ranked 5). While the allelic models of XRCC3 rs861539:C>T and MMP3 rs3025058: 5A>6A ranked first for predicting OSF in group 2 and group 3, respectively. CONCLUSION: Some specific SNPs are significantly related to the risk of OSF. Among them, the dominant model of CYP1A1 rs1048943:A>G may be the most strongly associated genetic model with OSF risk. Future large-sample, well-designed studies with detailed genotype data are needed to validate the roles of these SNPs in OSF risk.

Humans↗

PubMed2026

Mineral-driven molecular signatures of energy metabolism underpin sperm motility in buffalo.

The success of spermatogenesis depends on the interplay of various biomolecules that ultimately determine sperm quality. In this study, RNA-seq analysis of frozen-thawed buffalo sperm (n = 8) revealed the presence of 263 mineral-associated genes (>1 FPKM) in high (n = 4) and 181 in low motile (n = 4) sperm groups. Among these, 177 mineral-associated genes were commonly expressed between them, and the majority were upregulated (>1 fold), LOC102391588 (ncRNA; 37-fold), ZNF699 (26.5-fold), MYZAP (13-fold), etc., in the high motile group. The expression of selected mineral-associated genes was validated. The top enriched functions in commonly expressed genes were regulation of transcription by RNA polymerase II (FDR: 4.7 × 10⁻2; ZNF331, ZNF692, ZNF180, etc.), followed by spermatogenesis (FDR: 2.9 × 10⁻2; CALR3, ADAM18, ADAM29, etc.), proton transmembrane transport (FDR: 4.0 × 10⁻2; ATP6V0E1, ATP1A4, ATP6V1B2, etc.) and flagellated sperm motility (FDR: 2.3 × 10⁻1; CATSPERD, EFCAB6, CABS1, etc.). Additionally, the chromatin remodeling pathway (FDR: 3 × 10⁻2; PTP4A1, PPM1A, DUSP1, etc.) emerged as the most significant and may suggest that these minerals influence genome packaging and sperm functionality. Mineral-associated genes were predominantly associated with zinc (49%), followed by calcium (20%), phosphorus (10%), iron (5%), sodium (2%), potassium (2%), copper (1%) and other trace elements (11%). Although the current study uses frozen-thawed sperm, the findings indicate that mineral-associated genes are crucial for promoting membrane stability, energy production, motility and chromatin integrity, which may contribute to the superior fertilizing ability of sperm.

Animals↗

PubMed2026

Efficacy of CagriSema for Reaching Anthropometric Treatment Targets and Cardiometabolic Outcomes: A Secondary, Post hoc Analysis of REDEFINE 1.

AIMS: To assess the added value of absolute anthropometric targets alongside percentage weight loss in the clinical management of obesity. MATERIALS AND METHODS: The phase 3a, 68-week REDEFINE 1 trial randomised adults without diabetes with BMI ≥ 30 kg/m2, or ≥ 27 kg/m2 with ≥ 1 obesity-related complication, to once-weekly CagriSema 2.4 mg/2.4 mg, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo, plus lifestyle intervention. This secondary, post hoc analysis assessed the proportions of participants achieving BMI < 27 kg/m2 and/or WHtR < 0.53 targets, and percentage weight loss by anthropometric target. The association between the proportion of participants maintaining or achieving normalisation of four cardiometabolic outcomes: normoglycemia (glycated haemoglobin < 5.7% and fasting plasma glucose < 5.6 mmol/L); blood pressure (< 130/80 mmHg); triglycerides (< 1.7 mmol/L); lipids (high-density lipoprotein cholesterol ≥ 1.3 mmol/L [female] or ≥ 1.0 mmol/L [male]) and reaching anthropometric targets or change in body weight (%) was also assessed. RESULTS: The proportion of participants achieving both BMI < 27 kg/m2 and WHtR < 0.53 targets at week 68 was 30.3%, 19.1%, 9.0%, and 3.3% in participants who received CagriSema, semaglutide, cagrilintide, or placebo respectively. Both BMI and WHtR performed similarly as indicators for all four cardiometabolic outcomes. At more stringent cut-off values, anthropometric targets were better measures than percentage weight loss. CONCLUSIONS: The proportion of participants achieving anthropometric targets was greater with CagriSema Versus other treatments. These findings support further validation of BMI and WHtR anthropometric treatment targets and indicate a potential for indicating amelioration of clinical outcomes in obesity and a greater emphasis on target-based treatment strategies.

Humans↗

PubMed2026

Outcomes of Stage IVA Cervical Cancer Treated with Radiation Therapy: A Systematic Review and Meta-Analysis.

FIGO stage IVA cervical cancer, defined by bladder or rectal mucosal invasion without distant metastasis, is an uncommon but clinically challenging disease with limited high-quality evidence to guide management. We performed a systematic review and meta-analysis to evaluate survival outcomes, treatment-related morbidity, and prognostic factors in patients with stage IVA cervical cancer treated with definitive radiotherapy. Following PRISMA 2020 guidelines and PROSPERO registration (CRD42024602426), PubMed, Embase, and Web of Science were searched through February 2025. Eleven studies comprising 492 patients met eligibility criteria. Pooled random-effects analyses demonstrated 2-, 3-, and 5-year disease-free survival rates of 41.5% (95% CI, 28.1-55.0), 34.2% (95% CI, 21.1-47.3), and 30.9% (95% CI, 16.0-45.8), respectively. Corresponding overall survival rates were 56.0% (95% CI, 46.2-65.9), 45.9% (95% CI, 35.9-55.9), and 34.8% (95% CI, 26.4-43.3). Weighted median disease-free survival and overall survival were 15.6 and 33.6 months, respectively. The pooled incidence of vesicovaginal or rectovaginal fistula was 23.7% (95% CI, 12.9-34.6). Adverse prognostic factors included pelvic nodal involvement, hydronephrosis, rectal invasion, omission of brachytherapy, and total EQD2 below 80-85 Gy. Concurrent chemoradiation and completion of brachytherapy were consistently associated with improved outcomes. Despite curative-intent treatment, long-term survival remains poor and treatment-related morbidity substantial. Durable pelvic control remains the principal therapeutic challenge. Concurrent chemoradiation with adequate-dose brachytherapy appears essential for optimal outcomes, while future stage IVA-specific studies incorporating image-guided adaptive brachytherapy, advanced radiotherapy techniques, and systemic treatment intensification are needed to improve survival and reduce treatment-related morbidity.

Humans↗

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 ≥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 48·4 years (SD 10·6), 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 28·8 [95% CI 7·2-115·2]; adjusted relative risk 6·3 [95% CI 2·5-15·9]; p<0·0001). 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

Nerve injury in revision total elbow arthroplasty: a systematic review and meta-analysis.

BACKGROUND: Revision total elbow arthroplasty (TEA) is technically demanding and carries a substantial risk of postoperative neurological complications because of scarring, altered anatomy, implant removal, and repeated humeral and ulnar exposure. The incidence, nerve distribution, and recovery profile of nerve injury after revision TEA remain incompletely defined. This study aimed to systematically review the literature to define the incidence, recovery profile, and risk factors for nerve injury after revision TEA. METHODS: A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidance. Thirteen retrospective case series were included, comprising 282 revision TEAs in 271 patients. Random-effects meta-analysis of proportions was undertaken where the data permitted. The primary outcome was postoperative nerve injury following revision TEA. Secondary outcomes included nerve type, recovery, secondary nerve-related procedures, infection, triceps insufficiency, metallosis, periprosthetic fracture, and re-revision. RESULTS: The pooled incidence of postoperative nerve injury was 22.3% (95% confidence interval [CI] 16.3 to 29.6; I2 = 34.6%). The crude incidence was 60 of 282 revisions (21.3%, 95% CI 16.6 to 26.5). The ulnar nerve was involved in 66.7% of all nerve injuries, the radial nerve in 31.7%, and the median nerve in 1.7%. No significant difference in pooled nerve-injury incidence was identified between studies published before 2010 and those published from 2010 onwards (22.9% vs. 21.4%, P = .837). Recovery reporting was heterogeneous; among injuries with numerically extractable outcomes, 85.4% improved partially or completely (95% CI 72.2 to 93.9). Secondary nerve-related procedures were reported in 7 studies. Pooled complication estimates were 10.2% for infection, 13.6% for triceps insufficiency, 25.5% for metallosis, 15.9% for periprosthetic fracture, and 14.0% for re-revision. CONCLUSIONS: Postoperative nerve injury is a common and clinically important complication of revision TEA, affecting approximately 1 in 5 cases. The ulnar nerve is most frequently involved, although radial nerve injury accounts for a substantial proportion of cases. Many neuropathies improve during follow-up, but persistent deficits and the need for secondary nerve-related procedures are not uncommon. Future studies should adopt standardized neurological definitions and reporting to improve comparability and guide preventive surgical strategies.

Humans↗

PubMed2026

Impact of Baseline Polyneuropathy Severity on Eplontersen Efficacy in the NEURO-TTRansform Clinical Trial.

BACKGROUND AND AIMS: In the NEURO-TTRansform clinical trial (NCT04136184), eplontersen improved neuropathy impairment and quality of life (QoL) through Week 66 versus the NEURO-TTR historical placebo in patients with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN). This analysis assessed the impact of baseline ATTRv-PN severity on eplontersen response in patients from NEURO-TTRansform. METHODS: This post hoc analysis grouped patients into tertiles by baseline Neuropathy Impairment Score (NIS): T1 (least baseline impairment: 3.5 to < 27.5; n = 67), T2 (27.5 to < 55.0; n = 67), and T3 (55.0 to < 127.8; n = 66). Outcomes assessed were neuropathy impairment (modified NIS+7 [mNIS+7] and NIS, Neuropathy Symptom and Change, Polyneuropathy Disability), QoL (Norfolk QoL-Diabetic Neuropathy), physical functioning (36-Item Short-Form Health Survey Physical Component Summary), nutritional status (modified body mass index), and serum transthyretin levels; these were compared with NEURO-TTR historical placebo. Autonomic dysfunction (Composite Autonomic Symptom Score-31), disability (Rasch-built Overall Disability Scale), and walking speed (10-Meter Walk Test) were also assessed. Final assessments were carried out following 65/66 or 81/85 weeks of treatment. RESULTS: Mean mNIS+7 composite scores were maintained over 85 weeks with eplontersen (changes from baseline of -4.5 [T1], -1.3 [T2], and -2.6 [T3] points). Other disease parameter scores were similarly maintained or improved with eplontersen. Patients receiving placebo experienced disease worsening across outcomes. T1 mean disease scores were typically better than in T2 and T3. INTERPRETATION: Consistent, sustained benefits of eplontersen were observed regardless of baseline ATTRv-PN severity. These findings strengthen the importance of early treatment initiation for patients with ATTRv-PN across the disease spectrum.

Humans↗

PubMed2026

Clinical Trial: Effectiveness and Safety of a Novel Anal Insert Device for Treatment of Faecal Incontinence.

BACKGROUND: Treatment options for medically-refractory faecal incontinence (FI)-including anorectal biofeedback, dextranomer injection, and sacral nerve stimulation-are limited and outcomes are often suboptimal. Anal or vaginal insert devices are infrequently used. AIMS: We evaluated the safety and effectiveness of a new anal insert device (StaySure) in patients with FI. METHODS: Patients with FI for ≥ 6 months and ≥ 4 moderate or large FI episodes during a 4-week baseline entered a 2-4 week fitting/run-in period to individualise device size (10 or 13 mm) followed by a 4-week treatment period. Outcomes included effectiveness, safety, and quality of life (QoL). The primary outcome was the proportion achieving a ≥ 50% reduction in FI frequency. RESULTS: Of 124 enrolled patients, 98, 71, and 61 progressed through the baseline, fitting/run-in, and treatment phases respectively, with few exclusions due to device intolerance. In the intent-to-treat cohort of 59 participants (93% women), mean (SD) number of days with FI declined from 13.2 (7.0) to 6.3 (6.9), and FI weekly episodes declined from 5.4 (6.9) to 2.1 (5.1) (69% reduction; p < 0.001) with similar results for both device sizes. The primary endpoint was achieved in 76.3% of participants; 54.2% achieved ≥ 75% reduction. The FIQoL overall score increased from a mean (SD) of 1.9 (0.6) to 2.3 (0.6) (p < 0.001), indicating improved QoL. Improvements in FI frequency, FIQoL exceeded minimal clinically important difference thresholds, confirming clear clinical benefit. No treatment-related serious adverse events were reported. CONCLUSIONS: The StaySure anal insert device is safe, well tolerated, and effective in reducing FI in patients with moderate to severe symptoms refractory to conservative therapies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03898778.

Adult↗

PubMed2026

Transcranial Alternating Current Stimulation at 40 Hz Improves Social Functioning in Children With Autism Spectrum Disorder: A Randomized Clinical Trial.

BACKGROUND: Autism spectrum disorder (ASD) lacks rapid and effective interventions for its core social difficulties. The right temporoparietal junction (rTPJ), a critical hub for social cognition, together with gamma band abnormalities implicated in ASD, provides a promising neuromodulation target. METHODS: In this randomized, double-blind, sham-controlled trial, 47 children with ASD (39 male; mean [SD] age = 8.79 [2.71] years) were assigned to receive either 21 sessions of 40-Hz high-definition transcranial alternating current stimulation (tACS) targeting the rTPJ (3 sessions/day for 7 days) or sham stimulation, with assessments conducted at baseline, postintervention (week 1), and a 3-week follow-up (week 4). The primary outcome was change in Ohio State University Autism Rating Scale-DSM-5 (OARS-5) total scores. Secondary outcomes included the Aberrant Behavior Checklist-Second Edition, Social Responsiveness Scale-Second Edition, and Short Sensory Profile. Eye-tracking metrics during Frith-Happé animations were exploratory measures of theory of mind (ToM)-related social cognitive processing. RESULTS: The active group demonstrated significant improvements in OARS-5 total scores at week 1 (mean difference = -1.13, 95% CI [-1.78 to -0.47], p < .001) and week 4 (mean difference = -1.47, 95% CI [-2.20 to -0.74], p < .001). Improvements in selected behavioral and sensory domains were observed. Average fixation duration during ToM animations showed a significant group × time interaction. No serious adverse events occurred. CONCLUSIONS: These findings suggest that 40-Hz tACS targeting the rTPJ may be associated with rapid improvements in ASD symptom severity, particularly social functioning, in children with ASD, while being well tolerated. Clinical significance requires further evaluation.

Humans↗

PubMed2026

Prognostic significance of NLRP-3 expression in solid cancers: a systematic review and meta-analysis.

BACKGROUND: The inflammasome is a critical immunological sensor comprised of NLRP-3, ASC, and CASPASE-1. Mutations in NLRP-3 are prevalent in inflammatory diseases. However, the role of NLRP-3 in cancer is controversial. This study investigates whether NLRP-3 expression is associated with clinical outcomes in patients with solid cancers. METHODS: PubMed (MEDLINE), Embase, Cochrane, and Google Scholar were searched for articles reporting NLRP-3 expression and disease outcome data in cancer patients. RevMan Review Manager was used to calculate pooled hazard ratios and Mantel-Haenszel pooled odds ratios. RNA sequencing datasets from the TCGA Pan-Cancer (PANCAN) were used for external validation. RESULTS: Patients with higher NLRP-3 expression showed a significant association with larger tumor size, advanced tumor grade, TNM stage, and presence of metastasis. High NLRP-3 expression has a significant association with poor OS (HR:2.12, 95% CI = 1.49-3.03), p < 0.0001) and DFS (HR:1.86, 95% CI = 1.30- 2.65, p = 0.0007). Subgroup analysis showed that higher NLRP-3 expression is associated with worse OS in head and neck cancer (HR: 2.77, 95% CI = 1.88-4.09, p < 0.00001), colorectal cancers (HR:2.14, 95% CI= 1.59- 2.87, p < 0.00001), and pancreatic cancer patients (HR: 3.19, 95% CI = 1.73-5.91, p = 0.0002). CONCLUSION: High NLRP-3 expression is associated with advanced disease and poor outcomes in many solid tumours.

Humans↗

PubMed2026

Structural complexity and mechanistic diversity of MECOM rearrangements in myeloid neoplasms.

Rearrangements involving MECOM at chromosome 3q26.2 are recurrent in myeloid neoplasms, classically represented by inv(3)(q21q26.2) and t(3;3)(q21;q26.2), which reposition the GATA2-distal haematopoietic enhancer and drive aberrant EVI1 overexpression. However, the full structural and mechanistic diversity of MECOM rearrangements (MECOM-r) is yet to be explored. We retrospectively analysed 97 cases with cytogenetically defined MECOM-r and identified 12 with complex rearrangements using GTG-banded karyotyping and tri-colour interphase/metaphase fluorescence in situ hybridisation analyses. These 12 cases demonstrated remarkable structural heterogeneity. The abnormalities encompassed translocations, inversions, insertions, duplications, and deletions, which often coexisted within the same specimen as multiple rearranged subclones. Insertional events emerged as a distinct mechanism of MECOM activation. These encompassed insertions of MYNN and/or MECOM into chromosomes 1 and 6, insertion of chromosome 8 segment into MECOM, and inverted insertions between homologous chromosome 3 segments. Recurrent breakpoints at 3q21 across multiple cases, together with localised copy number imbalances frequently involving the MYNN and GOLIM4 loci at 3q26.2, underscore the architectural fragility of these two regions. Co-occurring abnormalities such as -5/del(5q), -7/del(7q), and TP53 loss were common, reflecting a permissive genomic background for chromosomal reassembly. Our findings expand the mechanistic landscape of MECOM-r beyond canonical inv(3)/t(3;3), establishing 3q21 and 3q26.2 as structural 'hotspots' and genomic instability hubs. Distinct from fusion-driven oncogenes such as KMT2A, MECOM activation results from enhancer hijacking and regional structural remodelling, leading to EVI1 overexpression and clonal evolution in myeloid malignancies.

Humans↗

PubMed2026

Efficacy and safety of once-weekly semaglutide 2·4 mg in Chinese adults with overweight or obesity (STEP 12): a randomised, double-blind, placebo-controlled, multicentre, phase 3b trial.

BACKGROUND: Semaglutide 2·4 mg is a GLP-1 receptor agonist that reduces bodyweight, and provides other cardiometabolic benefits, among people with a BMI at least 30 kg/m2 or at least 27 kg/m2 and with weight-related comorbidities. This trial aimed to evaluate the efficacy, tolerability, and safety of semaglutide 2·4 mg in adults from mainland China and Taiwan with overweight or obesity according to locally defined, BMI thresholds. METHODS: This completed randomised, double-blind, placebo-controlled, multicentre, two-armed, parallel-group, phase 3b trial (STEP 12) was conducted at 19 sites across mainland China and Taiwan. Adults with a BMI of 24-<28 kg/m2 and at least one weight-related comorbidity, or a BMI of 28-<30 kg/m2, with or without type 2 diabetes, were randomly assigned (2:1) to once-weekly subcutaneous semaglutide 2·4 mg or placebo, plus lifestyle intervention, for 44 weeks. Randomisation was performed by the study sponsor using the Randomisation Trial Supplies Management System. Coprimary endpoints were percentage change in bodyweight and the proportion of participants achieving at least 5% bodyweight reduction. Safety was analysed descriptively in all participants who received the trial intervention. Missing data at week 44 were imputed with washout multiple imputation. This study is registered with ClinicalTrials.gov, NCT06041217, and is completed. FINDINGS: Between Sept 15, 2023, and May 7, 2025, of 254 screened participants, 161 (66·5%) of 242 participants were randomly assigned to semaglutide 2·4 mg and 81 (33·5%) to placebo; 121 (50·0%) participants were female, and 47 (19·4%) participants had type 2 diabetes. Bodyweight reduction was greater with semaglutide versus placebo (-12·1% [SE 0·6] vs -2·2% [0·8]; estimated treatment difference -9·9 percentage points [95% CI -11·8 to -8·0]; p<0·0001), with a greater proportion of participants achieving at least 5% bodyweight reduction (80·5% vs 24·4%; odds ratio [OR] 14·8 [95% CI 7·4 to 29·6]; p<0·0001). Adverse events were reported in 141 (87·6%) of 161 participants in the semaglutide 2·4 mg group and 61 (75·3%) of 81 participants in the placebo group, with gastrointestinal disorders being the most common. INTERPRETATION: Semaglutide 2·4 mg provided a superior reduction in bodyweight versus placebo in Chinese adults with overweight or obesity. The safety profile was consistent with the known profile of semaglutide. FUNDING: Novo Nordisk A/S. TRANSLATION: For the Mandarin translation of the abstract see Supplementary Materials section.

Adult↗

PubMed2026

Impact of neoprene wetsuits on lung volumes and work of breathing: implications for military diver safety and performance.

INTRODUCTION: Neoprene wetsuits may impose mechanical constraints on the chest wall, potentially altering respiratory function. This study investigated the impact of neoprene wetsuits on lung volumes, airway mechanics, and work of breathing (WOB) in healthy male divers. METHODS: A randomised crossover trial was conducted with 31 male divers at the Royal Netherlands Navy Diving Medical Centre. Participants underwent pulmonary function testing, including spirometry, body plethysmography, the forced oscillation technique (FOT), and diffusion capacity measurements, both with and without a hoodless standardised 5 mm neoprene full body wetsuit with a neoprene neck seal. Primary outcomes included changes in forced vital capacity (FVC), functional residual capacity (FRC), airway resistance (Raw), reactance (Xrs), and WOB. RESULTS: Wearing a neoprene wetsuit led to statistically significant reductions in FVC (2.8%, P < 0.05), forced expiration in one second (2.9%, P < 0.05), FRC (4.0%, P < 0.05), and expiratory reserve volume (10.9%, P < 0.05), alongside increases in inspiratory capacity and tidal volume. Raw increased significantly (P < 0.05), while the FOT revealed altered airway mechanics, evidenced by increased Xrs at multiple frequencies (P < 0.05). Diffusion capacity remained unchanged, suggesting preserved alveolar-capillary function. CONCLUSIONS: Neoprene wetsuits induce mechanically restrictive effects on the chest wall, reducing static and dynamic lung volumes and increasing WOB. While these changes may not be clinically relevant at rest, their impact needs to be determined during strenuous or prolonged dives, particularly when combined with other equipment that limits thorax excursions. Future research should explore the effects of the military 5 mm wetsuit under immersed conditions to better understand their operational impact on diver performance and safety.

Male↗

PubMed2026

Opioid-sparing anesthesia based on opioid-free principles for early recovery after total knee arthroplasty: A randomized controlled trial.

OBJECTIVE: To evaluate whether an opioid-sparing anesthesia strategy (OSA), based on opioid-free anesthesia (OFA), improves early postoperative recovery quality and optimizes functional outcomes after total knee arthroplasty (TKA), compared with conventional opioid-based anesthesia (OBA). DESIGN: A randomized controlled trial with blinding of patients, surgeons, and outcome assessors. SETTING: Single center, July 2025 to February 2026. PATIENTS: 98 adult patients scheduled for elective unilateral TKA. INTERVENTION: Patients were randomized to the OSA or OBA group. The OSA regimen used esketamine and dexmedetomidine as the primary analgesic backbone, whereas the OBA regimen was opioid-based. Both groups received preoperative femoral nerve block and were administered oxycodone at skin incision and closure. Postoperatively, both groups received the same multimodal analgesia and patient-controlled analgesia. MEASUREMENTS: The primary outcome was the 24-h postoperative Quality of Recovery-15 (QoR-15) score. Secondary outcomes included 48-h QoR-15; Oxford Knee Score (OKS) and EQ-5D-3L at 1 and 3 months; high pain at 1 month and chronic postsurgical pain at 3 months. Exploratory outcomes included postoperative C-reactive protein (CRP), and postoperative nausea and vomiting (PONV), among others. RESULTS: At 24 h postoperatively, QoR-15 was higher in the OSA group than in the OBA group (118.4 ± 11.5 vs 113.3 ± 12.2; adjusted difference 5.12, 95% CI 0.51-9.74; P = 0.029), and this advantage persisted at 48 h (adjusted difference 5.54, 95% CI 1.57-9.52; P = 0.007). The OSA group had a lower incidence of PONV (P = 0.025) and lower postoperative CRP levels (P = 0.001). At 1 month, OKS was higher in the OSA group (adjusted difference 2.31, 95% CI 0.34-4.27; P = 0.022), with no significant differences in other secondary outcomes. CONCLUSION: In TKA, this OFA-based OSA strategy improved early postoperative QoR-15 scores. However, the QoR-15 difference did not reach the minimal clinically important difference, so its clinical relevance remains uncertain.

Humans↗

PubMed2026

Structured Visualization for Laparoscopic Skill Acquisition:A Randomized Controlled Study.

OBJECTIVE: To evaluate whether structured visualization can support acquisition of basic laparoscopic skills during simulation training and whether this approach can achieve outcomes comparable to repeated physical practice. DESIGN: Prospective randomized comparative study. SETTING: Simulation-based laparoscopic skills training at a university-affiliated teaching center. PARTICIPANTS: Fifty laparoscopy-naive medical students were randomly assigned to a laparoscopic practice group or a visualization group. The laparoscopic practice group performed a validated Gynecological Endoscopic Surgical Education and Assessment (GESEA) Laparoscopic Skills Training and Testing (LASTT) hand-eye coordination task 7 consecutive times. The visualization group performed the same task physically on attempts 1, 4, and 7, while attempts 2, 3, 5, and 6 consisted of guided visualization. Each attempt lasted up to 2 minutes, and performance was scored as the number of correctly placed rings (range 0-12). RESULTS: Baseline performance was comparable between groups (2.92 ± 2.14 vs 2.88 ± 1.72; p = 0.94). Both groups improved significantly over time (p < 0.001). No statistically significant between-group differences were found on the 4th attempt (6.52 ± 3.25 vs 5.76 ± 2.57; p = 0.48) or 7th attempt (8.24 ± 2.86 vs 7.44 ± 2.99; p = 0.39). The final physical performance of the visualization group was significantly better than the 3rd physical attempt of the laparoscopic practice group (p = 0.025). CONCLUSIONS: Structured visualization may support early laparoscopic skill acquisition and achieve short-term outcomes comparable to repeated hands-on simulator training. Visualization should be considered an adjunct, rather than a replacement, for physical practice in simulation-based laparoscopic education.

Laparoscopy↗

PubMed2026

Impact of oxytocin discontinuation on fetal heart rate and uterine contractility: A pre-specified ancillary analysis embedded within a randomized trial.

INTRODUCTION: Oxytocin is widely used to augment uterine contractions during labor. However, its use has been associated with fetal heart rate (FHR) abnormalities and neonatal morbidity, which may be reduced by discontinuing oxytocin during labor. We aimed to assess the impact of oxytocin discontinuation at the onset of the active phase of labor on FHR patterns and uterine contractility. MATERIAL AND METHODS: This study is a pre-specified ancillary analysis of the STOPOXY trial, a multicenter, randomized, open-label, controlled superiority trial conducted in 21 French maternity units between January 2020 and January 2022, which aimed to assess the impact of oxytocin discontinuation during active labor on neonatal morbidity. Participants who received oxytocin before 4 cm dilation were randomly assigned (1:1) to either oxytocin discontinuation or oxytocin continuation. For the present analysis, we included women from the per-protocol discontinuation group of the parent trial. Inclusion was restricted to the six centers with electronic cardiotocography storage where valid cardiotocography recordings were available for at least 1 h before and 1 h after oxytocin discontinuation. Using a paired before-and-after design, FHR parameters (classified according to FIGO criteria) and uterine activity were compared during the 60 min preceding versus the 60 min following oxytocin discontinuation by independent obstetricians blinded to neonatal outcomes. Changes in FHR pattern were categorized as no change, improvement, or deterioration. RESULTS: 284 women fulfilled the eligibility criteria. Following oxytocin discontinuation, mean FHR increased (135 vs. 137.5 bpm; p < 0.002) and FHR variability significantly changed (p = 0.010), with a lower rate of reduced variability (3.9% vs. 2.5%) and a higher rate of normal variability (48.2% vs. 53.3%). The proportion of tracings with decelerations significantly decreased (64.1% vs. 48.6%; p < 0.001). Uterine activity decreased, with fewer uterine contractions (4.0 vs. 3.5 contractions per 10 min; p < 0.001). CONCLUSIONS: Among women receiving oxytocin during early labor, discontinuation at the onset of the active phase was associated with improved FHR patterns and reduced uterine activity, suggesting a lower fetal stress and tachysystole. Further studies are needed to assess whether these changes affect labor management or maternal experience.

Humans↗

PubMed2026

Effect of walking training on blood glucose control and metabolic health in patients with type 2 diabetes: A systematic review and meta-analysis.

OBJECTIVE: To systematically evaluate the improvement effect of walking training on blood glucose control and metabolic health indicators in type 2 diabetes patients, and to explore the effect of different intervention program characteristics on the efficacy through subgroup analysis. METHOD: The system searched PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO databases, with a search period from the establishment of the database to March 15, 2026. Include a randomized controlled trial with the main intervention measures of walking behavior, with an intervention period of ≥8 weeks. Two researchers independently conducted literature screening, data extraction, and bias risk assessment. Meta-analysis was conducted using RevMan 5.4 software, with mean difference (MD) and its 95% confidence interval (CI) as effect measures for continuous variables. Select fixed effects model or random effects model for combined analysis based on heterogeneity size, and conduct subgroup analysis according to intervention program characteristics. RESULTS: Totally 5 randomized controlled trials were included, including 483 patients with type 2 diabetes (241 cases in the intervention group and 242 cases in the control group). Participants had a mean age of 54.2 ± 6.5 years, BMI of 29.1 ± 3.2 kg/m2, and 48.5% were male. The meta-analysis results showed that walking training significantly reduced glycated hemoglobin levels, with a combined effect of -0.48% (95% CI: -0.60 to -0.36, P < 0.00001), There is moderate heterogeneity among the studies (I2 = 67%). Subgroup analysis showed that the "walking + other interventions" subgroup (combined effect size -0.58%, 95% CI: -0.96 to -0.20) and the "clear step target" subgroup (combined effect size -0.52%, 95% CI: -0.65 to -0.39) had larger effect sizes and lower heterogeneity within the subgroups. The bias risk assessment shows that the overall quality of the included research methodology is good. CONCLUSION: Walking training can significantly improve the blood glucose control in patients with type 2 diabetes. Combined with diet or behavioral intervention, setting clear goals for the number of steps may achieve better results. Walking training can be used as an effective auxiliary treatment for the management of type 2 diabetes in clinical promotion. Due to limitations in the number and quality of studies included, the above conclusions still require more high-quality research to validate.

Humans↗