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PubMed2026

Quality of life and gender identity in females with congenital adrenal hyperplasia after genital restoration surgery: A single-center experience.

BACKGROUND: Legislation restricting surgical interventions in children with differences of sex development (DSD) has intensified debate about female genital restoration surgery (FGRS) in patients with congenital adrenal hyperplasia (CAH). Long-term patient-reported outcomes are needed regarding the optimal timing of surgery. OBJECTIVE: We aimed to assess health-related quality of life (HRQoL), gender identity, and family satisfaction regarding surgical timing and outcome in females with CAH following genital restoration surgery. STUDY DESIGN: Cross-sectional survey of CAH patients who underwent surgery between January 2007 to December 2016 at our institution. Validated instruments (KINDL questionnaire for HRQoL, Utrecht Gender Dysphoria Scale, UGDS) and structured telephone interviews were employed. RESULTS: Data on HRQoL was available for 25 patients (self- and/or parent-reported) out of 56 eligible patients (45% response rate). Median age at first surgery was 6 months (range: 3-137 months). Patients' age at time of participation ranged from 2 to 28 years. All had 21-hydroxylase deficiency (92% salt-wasting form) with Prader grades ranging from II-V. Wound dehiscence requiring secondary suturing occurred in 15% of patients with primary surgery at our center, while only one (4%) patient developed vaginal stenosis after early primary vaginoplasty. Two additional patients (8%) with prior outside surgery required vaginal revision after FGRS at age 12. HRQoL scores were comparable to healthy reference populations across most age groups. Children aged 3-6 and adolescents and young adults showed no significant difference from reference values, while children aged 7-13 showed a slight elevation. None of five patients ≥14 years demonstrated gender dysphoria (all UGDS scores <40, threshold ≥40). 14 patients and families were also interviewed by telephone. All preferred early surgical timing. No family expressed regret about the decision or preferred delayed surgery. DISCUSSION: This study provides validated intermediate-term patient- and parent-reported outcomes after FGRS in CAH. Key limitations include the small sample size, single-center design, and young age of most patients. Selection bias may exist, though participating families included those who underwent revision surgery. The absence of a non-operated comparison group reflects current clinical reality, as nearly all CAH patients with urogenital sinus underwent surgical correction. CONCLUSIONS: Females with CAH reported normal HRQoL and a comfortable female gender identity after early FGRS. The patients and their families expressed a preference for early surgery. However, there is need for longer-term follow-up to assess sexual function and reproductive outcomes as well comparison of outcomes with a non-operated group.

Humans↗

PubMed2026

Phentermine/Topiramate in Obese, Diabetic Uric Acid Stone Formers: An Open-Label Randomized Feasibility Trial.

PURPOSE: The purpose of this study was to determine whether medical treatment of obesity, diabetes, and low urine pH with combination phentermine/topiramate affects uric acid (UA) kidney stone burden. MATERIALS AND METHODS: Participants with obesity, diabetes mellitus, normal renal function, urine pH < 5.8, and stone analysis ≥ 80% UA were block randomized (2:1 ratio) to phentermine 18.75 mg/topiramate 100 mg vs pragmatic controls for an 18-month, prospective, open-label feasibility study with dose escalation. The primary outcome was change in CT stone volume. Secondary outcomes included medication adherence; patient safety; and change in anthropometrics, laboratory studies, and body composition. RESULTS: Nineteen participants (age 62.1 ± 9.8 years; 68% male; mean BMI = 36.3 ± 2.9 kg/m2) were randomized, and 15 completed the study with 73% pill adherence and no serious adverse events. Stone volume by intention-to-treat analysis fell by 52% in the intervention group and rose by 8.6% in the control group (P = .10), with per-protocol analysis demonstrating statistically significant stone volume reduction (P = .02). At study end and compared with means of controls, the intervention group had greater weight loss (-10.2 vs +2.9 kg), reduction in hemoglobin A1c levels (-0.2 vs +0.5), lower 24-hour urine citrate (309 ± 81 vs 951 ± 782 mg), and lower UA supersaturation (0.7 ± 1.1 vs 1.8 ± 1.0), along with higher 24-hour urine pH (6.2 ± 0.5 vs 5.5 ± 0.4) and calcium phosphate supersaturation (0.9 ± 0.8 vs 0.2 ± 0.1; all P < .05). CONCLUSIONS: Among obese participants with diabetes mellitus and UA nephrolithiasis, phentermine/topiramate was well tolerated and demonstrated significant stone burden reductions by per-protocol analysis. The intervention group also had greater weight loss, higher urinary pH, and lower hemoglobin A1c and urinary citrate levels. These data provide a framework to study the impact of this novel alternative UA therapy on a wider range of patients with obesity and diabetes.

Aged↗

PubMed2026

Robust error-minimization in the genetic code across physicochemical metrics and variant codes: A graph-theoretic analysis in GF(2)6.

The standard genetic code reduces the impact of point mutations, but the robustness of this property across physicochemical metrics, naturally occurring variant codes, and codon-reassignment mechanisms remains incompletely quantified. Embedding the 64 codons in GF(2)6 represents the hypercube Q6 as a coordinate-dependent subgraph of the encoding-independent single-nucleotide mutation graph H(3,4), and enables continuous ρ-interpolation between the two. Under a quartet-pattern shuffle null (n=10,000), the standard code is significantly low-cost across four established, code-independent physicochemical distance metrics with partially overlapping content (Grant ham p=0.0062; Miyata p<0.001; Woese polar requirement p=0.003; Kyte-Doolittle hydropathy p=0.001), and the signal strengthens monotonically as ρ moves Q6→H(3,4). A structure-aware sensitivity analysis under the alignment-derived ProtSub matrix (Jia & Jernigan 2021) yields the most extreme percentile of any measure tested (p=0.0004; all five p-values pass Bonferroni at α=0.05). Across the 27 NCBI translation tables, near-optimality is preserved: 11 of 12 informative-distance variants retain top-5% placement after BH-FDR correction. Natural codon reassignments avoid disrupting codon-family connectivity: under the encoding-independent H(3,4) adjacency, observed events are topology-breaking at relative risk 0.32 versus the candidate landscape (permutation p≤10-4). The H(3,4) result is stable by construction; the Q6 decomposition is representation-specific and fails to show depletion under 8 of 24 base-to-bit encodings, so we report H(3,4) as the primary test and Q6 as a sensitivity. Event-level conditional-logit modelling shows that topology avoidance and local physicochemical cost provide complementary, only weakly correlated signal (rs=0.15), and that topology adds explanatory value beyond physicochemistry under both Q6 and encoding-independent H(3,4) adjacency. Retrospective reanalysis of nine genome-recoding datasets is consistent with codon-family topology operating as an evolutionary-trajectory constraint distinct from acute engineering fitness. The contribution is the second axis: code evolution is jointly constrained by physicochemical smoothness and codon-family topological integrity, and these two constraints are partly independent.

Codon reassignment↗

PubMed2026

Systematic evaluation of one-dimensional-to-two-dimensional near-infrared spectroscopy transformations with deep learning for quantifying coconut sap adulteration.

Near-infrared (NIR) spectroscopy have limitations when combined with deep learning (DL) algorithms because they rely on low-dimensional datasets. Therefore, we investigated the potential of transforming one-dimensional (1D) NIR spectra into two-dimensional (2D) spectrograms using synchronous and asynchronous techniques and the continuous wavelet transform (CWT) and their effectiveness by integrating with DL for detecting adulteration in coconut sap. NIR spectra (12,500-4000 cm-1) were collected from binary mixtures (0%-100%;w/w). The performance of all DL (convolutional neural networks-CNN, AlexNet and ResNet) models was compared with that of partial least squares (PLS). The models were ranked in the mentioned order based on their performances: 2D-CWT > 2D-asynchronous > 2D-synchronous > 1D/2D-PLS. The important features of the best model can be explained and visualized using gradient-weighted-class-activation-mapping. The findings highlight that the 1D-to-2D NIR data transformation combined with DL is a highly robust approach because it addresses the feature representation gap in NIR data and effectively captures the spatial-spectral correlations.

Spectroscopy, Near-Infrared↗

PubMed2026

Pain outcomes of pediatric circumcision patients following administration of pre-operative ketorolac: A randomized clinical trial.

INTRODUCTION: Circumcision is a common surgical intervention, and pain is the most common complaint. Poorly managed pain can increase morbidity and reduce patient and parent satisfaction. Ketorolac, a non-steroidal anti-inflammatory drug (NSAID), provides analgesia and may be effective in reducing pain after circumcision in pediatric patients. STUDY OBJECTIVES: The primary objective was to determine the effect of pre-operative intravenous ketorolac versus normal saline placebo on parental perception of postoperative pain at 24 h. We also explored the effect of ketorolac on postoperative pain scores, incidence of bleeding, incidence of vomiting, and analgesic use. MATERIALS AND METHODS: A prospective, randomized, single-blinded trial was conducted at a single tertiary children's hospital. Patients aged 1-17 presenting for circumcision were included and randomized to either normal saline injectate or ketorolac (0.5 mg/kg, maximum 30 mg). Postoperative delirium and pain scores were recorded in the post-anesthetic care unit. Parents completed the parents' postoperative pain measure (PPPM) at 24 h. The CONSORT criteria and checklist were used to guide reporting of this randomized controlled trial. RESULTS: A total of 100 participants were included. 50 participants were in each group. Mean (SD) PPPM score 24 h after normal saline and ketorolac was 6.1 (3.4) and 5.5 (3.3), respectively for a mean difference of -0.55 points [95% CI: -1.9 to 0.83; p = 0.427]. The mean (95% CI) fixed effect size of ketorolac on post anesthetic care unit reported Face, Leg, Activity, Cry, Consolability score was -0.17 (-0.77 to 0.43, p = 0.585) points, while the mean (95% CI) effect size of ketorolac on numerical rating scale was -1.2 (-2.2 to -0.18, p = 0.026) points. DISCUSSION: Pre-operative intravenous ketorolac, compared to normal saline placebo, did not result in a difference in parental perception of postoperative pain at 24 h after circumcision surgery. As part of exploratory analyses, those receiving ketorolac had modestly lower mean immediate postoperative pain scores, likely not of clinical importance. Ketorolac has often been avoided due to concerns of increased bleeding risk, however it is important to consider that there is no substantial evidence to support this. This is the first study to our knowledge evaluating the effect of ketorolac in pediatric circumcision patients. While the PPPM score is a family centered outcome, it is an indirect measurement of pediatric pain. CONCLUSIONS: Pre-operative intravenous ketorolac was not associated with lower parental reported pain scores at 24 h compared to normal saline placebo after pediatric circumcision surgery. CLINICAL TRIAL REGISTRATION: NCT02973958.

Humans↗

PubMed2026

Single-center experience with isolated male epispadias: Outcomes of Thiersch-Duplay and modified Cantwell-Ransley repairs by anatomical subtype.

BACKGROUND: Isolated male epispadias (IME) is a rare congenital malformation. Surgical repair aims to improve urinary function, correct penile curvature, reconstruct the urethra and glans, and preserve future sexual function. Because available series are small, the influence of anatomical subtype and operative technique on outcome remains incompletely defined. OBJECTIVE: To report single-center outcomes of Thiersch-Duplay and modified Cantwell-Ransley repairs for IME, with attention to anatomical subtype, complications, and age-appropriate continence outcomes. METHODS: We retrospectively reviewed boys with IME who underwent primary urethral reconstruction in my hospital, Capital Medical University, from May 2005 to June 2024. Data were locked on 30 June 2024. Primary outcomes were postoperative complications graded by the Clavien-Dindo system and urinary continence at last follow-up in patients aged 5 years or older. Secondary outcomes included improvement of preoperative incontinence, ICIQ score, subsequent bladder neck reconstruction, penile appearance/residual curvature when documented, and patient/parent-reported sexual function. RESULTS: Sixty-seven patients were included: 35 underwent modified Cantwell-Ransley repair and 32 underwent Thiersch-Duplay repair. The cohort included 26 glanular (38.8%), 23 penile (34.3%), and 18 penopubic (26.9%) cases. Median age at surgery was 28 months in both groups. Median age at last follow-up was 92.8 months (IQR 63.9-108.4) after modified Cantwell-Ransley repair and 137.9 months (IQR 77.9-172.6) after Thiersch-Duplay repair (P = 0.011). Procedure distribution differed by meatal location (P = 0.036), although penopubic cases were treated with both procedures. Total complications occurred in 5/35 and 5/32 patients, respectively. Formal continence analysis included 26 modified Cantwell-Ransley patients and 27 Thiersch-Duplay patients aged 5 years or older. Postoperative urinary incontinence persisted in 14/26 (53.8%) and 12/27 (44.4%), respectively. Among age-eligible patients with preoperative incontinence, any improvement was documented in 13/20 (65.0%) and 14/17 (82.4%), and complete remission occurred in 6/20 (30.0%) and 5/17 (29.4%), respectively. Three patients, all with penopubic epispadias treated with Thiersch-Duplay repair, subsequently underwent bladder neck reconstruction for persistent incontinence. Erectile function data were available in 37/67 patients (55.2%). CONCLUSIONS: In this large single-center retrospective cohort, Thiersch-Duplay and modified Cantwell-Ransley repairs had comparable overall complication rates. Continence and reoperation patterns were strongly influenced by anatomical subtype, with penopubic epispadias representing the highest-risk group. These findings support individualized, anatomy-conscious operative planning and prospective evaluation of standardized selection criteria, rather than a single prescriptive algorithm. CLINICAL/TRANSLATIONAL IMPLICATION: This series supports standardized reporting of anatomical subtype, age-appropriate continence outcomes, and graded complications when counseling families and comparing outcomes across centers. LEVEL OF EVIDENCE: Level III.

Humans↗

PubMed2026

The effect of dietetic counseling combined with digital tools intervention on hemodynamic markers in Greek adults: The GATEKEEPER Study.

BACKGROUND AND AIM: Hypertension is a leading cardiovascular risk factor with substantial global impact on morbidity, mortality, and healthcare costs. While lifestyle interventions remain central to management, mHealth technologies offer promising adjunctive support, though their clinical effectiveness remains uncertain. This study evaluated whether combining dietetic counseling with digital tools improves hemodynamic markers in adults aged ≥55 years with increased cardiometabolic risk. METHODS AND RESULTS: This 3-month RCT (NCT05031299) included 954 adults with at least one metabolic syndrome risk factor, allocated 1:1:1 to Standard Care (dietetic counseling), Platform (counseling plus web-based platform), or Platform + Devices (counseling plus platform plus wearables). Outcomes included anthropometrics, lifestyle characteristics, blood pressure, pulse pressure, and estimated pulse wave velocity, analyzed using linear mixed-effects models adjusted for age and sex. All groups improved over 3 months. Waist circumference decreased by -6.29, -4.92, and -4.69 cm across Standard Care, Platform, and Platform + Devices groups respectively, and systolic blood pressure declined by -4.84 to -7.15 mmHg across groups. The Platform + Devices group showed greater increases in physical activity (94.62 MET-min/week; 95% CI 66.49 to 122.76) and greater reductions in pulse pressure (-3.90 mmHg; -6.58 to -1.22) versus Standard Care. Weight loss was associated with lower odds of hypertension (OR 0.4; 95% CI 0.2-0.7), greater likelihood of hypertension reversal (OR 3.6; 1.2-10.3), and higher probability of achieving normal pulse pressure (OR 1.8; 1.1-3.1). CONCLUSIONS: Dietary lifestyle intervention improved cardiometabolic outcomes, with limited added benefit from digital tools. Weight loss was the primary driver of hemodynamic improvement.

Aged↗

PubMed2026

A two-center randomized clinical superiority trial of single-anastomosis sleeve ileal bypass versus sleeve gastrectomy for severe obesity: SASSY study protocol.

BACKGROUND: Single-anastomosis sleeve ileal bypass is a novel metabolic bariatric surgery intended to enhance metabolic outcomes and reduce the risk of postoperative complications. Although preliminary outcome data for single-anastomosis sleeve ileal bypass are promising, evidence from adequately powered, randomized head-to-head comparisons is scarce. This trial compares the efficacy and safety of single-anastomosis sleeve ileal bypass versus sleeve gastrectomy in patients with class II obesity (body mass index = 35.0-39.9 kg/m²) with at least one obesity‑related comorbidity or class III obesity (body mass index ⩾40.0 kg/m²). METHODS: This two-center randomized clinical superiority trial enrolls patients eligible for metabolic bariatric surgery at two specialized Norwegian centers. Included patients are randomly assigned (1:1) to either single-anastomosis sleeve ileal bypass or sleeve gastrectomy with standardized perioperative treatment and care. The primary endpoint is the between-group difference in change in body mass index from baseline to 2 years after single-anastomosis sleeve ileal bypass versus sleeve gastrectomy. Secondary endpoints include additional weight loss outcomes, the prevalence of gastroesophageal reflux disease, surgical and postoperative complications, obesity-related comorbidities, nutritional status, bone mineral density, gastrointestinal symptoms, quality of life, and rates of revisional and conversion surgery. All endpoints will be evaluated at 2 and 5 years after surgery. Statistical analyses utilize linear mixed models and analysis of covariance within an intention-to-treat framework. DISCUSSION: This trial will provide high-level evidence with robust and comparative outcome data on single-anastomosis sleeve ileal bypass and sleeve gastrectomy, aiming to clarify the clinical utility of single-anastomosis sleeve ileal bypass and inform surgical practice. Findings will address gaps in medium- and long-term evidence regarding weight loss, safety, comorbidity resolution, and quality of life following single-anastomosis sleeve ileal bypass.

Humans↗

PubMed2026

Balanced Fluid or 0.9% Saline in Children Treated for Septic Shock.

BACKGROUND: Whether treatment with balanced crystalloid fluid leads to better outcomes than 0.9% saline in children treated for septic shock is debated. METHODS: In this pragmatic clinical trial conducted at 47 emergency departments in five countries, patients (2 months to <18 years of age) with suspected septic shock and abnormal perfusion were randomly assigned to receive fluid resuscitation with either balanced fluid or 0.9% saline for up to 48 hours. The primary outcome was a major adverse kidney event (a composite of death, new renal-replacement therapy, or persistent kidney dysfunction) at 30 days after enrollment or hospital discharge, whichever occurred first. RESULTS: Of 9041 enrolled patients, 277 (6.1%) in the balanced-fluid group and 282 (6.2%) in the 0.9%-saline group withdrew from the trial, leaving 4235 and 4247 patients, respectively, for analysis. A primary-outcome event occurred in 137 patients (3.4%) in the balanced-fluid group and in 124 (3.0%) in the 0.9%-saline group (difference, 0.4 percentage points; 95% confidence interval [CI], -0.5 to 1.3; risk ratio, 1.10; 95% CI, 0.88 to 1.40; P = 0.85). The median number of hospital-free days during 28 days after enrollment was 23 (interquartile range, 19 to 25) in both groups. Hyperchloremia occurred in 868 patients (31.4%) in the balanced-fluid group and in 1383 (49.0%) in the 0.9%-saline group; hypernatremia in 52 (1.8%) and 89 (3.1%), respectively; and hyperlactatemia in 260 (19.8%) and 228 (16.7%). No differences in other safety outcomes or adverse events were seen. CONCLUSIONS: Among children treated for septic shock, no significant difference was seen in the incidence of death, new renal-replacement therapy, or persistent kidney dysfunction when fluid resuscitation was administered with balanced fluid as compared with 0.9% saline. (Funded by Eunice Kennedy Shriver National Institute of Child Health and Human Development and others; PRoMPT BOLUS ClinicalTrials.gov number, NCT04102371.).

Adolescent↗

PubMed2026

Recovery of polysaccharides from marc and pomace through sequential extractions assisted by ultrasound, enzymes and acid maceration.

This study evaluated the pilot-scale recovery of polysaccharides from Vitis vinifera pomace/marc using sequential extraction strategies combining high-power ultrasound (UAE), enzymes (EAE), and acid maceration (AAE). Laboratory-scale trials identified optimal conditions for enzyme dosage and liquid/solid ratio (L/S). Pilot-scale trials demonstrated that the extraction sequence and the processing byproducts influenced extraction efficiency, total soluble polysaccharide in the extract (TSP), and polysaccharide composition. Post-maceration at pH 3.2, with/without the maximum enzyme dose after UAE in a L/S of 1.3/1, improved structural polysaccharide extraction from Viura pomace, while Tempranillo marc showed better recovery of pectic families and TSP with UAE + EAE. Separating grape pomace extract (UAE) from the post-maceration stage at pH 3.2 produced two extracts: E1, with higher yield (19.9%), enriched in structural polysaccharides and oligosaccharides, and E2, enriched in high and medium molecular weight pectic polysaccharides (58.03%), a low degree of esterification (17.1%) and more complex rhamnogalacturan structures.

Polysaccharides↗

PubMed2026

Which radiographic plane should be used to quantify the distal tibia angle on weightbearing CT images?

BACKGROUND: Precise quantification of distal tibial alignment is essential for planning corrective osteotomies and ankle joint replacement surgery. The lateral distal tibial angle (LDTA) is the principal radiographic parameter used for this purpose. While LDTA is increasingly measured on weightbearing cone-beam CT (WBCT) using two-dimensional coronal slices, the optimal measurement plane remains unclear. METHODS: In this retrospective comparative study, full-leg WBCT scans of patients scheduled for supramalleolar osteotomy (n = 20; mean age 47 ± 12.8 years) were analyzed. LDTA was measured on three coronal planes of the distal tibial plafond (anterior edge, mid-dome, posterior edge) and compared with semi-automated three-dimensional (3D) tibial alignment measurements as the reference standard. RESULTS: Mid-dome LDTA showed no significant difference from the 3D reference (p > 0.05) and demonstrated excellent agreement. Anterior measurements significantly overestimated LDTA, while posterior measurements underestimated it (both p < 0.05), with only fair agreement. CONCLUSION: LDTA should be measured at the mid-dome of the distal tibial plafond on WBCT to ensure accurate and reproducible alignment assessment. LEVEL OF EVIDENCE: Level III - Retrospective Comparative Study.

Humans↗

PubMed2026

[Effect of electroacupuncture combined with suspension exercise therapy on lower limb motor function in elderly patients with post-stroke spastic hemiplegia].

OBJECTIVE: To observe the efficacy of electroacupuncture (EA) combined with suspension exercise therapy in elderly patients with post-stroke spastic hemiplegia and its effect on lower limb motor function. METHODS: A total of 120 elderly patients with post-stroke spastic hemiplegia were enrolled. Using a 2×2 factorial design, all the patients were assigned to a group A (conventional treatment), a group B (conventional treatment combined with suspension exercise therapy), a group C (conventional treatment combined with EA at Jiaji [EX-B2] and limb acupoints), and a group D(conventional treatment combined with suspension exercise therapy and EA at Jiaji [EX-B2] and limb acupoints), with 30 patients in each group. The main acupoints were bilateral Jiaji (EX-B2) points at the C2-C7, T2-T12, L1-L5, and S1 segments. The adjunct acupoints included Jianyu (LI15), Binao (LI14), Huantiao (GB30), Chengfu (BL36), etc. on the affected side.Continuous wave was applied at a frequency of 100 Hz with a current intensity of 1.5-3.0 mA, and needles were retained for 30 min, once daily for 4 weeks. Before treatment and after 2 and 4 weeks of treatment, the modified Ashworth scale (MAS),Fugl-Meyer assessment (FMA), Berg balance scale (BBS), and Barthel index scores were evaluated in the four groups. Root mean square (RMS) values of surface electromyography (sEMG) of the erector spinae and rectus abdominis muscles on the affected side, as well as balance function indexes, including the mean pressure symmetry index (SI), contact area SI, ellipse area, and displacement distances of the center of pressure in the anteroposterior (AP) and mediolateral (ML) directions, were measured. Clinical efficacy was also compared among the four groups. RESULTS: After 2 and 4 weeks of treatment, MAS scores in all groups were lower than those before treatment (P<0.05), whereas FMA, BBS, and Barthel index scores were higher than those before treatment (P<0.05). After 4 weeks of treatment, MAS scores were lower than those after 2 weeks of treatment (P<0.05), whereas FMA, BBS, and Barthel index scores were higher than those after 2 weeks of treatment (P<0.05) in the four groups. At both 2 and 4 weeks after treatment, group D had lower MAS scores (P<0.05) and higher FMA,BBS, and Barthel index scores (P<0.05) than the other three groups. After 2 and 4 weeks of treatment, RMS values of sEMG of the erector spinae and rectus abdominis muscles on the affected side at all tested angles were higher than those before treatment in all groups (P<0.05), and the values after 4 weeks of treatment were higher than those after 2 weeks of treatment(P<0.05). At both 2 and 4 weeks after treatment, all these indexes in the group D were higher than those in the other three groups (P<0.05). After 2 and 4 weeks of treatment, the mean pressure SI, contact area SI and ellipse area of each group were lower than those before treatment (P<0.05). After 4 weeks of treatment, the mean pressure SI, contact area SI and ellipse area of each group were lower than those after 2 weeks of treatment (P<0.05). After 2 and 4 weeks of treatment, the AP displacement distances of groups A, C and D were lower than those before treatment (P<0.05), and after 4 weeks of treatment, the AP displacement distances of groups A, C and D were lower than those after 2 weeks of treatment (P<0.05);after 2 weeks of treatment, there was no statistically significant difference in AP displacement distance in the group B compared with before treatment (P>0.05), and after 4 weeks of treatment, the AP displacement distance of group B was lower than that before treatment (P<0.05). After 2 weeks of treatment, there was no statistically significant difference in ML displacement distance in group A compared with before treatment (P>0.05); after 4 weeks of treatment, the ML displacement distance of group A was lower than that before treatment (P<0.05). After 2 and 4 weeks of treatment, there was no statistically significant difference in ML displacement distance in the group B compared with that before treatment (P>0.05).After 2 and 4 weeks of treatment, the ML displacement distances of groups C and D were lower than those before treatment(P<0.05), and after 4 weeks of treatment, the ML displacement distances of groups C and D were lower than those after 2 weeks of treatment (P<0.05). At both 2 and 4 weeks after treatment, mean pressure SI, contact area SI, ellipse area, and AP and ML displacement distances in the group D were lower than those in the other three groups (P<0.05). Factorial analysis of variance showed that EA had the strongest main effect on FMA score (F=6.243, P<0.05), suspension exercise therapy had the strongest main effect on BBS score (F=6.292, P<0.05), and the interaction effect was most significant for MAS score (F=5.941, P<0.05), indicating that the combined therapy produced a greater synergistic effect on reducing muscle tone than on the other outcome measures. The total effective rate in the group D was 93.3% (28/30), which was higher than those in the group A (53.3% [16/30]), group B (56.7% [17/30]), and group C (66.7% [20/30], P<0.05). CONCLUSION: EA combined with suspension exercise therapy could effectively promote the recovery of lower limb function in elderly patients with post-stroke spastic hemiplegia, improve motor and balance functions, and enhance activities of daily living.

Humans↗

PubMed2026

Reinforcement learning-based dynamic ensemble for missense variant effect prediction and tiered prioritization of VUS.

BACKGROUND: Accurate classification of missense variants remains a challenging task despite major advances in genomics. Numerous computational models have been developed to assist in variant classification, but often require repeated integration and benchmarking efforts. Ensemble methods have been proposed to overcome the limitations of single predictors, but mostly rely on fixed, predefined weights that constrain their ability to capture interactions among predictive signals. METHODS: We present GenixRL, a dynamic ensemble framework that reformulates model fusion as a reinforcement learning optimization problem. GenixRL uses a Q-learning agent to learn a policy that dynamically weights the probabilistic outputs of complementary predictors, including BayesDel (addAF and noAF), ClinPred, and MetaRNN. Replacing static weighting with policy learning allows GenixRL to adaptively identify optimal weightings and substantially improve classification accuracy. RESULTS: In benchmark evaluation against 25 state-of-the-art predictors, GenixRL achieved an AUROC of 0.9644 on an independent ClinVar dataset. On saturation genome editing assays for BRCA1 and BRCA2, GenixRL achieved the best performance and ranked highest on 14 of 17 clinically significant genes in a zero-shot evaluation. Applied to uncertain and conflicting ClinVar variants, GenixRL enabled tiered, evidence-based prioritization of hundreds of thousands of variants as likely pathogenic or pathogenic with high confidence, supported by orthogonal population evidence from gnomAD. CONCLUSION: GenixRL advances pathogenicity prediction for missense variants and provides an adaptive ensemble that sorts variants of uncertain significance into tiered candidates for expert curation and functional validation.

Mutation, Missense↗

PubMed2026

Mul-PheG2P: decoupled learning and prediction-space fusion enables robust and interpretable multi-phenotype genomic prediction.

Genomic prediction of multiple phenotypes is crucial in modern plant breeding; however, existing methods struggle with negative transfer and lack interpretability, particularly across high-dimensional small-sample data and diverse species. To address this, we propose Mul-PheG2P, a novel paradigm based on decoupled learning and predictive space fusion. It employs a two-stage design: first training phenotype-specific encoders using genetic data, then decoupling phenotype-specific learning from cross-phenotype aggregation via an interpretable prediction layer. Mul-PheG2P outperforms existing methods across diverse crop datasets, including maize (Zea mays), wheat (Triticum aestivum), and tomato (Solanum lycopersicum). It provides a multi-scale interpretability chain: at the macro level, it quantifies phenotypic contributions via attention-based weighting; at the micro level, Integrated Gradients reveal the genetic basis of predictions. Notably, the model successfully identified the CCT (CONSTANS, CO-like, and TOC) motif regulating photoperiodism and the SQUAMOSA (SQUAMOSA promoter binding protein) promoter for inflorescence development, confirming its ability to capture functional biological mechanisms. These results highlight the high performance and interpretability of Mul-PheG2P, showcasing its value for low-cost, large-scale screening to advance precision breeding.

Phenotype↗

PubMed2026

Rationale, design, and experiences from the vanguard phase of the bariatric surgery for the reduction of cardiovascular events (BRAVE) trial.

BACKGROUND: Observational studies suggest that metabolic/bariatric surgery (MBS) reduces mortality and major adverse cardiovascular events in patients with obesity, but adequately powered randomized trials (RCTs) are lacking. The Bariatric Surgery for the Reduction of Cardiovascular Events (BRAVE) trial was designed to address this evidence gap. METHODS: BRAVE is an investigator-initiated, multi-center, open-label RCT with blinded endpoint adjudication comparing MBS vs guideline-based medical weight management (MWM) in adults with obesity and high-risk cardiovascular disease (CVD). Eligible participants have a body-mass index ≥35 kg/m² or ≥30 kg/m² with type 2 diabetes or age >55 years, and prior myocardial infarction (MI), coronary intervention, heart failure (HF), atrial fibrillation (AF) with elevated CHA₂DS₂-VASc score, cerebrovascular disease, or peripheral arterial disease. Participants are randomized 1:1 to MBS (sleeve gastrectomy, Roux-en-Y gastric bypass, or duodenal switch) or MWM, which includes dietary, behavioral, and pharmacologic therapies. The primary outcome is the composite of all-cause death, MI, stroke, HF events, coronary revascularization, AF hospitalization, and renal events. A vanguard phase of 200 participants was implemented to optimize recruitment and logistics. RESULTS: As of October 2025, 2,514 individuals have been screened from 17 centers in Canada, Brazil, Italy and Spain, with 444 entered MBS work-up, and 200 have been randomized. The randomized cohort (mean age 59.8 years; 37% female; mean BMI 44.0 kg m⁻²) has high burden of hypertension (82%), diabetes (45%), coronary artery disease (44%), HF (39%), and AF (48%). Recruitment barriers were identified and addressed through targeted education and enhanced patient engagement. CONCLUSIONS: BRAVE is the first large RCT evaluating whether MBS safely reduces major cardiovascular events compared with medical therapy in high-risk patients with obesity. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05531474.

Humans↗

PubMed2026

Efficacy and safety of Vertebral Body Sliding Osteotomy (VBSO) versus Anterior Cervical Corpectomy and Fusion (ACCF): A systematic review and meta-analysis.

Anterior cervical corpectomy and fusion (ACCF) is an established treatment for complex cervical myelopathy and ossification of the posterior longitudinal ligament (OPLL), yet it carries risks of dural injury and graft-related failure. Vertebral body sliding osteotomy (VBSO) is a novel technique that avoids direct OPLL manipulation by translating the vertebral body anteriorly to enlarge the spinal canal. Although early studies suggest VBSO may reduce complications, evidence remains limited to retrospective cohorts from the technique's developers, with no high-level synthesis directly comparing it to ACCF. We therefore conducted this meta-analysis to compare clinical outcomes, complications, and radiographic parameters between VBSO and ACCF, while critically evaluating the certainty of the evidence and its generalizability. A systematic search of PubMed, Embase, Scopus, the Cochrane Library, and Web of Science (through June 2025) identified four retrospective cohort studies (449 patients; VBSO n = 209, ACCF n = 240). A critical limitation of the included evidence is that all studies originated from a single institution (Asan Medical Center, Seoul, Korea) with overlapping enrollment periods (2006-2020), increasing the risk of duplicate patient cohorts. Furthermore, the first author (D.-H. Lee) is the same across all included studies, introducing substantial surgeon-expertise bias. Outcomes included neurological recovery, functional outcomes, complications, and radiographic parameters. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Neurological recovery and functional outcomes were comparable between groups. ACCF showed slightly higher postoperative JOA scores (MD -0.59, 95% CI -0.96 to -0.22; p < 0.01), though the clinical relevance is uncertain. VBSO was associated with reduced risks of graft subsidence (RR 0.23; p < 0.01), pseudarthrosis (RR 0.25; p < 0.01), revision surgery (RR 0.17; p < 0.01), and neurological deterioration (RR 0.17; p = 0.02). CSF leakage appeared to be less frequent with VBSO, but the difference was not statistically significant. VBSO was also associated with greater postoperative cervical lordosis and shorter hospital stays. However, these findings must be interpreted with extreme caution: leave-one-out sensitivity analyses revealed that the results for postoperative JOA score, neurological deterioration, and pseudarthrosis were fragile and driven by a single large study, meaning these apparent advantages may not be robust. In addition, GRADE assessment revealed very low certainty across all assessed outcomes. Given the very low certainty of evidence, the preliminary nature of the available data, the fragility of several key findings, and the critical limitations of the underlying studies (single institution, overlapping patient cohorts, developer bias, and systematic imbalance in follow-up duration), the observed differences should be considered hypothesis-generating rather than definitive. VBSO should not be considered a proven superior alternative to ACCF based on the current evidence. Prospective, multicenter, international studies with balanced follow-up durations conducted by independent surgical teams are required before broader adoption can be recommended.

Humans↗

PubMed2026

Towards microplastic bioremediation: Fungal degradation of pristine and pretreated high-density polyethylene and polystyrene.

Microplastic (MP) contamination has become a significant ecological issue because of its enduring existence in the ecosystem and its possible negative impacts. Therefore, using degrading strategies to eliminate these stubborn polymers has been a subject of scientific research. However, the currently used degradation methods are relatively inefficient. Given the pervasiveness of High-Density Polyethylene (HDPE) and Polystyrene (PS) and their resistance to biodegradability, disposal strategies are critical and must be addressed. This manuscript examines the biodegradation of pristine and UV-treated HDPE and PS MPs by Aspergillus flavus species in minimal growth media over 70 days. The maximum weight loss observed at 70 days for pristine HDPE and PS in sole carbon source (SCS) media was (29.33 ± 0.28) % and (17.67 ± 0.35) %, respectively. Whereas, for UV-treated HDPE and PS MPs, the % weight reduction was (33 ± 0.21) % and (25 ± 0.19) %, respectively. UV-treated MPs exhibited greater weight reduction, as UV induced oxygenated functional groups enhance polymer susceptibility to enzymes, thereby promoting biodegradation. HDPE MPs typically show a higher proportion of particles in the lower size range compared to PS MPs. This assertion was based on the weight loss, particle size distribution, and SEM analysis. Furthermore, chemical changes were evaluated using Fourier transform Infrared Spectroscopy (FTIR) analysis, which also displayed chemical oxidation occurring during biodegradation. Liquid Chromatography-Mass Spectrometry (LC-MS) results indicate that UV pretreatment enhances biodegradability by promoting chain scission. These findings further suggest that this fungus's natural and ubiquitous occurrence in terrestrial and marine environments may actively contribute to MP biodegradation while requiring few nutrients.

Microplastics↗

PubMed2026

Ketoacidosis with SGLT2 inhibitors in routine clinical practice of type 2 diabetes: Scandinavian cohort and nested case-control study.

BACKGROUND: SGLT2 inhibitors increase the risk of ketoacidosis, but data from routine clinical practice are scarce. We used nationwide registers with the aim of assessing the incidence, risk factors, and prognosis of ketoacidosis during SGLT2 inhibitor treatment in patients with type 2 diabetes. METHODS: In this cohort and nested case-control study we used data from three Scandinavian countries. In a cohort of SGLT2 inhibitor-treatment episodes among patients with type 2 diabetes aged at least 18 years in Sweden, Denmark, and Norway, we estimated ketoacidosis incidence. Using a nested case-control design (matched on age, sex, region of birth, calendar time, and time since treatment initiation), we assessed risk factors and precipitating or co-occurring events. Changes in diabetes medications were evaluated. FINDINGS: The study period was Jan 1, 2013, to Dec 31, 2021, in Denmark and Sweden, and Jan 1, 2013, to Dec 31, 2022, in Norway. We included 322 597 treatment episodes among 282 282 patients with type 2 diabetes (mean age 63 years, 116 521 [36·1%] of 322 597 women). During a median (IQR) follow-up of 1·3 (0·7-2·8) years, 1452 ketoacidosis events occurred (incidence 2·43 per 1000 person-years). Although highest shortly after initiation, risk persisted throughout follow-up. Strong risk factors included high HbA1c (≥83 vs ≤52 mmol/mol: odds ratio [OR] 15·37 [95% CI 11·50-20·53]), malnutrition (OR 10·54 [7·32-15·18]), previous ketoacidosis (OR 10·40 [7·09-15·24]), low BMI (<20 kg/m2vs 20 to <25 kg/m2: OR 9·98 [5·68-17·53]), and recent hypoglycaemia (OR 5·22 [2·60-10·49]). Infection was the most common precipitating or co-occurring event (454 [31·8%] of 1428 vs 862 [6·1%] of 14 233 for ketoacidosis cases vs controls; OR 7·60 [6·62-8·71]). The strongest associations were observed for alcohol intoxication, acute renal events, acute abdomen, stroke, and major surgery, although associations for some transient exposures, particularly milder conditions, might have been overestimated because of under-registration among controls. Exploratory analyses suggested that the observed associations were largely general to patients with type 2 diabetes rather than specific to SGLT2 inhibitor use. At 1 year after ketoacidosis, 211 (25·1%) of 842 remained on SGLT2 inhibitors and insulin use increased from 269 (31·9%) of 842 to 615 (73·0%) of 842. INTERPRETATION: Ketoacidosis risk with SGLT2 inhibitors varies greatly by patient characteristics and is not confined to early in treatment. Risk should be assessed throughout treatment, and patients should be instructed to pause treatment during acute illness and stress. FUNDING: Region Stockholm, Swedish Society of Medicine, Karolinska Institutet.

Journal Article↗