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PubMed2026

Exercise with motor cortex high-definition transcranial direct current stimulation enhances cardiovascular efficiency and lower-limb function in multiple sclerosis: A crossover, double-blind, and proof-of-principle study.

Combining exercise with high-definition transcranial direct current stimulation (HD-tDCS) could offer a strategy to help people with Multiple Sclerosis improve outcomes. In this crossover study, participants with MS (Expanded Disability Status Scale ≥3.0, n = 12) and controls (n = 10) completed baseline testing, followed by three randomized experimental conditions: 1) exercise+active HD-tDCS; 2) exercise+sham HD-tDCS; and 3) HD-tDCS alone. Exercise performance metrics [heart rate, work rate, heart rate-to-work rate (HR/WR) ratio, and perceived exertion] were compared across the exercise conditions. Secondary outcomes included the Symbol Digit Modalities Test (SDMT), Timed 25-Foot Walk (T25F), Nine-Hole Peg Test (9HPT), and acute symptom ratings (fatigue and pain), assessed pre-, immediately post-, and 1h-Post. Cardiovascular efficiency (HR/WR ratio) significantly improved during exercise+HD-tDCS compared to exercise alone, particularly in older MS participants (p = 0.010). SDMT declined immediately post HD-tDCS alone, 1h-post-exercise alone, and at both time points during exercise+active HD-tDCS (p < 0.05). Both groups increased walking speed only post-exercise+active HD-tDCS, while no condition affected upper-limb function (p < 0.05). These results are in line with the tDCS literature in the general population, suggesting that tDCS improves exercise performance and selectively improves engaged motor function. The trade-off between physical and cognitive outcomes underscores the importance of personalized neuromodulation strategies in neurorehabilitation to maximize therapeutic benefits while minimizing adverse effects, and warrants further large-scale, long-term investigations of this approach in MS.

Humans↗

PubMed2026

Association between Kidney Tubular Secretory Clearance with Cognitive Function among Adults with CKD in the Systolic Blood Pressure Intervention Trial.

BACKGROUND: Persons with CKD are disproportionally affected with cognitive impairment, yet the pathophysiology linking the two conditions is unclear. Because kidney tubule secretion is essential for clearance of medications, uremic toxins, and metabolites, we hypothesized that worse tubular secretion would be associated with reduced cognitive function in CKD. METHODS: The Systolic Blood Pressure Intervention Trial tested a systolic blood pressure target <120 mmHg vs. <140 mmHg in hypertensive individuals at high cardiovascular risk. In paired blood and urine specimens from 1,937 participants with eGFR <60 ml/min/1.73m2, we measured 10 endogenous tubule-secreted metabolites and calculated a urine/plasma ratio for each, then averaged these to generate a summary secretion score. We used unadjusted and multivariable-adjusted linear regression and mixed models to evaluate cross-sectional and longitudinal associations of the secretion score with the Montreal Cognitive Assessment, Digit Symbol Coding, and Logical Memory immediate and delayed tests-measured at baseline and months 24 and 48 of follow-up. Multivariable Cox regression evaluated associations with incident probable dementia and mild cognitive impairment, adjudicated by prespecified criteria. RESULTS: Mean age was 73 ± 9 years, 41% were women, mean eGFR was 48.2 ± 11.4 ml/min/1.73m2, median albuminuria was 14.8 [7.1-48.6] mg/g. Lower secretion score was associated with a 0.06 higher adjusted logical memory delayed score (95% CI: 0.02, 0.11) but not with other cognitive tests at baseline or longitudinal cognitive decline. After a median 4.1 years of follow-up, 118 developed probable dementia and 187 developed mild cognitive impairment. Each 1-SD lower secretion score was associated with lower risk of probable dementia (HR 0.78, 95% CI: 0.63, 0.98) but not mild cognitive impairment. CONCLUSIONS: Among Systolic Blood Pressure Intervention Trial participants with CKD, lower estimated tubular secretion was not associated with worse cognition at baseline or during longitudinal follow-up.

Journal Article↗

PubMed2026

Flap Versus Tunneling for Horizontal Ridge Augmentation With FDBA and i-PRF: A Randomized Controlled Clinical Trial.

AIM: This study evaluated the efficacy of conventional flap and tunneling techniques for horizontal alveolar ridge augmentation using freeze-dried bone allograft (FDBA) particles combined with injectable platelet-rich fibrin (i-PRF). MATERIALS AND METHODS: Forty-five patients were randomly allocated to one of three groups (n = 15 each): conventional flap (CF), tunneling with membrane (TM), or tunneling without membrane (TnM). Preoperative ridge width was measured via cone beam computed tomography (CBCT). All augmentation procedures incorporated FDBA and i-PRF; an absorbable collagen membrane was applied in the CF and TM groups. Follow-up assessments, including CBCT imaging and histomorphometric analysis, were conducted 6 months postoperatively. For normally distributed data, ANOVA with Tukey's post hoc test and paired samples t-test were applied. Non-normally distributed data were analyzed using Kruskal-Wallis, Mann-Whitney U, and Wilcoxon signed-rank tests. RESULTS: Statistical analysis was performed on 43 patients. All groups demonstrated an increase in ridge width after 6 months. At the 2 mm level, the mean width gain was 1.28 mm (95% CI: 0.17 to 2.40) in the TM group, 2.85 mm (95% CI: 1.80 to 3.89) in the TnM group, and 1.95 mm (95% CI: 1.07 to 2.83) in the CF group. However, statistical analysis revealed no significant intergroup variation (p > 0.05). Histomorphometric assessments similarly demonstrated comparable outcomes across all groups, with no statistically significant differences observed (p > 0.05). CONCLUSION: Within the limitations of this study, the tunneling technique, regardless of membrane use, appears to be a clinically viable alternative to the conventional flap method for horizontal alveolar ridge augmentation. However, further studies with longer follow-up periods are required to substantiate these findings. TRIAL REGISTRATION: irct.behdasht.gov.ir identifier: IRCT 20101204005305N21.

Humans↗

PubMed2026

A Meta-learning-driven strategy for adulteration detection in sweet potato starch and vermicelli using Raman spectroscopy.

To address the widespread adulteration of sweet potato starch and its vermicelli with cheaper starches and overcome conventional supervised learning's dependency on large labeled datasets, this study developed a few-shot discrimination method integrating Raman spectroscopy with meta-learning. We constructed a meta-learning framework using cassava- and wheat-adulterated sweet potato starch as the source domain for training, with potato-adulterated sweet potato starch and cassava-adulterated sweet potato vermicelli as two target domains for testing. Raman spectra showed high consistency between sweet potato vermicelli and its raw starch, laying the foundation for cross-domain detection. Testing yielded comprehensive classification accuracies of 95.33% and 98.00% for the two target domains, significantly outperforming SVM, RF, and CNN (max. 85.24%). This approach effectively identifies subtle starch variety differences in complex adulteration, providing novel food quality inspection solutions and verifying the feasibility of raw material-to-finished product cross-domain detection.

Ipomoea batatas↗

PubMed2026

SBUF-SMUF: On the path to the optimum hemofiltration technique in pediatric cardiopulmonary bypass: A randomized clinical trial.

BACKGROUND: Hemofiltration during pediatric cardiopulmonary bypass (CPB) is essential to mitigate hemodilution, inflammatory responses, and postoperative complications. Conventional ultrafiltration (CUF) is widely practiced, but novel methods such as subzero balanced ultrafiltration combined with simple modified ultrafiltration (SBUF-SMUF) may offer superior outcomes. OBJECTIVE: To compare the clinical efficacy and safety of CUF versus SBUF-SMUF in pediatric patients undergoing open-heart surgery. METHODS: In this prospective randomized, outcome-assessor-blinded clinical trial, 80 pediatric patients with congenital heart disease were allocated to either CUF (n = 40) or SBUF-SMUF (n = 40) during CPB. Baseline demographics, intraoperative characteristics, fluid balance, blood product utilization, and postoperative outcomes were assessed. Statistical analysis was conducted using independent t-tests, Chi-square tests, and Fisher's exact tests. Statistical significance was defined as a two-tailed p-Value of less than 0.05. RESULTS: Demographic and preoperative variables were comparable between groups. Mean fluid balance was significantly positive in the CUF group (+192.1 ± 178.8 mL) but negative in the SBUF-SMUF group (-105.0 ± 78.9 mL, p < 0.001). The SBUF-SMUF group required significantly less intraoperative PRBC (141.7 ± 70.2 vs. 261.0 ± 68.8 mL, p < 0.001) and postoperative FFP transfusion (2% vs. 10%, p = 0.020). Post-bypass hematocrit levels were higher (31.2% vs. 27.3%, p = 0.001) and extubation occurred earlier in the SBUF-SMUF group (1.05 ± 1.03 vs. 2.27 ± 2.37 days, p = 0.006). No significant differences were observed in potassium levels or incidence of acute kidney injury. CONCLUSION: The SBUF-SMUF technique is safe, effective, and superior to CUF in optimizing fluid balance, reducing blood product utilization, and facilitating earlier extubation in pediatric cardiac surgery. No additional risk of oliguria or electrolyte imbalance was observed compared to CUF. Its simplicity and reproducibility support its consideration as a standard approach in pediatric CPB.

Humans↗

PubMed2026

Skin barrier repairing and anti-aging effects evaluation of a comprehensive topical regimen incorporating niacinamide, Pro-Xylane, and panthenol after PicoWay laser: a randomized controlled study.

Pro-Xylane is a potent anti-aging ingredient; however, there is limited knowledge regarding whether a comprehensive post-procedure regimen incorporating a combination of Pro-Xylane, niacinamide, and panthenol alongside other active agents can deliver synergistic benefits for both skin barrier repair and anti-aging. This study assesses the effectiveness of the REGENMEDIC cream (anti-aging cream) and REGENMEDIC serum (anti-aging serum) in promoting skin barrier recovery and enhancing anti-aging effects following PicoWay laser treatment. A 112-day randomized controlled trial was conducted with 88 Chinese females, who were divided into two groups: the test group, using REGENMEDIC cream and Serum following PicoWay laser treatment, and the control group, using standard care regimen consisting of a standard cream. Skin barrier-repairing effects were assessed during the initial 14 days following a single use of REGENMEDIC cream, while skin elasticity, firmness, wrinkles and skin tone were evaluated over the 112-day study period after the combined use of REGENMEDIC cream and Serum. The test group exhibited lower transepidermal water loss (TEWL) and higher hydration after 14 days compared to the control group, along with a more significant reduction in skin redness. After 112-day use of REGENMEDIC cream and serum, test group showed increased skin elasticity and firmness, reduced wrinkles, and an overall improvement in skin tone and texture. Dermatologists reported excellent tolerability, with minimal adverse events. Initial application of the REGENMEDIC cream facilitated rapid skin barrier repair, while the subsequent sequential regimen incorporating the serum yielded significant long-term anti-aging benefits following PicoWay laser treatment. This study demonstrates that targeting multiple physiological pathways-specifically hydration, barrier integrity, and cellular senescence-provides a robust therapeutic option for amplifying the anti-aging outcomes of aesthetic procedures.

Humans↗

PubMed2026

Whole-exome characterization of host genetic variation in HIV-associated genes across the high-prevalence Mizo population, Northeast India.

BACKGROUND: The Mizoram state of Northeast India has one of the highest HIV prevalence rates in Asia, yet the host genetic factors influencing HIV susceptibility in this Tibeto-Burman population remain uncharacterised. METHODS: We performed whole-exome sequencing using Illumina NovaSeq 6000, mean coverage 100X on 76 HIV-negative Mizo individuals. Variants were called using GATK HaplotypeCaller v4.3 against GRCh38p14, annotated with ANNOVAR, and filtered using hard-quality thresholds (QD ≥ 2, SOR ≤ 3, MQ ≥ 40, DP ≥ 10, GQ ≥ 20). The allele frequencies were compared against gnomAD v2.1.1 population databases. Hardy-Weinberg equilibrium was assessed using the Wigginton exact test with Bonferroni correction. RESULTS: Post-quality filtering resulted in 12,011 sample-variants across 2,821 unique positions from 36 HIV-associated loci (33 protein-coding genes, 2 chemokine ligands, and 3 lncRNA targets). Of these, 784 observations (51 unique positions) were high-impact nonsynonymous or loss-of-function variants. ADAR rs2229857 (p.K384R, NM_015840) was the most frequently observed variant (Mizo carrier frequency = 0.895; 95% CI: 0.806-0.946). CXCR1 rs16858808 (p.R335C) showed the greatest population enrichment (Mizo carrier frequency = 0.197; 95% CI: 0.123-0.300; 7.65-fold carrier-frequency enrichment versus gnomAD South Asian; CADD = 15.60). Sixteen of 20 tested variants deviated from Hardy-Weinberg equilibrium after Bonferroni correction (p < 0.0025), predominantly showing excess homozygosity consistent with the endogamous Mizo population. The protective variant CCR5-Δ32 was absent in all the 76 individuals tested. CONCLUSION: This first whole-exome characterization of HIV host genes in the Mizo population identifies CXCR1 rs16858808 as the most population-enriched functional variant and reveals a pervasive endogamy signature. These findings provide a population-specific genetic framework for future HIV susceptibility studies and ART pharmacogenomics research.

Humans↗

PubMed2026

Molecular Landscape and Advanced Diagnostic Technologies for BRAF Mutations in Cancer: From Quantitative PCR and ddPCR to CRISPR-Based Platforms.

BRAF mutations are key oncogenic alterations across multiple malignancies, including melanoma, thyroid carcinoma, colorectal cancer, non-small cell lung cancer, glioma, and hairy cell leukemia. The most prevalent variant, BRAF-V600E, induces constitutive activation of the MAPK signaling pathway, promoting tumor progression and influencing therapeutic responsiveness. Accurate detection of BRAF alterations is therefore essential for molecular classification, prognostic assessment, treatment selection, and resistance surveillance. This review summarizes the molecular heterogeneity of BRAF mutations and critically evaluates current diagnostic methodologies. Conventional approaches such as allele-specific PCR and Sanger sequencing are compared with advanced quantitative platforms, including high-resolution melting analysis, droplet digital PCR, and next-generation sequencing, with emphasis on analytical sensitivity, mutation coverage, and clinical applicability. Emerging technologies such as CRISPR-based assays, rolling circle amplification systems, and nanoparticle-based biosensors and point-of-care diagnostic platforms are also discussed for their potential to enhance ultra-sensitive detection, particularly in liquid biopsy settings. These emerging tools are highlighted for their potential to enable ultra-sensitive, rapid, and decentralized mutation detection, particularly in liquid biopsy settings. Key challenges, including intratumoral heterogeneity, low allele-frequency variants, FFPE-associated artifacts, and clonal evolution under therapeutic pressure, are examined within a translational framework. In addition, we examine critical barriers to clinical implementation, including standardization, cost, and global accessibility of molecular diagnostics, and outline potential solutions through scalable technologies and decentralized testing strategies. We propose that optimal BRAF testing requires a mutation subclass-informed and clinically integrated strategy combining comprehensive baseline profiling with longitudinal molecular monitoring. Future diagnostic paradigms will likely integrate multi-omics data and artificial intelligence (AI)-assisted interpretation to refine precision oncology implementation. Looking forward, we propose that optimal BRAF testing will require integration of multi-omics profiling with AI-assisted interpretation, enabling automated variant classification, real-time clinical decision support, and improved prediction of therapeutic response and resistance.

Humans↗

PubMed2026

Contact tracing for hepatitis C: perspectives of people with experience of substance use and hepatitis C on intervention acceptability.

INTRODUCTION: Chronic hepatitis C (HCV) is a major cause of cirrhosis and hepatocellular carcinoma. In the UK, the principal risk factor for HCV is injecting drug use. The introduction of direct acting anti-virals (DAA's) have transformed HCV care, with cure rates of over 95%. However, HCV is often asymptomatic, and reinfection is a concern. Modelling and real-life studies demonstrate the potential effectiveness of a contact tracing approach for finding people who have acquired HCV through injecting drug use. However, it is not used routinely in the UK. This qualitative study was undertaken to assess the acceptability of a contact tracing approach to identify people who have injected drugs with an index patient recently diagnosed with HCV. METHODS: Twelve people with lived or living experience of injecting drug use and an HCV diagnosis were interviewed using semi-structured interview topic guides. Participants were purposefully selected according to the inclusion criteria and to ensure there was an even spread of male and female participants. Sekhon's Theoretical Framework of Acceptability, incorporating seven components (affective attitude, burden, ethicality, intervention coherence, opportunity cost, perceived effectiveness, and self-efficacy) was used to analyse data from interview transcripts. RESULTS: A sample of 12 people who inject drugs in the UK indicated that a contact tracing approach was acceptable across two components of Sekhon's acceptability framework: affective attitude and ethicality. Participants broadly found the idea of tracing people who may be at risk of contracting HCV acceptable, and the approach aligned with their value systems. A contact tracing approach would help alleviate concerns about putting other people's lives at risk through HCV transmission and was seen as a 'sensible' way of finding people at risk. However, there were caveats to this acceptability. Contact tracing approaches delivered by mainstream health, or governmental organisations increased burden, opportunity costs and perceived effectiveness of a contact tracing approach for HCV, particularly within contexts of exclusion and criminalisation of people who inject drugs. Burden and opportunity costs were also affected by individual experiences and risks of violence, sexual violence and abuse. There was a lack of knowledge of contact tracing approaches amongst respondents, leading to a lack of intervention coherence and misunderstandings of what contact tracing was and how it would work. Trusted relationships with NGOs and HCV specialist nurses reduced burden and increased confidence and ability (self-efficacy) to engage with a contact tracing approach. CONCLUSION: People who inject drugs broadly perceive contact tracing as an acceptable method of finding people who are at risk of HCV. However, this acceptability is based on specific modes of delivery through trusted organisations. Findings further highlight the importance of naming and describing contact tracing approaches appropriately, as well as assessing and mitigating against potential risk to index patients, to increase self-efficacy and capacity to engage. Considering these findings, the potential for expanding existing contact tracing approaches should be explored to ensure the UK reaches and maintains its elimination targets.

Humans↗

PubMed2026

Effects of Blood Flow Restriction Training at Different Levels of Arterial Occlusion Pressure on Body Composition and Athletic Performance in Youth Soccer Players: A Randomized Controlled Trial.

This study aimed to investigate the effects of low-load blood flow restriction training (BFRT) performed at different levels of arterial occlusion pressure (AOP) on body composition, maximal strength, and athletic performance in youth soccer players. Twenty-four male youth soccer players were randomly assigned to 40% AOP group, 60% AOP group, or control group. Participants in the BFRT groups performed lower-limb resistance training at 30% of one-repetition maximum (1RM) under the corresponding pressure conditions, whereas the control group trained without BFR. Training was conducted three times per week for six weeks. Body composition, back squat 1RM, countermovement jump (CMJ), T-test, and 30-m sprint performance were assessed before and after the intervention. Results showed that lower-limb muscle mass increased significantly in both the 40% AOP group (mean change = 0.55 kg, 95% CI: 0.13 to 0.97 kg, P = 0.010) and the 60% AOP group (mean change = 0.83 kg, 95% CI: 0.37 to 1.29 kg, P < 0.001), with the 60% AOP group showing significantly greater gains than the control group (between-group difference = 1.48 kg, 95% CI: 0.40 to 2.56 kg, P = 0.008). Back squat 1RM improved significantly in both the 40% AOP group (mean change = 6.50 kg, 95% CI: 3.90 to 9.10 kg, P < 0.001) and the 60% AOP group (mean change = 9.25 kg, 95% CI: 6.75 to 11.75 kg, P < 0.001), with the 60% AOP group demonstrating superior strength gains compared with the 40% AOP group (between-group difference = 2.94 kg, 95% CI: 0.20 to 5.68 kg, P = 0.048). CMJ height and T-test performance improved significantly in both the 40% AOP group (CMJ: mean change = 2.07 cm, 95% CI: 0.80 to 3.34 cm, P = 0.002; T-test: mean change = -0.23 s, 95% CI: -0.35 to -0.11 s, P = 0.001) and the 60% AOP group (CMJ: mean change = 2.65 cm, 95% CI: 1.00 to 4.30 cm, P = 0.003; T-test: mean change = -0.26 s, 95% CI: -0.38 to -0.14 s, P < 0.001), with no significant differences between the two BFRT groups (all P > 0.05). No significant changes were observed in 30-m sprint performance across groups (all P > 0.05). This study showed that six weeks of low-load (30% 1RM) blood flow restriction training performed at both 40% and 60% AOP was associated with improvements in lower-limb muscle mass, squat strength, and selected aspects of athletic performance in youth soccer players, compared with low-load training without BFR. While both pressure levels elicited comparable improvements in CMJ and agility performance, training at 60% AOP was associated with greater adaptations in lower-limb muscle mass and squat strength, with no additional benefits observed for 30-m sprint performance.

Humans↗

PubMed2026

The Impact of Baseline Negative Emotions on Postoperative Quality of Life in Adolescent Idiopathic Scoliosis Patients: A 2-Year Follow-Up Study.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that develops during puberty without a clear etiology. Beyond physical manifestations, AIS severely impacts adolescents' psychological and social well-being, leading to anxiety, depression, and low self-esteem. While advancements in surgical techniques have enhanced objective outcomes, existing studies on AIS have primarily focused on objective indices, with limited attention to the long-term impact of preoperative negative emotions on patient-reported subjective quality of life. METHODS: This was a retrospective cohort study. A total of 112 eligible AIS patients who underwent posterior spinal correction surgery between April and August 2023 were enrolled. Inclusion criteria included confirmed AIS, completion of 2-year follow-up, and informed consent; exclusion criteria included missing imaging/questionnaire data, comorbid psychiatric/neurological diseases, or prior spinal surgery. Patients were grouped using the Hospital Anxiety and Depression Scale (HADS) administered on admission. Quality of life was assessed preoperatively and 2 years postoperatively using the Scoliosis Research Society-22 (SRS-22, evaluating self-image, mental health, pain, function, treatment satisfaction) and Short Form 36 Health Survey (SF-36, assessing 8 physical and mental health dimensions). Statistical analysis was performed via SPSS, using independent t-tests, paired t-tests, Mann-Whitney U test, and chi-square test. p < 0.05 was considered significant. RESULTS: There were no significant differences in baseline characteristics (age, gender, BMI, surgical parameters, scoliosis type, preoperative/postoperative Cobb angles) between the two groups (all p > 0.05). Preoperatively, SRS-22 and SF-36 scores showed no inter-group differences (all p > 0.05). Postoperatively, the Negative Emotion Group had significantly lower scores in SRS-22 mental health (3.9 ± 0.3 vs. 4.5 ± 0.2) and treatment satisfaction (4.0 ± 0.3 vs. 4.6 ± 0.7), as well as SF-36 general health (68.6 ± 6.4 vs. 79.7 ± 13.3), role-emotional (61.3 ± 9.3 vs. 70.8 ± 9.7), and mental health (61.8 ± 14.3 vs. 68.9 ± 10.7) (all p < 0.05); no inter-group differences were observed in physical function-related dimensions. Both groups showed significant improvements in physical function-related dimensions postoperatively. The Non-Negative Emotion Group also exhibited significant improvements in SRS-22 self-image/pain and SF-36 bodily pain (all p < 0.05), while the Negative Emotion Group showed no significant improvements in these dimensions. CONCLUSIONS: Preoperative anxiety and depression do not affect the recovery of physical function in AIS patients after spinal correction surgery but significantly impede improvements in subjective quality of life dimensions, including mental health and treatment satisfaction. These findings highlight the need to integrate psychological assessment and targeted interventions into the perioperative management of AIS. Such a patient-centered approach will help optimize both physical and psychological outcomes, ultimately achieving comprehensive rehabilitation for AIS adolescents.

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

Manual, digital, and AI tumour-infiltrating lymphocyte scoring: a secondary analysis of the APHINITY randomised trial.

BACKGROUND: Stromal tumour-infiltrating lymphocytes (sTILs) are prognostic in early-stage HER2-positive breast cancer, but their role in the context of dual HER2 blockade remains undefined. We evaluated manual, digital, and artificial intelligence (AI)-based sTIL quantification, together with AI-derived spatial metrics, for prognostic and treatment-benefit stratification using tumour samples from the phase 3 APHINITY trial. METHODS: In the APHINITY trial, 4805 patients were randomly assigned to receive chemotherapy plus trastuzumab with pertuzumab or chemotherapy plus trastuzumab with placebo. Median follow-up was 74·1 months (IQR 68·3-75·4). We analysed 4262 haematoxylin and eosin-stained images using manual assessment, an automated digital approach, AI-based lymphocyte quantification (AI percentage lymphocytes), and two AI-derived spatial features (AI-TIL and immune hotspot). Interobserver reproducibility was assessed in 262 randomly chosen tumour samples scored independently by five pathologists. Multivariable Cox models were used to assess associations between TIL levels and invasive disease-free survival (primary outcome in APHINITY), distant recurrence-free interval, and overall survival. The heterogeneity of pertuzumab benefit was evaluated using subgroup analyses, subpopulation treatment effect pattern plot analyses, and nested Cox models with treatment-by-biomarker interaction terms. FINDINGS: Manual scoring showed high interobserver reproducibility (intraclass correlation coefficient 0·84 [95% CI 0·79-0·88]). Concordance between manual and automated methods was modest. AI-based scoring (AI percentage lymphocytes) reclassified 120 (11·6%) of 1035 node-positive tumours from immune-low (by manual scoring) to immune-high; this subgroup of patients showed greater separation of 5-year invasive disease-free survival curves between pertuzumab and placebo groups compared with patients whose tumours were concordantly classified as immune-low by both manual and AI-based approaches. Higher levels of TILs were associated with improved invasive disease-free survival for all sTIL measurement approaches and spatial measurements (hazard ratios [HRs] 0·41-0·93). Pertuzumab was associated with improved invasive disease-free survival at higher sTIL levels across all measurement approaches (HRs 0·36-0·48), but was not associated with higher values of spatial measures. The largest 6-year absolute improvements with pertuzumab were observed in patients with node-positive disease whose tumours scored in the highest level of immune infiltration of manual sTIL scoring (≥70·0%; mean absolute improvement 12·1 percentage points [SD 2·8]). In nested prognostic and predictive models, AI-based immune hotspot scores provided the most consistent additional information when combined with any sTIL measurement (all p<0·010). INTERPRETATION: Standardised manual sTIL scoring was reproducible, and digital and AI-based methods showed consistent prognostic stratification and potential for treatment-benefit stratification despite only modest correlation between platforms. AI spatial metrics provided complementary information beyond sTIL density and could support more scalable immune assessment. Future studies are needed to validate these approaches in independent cohorts and to clarify their clinical utility for stratifying contemporary HER2-directed therapies. FUNDING: None.

Humans↗

PubMed2026

Effects of positive psychotherapy on anxiety and quality of life in chronic Urticaria.

INTRODUCTION: Individual, social, and economic consequences including anxiety and poor quality of life are recognised to result from allergic disorders. A positive, realistic viewpoint that emphasises balance and the body is provided by positive psychotherapy. The purpose of this randomized, controlled intervention study was to investigate how counseling based on positive psychotherapy affected anxiety and quality of life. METHODS: Patients in the intervention group had eight sessions of individual counseling based on positive psychotherapy in addition to standard treatment. Other than standard care, the members of the control group received no interventions. The Dermatological Quality of Life Scale (DYQS), Urticaria Activity Score, State-Trait Anxiety Scale, and Personal Information Form were employed as data collection instruments. The study had 66 patients with Chronic Spontaneous Urticaria (CSU), 32 of whom were in the intervention group and 34 of whom were in the control group. RESULTS: The mean scores of the intervention group decreased significantly from pre-test to post-test for urticaria activity (UAS7: 28.22 ± 11.17 to 4.22 ± 4.30, p < 0.001), dermatological quality of life (DLQI: 38.63 ± 7.61 to 5.09 ± 6.19, p < 0.001), situational anxiety (61.63 ± 7.73 to 26.03 ± 4.71, p < 0.001), and trait anxiety (61.56 ± 7.90 to 25.13 ± 3.66, p < 0.001). Furthermore, post-test scores between the intervention and control groups showed statistically significant differences in favor of the intervention group in all primary outcomes, including the total UAS7 score (intervention: 4.22 ± 4.30 vs. control: 21.56 ± 11.81, p < 0.001) and the total dermatological quality of life score (intervention:5.09 ± 6.19 vs. control:30.85 ± 10.17, p < 0.001). CONCLUSIONS: Counseling based on positive psychotherapy has been shown to improve people's quality of life while lowering anxiety and urticaria symptoms. This study demonstrates how these treatments can enhance the quality of life for patients with chronic urticaria by lowering their anxiety and illness symptoms.

Humans↗

PubMed2026

Review: The African turquoise killifish as a model for the integrative physiology of vertebrate aging.

With increasing emphasis on extending healthy lifespan, aging research requires vertebrate models that permit efficient mechanistic investigation and intervention testing within practical time and cost constraints. The African turquoise killifish (Nothobranchius furzeri) has attracted growing attention because it combines an exceptionally short life cycle with an intact vertebrate physiological context and an expanding genetic toolkit, enabling relatively rapid evaluation of candidate aging interventions and mechanistic analysis across molecular, tissue, and organismal levels. This review assesses N. furzeri from an integrative-physiology perspective, focusing on germline-soma interactions, gut microbiota-host crosstalk, nutrient sensing and metabolic remodeling, temperature responsiveness, and AMPK-mTOR-linked programs. It also examines expanding genome-engineering and reporter approaches that support mechanistic and tissue-resolved investigation of these physiological processes. Building on recent reviews of killifish biology, disease modeling, regeneration, and the hallmarks of aging, we synthesize evidence across major intervention domains, distinguish established phenotypic effects from incompletely resolved mechanisms, and highlight functional endpoints, methodological standardization, and the appropriate interpretation of the model's translational relevance. Together, these features position N. furzeri as a strategically useful vertebrate platform for rapid mechanistic testing, intervention evaluation, and prioritization of aging-related pathways. Future progress will require improved methodological standardization, tissue-resolved causal studies, and question-driven cross-species validation where appropriate.

Animals↗

PubMed2026

Breastfeeding Outcomes After Radiofrequency Ablation and Surgical Excision of Fibroadenomas Compared to Natural History: A Retrospective Cohort Study.

BACKGROUND: Fibroadenomas, common benign breast tumors in women of reproductive age, are increasingly managed with minimally invasive radiofrequency ablation (RFA) or surgical excision. However, their impact on breastfeeding outcomes remains underexplored. We aimed to assess breastfeeding ability and breast tissue changes in women treated with RFA or surgery compared to those with untreated fibroadenomas. METHODS: In this retrospective cohort study, we evaluated 153 women with biopsy-confirmed fibroadenomas across five groups: RFA with prior breastfeeding (RFA-PreBF; n = 26), RFA with posttreatment breastfeeding (RFA-PostBF; n = 22), surgical excision with prior breastfeeding (Surgical-PreBF; n = 30), surgical excision with posttreatment breastfeeding (Surgical-PostBF; n = 20), and noninterventional with breastfeeding (Observation-BF; n = 55). Breastfeeding ability was assessed using a 5-point scale, and breast tissue changes were evaluated via ultrasound at 18 months, and all breastfeeding attempts occurred at a minimum of 12 months postprocedure. Fisher's exact test compared complete lactation failure rates, and a power analysis validated the study design (Fig. 1). FINDINGS: The combined RFA group (n = 48) had a higher complete lactation failure rate (14.6%) than the Observation-BF group (3.6%; Fisher's exact test, p = 0.045). Similarly, the combined surgical group (n = 50) had a higher complete lactation failure rate (16.0%) than the Observation-BF group (p = 0.034). When pooled, the combined intervention group (n = 98) showed a complete lactation failure rate of 15.3% versus 3.6% in the Observation-BF group. Residual tissue correlated with lactation impairment in the RFA group (Spearman's ρ, p < 0.05). Ultrasound showed no tumor recurrence, with cystic changes in some cases not linked to breastfeeding impairment. Power analysis confirmed 80% power to detect a medium effect size (f = 0.25, Fig. 1), supporting the study's robustness.7 RFA-PreBF (n = 26), RFA-PostBF (n = 22), Surgical-PreBF (n = 30), Surgical-PostBF (n = 20), and Observation-BF (n = 55). Breastfeeding ability was assessed using a 5-point scale, and breast tissue changes were evaluated via ultrasound at 18 months. Fisher's exact test compared complete lactation failure rates, and a power analysis validated the study design (Fig. 1).[Figure: see text]Interpretation:RFA and surgical excision are effective for fibroadenoma management but increase the risk of complete lactation failure compared to untreated fibroadenomas. Careful patient selection, precise procedural techniques, and vigilant posttreatment monitoring are essential to optimize breastfeeding outcomes, particularly for women planning future pregnancies.

Humans↗

PubMed2026

Do wound protectors reduce contamination in total shoulder arthroplasty? A randomized controlled trial.

HYPOTHESIS: Cutibacterium acnes is the most frequent cause of shoulder prosthetic joint infection with skin edges as a source of wound contamination. The primary purpose of this study was to determine if the use of a wound protector device decreases the deep wound bacterial colonization in primary shoulder arthroplasty. The secondary purpose was to assess the effect of device usage on deltopectoral muscle and cephalic vein injury. METHODS: This was a prospective, randomized controlled trial. A total of 100 patients undergoing primary total shoulder arthroplasty were enrolled and randomized into 2 groups: a wound protector group and a control group. Five patients withdrew from the study, leaving 48 patients in the wound protector group and 47 controls. Three deep wound culture swabs were taken after final arthroplasty implantation. The surgeon also graded deltoid, pectoralis major, and cephalic vein injury on a 0-3 scale based on modification to the Tscherne classification of soft tissue injury. The primary outcome of this study was positive culture results for C acnes. Secondary outcomes included total bacterial culture positivity as well as soft tissue injury grades. A subanalysis removing likely contaminant positive cultures (growth >7 days and 1 colony only) was also performed. Comparisons between groups were made using Fisher exact test for categorical outcomes and t tests and Mann-Whitney U tests for continuous variables. RESULTS: The use of a wound protector did not result in any significant differences compared with controls in the rate of positive cultures for C acnes (15% vs. 21%, P = .593) or all bacteria (15% vs. 26%, P = .304). Removing likely contaminant positive cultures did not demonstrate any significant difference in culture positivity (9% vs. 17%, P = .355, for C acnes; 9% vs. 19%, P = .231, for all bacterial species). The wound protector group had better soft tissue injury scores for the deltoid muscle (P < .001) and pectoralis muscle (P < .001). No difference in cephalic vein injury was noted between the 2 groups (P > .05). No difference in surgical time was noted. CONCLUSION: The use of a surgical wound protector device in total shoulder arthroplasty did not significantly decrease bacterial colonization of the deep wound. However, soft tissue damage to the deltoid and pectoralis muscle was less severe in the wound protector group. These findings suggest that this device reduces iatrogenic soft tissue injury.

Humans↗

PubMed2026

Financial incentives and health coaching to improve glycemic outcomes among young adults with type 1 diabetes: A factorial randomized trial (SweetGoals).

AIM: This study aimed to improve glycemic control among young adults with type 1 diabetes (T1D), an at-risk and understudied population. METHOD: N = 300 young adults with T1D recruited nationally were randomized to the factorial combination of (1) financial incentives targeting glucose checking and mealtime behaviors and (2) web health coaching focused on increasing motivation and goal setting for self-management behaviors. All received a smartphone app that accessed device data and provided weekly goal feedback. The intervention lasted 6 months. HbA1c (A1c) was assessed at baseline, +6 months, and +12 months. The mean number of glucose checking and mealtime goals met per week during the intervention were tested as mediators of intervention effects on A1c at 12 months. RESULTS: A1c was significantly reduced from baseline to +12 months across all participants. Indirect effects of both incentives and coaching on A1c reductions were significant and partially mediated by mealtime but not glucose checking goal achievement. There was no synergistic (interaction) effect of incentives and coaching. CONCLUSION: Incentives and coaching both improved critical mealtime behavior but through different strategies. These results suggest that either intervention would be suitable for future testing and dissemination, and that lower cost of incentives may favor their prioritization.

Adolescent↗