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PubMed2026

Beyond Glycaemia: Fear of Hypoglycaemia, Cognition and Functional Mobility After Advanced Hybrid Closed-Loop Therapy in Older Adults With Type 1 Diabetes: A Prespecified Secondary Analysis of a Randomised, Single-Centre Study.

BACKGROUND: Evidence on psychological, cognitive and functional outcomes of advanced diabetes technologies in older adults with long-standing type 1 diabetes (T1D) remains limited. We evaluated whether initiation of advanced hybrid closed-loop (AHCL) therapy was associated with changes in fear of hypoglycaemia, diabetes distress, psychological well-being, cognition, frailty-related measures and mobility-related function in adults aged ≥ 65 years with T1D. METHODS: This prespecified, exploratory secondary analysis was conducted within a single-centre, open-label, randomised, controlled, parallel-group trial including adults aged ≥ 65 years with long-standing T1D. Participants were randomly assigned (1:1) to initiate AHCL therapy using the MiniMed 780G system or to continue standard diabetes treatment. The secondary outcomes included WHO-5, the 17-item Diabetes Distress Scale (DDS), Hypoglycemia Fear Survey-II (HFS-II), Montreal Cognitive Assessment, Digit Symbol Substitution Test, Fried frailty phenotype and performance-based functional measures. No formal sample-size calculation was performed for these secondary outcomes. RESULTS: Thirty-one participants were randomised and 29 completed 12 months of follow-up and were included in the treatment-effect analyses. In the baseline-adjusted primary analysis, AHCL therapy was associated with a lower HFS-II score than standard treatment (adjusted mean difference -18.9; 95% CI: -32.4 to -5.4; nominal p = 0.008), although this finding did not remain statistically significant after Holm correction (adjusted p = 0.104) or in an exploratory model additionally adjusted for sex (difference -13.6; 95% CI: -32.2 to 5.0; p = 0.145). Diabetes distress, psychological well-being, global cognition and processing speed did not differ between groups. In sex-adjusted sensitivity analyses, the between-group differences remained statistically significant for 6-min walk distance (92.6 m; 95% CI: 36.8 to 148.3; p = 0.002) and Timed Up and Go performance (-2.27 s; 95% CI: -4.28 to -0.27; p = 0.028), but not for gait speed (0.27 m/s; 95% CI: -0.05 to 0.59; p = 0.099). At 12 months, 12 of 14 AHCL participants were robust and 2 were pre-frail; in the control group, 11 of 15 were robust and 4 were pre-frail. No participant was classified as frail at follow-up. CONCLUSIONS: In this small, selected cohort, AHCL therapy was associated with a nominally lower fear-of-hypoglycaemia score and better performance on selected mobility-related tests over 12 months. The fear-of-hypoglycaemia finding did not remain statistically significant after correction for multiple comparisons or additional adjustment for sex. Six-minute walk distance and Timed Up and Go remained statistically significant in the exploratory sex-adjusted sensitivity analyses, whereas the gait-speed difference did not. No measurable between-group deterioration in global cognition or processing speed was observed. These exploratory findings require confirmation in larger studies with balanced representation by sex and direct measurement of physical activity. These findings also support a person-centred clinical message: older age alone should not be regarded as a barrier to AHCL when treatment is introduced with individualised education and appropriate ongoing support.

Humans↗

PubMed2026

Remotely Supervised, Home-Based Transcranial Direct Current Stimulation for Major Depressive Disorder: Systematic Review and Meta-Analysis.

BACKGROUND: Major depressive disorder affects over 280 million people worldwide, and access to effective treatment remains limited. Transcranial direct current stimulation (tDCS) is a noninvasive option, and portable devices now allow for home-based delivery under varying degrees of remote supervision. OBJECTIVE: This study aimed to systematically review and meta-analyze the efficacy, safety, feasibility, and acceptability of home-based and remotely supervised tDCS for depressive disorders. METHODS: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 and PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses literature search extension) guidelines, we searched MEDLINE, Embase, Web of Science, the Cochrane databases, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform up to July 2025, with backward and forward citation searching. Two reviewers independently screened records, extracted data, and assessed risk of bias (version 2 of the Cochrane risk-of-bias tool for randomized trials, Newcastle-Ottawa Scale for observational studies, and Critical Appraisal Skills Programme for qualitative studies) and certainty of evidence (Grading of Recommendations Assessment, Development, and Evaluation; GRADE). RESULTS: This review included 12 distinct studies (16 reports), of which 6 (50%) were randomized sham-controlled trials forming the meta-analytic pool. Active home-based tDCS produced a small, statistically significant improvement over sham (pooled Hedges g=0.36, 95% CI 0.06-0.66; P=.03; I2=34.3%). The effect was not robust to removal of the single largest positive trial (omitting the one study from 2025: g=0.39, 95% CI -0.12 to 0.91), and trial-level results were mixed: the 2 largest trials (one unsupervised [n=210] and one self-administered [n=141]) were negative on their primary depression outcomes, whereas the largest real-time supervised trial (n=174) was positive (between-group 95% CI 0.51-4.01; P=.01). This estimate was concordant in direction with an independent peer-reviewed meta-analysis of overlapping trials, which reported a pooled Montgomery-Åsberg Depression Rating Scale reduction (weighted mean difference -2.74, 95% CI -4.19 to -1.29) and Hamilton Depression Rating Scale reduction (weighted mean difference -2.24, 95% CI -4.16 to -1.49), attenuating to nonsignificance (P>.05) in major depressive disorder without comorbid cognitive impairment. The pooled effect fell at or near the minimal clinically important difference. GRADE certainty was moderate. Adverse events were predominantly mild: one pilot study was terminated early for skin lesions, and one nonfatal suicide attempt occurred in an unsupervised trial. CONCLUSIONS: Home-based and remotely supervised tDCS produces a small, statistically significant but clinically modest antidepressant effect that is sensitive to the inclusion of the largest positive trial, with the 2 largest trials being negative. The available controlled evidence does not establish supervision intensity as a determinant of efficacy. Current data are insufficient to recommend routine clinical adoption; adequately powered trials with standardized supervision and longer follow-up are needed.

Humans↗

PubMed2026

Non-destructive prediction of lead content in oilseed rape leaves by fluorescence hyperspectral technology based on neural network.

Based on fluorescence hyperspectral imaging (FHSI), this study targeted rapid, non-destructive quantification of lead (Pb) content in oilseed rape leaves treated with varying silicon (Si) concentrations, acquiring fluorescence spectra over the 484.43-1001.61 nm wavelength range. To optimize spectral data quality, preprocessing methods (Savitzky-Golay smoothing, first derivative, detrending) were comprehensively compared. Characteristic wavelengths were then selected via interval variable iterative shrinkage, which effectively compressed data dimensionality and reduced computational load. A hybrid SE-CL1DA model, fusing a 1D convolutional neural network, a long short-term memory network and SE attention mechanism was constructed, with Bayesian optimization tuning hyperparameters to boost stability. The BO-SE-CL1DA outperformed both traditional machine learning and insufficiently optimized deep learning model (Rp2=0.9609, RMSE = 0.0377 mg/kg, RPD = 5.1736), thus enabling accurate Pb estimation, supporting Si-regulated heavy metal stress management and facilitating agricultural contamination monitoring.

Plant Leaves↗

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

Clinical Performance of Bulk-Fill Versus Incremental Composite Placement Approaches in Vital Posterior Teeth: A 24 Months Randomized Controlled Trial.

BACKGROUND: Composite resin placement technique may influence marginal integrity, polymerization stress distribution, and long-term clinical performance of posterior restorations. This randomized controlled clinical trial evaluated the 24-month clinical performance of four different placement techniques in Class I posterior composite restorations. METHODS: Fifty patients aged 20-35 years presenting with four occlusal carious lesions each were enrolled, resulting in 200 restorations. Cavities (4-5 mm depth) were prepared according to caries extension. Restorations were randomly allocated into four equal groups (n = 50) according to placement technique: stamp technique, snowplow technique, modified incremental "pizza" technique, and bulk-fill technique. All materials were applied following manufacturers' instructions. Clinical evaluation was performed at baseline and after 6, 12, and 24 months using FDI criteria. Functional (fracture/retention, marginal adaptation), esthetic (marginal staining, anatomical form), and biological (postoperative sensitivity, secondary caries) properties were assessed by two calibrated evaluators. Statistical analysis was performed at a significance level of α = 0.05. RESULTS: Thirty-eight patients with a total of 152 restorations were evaluated at the end of the 24 months in line with FDI at the end of the study with 76% recall rates. No statistically significant differences were observed among groups regarding fracture/retention or secondary caries (p > 0.05). Marginal adaptation and marginal staining demonstrated minor deterioration over time across all groups, with statistically significant intergroup differences found (p < 0.05). Postoperative sensitivity was minimal and transient in all groups with no significant difference (p = 0.181). CONCLUSIONS: Within the limitations of this 24-month follow-up, the four placement techniques demonstrated comparable clinical performance in Class I posterior composite restorations. Selection of technique may therefore be guided by clinical preference and procedural efficiency rather than differences in short-term clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07415317.

Humans↗

PubMed2026

Exploring Implementation of Cantonese Radio Broadcasting as a Mental Health Promotion Initiative for Linguistically Isolated Immigrants.

Digital-first public health efforts often miss linguistically isolated immigrant communities because of structural barriers and stigma. Ethnic legacy media can reach these groups, but keeping programs funded and operational over the long term is frequently difficult. This Practice Note examines a Cantonese-language radio health program in "Los Angeles County" that ran 128 live broadcasts across a full 12-year Chinese zodiac cycle. Instead of a top-down clinical model, the show endured by acting as an informal community navigation hub. We examine two recurring administrative frictions: anonymous off-air calls about urgent economic needs (e.g., hotel job referrals) and on-air audience corrections of mispronounced medical terms. We argue these interactions should be seen not as disruptions but as measurable indicators of structural trust that sustain programs. We offer practical guidance for recruiting undergraduates to expand reach via ethnic print newspapers, using peer-recovery milestones to amplify impact. The note concludes with a pragmatic blueprint for health educators to manage professional boundaries, preserve commercial-clinical separation, and uphold cultural safety in isolated communities.

Chinese American health↗

PubMed2026

Hot vs cold knife for endoscopic ablation of posterior urethral valves: a systematic review by the EAU-YAU paediatric urology working group.

INTRODUCTION: Posterior urethral valves (PUV) are the most frequent cause of congenital lower urinary tract obstruction in males. Despite early surgical ablation, up to 22% of patients develop chronic kidney disease and 11% progress to end-stage renal disease. Multiple endoscopic modalities have been described for valve ablation but the optimal technique remains uncertain. This systematic review aims to determine whether cold or hot knife ablation provides superior effectiveness for primary endoscopic treatment of PUV in a single surgical session. MATERIAL AND METHODS: A systematic search of PubMed and Embase databases was conducted to identify studies comparing cold and hot knife techniques for endoscopic ablation of PUV in children, covering all publications up to December 2025. The review was performed in accordance with PRISMA 2020 guidelines and was prospectively registered in PROSPERO (ID CRD420251180556). Original studies including patients <18 years who underwent primary valve ablation with postoperative cystoscopy or VCUG and ≥6 months of follow-up were included. Quality assessment was done using RoB 2.0 for randomized trials and MINORS for observational studies. RESULTS: A total of 1581 studies were identified, of which 26 met the inclusion criteria, comprising one randomized controlled trial, five prospective, and 20 retrospective studies constituting a sum of 1725 paediatric patients. The overall methodological quality of included studies was moderate, with marked heterogeneity in design, follow-up duration, and outcome reporting, limiting direct comparisons across series. Thus statistical analysis was not possible. Of these, 829 (48.1%) underwent cold valve ablation and 896 (51.9%) underwent hot ablation techniques. Within the cold group, most patients were treated with a cold knife (80.2%), followed by balloon dilatation (7%), the Mohan valvotome (6.5%), cold hook (5%), and, rarely, a modified venous valvulotome (1.3%). Among hot techniques, 32.8% of procedures were performed by electro-fulguration with a resectoscope, 29.4% using a Bugbee electrode, 23.8% with a hook electrode and 14% with laser-based systems. Follow-up ranged from 6 months to 22 years across studies. Single-session success rates for valve ablation ranged from 22% to 100% in the cold resection group and from 71.4% to 100% in the hot resection group. Reintervention for residual valves was reported in 0%-78% of cold cases and in 0%-28.6% of hot resections. Urethral stricture rates ranged from 0% to 11.1% after cold incision and from 0% to 23.8% after hot techniques. Reporting of postoperative outcomes such as urinary tract infection, incontinence, bladder dysfunction, vesicoureteral reflux (VUR) resolution, hydronephrosis improvement, and renal function varied widely among studies and was assessed using different methodologies. CONCLUSIONS: Both cold and hot ablation techniques for PUV achieved high single-session success rates and low complication rates. Cold resection appeared slightly safer, although this finding should be interpreted cautiously given the heterogeneity and observational nature of the available data.

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

Furanic compounds in different coffee extraction systems: Analysis of the main influencing factors and correlation with acrylamide.

This study investigates how different coffee types representative of distinct roast profiles and brewing methods jointly affect the occurrence of furanic compounds and acrylamide in brewed coffee. Coffees were prepared using eight extraction methods (AeroPress, Clever, Chemex, French Press, Moka, Pure Brew, Turkish and V60). Five furanic compounds (furfural, furfuryl acetate, 5-methylfurfural, furfuryl alcohol and 5-hydroxymethylfurfural) were quantified in coffee powders and brews by HS-SPME-GC-MS, while acrylamide was determined by UHPLC-MS/MS. Moka and Turkish brews consistently exhibited the highest concentrations of furanic compounds, whereas paper-filtered pour-over methods (V60 and Chemex) showed the lowest levels. Pearson correlation analysis revealed coffee-dependent relationships between furanic compounds, acrylamide and extraction parameters with the strongest associations observed in dark-roasted coffee, reflecting advanced Maillard reaction chemistry. Overall, these results demonstrate that contaminant levels arise from the combined effects of intrinsic coffee chemistry and brewing mechanics and support targeted mitigation strategies: such as roast selection and brewing method optimization.

Acrylamide↗

PubMed2026

Survival by Race and Ethnicity in Children and Adolescents/Young Adults With Relapsed/Refractory Hodgkin Lymphoma: A Pooled Analysis of Children's Oncology Group Trials.

PURPOSE: Despite 5-year survival rates of over 90% among children and adolescents/young adults (CAYAs) with classic Hodgkin lymphoma (cHL), 15%-20% relapse after frontline therapy. Prior analysis of frontline Children's Oncology Group (COG) clinical trials demonstrated that, despite similar rates of relapse, non-Hispanic Black (NHB) and Hispanic (vs. non-Hispanic White [NHW]) patients experienced higher post-relapse mortality. It is unknown whether post-relapse disparities persist when second-line treatment is delivered in a cooperative group trial setting. We examined overall survival (OS) by race and ethnicity in CAYAs enrolled in COG trials for relapsed/refractory (r/r) cHL. METHODS: A pooled analysis of individual-level data from CAYAs (≤ 29 years) receiving therapy for r/r cHL on COG clinical trials (2001-2016) was conducted. The Kaplan-Meier method estimated 3-year OS by racial and ethnic groups. Cox regression models examined associations of race and ethnicity and OS, adjusted for age, insurance, first versus ≥2 relapse, and time from initial diagnosis to relapse trial enrollment. RESULTS: Among 175 CAYAs treated on COG trials for r/r cHL (5.7% Asian or Pacific Islander, 14.9% Hispanic, 14.3% NHB, 61.7% NHW, 3.4% other), at median follow-up of 4.9 years, 3-year OS was 82.1% (95% confidence interval [CI], 75.3%-87.1%) and did not differ by race and ethnicity (p = 0.36). In multivariable analyses, shorter time from diagnosis to relapse trial enrollment (p = 0.01) and ≥2 relapses (vs. first, p = 0.004) conferred worse OS, with no significant effect of race and ethnicity (p = 0.43). CONCLUSION: Post-relapse survival did not differ by race and ethnicity among CAYAs enrolled in COG trials for r/r cHL, suggesting access to clinical trials may mitigate OS disparities.

Humans↗

PubMed2026

Astigmatic vector outcomes after FS-LASIK versus SMILE for high myopic astigmatism: a single-center retrospective comparative cohort study without cyclotorsion compensation.

PURPOSE: To compare astigmatic correction vector outcomes between femtosecond laser-assisted in situ keratomileusis (FS-LASIK) and small-incision lenticule extraction (SMILE, also termed Keratorefractive Lenticule Extraction, KLEx) without intraoperative cyclotorsion compensation in patients with high myopic astigmatism (- 2.00 to - 3.75 D), and to clarify procedure-specific correction tendencies under this non-standardized alignment protocol. METHODS: This single-center retrospective comparative cohort study enrolled 155 eyes (one eye randomly selected per patient) that underwent FS-LASIK (80 eyes) or SMILE/KLEx (75 eyes) for high myopic astigmatism correction from January 2023 to July 2024 in Beijing Fenglian Jiayue Lige Clinic. Intraoperative cyclotorsion compensation was intentionally disabled to isolate inherent procedural astigmatism correction characteristics. Standardized Alpins vectorial analysis was performed at 3 months and 12 months postoperatively. PRIMARY ENDPOINT: 12-month Alpins correction index (CI). Multivariable propensity score adjustment was applied to mitigate confounding by clinical treatment selection bias. Statistical multiplicity control was implemented for secondary vector and visual outcomes. RESULTS: Baseline demographic, refractive, corneal and ocular biometric parameters were balanced between groups after propensity matching. No statistically significant intergroup differences were detected in uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), residual cylinder, safety index or efficacy index at 3 and 12 months (all P > 0.05). Under the non-cyclotorsion-compensated protocol, significant intergroup differences were identified in the magnitude of surgically induced astigmatism (SIA), correction index (CI), and magnitude error (ME) at both follow-up timepoints (all P < 0.0001). Target induced astigmatism (TIA), difference vector (DV), index of success (IOS), and angle error (AE) magnitudes were comparable between groups (all P > 0.05). The vector mean axis of DV differed significantly between groups at 3 and 12 months (Watson-Williams circular test, all P < 0.0001). No reoperations were documented in clinic medical records for either cohort. No standardized dry eye questionnaires, tear film testing or corneal nerve density metrics were collected to quantify dry eye adverse events; only unstructured clinical notes were reviewed for complication screening. CONCLUSIONS: Under surgical alignment without cyclotorsion compensation, FS-LASIK and SMILE/KLEx both yielded acceptable visual and refractive safety/efficacy for high myopic astigmatism (- 2.00 to - 3.75 D) at 1-year follow-up, but demonstrated divergent astigmatism correction tendencies: FS-LASIK exhibited relative astigmatism overcorrection (vector mean DV: - 0.35 ± 0.43 D × 91°, CI > 1), while SMILE/KLEx showed relative undercorrection (vector mean DV: - 0.21 ± 0.53 D × 12°, CI < 1). These correction biases are specific to the study's manual limbal alignment protocol without cyclotorsion tracking and cannot be generalized to modern optimized surgical platforms equipped with automated cyclotorsion compensation. Residual refractive errors across both groups are likely multifactorial, including differential corneal stromal healing responses, divergent femtosecond/excimer laser tissue modification mechanisms, and uncorrected intraoperative ocular cyclotorsion.

Humans↗

PubMed2026

Restrictive vs Liberal Transfusion Strategy in Traumatic Brain Injury: A Secondary Analysis of the TRAIN Trial.

IMPORTANCE: Anemia is a prevalent condition among patients with traumatic brain injury (TBI); however, the optimal hemoglobin (Hb) threshold to initiate red blood cell transfusion (RBCT) is not well defined. OBJECTIVE: To assess which of 2 different Hb thresholds for guiding RBCT in patients with anemia and TBI is associated with a more favorable neurological outcome. DESIGN, SETTING, AND PARTICIPANTS: This was a preplanned secondary analysis of the Transfusion Strategies in Acute Brain Injured Patients multicentric randomized clinical trial, conducted in 72 intensive care units across 22 countries between September 1, 2017, and December 31, 2022. Follow-up was completed June 30, 2023. Only patients with TBI were included in the present analysis, conducted from February to May 2025. INTERVENTIONS: Liberal (transfusion at Hb <9 g/dL [to convert to g/L, multiply by 10.0]) vs restrictive (transfusion at Hb <7 g/dL) RBCT strategy over a maximum of 28 days. MAIN OUTCOME AND MEASURES: The primary outcome was the occurrence of unfavorable neurological outcome, defined as a Glasgow Outcome Scale Extended score of 1 to 5 (overall range, 1-8, with higher scores indicating more favorable outcome) at 180 days. In addition, 14 prespecified serious adverse events, including infection and cerebral ischemia, were assessed. Data were analyzed using both the intention-to-treat and per-protocol principles. RESULTS: Of 486 patients who presented with TBI (mean [SD] age, 46.8 [17.6] years; 347 [71.4%] male), 475 were included in the primary outcome analysis: 236 were randomized to the liberal transfusion strategy group and 239 to the restrictive transfusion strategy group. Both groups had similar baseline characteristics. In total, 534 RBCTs were administered in the liberal transfusion strategy group, compared with 246 RBCTs in the restrictive group. At 180 days after randomization, 138 patients (58.5%) in the liberal group had unfavorable neurological outcome compared with 161 patients (67.4%) in the restrictive group (relative risk [RR], 0.86 [95% CI, 0.75-1.00]; P = .047; fragility index = 1). There were no significant differences in the occurrence of secondary outcomes (eg, 28-day mortality: 42 of 240 [17.5%] vs 51 of 244 [20.9%]; RR, 0.84 [95% CI, 0.58-1.21]; P = .34) or serious adverse events (eg, RR, 1.13 [95% CI, 0.88-1.43]; P = .34 for infection and RR, 0.87 [95% CI, 0.40-1.90]; P = .72 for cerebral ischemia). After adjustment for several confounders, being randomized to the liberal group was associated with a lower observed probability of unfavorable neurological outcome (odds ratio, 0.60 [95% CI, 0.38-0.94]; P = .03). CONCLUSIONS AND RELEVANCE: In this secondary analysis of a multicenter randomized clinical trial, a liberal RBCT strategy was associated with a lower risk than a restrictive RBCT strategy of unfavorable neurological outcome at 180 days among patients with TBI. These findings should be interpreted with caution in light of the inherent uncertainty of the estimate. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02968654.

Humans↗

PubMed2026

Long-term (>7-year) parental consumption of genetically modified maize (Cry1Ab/Cry2Aj and EPSPS) induces no adverse sperm DNA methylation alterations across two generations of cynomolgus monkeys.

This study assessed the long-term safety of genetically modified (GM) maize from a male reproductive perspective, using a non-human primate model. We analyzed the sperm DNA methylation profiles in cynomolgus monkeys fed GM maize, non-GM parental maize, or a conventional diet over two generations (F0/F1). Whole-genome bisulfite sequencing (WGBS) revealed no significant differences in global methylation levels among groups. The identified differentially methylated regions (DMRs) were short, enriched in non-regulatory genomic areas, and did not cluster after treatment. Functional enrichment analysis showed that DMR-associated genes were consistently involved in the same core biological pathways (e.g., mTOR and Wnt signaling) across all dietary comparisons. These findings indicate that GM maize consumption did not induce specific adverse epigenetic alterations in sperm, with the observed changes reflecting common physiological adaptations to dietary variations rather than GM-related effects.

Animals↗

PubMed2026

The present and future of nonviral delivery-based genome editing for hereditary hearing loss.

PURPOSE OF REVIEW: This review summarizes nonviral genome-editing delivery platforms for hereditary hearing loss, focusing on lipid nanoparticles (LNPs) and engineered virus-like particles (eVLPs), and discusses their advantages over adeno-associated virus-based delivery, as well as the barriers to clinical translation. RECENT FINDINGS: Recent advances have established LNPs as a clinically advanced nonviral platform, although challenges related to inner ear biodistribution, cell type specificity, endosomal escape, and immunogenicity remain to be addressed. In parallel, eVLPs have undergone substantial technical evolution, progressing from early low efficiency systems to advanced base editor- and prime editor-eVLP architectures that enhance cargo loading and editing efficiency. Extracellular vesicle-based genome editing has also emerged as an additional platform, although issues related to reproducibility, loading efficiency, and scalability remain major hurdles. SUMMARY: Nonviral genome editing platforms expand the therapeutic toolkit for hereditary hearing loss by enabling transient delivery of genome editors with potential safety advantages. Future efforts should focus on characterizing biodistribution and immunogenicity, refining cell type-specific tropism, and establishing scalable manufacturing processes to enable successful clinical translation.

Humans↗

PubMed2026

Machine learning-ready genomic biomarkers: ATF3 polymorphisms predict postoperative analgesic demand through AI-compatible phenotyping.

PURPOSE: To determine whether ATF3 polymorphisms can serve as genetic biomarkers for machine learning-based precision analgesia by establishing a genotype-phenotype association suitable for predictive modeling of postoperative opioid requirements. METHODS: In a prospective cohort of 167 adults undergoing abdominal surgery, ATF3 SNPs rs3122721 and rs3125293 were genotyped. A structured dataset architecture was developed to represent genetic profiles as input features for supervised learning models, enabling translational analysis of genotype‑dependent opioid consumption over 72 h. RESULTS: Patients with homozygous genotypes of the ATF3 SNPs had significantly higher opioid requirements than non‑carriers, despite reporting similar subjective pain scores. This consistent genotype‑dependent pattern provided a clinically relevant phenotype suitable for integration into predictive algorithms. CONCLUSION: ATF3 genotyping offers a promising biomarker for computationally informed precision analgesia. By linking genomic variability to clinically meaningful outcomes within a structured clinical and genomic framework, this approach supports the future development of risk-stratified clinical decision-support systems to optimize postoperative pain management.Trial registration ChiCTR1900021991, registered 30 April 2019. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at https://doi.org/10.1007/s13755-026-00480-9.

ATF3↗

PubMed2026

Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus.

BACKGROUND: Magnesium sulphate is a common therapy in perinatal care. Its benefits when given to women at risk of preterm birth for fetal neuroprotection (prevention of cerebral palsy for children) were shown in a 2009 Cochrane review. Internationally, use of magnesium sulphate for preterm cerebral palsy prevention is now recommended practice. As new randomised controlled trials (RCTs) and longer-term follow-up of prior RCTs have since been conducted, this review updates the previously published version. OBJECTIVES: To assess the effectiveness and safety of magnesium sulphate as a fetal neuroprotective agent when given to women considered to be at risk of preterm birth. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 17 March 2023, as well as reference lists of retrieved studies. SELECTION CRITERIA: We included RCTs and cluster-RCTs of women at risk of preterm birth that assessed prenatal magnesium sulphate for fetal neuroprotection compared with placebo or no treatment. All methods of administration (intravenous, intramuscular, and oral) were eligible. We did not include studies where magnesium sulphate was used with the primary aim of preterm labour tocolysis, or the prevention and/or treatment of eclampsia. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed RCTs for inclusion, extracted data, and assessed risk of bias and trustworthiness. Dichotomous data were presented as summary risk ratios (RR) with 95% confidence intervals (CI), and continuous data were presented as mean differences with 95% CI. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included six RCTs (5917 women and their 6759 fetuses alive at randomisation). All RCTs were conducted in high-income countries. The RCTs compared magnesium sulphate with placebo in women at risk of preterm birth at less than 34 weeks' gestation; however, treatment regimens and inclusion/exclusion criteria varied. Though the RCTs were at an overall low risk of bias, the certainty of evidence ranged from high to very low, due to concerns regarding study limitations, imprecision, and inconsistency. Primary outcomes for infants/children: Up to two years' corrected age, magnesium sulphate compared with placebo reduced cerebral palsy (RR 0.71, 95% CI 0.57 to 0.89; 6 RCTs, 6107 children; number needed to treat for additional beneficial outcome (NNTB) 60, 95% CI 41 to 158) and death or cerebral palsy (RR 0.87, 95% CI 0.77 to 0.98; 6 RCTs, 6481 children; NNTB 56, 95% CI 32 to 363) (both high-certainty evidence). Magnesium sulphate probably resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.96, 95% CI 0.82 to 1.13; 6 RCTs, 6759 children); major neurodevelopmental disability (RR 1.09, 95% CI 0.83 to 1.44; 1 RCT, 987 children); or death or major neurodevelopmental disability (RR 0.95, 95% CI 0.85 to 1.07; 3 RCTs, 4279 children) (all moderate-certainty evidence). At early school age, magnesium sulphate may have resulted in little to no difference in death (fetal, neonatal, or later) (RR 0.82, 95% CI 0.66 to 1.02; 2 RCTs, 1758 children); cerebral palsy (RR 0.99, 95% CI 0.69 to 1.41; 2 RCTs, 1038 children); death or cerebral palsy (RR 0.90, 95% CI 0.67 to 1.20; 1 RCT, 503 children); and death or major neurodevelopmental disability (RR 0.81, 95% CI 0.59 to 1.12; 1 RCT, 503 children) (all low-certainty evidence). Magnesium sulphate may also have resulted in little to no difference in major neurodevelopmental disability, but the evidence is very uncertain (average RR 0.92, 95% CI 0.53 to 1.62; 2 RCTs, 940 children; very low-certainty evidence). Secondary outcomes for infants/children: Magnesium sulphate probably resulted in little to no difference in severe intraventricular haemorrhage (grade 3 or 4) (RR 0.81, 95% CI 0.64 to 1.04; 6 RCTs, 6542 infants; moderate-certainty evidence) and may have resulted in little to no difference in chronic lung disease/bronchopulmonary dysplasia (average RR 0.92, 95% CI 0.77 to 1.10; 5 RCTs, 6689 infants; low-certainty evidence). Primary outcomes for women: Magnesium sulphate may have resulted in little or no difference in severe maternal outcomes potentially related to treatment (death, cardiac arrest, respiratory arrest) (RR 0.32, 95% CI 0.01 to 7.92; 4 RCTs, 5300 women; low-certainty evidence). However, magnesium sulphate probably increased maternal adverse effects severe enough to stop treatment (average RR 3.21, 95% CI 1.88 to 5.48; 3 RCTs, 4736 women; moderate-certainty evidence). Secondary outcomes for women: Magnesium sulphate probably resulted in little to no difference in caesarean section (RR 0.96, 95% CI 0.91 to 1.02; 5 RCTs, 5861 women) and postpartum haemorrhage (RR 0.94, 95% CI 0.80 to 1.09; 2 RCTs, 2495 women) (both moderate-certainty evidence). Breastfeeding at hospital discharge and women's views of treatment were not reported. AUTHORS' CONCLUSIONS: The currently available evidence indicates that magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus, compared with placebo, reduces cerebral palsy, and death or cerebral palsy, in children up to two years' corrected age. Magnesium sulphate may result in little to no difference in outcomes in children at school age. While magnesium sulphate may result in little to no difference in severe maternal outcomes (death, cardiac arrest, respiratory arrest), it probably increases maternal adverse effects severe enough to stop treatment. Further research is needed on the longer-term benefits and harms for children, into adolescence and adulthood. Additional studies to determine variation in effects by characteristics of women treated and magnesium sulphate regimens used, along with the generalisability of findings to low- and middle-income countries, should be considered.

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PubMed2026

Transcranial Magnetic Stimulation for Patients with Exposure Therapy Resistant Obsessive-Compulsive Disorder (TETRO): Study Protocol for a Multicenter Randomized Controlled Trial.

BACKGROUND: Obsessive-compulsive disorder (OCD) is a disabling mental disorder, characterized by obsessions, compulsions, and substantial morbidity. Approximately 50% of adults with OCD fail to achieve satisfactory outcomes from first-line treatments, such as exposure therapy with response prevention (ERP), with or without medication. This leads to chronic social, educational, and occupational impairment. While invasive procedures such as deep brain stimulation are available for severe, treatment-refractory cases, a need remains for less invasive alternatives. Repetitive transcranial magnetic stimulation (rTMS), a noninvasive intervention, shows promise in reducing OCD symptoms. Unlike in depression, rTMS is not yet reimbursed for OCD in the Dutch healthcare system. OBJECTIVE: This study examines the efficacy and cost-effectiveness of low-frequency (1Hz) rTMS targeting the presupplementary motor area (pre-SMA) compared to sham rTMS as an adjuvant treatment to ERP in adults with OCD with inadequate response to first-line treatment. METHODS: A total of 250 adults with OCD will be enrolled in this multicenter randomized controlled trial. Participants will be randomly assigned to ERP combined with either active or sham 1Hz rTMS over the pre-SMA. Treatment is administered 4 times weekly for at least 5 weeks (20 rTMS-ERP sessions), with optional extension of 1 to 2 weeks, up to 28 rTMS-ERP sessions. Clinical assessments occur at baseline, weekly during treatment, posttreatment, and at 3, 6, and 12 months follow-up. Participants undergo pre- and posttreatment (functional) (MRI) scans, including a symptom provocation task. Blood sampling takes place pre- and posttreatment and at 3-month follow-up. The primary outcome is OCD severity at posttreatment, as measured by the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS). Secondary outcomes include functional improvement, quality of life, and societal costs. Pretreatment symptom profiles, genotype, and brain network topology will be analyzed as predictors of response and relapse risk. Pre-to-post treatment change in blood-based and magnetic resonance (MR)-based neuroplasticity markers will help explore differential mechanisms between ERP alone and combined rTMS-ERP. We expect that the verum rTMS protocol will be cost-effective compared to sham-rTMS. RESULTS: Recruitment started in April 2022, and as of February 2026, 201 participants have been enrolled. Posttreatment assessments are projected to be completed in December 2026, with final one-year follow-up evaluations anticipated by the end of 2027. CONCLUSIONS: To our knowledge, this study is the first adequately powered randomized controlled trial examining efficacy, cost-effectiveness, and mechanism of action of rTMS for OCD as adjuvant therapy to ERP. In case of efficacy and/or cost-effectiveness, it will pave the way for rTMS as insured health care for adults with OCD in the Netherlands, and possibly other European countries. Furthermore, this trial will provide insight into the mechanisms of treatment response to intensive ERP, with and without adjunctive rTMS, as well as potential side effects, individual variability, and long-term outcomes in adults with OCD.

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PubMed2026

Prevalence of Slowly Expanding Lesions in Patients With Multiple Sclerosis: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Chronic active lesions (CALs) reflect chronic inflammation in multiple sclerosis (MS). Slowly expanding lesions (SELs) are CALs identified on conventional MRI by linear, concentric expansion over time, while paramagnetic rim lesions (PRLs) are CALs characterized by a paramagnetic rim on susceptibility-sensitive MRI. However, the prevalence of SELs and their overlap with PRLs remain unclear. The aims of this study were to (1) estimate the proportion of SELs among all T2 lesions and the proportion of patients with at least 1 SEL and (2) assess the proportion of SELs overlapping with PRLs. METHODS: We systematically searched PubMed, Scopus, Web of Science, and Embase on February 1, 2026, for studies evaluating SELs in MS. At least 2 authors independently assessed study eligibility. Primary outcomes were the pooled proportion of SELs among T2 lesions and the proportion of patients with at least 1 SEL. We estimated mean per-patient volumes of SELs and total T2 lesions and the proportion of SELs overlapping with PRLs. Random-effects generalized linear mixed-effects models and inverse-variance methods were used, with between-study heterogeneity assessed using τ2 and I2 and robustness using sensitivity analyses. Univariable meta-regression explored heterogeneity. PROSPERO: CRD42024603778. RESULTS: Of 5,980 records, 20 studies comprising 4,786 patients with MS were included (mean age: 43.6 ± 6.3 years; 63.7% female). Sample sizes varied by outcome. SELs accounted for 14% (95% CI 10-21) of all T2 lesions, and 78% (67-85) of patients had at least 1 SEL. After sensitivity analysis, per-patient mean volumes were 1.42 mL (0.79-2.06) for SELs and 10.6 mL (8.53-12.67) for total T2 lesions. In total, 11% (6-20) of SELs overlapped with PRLs. In subgroup analyses, proportions of SELs were similar in relapsing-remitting and progressive MS (15%), but the proportion of patients with at least 1 SEL was higher in progressive MS. Between-study heterogeneity was high across analyses with no significant sources identified. DISCUSSION: Although SELs represent a minority of T2 lesions, most patients have at least 1 SEL and a subset overlaps with PRLs, suggesting a partial correspondence between these 2 imaging markers of chronic inflammatory activity. Limitations include possible publication bias, high unexplained heterogeneity, differences in SEL identification methods, and differences in MRI time point number/timing.

Humans↗