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PubMed2026

Norgestrel drives mitochondrial collapse and plasma membrane impairment in Pacific oyster (Crassostrea gigas) sperm by triggering premature acrosome reaction.

The toxic mechanisms of norgestrel (NGT), an emerging marine pollutant, on the sperm from externally fertilized invertebrates remain elusive. This study employed an integrated physiological and multi-omics framework to elucidate how NGT (10 and 1000 ng/L) disrupts acrosome reaction (AR) signaling machinery, thereby impairing the functional integrity of Pacific oyster (Crassostrea gigas, also known as Magallana gigas) sperm. Exposure to NGT triggered a significant, dose-dependent premature AR, characterized by elevated acrosin activity and a loss of acrosomal integrity. Multi-omics integration supports a model in which this premature exocytosis is linked to signaling disturbances, including disruption of calcium signaling and reduced transcript abundance of calmodulin (CaM) and the primary recognition protein zonadhesin (Zan). This signaling interference induced an premature AR, subsequently driving a cascade of bioenergetic and structural failures. At the mitochondrial level, NGT induced abnormal mitochondrial permeability transition pore (mPTP) opening and elevated the transcript levels of antioxidant defense genes (e.g., peroxiredoxin-5, PRDX5). These alterations indicate the occurrence of mitochondrial collapse. Concurrently, scanning electron microscopy verified localized plasma membrane wrinkling and pore formation in sperm. In addition, NGT exposure decreased the transcript abundance of cytoskeleton-related genes, including solute carrier family 26 member 6 (SLC26A6), actin (ACT), and tubulin polymerization promoting protein family member 3 (TPPP3). These molecular changes further disrupted membrane phospholipid homeostasis, as represented by altered glycerophospholipid metabolism. At the same time, cumulative cellular stress was associated with decreased transcript abundance of cytoprotective factors (e.g., baculoviral IAP repeat-containing proteins, birc2) and changes in apoptosis-related genes consistent with activation of a caspase-8-mediated apoptotic programme. In conclusion, NGT, as a representative synthetic progestin, exerts reproductive toxicity by interfering with signaling mediators to induce premature AR, which subsequently exhausts metabolic energy and triggers plasma membrane impairment. These findings provide a critical mechanistic basis for the aquatic ecological risk assessment of synthetic progestins.

Animals↗

PubMed2026

A flipped classroom approach compared with low-interactive online learning for pediatric pain management knowledge and instructional motivation in nursing students: A randomized controlled study.

AIM: This study aimed to compare a flipped classroom approach with low-interactive online learning in terms of nursing students' questionnaire-assessed pediatric pain management knowledge and instructional motivation. BACKGROUND: Pain management in children is a critical and multidimensional nursing responsibility. However, limited curricular time and opportunities for applied learning may restrict nursing students' preparedness in this area. Structured and interactive instructional formats, such as the flipped classroom, may support knowledge acquisition and motivation in pediatric nursing education. METHODS: This study employed a parallel-group randomized controlled trial design with a 1:1 allocation ratio. Eighty-eight third-year prelicensure nursing students were randomized to either the flipped classroom group (n = 44) or the low-interactive online learning group (n = 44). Due to attrition (2 intervention, 2 control), analyses included 42 participants per group (n = 84 in total). Data were collected between February and July 2022 using the Pediatric Pain Management Knowledge Scale for Nursing Students and the Instructional Materials Motivation Survey. This study was prospectively registered at ClinicalTrials.gov (Identifier: NCT07129044). RESULTS: At baseline, the groups were comparable in terms of knowledge and learning motivation. Following the intervention, the flipped classroom group demonstrated greater improvements in questionnaire-assessed pediatric pain management knowledge and instructional motivation than the low-interactive online learning group. Although scores declined from post-test to the three-month follow-up, they remained above baseline in the flipped classroom group. CONCLUSIONS: Within the context of this course, the flipped classroom approach was associated with greater improvement in questionnaire-assessed pediatric pain management knowledge and instructional motivation than low-interactive online learning. The findings should be interpreted as proximal educational outcomes rather than evidence of improved clinical competence or durable long-term effectiveness. Further studies using objective performance-based outcomes and longer follow-up periods are needed.

Humans↗

PubMed2026

Improved donor-site biomechanics and functional recovery with xenogeneic acellular dermal matrix after ALT flap harvest: A prospective randomized controlled study.

BACKGROUND: Donor-site management after anterolateral thigh (ALT) flap harvest is a significant yet underaddressed concern in reconstructive surgery for oral cancer. While xenogeneic acellular dermal matrix (Xeno-ADM) is common in soft-tissue repair, its efficacy for fascia lata reconstruction at the ALT donor site remains insufficiently characterized. This study aimed to assess the efficacy of xeno-ADM in fascia lata repair, focusing on compartment pressure, inflammatory and muscle injury biomarkers, and functional recovery. METHODS: In this prospective, randomized, single-blind trial, 200 patients undergoing ALT flap reconstruction were allocated to Xeno-ADM repair (n = 100) or primary closure (n = 100). Primary endpoints included compartment pressure, inflammatory markers in drainage fluid, serum muscle injury biomarkers, and functional outcomes. RESULTS: The xeno-ADM group showed significantly lower compartment pressures throughout postoperative days (POD) 1-5. Inflammatory markers in drainage fluid (CRP on POD 3 and 5) and serum muscle injury biomarkers (creatine kinase on POD 1 and 5) were significantly lower in xeno-ADM group. Functional outcomes were superior in the Xeno-ADM group, with faster gait recovery, lower pain scores at POD 7, and better lower-limb function at the 1- and 6-month follow-ups. Drainage duration did not differ between groups. Stratified analyses revealed that the benefits of xeno-ADM were more pronounced in patients with defect width >3 cm or a body mass index ≥24 kg/m2. CONCLUSION: Xeno-ADM provides a safe and effective approach for fascia lata repair, reducing biomechanical and inflammatory burdens while enhancing functional recovery. These findings support a transition from simple structural closure toward functional donor-site reconstruction.

Humans↗

PubMed2026

Serotypic and Genomic Diversity of Vibrio anguillarum in Rainbow Trout Farms in Turkey: Implications for Vibriosis Control and Vaccine Candidate Selection.

Outbreaks of vibriosis caused by Vibrio anguillarum are a persistent constraint on rainbow trout (Oncorhynchus mykiss) aquaculture. However, information on the population structure of field strains in Turkey has been lacking. Here, we report the first systematic serotypic, proteomic, and genomic characterization of 23 V. anguillarum isolates collected over 10 years from rainbow trout farms located in six major aquaculture regions of Turkey. Serological analyses based on microagglutination, supported by ELISA characterization of hyperimmune sera, identified a clear predominance of serotype O1, whereas isolate V12 exhibited a non-agglutinating, atypical O-antigen profile. Protein profiling (SDS-PAGE) and immunoblotting showed largely conserved whole-cell protein patterns among the isolates, but distinct immunogenic bands at 14, 18, and 40 kDa were detected in isolates V18 and V21. Long-read whole-genome sequencing revealed that most Turkish isolates grouped within the global O1 clade, while V12, V25, and V28 isolates occupied more distant branches. Comparative genomics demonstrated a conserved core virulence gene set (RTX toxins, siderophore and iron-uptake systems, motility and adhesion factors, Type VI secretion system), with strain-dependent variation in accessory loci such as anguibactin and T6SS-I. Experimental infections of rainbow trout demonstrated significant differences in virulence among isolates (p < 0.05), with the V18 isolate showing high, the V15 intermediate, and the V12 low-mortality rates. By elucidating the relationship among the serotype, immunogenic protein profiles, virulence gene repertoires, and in vivo pathogenicity, this study provides a comprehensive overview of the antigenic and genomic diversity of Vibrio anguillarum isolates from Turkey. Notably, the identification of V18 and V21 as promising candidate strains for further vaccine evaluation, characterized by high virulence and unique immunogenic features, provides a scientific foundation for the development of serotype-specific vaccination strategies to mitigate vibriosis-associated losses in aquaculture.

Animals↗

PubMed2026

Data-centric, robust, and explainable multimodal deep learning for clinical decision support: A systematic review.

PURPOSE: Multimodal deep learning is increasingly proposed for clinical decision support (CDS) under a "data-centric" framing that prioritizes label quality, missing-modality robustness, distribution shift, calibration, and explainability. Prior reviews have examined multimodal medical AI, CDS, and data-centric methods separately, but none address their intersection. We mapped the modalities, fusion strategies, and data-centric and explainability techniques used in this recent literature, quantified how often each is implemented rather than merely mentioned, assessed deployment-relevant evidence (external validation, clinical-outcome measurement, equity), and formally appraised study-level risk of bias. METHODS: Following the PRISMA 2020 statement (PROSPERO CRD420261427815; registered retrospectively), we screened 150 records and included primary, clinical, multimodal studies that applied machine or deep learning to a decision-support task and reported at least one quantitative result. Two reviewers screened and extracted data with consensus adjudication. Each study was coded against pre-specified operational definitions, separating implemented or empirically evaluated techniques from those only mentioned. Study-level risk of bias was assessed with PROBAST + AI. Synthesis was narrative. RESULTS: Thirty-one studies met inclusion; 30 (97%) were published between 2024 and 2026, with a median of three modalities (range 2-6), most commonly structured EHR (71%) and imaging (39%). Data-centric techniques were frequently reported (74-84% across label-noise, distribution-shift, calibration, missing-modality and class-imbalance handling; equity 61%). However, external validation was reported in only 4/31 studies (13%), a clinical or provider outcome in 3/31 (10%), and no study reported routine deployment. Overall risk of bias was high in 27/31 studies (87%), driven by the analysis domain. CONCLUSION: Within this recent, self-selected slice of the field, technical robustness and explainability techniques are widely reported but rarely validated out-of-distribution or against clinical outcomes, and the underlying evidence is at high risk of bias. Progress requires external multi-site validation, clinical-outcome measurement, formal bias appraisal, and adherence to AI reporting standards (e.g., TRIPOD + AI) before deployment can be justified.

Deep Learning↗

PubMed2026

A Conserved 3'UTR Stem-loop Directs UPF1/eIF4AIII-Dependent Regulation of GABARAPL1 mRNA.

RNA-binding proteins (RBP) interact with mRNA untranslated regions containing cis-regulatory elements to govern mRNA localization, stability, and translational efficiency. Among these trans-regulatory factors, RNA helicase UPF1 is a central factor which play a role in multiple mRNA decay pathways, including nonsense-mediated mRNA decay (NMD). NMD is triggered when an exon-junction complex (EJC) is located downstream of a premature termination codon. However, in some cases, NMD can be activated in an EJC-independent manner through mechanisms involving the 3'UTR. In the present study, we focused on the GABARAPL1 3'UTR, as previous studies had shown that this region plays a key role in NMD targeting, although the underlying molecular mechanism had not yet been elucidated. Unlike canonical NMD targets such as SC35, we found that the chemical inhibition of eIF4AIII helicase activity did not affect GABARAPL1 transcript levels, indicating that this transcript is regulated through its 3'UTR via an EJC-independent mechanism. We therefore investigated the potential presence of cis-regulatory element within the 3'UTR of GABARAPL1 which can regulate mRNA and protein levels in a UPF1-dependent manner. Furthermore, we identified a conserved RNA region spanning nucleotides 364-421 involved in GABARAPL1 targeting and used biochemical analysis to demonstrate the direct binding of UPF1 and eIF4AIII to this RNA region, to analyse its secondary structure in solution, and to map the protein-binding sites. By complementing these approaches with molecular modelling, we showed that this stem-loop adopts a stable global fold but a local flexibility and dynamic behaviour properties. Together, our results support the role of UPF1 and eIF4AIII as specific regulators of GABARAPL1 transcript and reveal a novel RNA regulatory element within its 3'UTR, which provides a completely unexpected binding site for these factors.

3' Untranslated Regions↗

PubMed2026

Dual-Reporter Gene-Based Multimodal Imaging for Tracking Mesenchymal Stem Cells in Diabetic Skin Wound Repair.

BACKGROUND: Diabetic foot ulcer (DFU) is a clinically challenging complication characterized by poor healing outcomes, and conventional therapies provide limited benefit. Mesenchymal stem cell (MSC) transplantation offers a promising strategy for DFU repair. However, the low survival of transplanted MSCs in the hostile wound microenvironment, coupled with the lack of real-time, non-invasive methods to track these cells in vivo, severely hampers their therapeutic efficacy and clinical translation. METHODS: We engineered MSCs to co-express a dual reporter system comprising near-infrared fluorescent protein (iRFP) and ferritin heavy chain (FTH1). These modified cells were then integrated with a fibrin glue (FG) scaffold to create a unified platform that supports both multimodal imaging and therapeutic function within skin wounds. First, FTH1 overexpression enhances the antioxidant capacity of MSCs, while the FG scaffold provides structural support; this combination enhances cell survival and retention. Second, the iRFP/FTH1 dual reporter enables near-infrared fluorescence imaging and MRI-based localization, establishing a multimodal platform for real-time cell tracking. RESULTS: In a full-thickness skin defect model in diabetic mice, multimodal imaging revealed that transplanted cells persisted in the wound area for approximately seven days. Treatment with iRFP/FTH1-MSCs/FG significantly accelerated wound closure and promoted hair follicle regeneration and angiogenesis. Additionally, local iron deposition resulting from FTH1 expression enhanced fibroblast migration and collagen synthesis, further facilitating extracellular matrix remodeling. Mechanistic studies demonstrated that this therapy drives macrophage polarization toward the anti-inflammatory M2 phenotype and activates the PI3K-AKT-VEGF signaling pathway. These complementary effects synergistically enhance tissue regeneration and systematically improve diabetic wound healing. CONCLUSIONS: Collectively, this multimodal stem cell-scaffold system effectively integrates dynamic cell tracking with stem cell therapy during skin wound repair. It addresses a critical technical gap in visualizing stem cells within the wound microenvironment and provides valuable methodological and theoretical foundations for optimizing regenerative strategies for diabetic skin wounds.

Animals↗

PubMed2026

Experimental evolution reveals contrasting adaptive landscapes in lab and field environments.

Experimental evolution is widely used to infer microbial responses to environmental change, yet most laboratory studies impose constant, well-mixed conditions that differ fundamentally from fluctuating, spatially structured field environments. We compared genomic evolution in the leaf litter-associated bacterium Curtobacterium strain MMLR14_002 under control and warming treatments in laboratory culture and in a complementary field experiment. Laboratory-derived isolates accumulated more mutations per genome and exhibited stronger locus-level parallelism, with mutations recurring in a small number of coding loci. Field-derived isolates accumulated fewer mutations per genome, and these mutations rarely occurred in the same coding loci across replicate populations. Instead, field isolates exhibited a higher proportion of intergenic mutations, with mutations recurring in the same intergenic regions across independent field deployments. When coding mutations were detected in the field, they were distributed across functionally diffuse targets and more often involved metabolic pathways than the core cellular processes repeatedly targeted during laboratory evolution. Warming itself did not consistently influence mutation accumulation or the genomic distribution of mutations; instead, laboratory and field contexts primarily shaped the accumulation, targets, and repeatability of genomic change. These results suggest that laboratory thermal evolution identifies adaptive routes favored under sustained selection but may overestimate coding-level parallelism under heterogeneous field conditions. Bridging laboratory and field evolution will likely require experimental designs that incorporate temporal variability and spatial heterogeneity characteristic of natural systems.IMPORTANCEA central goal of experimental evolution is to infer how microbes evolve in nature from laboratory studies. Here, we evaluate this assumption by comparing genomic evolution of a leaf litter-associated Curtobacterium strain in laboratory and field warming experiments to identify broad patterns rather than isolate the contribution of any single environmental factor. We find that the strong parallelism at coding loci observed under laboratory conditions is reduced in the field, while mutations recurring in the same intergenic regions across field deployments suggest that parallel evolution in nature may more often involve regulatory noncoding regions rather than coding targets. These results show that environmental context reshapes adaptive landscapes and may limit the parallelism of coding-level genomic responses inferred from homogeneous laboratory conditions.

experimental evolution↗

PubMed2026

Pregnancy diet based on ancestral patterns increases growth in subcortical fetal brain regions.

Evidence on the biological basis for maternal nutrition effects on fetal and newborn neurodevelopment remains limited. This randomized controlled trial in Ecuador tested a maternal dietary pattern-derived from empirical studies of nutrition in human evolution and adapted locally-on offspring growth and brain development. Pregnant women (n = 215) in their first trimester were randomized to: 1) control (n = 104); or 2) Mikhuna ("nourish" in Kichwa) intervention (n = 111). The intervention, from 12 wk gestation to birth, consisted of a weekly food delivery (8 eggs, 500 g fish, and a variety of sustainably sourced fruits and vegetables) and a behavior change communication strategy encouraging diet diversity and limiting highly processed foods. Longitudinal data collection occurred at 12 wk, 21 wk, 35 wk gestation, and 2 wk postpartum, and included ultrasound imaging of fetal bone and brain parameters, maternal dietary intakes, anthropometry, socioeconomic and demographic variables, and other biomarkers. At close of intervention, a significantly higher percentage of women met the minimum dietary diversity threshold in Mikhuna (74.5%) vs. control groups (55.8%) (P = 0.004). Generalized linear regression models showed significant differences in Mikhuna compared to control for: corpus callosum length 0.19 cm (95% CI [0.02, 0.35]), gangliothalamic ovoid height 0.15 cm (95% CI [0.03 to 0.26]), and femur length -0.10 cm (95% CI [-0.19, -0.02]) from 21 wk to 35 wk; and corpus callosum Z 0.56 (95% CI [0.03, 1.09]) and femur length Z -0.21 (95% CI [-0.42, 0.00]) at 35 wk. The Mikhuna intervention increased the growth of subcortical fetal brain structures, which have established roles in motor control, cognition, and signal transmission.

Female↗

PubMed2026

Clinical performance evaluation of single-shade versus multi-shade composite resins in non-carious cervical lesions: a 36-month randomized clinical trial.

BACKGROUND: Composite resins are widely used as the material of choice for definitive restorations due to their ability to integrate functional and aesthetic aspects in dental rehabilitation. Recently, one-shade composite resins have been introduced to simplify the clinical workflow. OBJECTIVES: This study aimed to compare the clinical performance of a "chameleon effect" composite resin with that of a multi-shade composite resin in non-carious cervical lesions after 36 months of follow-up. METHODS: This study was a randomized, controlled, double-blind clinical trial with an equivalence design using a split-mouth approach. The sample consisted of 60 patients presenting at least two non-carious cervical lesions, totaling 120 restorations. Restorations were performed using two materials from the same commercial brand: Vittra Unique (one-shade group) and Vittra APS (multi-shade group). The clinical performance of the restorations was longitudinally evaluated according to the FDI criteria. Survival analysis was performed using Kaplan-Meier curves and the log-rank test, while other clinical parameters were compared using the chi-square test (α = 0.05). RESULTS: At baseline, no statistically significant differences were observed between the groups regarding the evaluated biological, functional, and aesthetic parameters (p > 0.05). Both materials demonstrated clinically acceptable performance according to the FDI criteria, with no significant differences between them. CONCLUSIONS: After 36 months, no significant differences were observed between the one-shade and the multi-shade composite resins in the restoration of non-carious cervical lesions. CLINICAL SIGNIFICANCE: This 36-month randomized clinical trial demonstrates that single-shade composite resins achieve structural durability and aesthetic integration equivalent to traditional multi-shade layering when restoring non-carious cervical lesions. This evidence validates a simplified, single-shade restorative workflow, significantly reducing chairside time and operator-dependent variables without compromising the clinical longevity.

Humans↗

PubMed2026

"It was good because they have a relationship with us": A qualitative study on low-threshold buprenorphine treatment at syringe services programs.

INTRODUCTION: Syringe service programs (SSPs) reach people who inject drugs with opioid use disorder (OUD) and are novel "low-threshold" venues to initiate buprenorphine treatment. The study investigated patients' experiences with SSP-initiated buprenorphine treatment, which could aid in improving buprenorphine treatment delivery at SSPs. METHODS: The study included 12 participants who completed qualitative exit interviews after a randomized controlled trial of buprenorphine treatment at SSPs. In the parent study, participants received buprenorphine treatment through an onsite model at an SSP or enhanced referral to a community health center based on the randomization sequence. Most participants started taking buprenorphine at home. Exit interviews included participants from both study arms, and the semi-structured interview guide focused on their experiences with clinicians, experiences initiating buprenorphine, prior experiences with OUD treatment, and perceptions about continuing buprenorphine treatment. Four researchers iteratively read, coded, and discussed each transcript, then they derived recurring themes using thematic analysis. RESULTS: Participants were mostly male, middle-aged, and 50% identified as Latino. Four main themes related to buprenorphine treatment initiation: 1) Onsite treatment facilitated buprenorphine prescription, but some participants also expressed a need for additional support; 2) Precipitated withdrawal complicated participants' buprenorphine initiation in both arms; 3) Participants largely experienced the SSPs as affirming and welcoming; and 4) Developing strong relationships with healthcare providers was critical to successful buprenorphine treatment initiation. CONCLUSIONS: The SSP-based model provided rapid access to buprenorphine prescriptions, but precipitated withdrawal was a common complication. Some participants desired additional support and guidance when they started taking buprenorphine at home. The findings point to a "low-threshold, high-touch" approach where participants receive expedited access to buprenorphine providers at SSPs but also additional support throughout the initiation process to avoid and/or manage precipitated withdrawal. Despite some challenges, SSP-based buprenorphine treatment was highly valued by study participants.

Humans↗

PubMed2026

Exploring precision risk in pediatric vesicoureteral reflux: Innate immune gene variations and reflux outcomes in the RIVUR cohort.

INTRODUCTION: Children with vesicoureteral reflux (VUR) are at increased risk for morbidity from recurrent urinary tract infections (UTIs), yet the factors influencing spontaneous VUR resolution remain poorly defined. This study evaluates whether genetic variations in key urinary innate immune effectors (DEFA1A3, DMBT1, and RNASE7) influences VUR resolution and interacts with prophylaxis to alter clinical response. METHODS: We conducted a secondary analysis of 303 RIVUR participants with available DEFA1A3 and DMBT1 copy number variation (CNV) data and RNASE7 rs1263872 genotype. Primary outcomes were (1) VUR improvement (decrease in grade) and (2) VUR resolution at study exit. Multivariable logistic regression models included genotype, treatment, and their interactions, adjusting for age, sex, baseline grade (high vs low), laterality, bowel/bladder dysfunction, and any UTI. Internal validation used 2000-sample bootstrap with bias-corrected and accelerated confidence intervals and influence diagnostics. RESULTS: Clinical covariates did not significantly predict VUR improvement. Children with DEFA1A3 CNV >5 had higher odds of improvement (OR 2.36, 95% CI 1.12-4.96, p = 0.023), an effect that remained significant in bootstrap analyses. High-grade VUR was associated with lower odds of resolution (OR 0.34, 95% CI 0.12-0.94, p = 0.038). A significant interaction was observed between prophylaxis and high DMBT1 copy number for VUR resolution (interaction OR 2.99, 95% CI 1.11-8.04, p = 0.031); no interaction was seen for improvement. RNASE7 rs1263872 was not associated with either outcome. CONCLUSION: Innate immune gene variation may contribute to heterogeneity in VUR outcomes. High DEFA1A3 copy number was associated with reflux improvement and a DMBT1-prophylaxis interaction was associated with reflux resolution. The results of this study is hypothesis-generating and prompt further evaluation to assess whether a subset of children may experience structural benefit from prophylaxis or have a more favorable natural history based on their innate immune genotype.

Humans↗

PubMed2026

Effects of intensive lifestyle interventions with calorie-carbohydrate-restricted diet versus time-restricted eating on appetite and binge eating in type 2 diabetes: A randomized controlled trial.

The impact of intensive lifestyle interventions on appetite regulation and binge eating in individuals with type 2 diabetes (T2D) remains unclear. This study evaluated the effects of combined lifestyle interventions on appetite responses and binge eating in overweight or obese adults with T2D. In a randomized trial, 120 participants with T2D were allocated to three groups (n = 40 each): (1) Calorie-carbohydrate restriction (CCR), (2) Time-restricted eating with CCR (TRE + CCR), or (3) Control. Intervention groups received structured exercise and behavioral education based on the Information-Motivation-Behavioral Skills model. Appetite perceptions (hunger, satiety, desire to eat, and prospective food consumption) and binge eating (Binge Eating Scale; BES and objective binge episodes) were evaluated at baseline, week 12, and week 24 using linear mixed models. Both CCR and TRE + CCR significantly improved subjective appetite compared with the control group at 12 and 24 weeks (all p < 0.01). At 24 weeks, hunger decreased by -24.1 mm (95% CI: -35.8, -12.5) in the CCR group and -32.7 mm (95% CI: -44.2, -21.3) in the TRE + CCR group. Satiety also increased by 21.7 mm (95% CI: 9.46, 33.9) and 29.4 mm (95% CI: 17.4, 41.4), respectively. Significant reductions were observed for desire to eat and prospective food consumption. In contrast, changes in BES and objective binge episodes were not significantly different between groups at any time point. No significant differences were detected between the CCR and the TRE + CCR groups. Intensive lifestyle interventions incorporating CCR or TRE + CCR effectively reduced appetite in adults with T2D but did not significantly affect binge eating. Future research should target individuals with higher baseline BES scores to clarify potential benefits for binge eating behavior.

Humans↗

PubMed2026

Evaluating a culturally adapted question prompt list to improve end-of-life communication among indonesian migrant caregivers: A randomized controlled trial with qualitative insights.

OBJECTIVE: Indonesian caregivers serve as essential providers of end-of-life (EOL) care in Taiwan. But often face communication challenges due to language, cultural, and hierarchical barriers. This study evaluated the effectiveness of a culturally adapted Question Prompt List (QPL). METHODS: This study employed a two-arm randomized controlled trial design supplemented with qualitative interviews. The study was conducted in a hospice ward and home care setting within a medical center in Taiwan. A total of sixty Indonesian caregivers were recruited and randomly assigned to either the intervention group (n = 30) or the control group (n = 30). The intervention group received routine end-of-life (EOL) education along with a culturally adapted Question Prompt List (QPL), which consisted of 37 items covering domains including the dying process, emotional support, communication, symptom management, and care decision-making. The control group received routine EOL education. Outcome measures included caregiving preparedness, communication self-efficacy, satisfaction, and question-asking behavior. In addition, semi-structured interviews were conducted with eight participants, and the data were analyzed using thematic content analysis. RESULTS: Analysis of covariance revealed no statistically significant between-group differences in caregiving preparedness (F = 1.58, p = .215 [-0.41, 0.44]) or communication selfefficacy (F = 0.83, p = .366 [-0.44, 0.79]). However, communication satisfaction was significantly higher in the intervention group (F = 4.19, p < .05 [0.04, 0.44]). The number of questions asked was also significantly higher in the intervention group (t = -4.35, p < .001 [-5.41, -1.98]). Thematic analysis of qualitative data identified 4 themes and 14 subthemes, illustrating how the QPL reduced anxiety, clarified care needs, and improved confidence. CONCLUSIONS: A culturally adapted QPL can enhance communication engagement and satisfaction among migrant caregivers. PRACTICE IMPLICATIONS: Integrating culturally tailored QPLs into caregiver education and palliative care practice may promote more inclusive and effective communication.

Humans↗

PubMed2026

Evaluating the Effectiveness of an Intimate Partner Violence Training Intervention on Healthcare Providers' Preparedness, Knowledge, and Experiences: A Mixed-Methods Study From Nepal.

Intimate partner violence (IPV) places a considerable burden on health systems globally due to its profound effects on women's health, and women who experience violence often seek care from healthcare providers (HCPs). However, HCPs often lack the preparedness and confidence to respond effectively, resulting in missed opportunities for support and care. This study, conducted in Nepal, evaluated the impact of structured training intervention on HCPs' perceived preparedness, knowledge, and attitudes toward managing IPV and its mental health consequences, including self-harm and suicidal tendencies. The study was nested within a larger cluster randomized trial. A convergent mixed-methods design with a comparison group was conducted among 46 female HCPs in all public hospitals (except one) and 17 primary healthcare centers in Madhesh Province, Nepal. The intervention group (n = 24) received a 10-day intensive IPV and mental health training, while the control group (n = 22) completed 3-day training. Quantitative data were collected using a validated self-administered Physician's Readiness to Manage IPV questionnaire and IPV consequences scale. Paired and independent t-tests were applied to assess changes. Insights from key informant interviews were thematically analyzed to explore participant experiences and perceived impacts. At baseline, over 80% of participants had not received IPV management training. Post-intervention, significant improvements were observed in HCPs perceived preparedness (median change 2.1; 95% confidence interval (CI): 1.1- 2.9), knowledge (median change 2.7; 95% CI: 2.0-3.1), and awareness of IPV consequences (mean difference 1.2; 95% CI: 0.5-2.0), with greater gains in the intervention group. Qualitative findings revealed enhanced confidence in identifying IPV, addressing psychological impacts, and supporting survivors through safety planning and referral. The training significantly improved HCPs' knowledge, preparedness, and confidence to manage IPV and related mental health issues, underscoring the need to scale similar programs to frontline providers, particularly in rural and underserved settings, to strengthen health system's response to IPV.

Humans↗

PubMed2026

Targeting cortico-striatal-amygdalar networks via theta-band frontoparietal synchronization in opioid use disorder: a randomized tACS-fMRI Trial.

Theta-band oscillation is integral to fronto-parietal connectivity in the executive control network and its top-down regulation on subcortical areas. External frontoparietal synchronization using theta-frequency transcranial alternating current (tACS) is a technology to potentially engage this network. In this pre-registered, triple-blind, sham-controlled trial (NCT03907644), we tested this intervention targeting the right frontoparietal network in people with opioid use disorder (OUD) to measure network engagement and behavioral outcomes. Sixty male participants with OUD were randomized to receive 20 min of active or sham 6 Hz tACS (HD electrodes over F4 and P4). Structural, resting-state, task-based fMRI drug cue reactivity, and repeated cue-induced craving assessments were collected immediately before and after stimulation. Pre-registered outcome measures were analyzed using time × group interaction models to examine (1) modulation of drug cue-related brain activity, (2) changes in craving, (3) alterations in functional connectivity, and (4) relationship between electric field, neural responses, and craving behavior. (1) A significant Time × Group interaction revealed decreased post-stimulation opioid cue-related activity in the active group relative to sham, involving key nodes in reward processing (ventral striatum, amygdala and ventral tegmental area) (FWE corrected α = 0.05) (2) subjective craving did not differ significantly between groups (3) Group by time generalized psychophysiological interaction analyses showed increased right frontoparietal network engagement (β = 2.63, p= 0.0308) following stimulation, and increased top-down inhibitory regulation of frontoparietal network on right ventral striatum (β = 1.99, p= 0.037) and left medial amygdala (β = 1.97, p= 0.039) (4) Electric field strength in the right frontal/parietal node predicted frontoparietal network engagement in the active group (r = 0.43, p= 0.02). Together, these findings demonstrate that theta-band frontoparietal tACS can modulate activity and task-dependent coupling within cortical-subcortical circuits in OUD, supporting network-targeted neuromodulation as a potential intervention for addiction.

Humans↗

PubMed2026

A systematic review and meta-analysis of OCT-based ophthalmic changes in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease marked by motor decline and respiratory failure. Optical coherence tomography (OCT), a non-invasive imaging technique, has been explored for detecting retinal structural changes that may reflect neurodegeneration in ALS. While some studies report thinning of retinal layers, findings remain inconsistent. Therefore, a meta-analysis is needed to clarify the extent of retinal involvement and the potential of OCT as a biomarker in ALS. METHODS: A systematic literature search was conducted across PubMed, EMBASE, and Cochrane databases for studies published between 2010 and May 2025. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and publication bias was evaluated through funnel plot asymmetry and Egger's test. Pooled effect sizes were calculated using random-effects models to account for between-study heterogeneity, and differences in OCT parameters between ALS patients and healthy controls were expressed as standardized mean differences (SMD) with 95% confidence intervals (CI). Statistical heterogeneity was quantified using the I2 statistic. RESULTS: A total of 17 studies were included in the present meta-analysis. The primary unadjusted global model demonstrated significant reduction of retinal nerve fibre layer (RNFL) thickness in ALS patients compared to controls (unadjusted SMD = -0.295, 95% CI: -0.522, -0.068). Upon applying a Design Effect variance inflation model to address fellow-eye non-independence, the pooled estimate remained robustly significant across a conservative range of intraclass correlations (SMD ranged from -0.256 to -0.249). Subgroup analyses revealed that RNFL thinning was particularly pronounced in spinal-onset ALS (SMD = -0.54, 95% CI: (-0.98, -0.10). When studies were stratified by the region of conduct, RNFL and macular thinning reached statistical significance only within the non-Asian subgroup, though the formal test for subgroup differences was not significant. CONCLUSION: This meta-analysis demonstrates significant bilateral RNFL thinning in ALS, with relative preservation of the Inner Nuclear Layer and Ganglion Cell Layer - Inner Plexiform Layer, supporting retinal neurodegeneration as a feature of this multisystem disorder. SYSTEMATIC REVIEW REGISTRATION: PROSPERO identifier CRD420251076035.

Humans↗

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↗