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PubMed2026

Uncovering molecular regulatory networks of low-temperature stress response in Trachinotus ovatus via integrated transcriptome and metabolome analyses.

Golden pompano (Trachinotus ovatus) is one of the most economically important marine fish species in China. It is susceptible to low-temperature stress, which significantly challenges its production and supply. Nevertheless, study on the regulatory mechanisms underlying low-temperature stress responses in golden pompano remains limited. Here, we firstly performed a time-series transcriptome analysis to reconstruct dynamic response patterns under low-temperature stress in golden pompano. Transcriptome profiling identified common differentially expressed genes (DEGs), including fos, hlf, and hmgb1, as well as condition-specific DEGs across distinct low-temperature stress groups. Based on cluster analysis, all DEGs were classified into five distinct expression patterns, reflecting diversified regulation of expression in golden pompano during low-temperature stress. Furthermore, condition-specific regulatory modules were explored via weighted gene co-expression network analysis (WGCNA), highlighting that the two module hub genes, serbf2 and lipc, might respond to low-temperature stress by regulating the lipid catabolic process. Subsequently, untargeted metabolomic analysis revealed that glycerophospholipid metabolism was a significantly enriched common pathway, highlighting its crucial role in mediating the response to low-temperature stress. Finally, by integrating transcriptomic and metabolomic analyses, a gene-metabolite interaction network associated with glycerophospholipid metabolism under low-temperature stress was established. These findings underscore the significance of multiple candidate genes and glycerophospholipid metabolism in golden pompano's response to low-temperature stress, thereby laying a solid molecular foundation for the development of low-temperature-tolerant fish strains.

Animals↗

PubMed2026

Evolutionary characterization and expression profiling of ACC and FASN genes in Chinese mitten crab Eriocheir sinensis.

Acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) are rate-limiting enzymes in the fatty acid biosynthetic pathway, yet their evolutionary relationships, sequence features, and expression profiles remain poorly understood in crustaceans, particularly in the economically important Chinese mitten crab (Eriocheir sinensis). Here, we identified and systematically analyzed ACC and FASN genes in E. sinensis using comparative genomic analyses across 43 species. ACC was highly conserved as a single-copy gene in invertebrates, in contrast to the multiple paralogs observed in vertebrates. Similarly, FASN was generally maintained as a single-copy gene across most taxa but exhibited lineage-specific expansion in certain insect groups. Phylogenetic and structural analysis revealed strong conservation of both genes within crustaceans, supported by multiple conserved motifs and canonical functional domains. Expression profiling showed predominant expression in the hepatopancreas and midgut, suggesting their potential involvement in crustacean lipid metabolism. During the molting cycle, ACC and FASN exhibited higher expression levels during stages C and D, suggesting an increased capacity for fatty acid biosynthesis before molting. In addition, dietary lipid levels experiment revealed that ACC and FASN expression responded dynamically to dietary lipid availability, with increased expression at moderate lipid levels but reduced expression under excessive lipid supplementation, indicating a possible adaptive transcriptional response to lipid status. Collectively, this study provides insights into the evolutionary conservation and expression dynamics of ACC and FASN and improves our understanding of lipid metabolic adaptation in crustaceans.

Animals↗

PubMed2026

Innovation-related perception as a key driver of alternative protein acceptance: evidence from an early-stage model for cultivated meat and algae-/microalgae-based alternative protein products in Italy.

Alternative proteins are increasingly considered part of the transition toward more sustainable food systems, yet their diffusion depends critically on consumer acceptance. This study investigates the early-stage acceptance of two alternative protein categories in Italy-cultivated meat and algae-/microalgae-based alternative protein products. Focusing on the first three phases of acceptance, the analysis examines how innovation-related perception (IRP) shapes consumer perceived value (CPV), consumer perceived risk (CPR), and subsequent affective (AFF), cognitive (COG), and conative (CON) responses. Data were collected through an online survey administered to 238 Italian respondents and analysed using partial least squares structural equation modelling (PLS-SEM). The results show that IRP is the main upstream driver of early-stage acceptance in both product domains: more favourable perceptions strongly increase perceived value and reduce perceived risk. In turn, CPV exerts a much stronger influence than CPR on both affective and cognitive attitudes. A tentative cross-model comparison suggests only a descriptive variation in the final transition toward conative acceptance: affective and cognitive responses were both significant in the two models, with a relatively larger affective coefficient for cultivated meat and more balanced coefficients for algae-/microalgae-based products. Overall, the findings support a process-based interpretation of alternative protein acceptance and highlight the central role of innovation-related perception in shaping early consumer responses. These results provide relevant implications for communication strategies, product positioning, and policy actions aimed at improving the acceptability of alternative proteins in food cultures characterised by strong culinary traditions.

Italy↗

PubMed2026

Adolescents' Growing Sensitivity to Psychosocial Stressors: Evidence From Two Decades of Health Behaviour in School-aged Children (HBSC) Data in the Nordic Countries.

PURPOSE: We tested a perception-based explanation for rising psychosomatic complaints among adolescents in the Nordic countries. Specifically, we examined whether adolescents have become more sensitive to psychosocial stressors, reflected in stronger associations between stressors and psychosomatic complaints in 2022 than in 2002. METHODS: Data were drawn from the 2002 to 2022 waves of the Health Behaviour in School-aged Children survey among 15-year-olds in five Nordic countries (N = 7,263 in 2002 and 6,739 in 2022). Psychosomatic complaints were examined in relation to stressors in the following three domains: interpersonal relationships, school-related strain, and body- and activity-related factors. Moderated regression analyses tested whether associations between stressors and complaints differed between survey years. Sex and perceived family finances were included as covariates. RESULTS: Four of five psychosocial stressors showed stronger associations with psychosomatic complaints in 2022 than in 2002. Perceived poor family finances, although less prevalent in 2022, were more strongly related to complaints. Girls consistently reported higher levels of psychosomatic complaints, and the association between school pressure and complaints was stronger among girls. DISCUSSION: Although several psychosocial stressors declined in prevalence, their associations with psychosomatic complaints strengthened over time. These findings suggest that rising complaints may reflect changes in how psychosocial stressors are linked to adolescents' psychosomatic symptoms, rather than increases in exposure to those stressors. This shift highlights the importance of considering how adolescents interpret and respond to everyday stress when addressing population trends in mental health.

Humans↗

PubMed2026

Antagonistic regulation by mango MiSPL9a and MiSPL9b regulates flowering time, drought and salt stress in Arabidopsis.

SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) transcription factors, which are unique to plants, contain a highly conserved SBP domain that regulates gene expression by binding to downstream targets. They play critical roles in various biological processes, especially in the regulation of flowering in plants. In this study, two SPL-like genes (MiSPL9a and MiSPL9b) were identified from mango genomic and transcriptomic data, and their sequence, expression and function were further analyzed. Sequence analysis revealed that MiSPL9a and MiSPL9b have open reading frames of 1173 bp and 1158 bp, respectively, with slight differences in the number of cis-regulatory elements within their promoter regions. Expression analysis under stress conditions revealed distinct patterns: MiSPL9a expression significantly differed under drought stress but did not significantly differ under salt stress, whereas MiSPL9b expression responded significantly to salt stress but changed minimally under drought stress. Phenotypic analysis of the transgenic Arabidopsis lines revealed that MiSPL9a overexpression delayed flowering, whereas MiSPL9b overexpression promoted early flowering. Under stress conditions, compared with wild-type plants, MiSPL9a-overexpressing plants presented increased drought tolerance but did not significantly differ. In contrast, MiSPL9b-overexpressing plants were sensitive to salt stress, with no notable phenotypic differences observed under drought conditions. Physiological assays revealed that under drought stress, MiSPL9a transgenic plants presented significantly reduced levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) and increased proline (Pro) content and superoxide dismutase (SOD) activity. Under salt stress, MiSPL9b transgenic plants presented opposite trends in terms of these physiological markers. In summary, both MiSPL9a and MiSPL9b are involved in the regulation of plant flowering time and stress responses, but their functions differ.

Arabidopsis↗

PubMed2026

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a ≥ 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans↗

PubMed2026

Effects of music interventions on seizure outcomes in people with epilepsy: a systematic review and meta‑analysis.

OBJECTIVES: To evaluate effects of music interventions on seizure outcomes in people with epilepsy. METHODS: We performed a systematic review and meta‑analysis of controlled and single‑arm studies. Searches were conducted in four English databases, two trial registries, and three Chinese databases, up to October 11, 2025. Dichotomous outcomes were pooled as odds ratios (ORs) and continuous outcomes as mean differences or standardized mean differences (SMD, Hedges' g) using random‑effects models. Heterogeneity was assessed with Cochran's Q and I2. Preplanned subgroup and leave‑one‑out sensitivity analyses examined control type and study influence. Risk of bias and evidence certainty were appraised. RESULTS: Fifteen studies were included. Single‑arm syntheses suggested benefit: pooled curative‑effect rate 0.715 (95 % CI 0.584-0.846) and pre-post IED reduction -0.51 (95 % CI -0.88 to -0.13). Controlled between‑group estimates were imprecise and heterogeneous. Pooled OR for seizure response was 2.71 (95 % CI 0.61-12.12, I2 = 81.2 %, p = 0.19). IED responder OR was 4.57 (95 % CI 0.84-24.86, I2 = 68.9 %). IED frequency SMD was -1.48 (95 % CI -3.06 to 0.10, I2 = 95.2 %). Seizure‑frequency SMD across controlled studies was -0.004 (95 % CI -1.772 to 1.763, I2 = 95.6 %). Results were sensitive to individual studies and limited by small samples and variable comparators. CONCLUSIONS: Music interventions show promising within‑study effects on seizure outcomes, but controlled evidence is inconclusive due to high heterogeneity and imprecision. High‑quality, adequately powered randomized trials with standardized interventions and matched active controls are needed.

Humans↗

PubMed2026

Coordinated use of three homocysteine methyltransferases supports l-methionine biosynthesis and environmental adaptation among plant-associated bacteria.

Plant pathogens colonize multiple plant-associated habitats throughout their life cycle, encountering distinct nutrient conditions and microbial communities. l-methionine is required for bacterial growth and environmental adaptation. However, how plant pathogens coordinate l-methionine biosynthetic pathways to adapt to different plant-associated environments remains poorly understood. Here, using the plant pathogen Xanthomonas campestris pv. campestris strain XC1 as a model, we show that three homocysteine methyltransferase pathways allow XC1 to catalyze the final step of l-methionine biosynthesis using different methyl donors and cofactors under different environmental conditions. Bioinformatic and transcriptional analyses identified three homocysteine methyltransferase-associated operons in XC1, mesMXD, mmuPM, and metHRHaHb, corresponding to the MesD-, MmuM-, and MetHaHb-dependent pathways, respectively. MesD uses an endogenously synthesized methyl donor and functions as the dominant homocysteine methyltransferase under l-methionine-limiting conditions, supporting bacterial growth, intracellular l-methionine accumulation, and full virulence. Furthermore, MmuM enables XC1 to use plant-derived S-methylmethionine for l-methionine biosynthesis, whereas MetHaHb enables XC1 to use vitamin B12 supplied by a neighboring bacterium for l-methionine biosynthesis in co-culture. Expression analyses showed that mesMXD was the only homocysteine methyltransferase-associated operon that responded to l-methionine availability, and its expression also decreased when S-methylmethionine- or vitamin B12-dependent pathways supported l-methionine biosynthesis. Comparative genomic analysis further showed that the three-homocysteine methyltransferase configuration is conserved in Xanthomonas and is also present in other plant-associated bacteria. Together, these findings show that a plant pathogen can coordinate endogenous, plant-derived, and microbially supported homocysteine methyltransferase pathways to maintain l-methionine biosynthesis, providing a metabolic strategy for adaptation to plant-associated environments.

Methionine↗

PubMed2026

Transcriptomic and RNAi analyses reveal chloride channel 3-associated osmoregulation in Litopenaeus vannamei under low-salinity stress.

Chloride channels and transporters are important for cellular volume regulation and salinity adaptation in euryhaline crustaceans, yet the intestinal transcriptional relationship between plasma-membrane and intracellular chloride pathways remains unclear in Litopenaeus vannamei. In this study, RNA interference of anoctamin 1 (ANO1) was combined with intestinal transcriptome sequencing under the production-relevant low-salinity condition of salinity 3. ANO1 silencing produced a focused transcriptional response, with 16 differentially expressed genes (DEGs) identified (11 upregulated and 5 downregulated). Functional enrichment indicated that these genes were associated with transporter activity, cytoskeletal organization, extracellular matrix-receptor interaction, membrane lipid metabolism, and vesicular processes. Notably, a transcript encoding chloride channel protein 3 (CLC-3) was significantly upregulated following ANO1 knockdown, suggesting a potential transcriptional relationship between ANO1 and CLC-3 in chloride homeostasis. Based on this finding, CLC-3 was selected for full-length cDNA cloning, sequence characterization, salinity-gradient expression analysis, and RNAi-based functional assessment. The cloned CLC-3 cDNA was 2883 bp in length and encoded an 850 amino acid protein containing a conserved voltage-gated chloride channel (Voltage-CLC) domain and two cystathionine β-synthase domains. Phylogenetic analysis placed LvCLC-3 within the intracellular CLC-c clade, and tissue distribution analysis showed the highest CLC-3 expression in the intestine. Intestinal CLC-3 expression responded nonlinearly to salinity variation, peaking at salinity 20. Under salinity 3, CLC-3 knockdown reduced ANO1, Na+/K+-ATPase alpha subunit, and Na+-K+-2Cl- cotransporter transcript levels, whereas glutamate-gated chloride channel expression increased. Mild hepatopancreatic structural alterations were also observed after CLC-3 knockdown. These findings suggest that CLC-3 is a salinity-responsive intracellular chloride-transporter candidate associated with intestinal ion-transport-related transcriptional responses after ANO1 suppression in L. vannamei, although the underlying physiological mechanism requires further validation.

Animals↗

PubMed2026

Phenotypic, physiological and transcriptomic analysis of graded salt stress responses in Pyrus betulifolia Bunge and functional characterization of the hub gene PbSTY46.

Pyrus betulifolia Bunge is a salt‑tolerant rootstock for pear, but its salt‑tolerance mechanisms remain largely unknown. In this study, P. betulifolia seedlings were subjected to graded NaCl stress at concentrations of 0 (CK), 50 (T1), 100 (T2), and 200 (T3) mM. We integrated phenotypic observation, physiological assessment, transcriptomic profiling, and functional gene validation to systematically elucidate its salt tolerance mechanisms. Salt stress inhibited seedling growth and root traits in a concentration-dependent manner, and T3 caused the most severe damage. Osmotic solutes responded differentially: soluble sugars peaked under T2, while proline peaked under T3. Antioxidant enzymes showed tissue-specific biphasic responses and declined after prolonged T3 stress. Meanwhile, chlorophyll and photosynthesis decreased, whereas anthocyanin increased, indicating a metabolic shift from photosynthesis to photoprotection. Transcriptome analysis revealed distinct responses depending on stress intensity: mild stress induced membrane lipid remodeling, moderate stress activated circadian rhythm and hormone signaling, and severe stress enhanced phenylpropanoid biosynthesis and thiamine metabolism. Gene Set Enrichment Analysis (GSEA) further highlighted progressive enrichment of phenylpropanoid biosynthesis, heme binding, and oxidoreductase activity. Weighted Gene Co‑expression Network Analysis (WGCNA) identified a blue module significantly positively correlated with root traits, from which the hub gene PbSTY46 was identified. Functional validation via overexpression, loss‑of‑function mutants, and pharmacological interventions (MeJA/DIECA) confirmed that PbSTY46 acts through JA signaling to enhance antioxidant enzyme activities and thereby confer salt tolerance. Collectively, P. betulifolia adopts a "survival‑first" strategy that coordinates growth arrest, osmotic homeostasis, and ROS scavenging. These findings establish PbSTY46 as a key regulator that links JA signaling to antioxidant defense. Thus, PbSTY46 represents a promising candidate for marker‑assisted breeding of salt‑tolerant pear cultivars.

Salt Stress↗

PubMed2026

Exploring sex differences in endocannabinoid system biomarkers and their relationship with antidepressant treatment outcomes in major depressive disorder: a CAN-BIND 1 secondary analysis.

BACKGROUND: Sex differences in major depressive disorder (MDD) are well documented, but it remains unclear whether sex-related variation in peripheral endocannabinoid system (ECS)-related biomarkers is detectable in MDD. OBJECTIVES: To examine baseline sex differences in ECS-related mRNA expression, DNA methylation, and single nucleotide polymorphisms (SNPs) in MDD, and associations between baseline ECS markers and antidepressant outcomes in sex-stratified analyses. METHODS: Among 178 participants with MDD from CAN-BIND-1, all received escitalopram for 8 weeks; non-responders then received adjunctive aripiprazole from Weeks 8-16.Response was defined as ≥ 50% reduction in MADRS score, and remission as MADRS ≤ 10. ANCOVAs examined baseline sex differences and sex-stratified biomarker associations with percent MADRS reduction at Weeks 8 and 16, as well as categorical response and remission outcomes. Covariates included site, baseline MADRS, age, and ethnicity. False discovery rate correction was applied. RESULTS: Baseline sex differences in methylation were observed for CACNA1H, GABRB2, MAGL, and GABRR2, though none survived correction. No baseline sex differences in mRNA expression or SNPs were detected after correction. Lower baseline DAGLA mRNA in males was associated with greater Week 8 symptom improvement (FDR corrected). This association was not observed in females. No associations with response or remission at Weeks 8 or 16 survived correction. IMPLICATIONS: Baseline sex differences in peripheral ECS-related markers were not detected in this sample. Larger studies are needed to verify whether ECS-related biomarkers, particularly DAGLA, contribute to antidepressant outcomes in a sex-specific manner.

Humans↗

PubMed2026

Faecal Microbiota Transplantation Reduces Lesion Severity and Medication Use in Canine Atopic Dermatitis: A Randomised, Placebo-Controlled, Double-Blinded Clinical Trial.

BACKGROUND: Faecal microbiota transplantation (FMT) is an established therapy for gastrointestinal disease, yet its role in canine atopic dermatitis (cAD) remains unclear. HYPOTHESIS/OBJECTIVES: We hypothesised that adjunctive FMT improves clinical severity and reduces symptomatic medication use in dogs with cAD. The objective was to evaluate efficacy and safety versus placebo. ANIMALS: Forty-six client-owned dogs with naturally occurring cAD were enrolled from a referral hospital population; 40 completed the study (FMT n = 20, placebo n = 20). MATERIALS AND METHODS: Prospective, randomised, placebo-controlled, double-blinded clinical trial. Dogs received daily oral lyophilised FMT capsules for 90 days plus three monthly rectal FMT administrations (Day [D]0, D30, D60) or placebo capsules with sham handling. Concomitant symptomatic therapies were permitted. Outcomes included Canine Atopic Dermatitis Extent and Severity Index, fourth iteration (CADESI-04), pruritus Visual Analog Scale (PVAS), Medication Score (D0-90) and Owner Global Assessment of Treatment Efficacy (OGATE, D90). RESULTS: CADESI-04 scores were lower with FMT at month (M) 2 (7 ± 6 vs. 16 ± 12; p = 0.006) and month 3 (8 ± 6 vs. 15 ± 12; p = 0.020). Sustained responders (≥ 50% CADESI-04 improvement at M2 and M3) were more frequent with FMT (35% vs. 5%; p = 0.044). In the FMT group, the medication scores were lower at M2 (16 ± 10 vs. 23 ± 11; p = 0.033) and M3 (13 ± 10 vs. 24 ± 15; p = 0.007) compared to placebo. PVAS decreased in both groups without between-group differences. OGATE favoured FMT (p = 0.028). FMT was well tolerated. CONCLUSIONS AND CLINICAL RELEVANCE: Adjunctive FMT reduced lesion severity and medication requirements, supporting its use as a safe microbiome-based add-on therapy in cAD.

Animals↗

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

Effect of flavored on!® nicotine pouch products on smoking behaviors: A sequential, multiple assignment, randomized controlled trial.

PURPOSE: To evaluate whether flavored versus unflavored nicotine pouch (NP) access affects cigarette reduction and smoke exposure among adults who smoke daily, and whether delayed flavor introduction affects these outcomes. METHODS: Adults who smoked ≥ 5 cigarettes/day (CPD) with interest in replacing cigarettes with NPs were enrolled in a remote, six-week, sequential multiple assignment randomized trial (n = 402 randomized; n = 400 analyzed). Participants were randomized to immediate access to seven NP flavors (Flavor), unflavored-only access for six weeks (Original), or unflavored-only for three weeks followed by flavor access (Delayed Flavor). Primary outcomes were ≥ 50% reduction in weekly mean expired-air carbon monoxide (CO) from baseline and mean CO at Week 6. Secondary outcomes included ≥ 50% CPD reduction, mean CPD, CO-verified 7-day abstinence, and incident smoke-free days. RESULTS: At Week 6, Flavor and Original did not differ in ≥ 50% CO reduction (14.3% vs 14.2%; IRR=1.0, 95% CI=0.6-1.8) or mean CO (18.3 vs 16.5 ppm; β=1.9, 95% CI=-1.3-5.0). CPD decreased across groups by Week 6, with no differences between Flavor and Original in ≥ 50% CPD reduction (50.3% vs 51.6%; IRR=1.0, 95% CI=0.8-1.2) or CO-verified abstinence (9.3% vs 8.9%; IRR=1.0, 95% CI=0.5-2.2). Flavor increased smoke-free days early, with attenuation over time. Among Week 3 non-responders, delayed flavor access increased ≥ 50% CPD reduction at Week 6 (33.3% vs 18.6%; IRR=1.8, 95% CI=1.0-3.2). CONCLUSIONS: NP access supported cigarette reduction regardless of flavor availability, but flavors may accelerate smoke-free days and improve response among individuals who do not reduce cigarette consumption with unflavored products alone.

Humans↗

PubMed2026

Comparing trajectories of cognitive functioning in treatment-resistant and non-resistant depression: a multicentre linear mixed-effects analysis.

BACKGROUND: Impaired cognitive functioning is a severe symptom in major depressive disorder (MDD). Recent evidence suggests it may be a central characteristic in its treatment resistant form (TRD), potentially constituting a clinical marker for treatment resistance and a target amenable to intervention. To date, cognitive functioning in TRD remains poorly understood and longitudinal investigations are scarce. METHODS: This observational prospective cohort study, including 320 patients diagnosed with MDD from the multicentre PROMPT study, examined differences in cognitive functioning between 118 TRD and 202 non-TRD patients over a period of twelve weeks in a real-world setting, using linear mixed modelling. Patients that failed to respond to at least two prior antidepressants trials at baseline were classified as TRD. RESULTS: TRD patients showed significantly poorer baseline performances than non-TRD patients in attention/processing speed (β = -0.45; 95%CI[-0.70, -0.19]; FDR-p = 0.003) and verbal memory (β = -0.45; 95%CI[-0.72, -0.18]; FDR-p = 0.003). Significant time × group interactions were observed in motor speed and verbal fluency tasks. Post-hoc-analyses revealed stagnation in TRD patients and significant improvement in non-TRD patients. Across all other tasks improvement was observed in both groups, and random effects showed large heterogeneity between patients, indicating notable individual differences in cognitive performances. CONCLUSIONS: The results suggest distinct recovery patters between non-TRD and TRD patients, and diminished functioning in TRD patients at the domain level. However, intact and diminished performances likely occur in both groups, warranting further investigation of cognitive heterogeneity. These short-term findings highlight the need for more comprehensive longitudinal research on cognition in TRD.

Humans↗

PubMed2026

Effects of Transcranial Direct Current Stimulation and Individualized Physical Therapy on Pain and Function in Individuals With Chronic Knee Pain: A Pilot Study.

BACKGROUND AND PURPOSE: Noninvasive brain stimulation is a promising neuromodulatory intervention for chronic pain. This study aimed to determine the impact that transcranial direct current stimulation (tDCS) in combination with individualized physical therapy (PT) has on pain and function in individuals with chronic knee pain. METHODS: This study was a preliminary pragmatic, triple-blinded, randomized, and sham-controlled clinical trial performed in an outpatient orthopedic physical therapy clinic. Participants participated in 5 sessions of active or sham tDCS followed by individualized PT intervention. Pain outcomes included the Numeric Pain Rating Scale, Movement-Evoked Pain, pressure pain thresholds (PPT), and the Central Sensitization Inventory. Functional outcomes included the 2-minute walk test, 5-time sit-to-stand test, quadriceps strength, knee range of motion, Patient Specific Functional Scale, and the Lower Extremity Functional Scale. RESULTS: Thirty participants with chronic knee pain completed the study. There were no significant differences observed for primary patient-centered pain and functional outcomes. For secondary outcomes, the active tDCS group had a significant effect (p < 0.05) on percent change in lateral joint line PPT and a significant multivariate effect of group on PPT change scores for 3-site and 5-site clusters (p < 0.05). Exploratory responder analyses demonstrated that the active tDCS group was 12.8 times more likely to achieve the minimum detectable change in quadriceps strength improvement compared with the sham tDCS group (p < 0.05). DISCUSSION: There were no significant between-group differences for primary pain and functional outcomes. However, the active tDCS group showed improvements in pain sensitivity, as measured by PPT, and quadriceps strength, which were superior to those seen in the sham tDCS group. These preliminary findings provide insight into possible mechanisms of tDCS in addressing pain as opposed to efficacy. Given that there were no clear between-group differences in patient-centered outcomes, there is insufficient evidence for routine tDCS use for chronic knee pain. TRIAL REGISTRATION: NCT06132412.

Humans↗

PubMed2026

Systematic Review of Pharmacologic Treatment for Migraine Prevention in Adults: Report of the AAN Guidelines Subcommittee and the American Headache Society.

BACKGROUND AND OBJECTIVES: This systematic review (SR) provides updated evidence-based conclusions regarding the use of pharmacologic migraine prevention in adults to inform a new joint American Academy of Neurology (AAN) and American Headache Society practice guideline. METHODS: A multidisciplinary panel conducted an SR following the 2017 AAN Clinical Practice Guideline Process Manual. Randomized controlled trials evaluating pharmacologic preventive treatments for adults with episodic or chronic migraine were included. Searches encompassed MEDLINE, Embase, and ClinicalTrials.gov from database inception through June 6, 2024. Studies were screened in duplicate, with dual independent risk-of-bias assessment. Outcomes included change in monthly headache days, ≥50% responder rate, and validated patient-reported quality of life (QOL) measures. Raw mean differences, standardized mean differences, and risk ratios were calculated. A modified Grading of Recommendations Assessment, Development, and Evaluation process was used to classify certainty of evidence. RESULTS: A total of 217 studies met inclusion criteria. For episodic migraine, high-confidence evidence showed that galcanezumab and erenumab are more effective than placebo in reducing headache frequency. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, fremanezumab, propranolol, topiramate, and valproate. Several additional oral agents including amitriptyline, bisoprolol, flunarizine, fluoxetine, levetiracetam, metoprolol, nifedipine, pizotifen, and telmisartan had low-confidence evidence suggesting possible benefit. For chronic migraine, high-confidence evidence supported reductions in headache frequency with fremanezumab, galcanezumab, and onabotulinumtoxinA. Moderate-confidence evidence supported benefit from atogepant, eptinezumab, erenumab, topiramate and valproate. Across both episodic and chronic migraine populations, erenumab, fremanezumab, galcanezumab, eptinezumab, rimegepant, atogepant, topiramate and onabotulinumtoxinA demonstrated improvements in patient-reported QOL outcomes on validated instruments. Evidence comparing active treatments was limited and generally of low or very low confidence, restricting conclusions about comparative effectiveness. DISCUSSION: This SR provides a comprehensive synthesis of evidence on pharmacologic migraine prevention in adults. High- and moderate-confidence findings confirm the efficacy of several established and newer preventive therapies and demonstrate improvements in patient-reported outcomes across multiple validated measures. These conclusions informed the development of evidence-based recommendations, presented in a companion publication, to guide clinicians in selecting preventive medications for adults with episodic and chronic migraine.

Humans↗

PubMed2026

Effectiveness of artificial intelligence in nursing simulation education: A systematic review, meta-analysis and bibliometric visualization analysis.

OBJECTIVES: To synthesize the roles and core functions of AI in nursing simulation education for nursing students via systematic review, quantitatively evaluate its effects on students' knowledge and skill outcomes through meta-analysis, and map the research landscape and development trends of this field through bibliometric visualization analysis. DESIGN: Systematic review, meta-analysis and bibliometric visualization analysis. DATA SOURCES: Eight electronic databases: PubMed, Web of Science, MEDLINE, ERIC, Academic Search Complete, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Chinese Science and Technology Journal Database (VIP) were employed to search studies from the time of construction to 16 December 2025. REVIEW METHODS: Studies meeting the inclusion criteria were screened. The revised Cochrane Risk of Bias tool (ROB 2) and Joanna Briggs Institute (JBI) critical appraisal checklists were used for quality assessment. Meta-analysis was performed with Review Manager 5.4, and bibliometric visualization analysis was conducted using VOSviewer 1.6.20 and Bibliometrix (based on R4.4.3). RESULTS: A total of 61 studies were included. AI primarily played two roles in nursing simulation education: peer-type new subject (n = 24) and direct mediator (n = 22). Meta-analysis showed that AI interventions significantly improved nursing students' knowledge (SMD = 1.49, 95% CI [0.55,2.43], p = 0.002) and skills (SMD = 0.66, 95% CI [0.02,1.31], p = 0.04). Bibliometric analysis identified that the United States of America and China were the two main contributing countries in this field, and the key motor themes included generative artificial intelligence, virtual patients, and geriatric care. CONCLUSIONS: AI exerts positive effects on nursing students' knowledge acquisition and skill enhancement in simulation education, with peer-type new subject and direct mediator as the dominant roles. Future research should focus on expanding AI applications in multi-specialty simulation scenarios, activating the data-driven value of machine learning, and strengthening international collaboration and standardization construction, so as to promote the sustainable development of AI-integrated nursing simulation education.

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