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The potential of clustering methods for pre-test triage in sleep medicine: A systematic review.

Sleep disorders exhibit substantial heterogeneity, and traditional classifications may not fully capture clinically relevant subtypes. Clustering techniques can identify patient subgroups that improve phenotypic characterization and may support personalized management. This systematic review evaluated the application of clustering in sleep medicine, with particular focus on its potential use as a pre-test triage tool prior to formal sleep testing. PubMed/MEDLINE, Embase, Web of Science, and Scopus were searched to February 2025. Eligible studies applied clustering to classify sleep disorders in adults. Two reviewers independently conducted screening, data extraction, and risk-of-bias assessment using QUADAS-2. The protocol was registered on PROSPERO. Fifty-one studies (1983-2025) were included, predominantly focused on obstructive sleep apnea (OSA) (n = 38, 74%). Hierarchical clustering (n = 20) and K-means clustering (n = 14) were the most frequently used techniques. Internal validation was reported in only 18% of studies, and external validation was reported in only 1 study. Seven studies relied exclusively on baseline clinical, demographic, or questionnaire data, representing pre-test scenarios, whereas most incorporated polysomnography-derived variables, limiting their applicability to early clinical stratification. Hierarchical clustering was the most commonly applied method; however, the overall lack of validation limits confidence in the robustness and clinical applicability of identified phenotypes. The potential role of clustering as a pre-test triage strategy remains largely unexplored, as most studies focused on post-diagnostic phenotyping and were affected by incorporation bias. Future research should prioritize pre-test clinical variables, rigorously validate internally and externally, and adopt standardized methodological and reporting practices to facilitate clinical translation.

Humans

Age-dependent reorganization of behavioral and striatal function in Cntnap2 knockout mice.

Autism spectrum disorder (ASD) is characterized by persistent deficits in social communication and the presence of restricted and repetitive behaviors. While ASD has a neurodevelopmental origin, it remains a lifelong condition, yet little is known about how its behavioral and neural features evolve across adulthood. Here, we investigated behavioral, synaptic, and structural alterations across the transition from early to mature adulthood in Cntnap2 knockout mice, a widely used model of ASD. Using a longitudinal behavioral approach combined with electrophysiological recordings and morphological analysis, we show that KO mice exhibit increased stereotyped and repetitive behaviors and reduced exploratory activity at both ages. However, detailed analysis of behavioral patterns revealed age-dependent differences, with early adult KO mice displaying increased behavioral persistence that later evolved into distinct patterns of behavioral sequences. These behavioral changes were associated with alterations in inhibitory synaptic transmission in the dorsolateral striatum (DLS), including changes in spontaneous inhibitory postsynaptic current (sIPSC) frequency and temporal structure. In parallel, mature adult KO mice showed structural remodeling of spiny projection neurons, characterized by increased distal dendritic arborization and age-dependent organization of dendritic spines. Together, our findings demonstrate that ASD-related alterations are not static but evolve across adulthood, revealing a multi-level reorganization of behavioral, synaptic, and structural features. These results highlight the importance of considering adulthood stages in ASD and provide new insights into the dynamic nature of the condition.

Animals

How to assess different types of abstract concepts in brain disorders: A systematic review.

The clinical evaluation of semantic knowledge has predominantly relied on tools targeting concrete concepts, whereas abstract knowledge has historically received limited attention despite its importance in everyday communication. Only a few instruments have explored the internal subdivision of abstract knowledge, likely due to the intrinsic difficulty of defining specific types of concepts or dimensions, resulting in a fragmented and heterogeneous neuropsychological assessment framework that limits our understanding of this domain. This systematic review examined the tools used to assess various types of abstract concepts in clinical populations. A literature search has been performed on the electronic databases of PubMed and Google Scholar (last update: October 2025). A total of 17 tests is reviewed, differing in the test characteristics, i.e. ranging from automatic to controlled processes and varying in ecological validity, the type of stimuli employed, and the abstract dimensions explored. Most studies have focused on neurodegenerative patients, while comparatively few have examined other clinical conditions. The risk of bias of the reviewed studies was assessed using an ad hoc developed instrument. This review highlights the need for future research to extend investigations to additional abstract domains and clinical populations, while also identifying key challenges related to stimulus selection and the determination of the most appropriate assessment framework.

Humans

The effect of antiretroviral therapy adherence on viral load suppression rate among people living with HIV in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: Antiretroviral therapy (ART) adherence is a key determinant of viral load suppression among people living with HIV (PLHIV). In Ethiopia, evidence on the magnitude of ART adherence and its effect on virological outcomes remains fragmented. This systematic review and meta-analysis aimed to estimate the pooled prevalence of ART adherence and viral load suppression, and to measure the association between adherence and viral suppression among PLHIV in Ethiopia. METHODS: This systematic review and meta-analysis used the PRISMA checklist for systematic reviews and meta-analyses. The review protocol has been registered onPROSPERO:(CRD420251125899). PubMed, ScienceDirect, Scopus, Epistemonikos, and Google Scholar were searched. The quality of included articles has been evaluated with a Newcastle-Ottawa Scale (NOS), adapted for observational studies. A random-effects model using restricted maximum likelihood (REML) with Knapp-Hartung adjustment was used to estimate pooled prevalence and odds ratio. Heterogeneity was assessed using I2, τ2, and Cochran's Q test. RESULTS: A total of 39 studies were included in the final analysis. The pooled prevalence of good ART adherence was 79.4% (95% CI: 74.8%-83.4%), while the pooled viral load suppression rate was 77.5% (95% CI: 72.5%-81.8%). The pooled odds ratio showed that good ART adherence was strongly associated with viral load suppression (OR = 6.30, 95% CI: 4.84-8.19). Substantial heterogeneity was observed across studies for both adherence and viral suppression outcomes (I2 > 90%). CONCLUSIONS: ART adherence and viral load suppression among PLHIV in Ethiopia are relatively high but remain below global targets. Good adherence was significantly associated with virologic suppression, highlighting adherence as a critical modifiable factor for achieving optimal treatment outcomes. Strengthening adherence support interventions is essential to improve virological success and advance progress toward HIV epidemic control.

Humans

Immersive virtual reality-assisted anatomy training improves endotracheal intubation performance in simulation: a randomized controlled trial among Chinese non-anesthesiology residents.

INTRODUCTION: This study aimed to compare immersive virtual reality (IVR)-assisted versus conventional anatomy training for teaching endotracheal intubation (ETI) to novice non-anesthesiology residents enrolled in China's Standardized Residency Training program. METHODS: A total of 90 non-anesthesiology residents without prior ETI experience were randomly assigned to either an IVR group receiving IVR-assisted anatomy training (n&#x2009;=&#x2009;45) or a control group receiving conventional anatomy training (n&#x2009;=&#x2009;45). All participants underwent a standardized teaching protocol. The primary endpoint was residents' ETI performance on a simulator, assessed using both the Global Rating Scale (GRS) and a task-specific checklist. The secondary endpoints included changes in written multiple-choice question (MCQ) scores and residents' evaluations of the course. RESULTS: In practical ETI assessments on a manikin, the IVR group achieved significantly higher scores on the task-specific checklist than the control group (90.34&#x2009;&#xb1;&#x2009;2.89 vs. 87.20&#x2009;&#xb1;&#x2009;3.29; p&#x2009;<&#x2009;0.001), whereas GRS scores were comparable between groups. Both groups showed significant post-training improvement in knowledge scores (p&#x2009;<&#x2009;0.001), with the IVR group showing a greater gain in theoretical knowledge (54.0% vs. 36.3%; p&#x2009;<&#x2009;0.001). Participants in the IVR group also expressed a stronger preference for their training method (80.8%) and reported higher levels of motivation, confidence, and enjoyment (all p&#x2009;<&#x2009;0.05). CONCLUSION: IVR-assisted anatomy training enhances the effectiveness of ETI training for novice non-anesthesiology residents, offering an interactive, engaging, and reproducible approach within China's Standardized Residency Training framework.

Humans

Comparison of clinical efficacy and gut microbiota characteristics in children with ASD treated with fecal microbiota transplantation and ketogenic diet.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, along with restricted, repetitive patterns of behavior. It is often accompanied by gastrointestinal dysfunction and gut microbiota dysbiosis. Fecal Microbiota Transplantation (FMT) and the Ketogenic Diet (KD) are interventions targeting the gut microbiota for ASD. METHODS: 30 participants were diagnosed with ASD according to DSM-5 and ADOS-2. ASD core symptoms were evaluated with CARS and ABC. Gut microbiota composition was analyzed by shotgun metagenomic sequencing. RESULTS: Both groups demonstrated significant improvements in core symptoms. In the FMT group, the mean CARS score significantly decreased from 34.87 to 33.53 (p&#x2009;<&#x2009;0.01); in the KD group, it declined from 35.13 to 33 (p&#x2009;<&#x2009;0.01). The mean ABC score reduced from 79.93 to 69.33 (p&#x2009;=&#x2009;0.064) in the FMT group and from 63.07 to 42.73 (p&#x2009;<&#x2009;0.01) in the KD group. Following the intervention, no statistically significant changes were observed in &#x3b1;-diversity or &#x3b2;-diversity within either group. LEfSe analysis revealed distinct post-intervention microbial signatures: FMT significantly enriched butyrate-producing taxa (Wujia chipingensis, Eubacterium sp. MSJ-33, and Butyrivibrio crossotus), while KD elevated Blautia massiliensis and decreased propionate metabolism -associated taxa (Veillonella sp. S12025-13 and Veillonella nakazawae). KEGG enrichment analysis revealed that KD enriched propionate metabolism (Fold enrichment&#x2009;=&#x2009;3.747, q&#x2009;=&#x2009;0.010) and aromatic compound degradation (Fold enrichment&#x2009;=&#x2009;3.591, q&#x2009;=&#x2009;0.010). CONCLUSIONS: Both interventions significantly improved clinical symptoms among children with ASD, potentially through distinct patterns of gut microbiota modulation. CLINICAL TRIALS NUMBER: NCT06348433 (03/21/2024).

Child

Prevalence of psychosis in South Asia: A systematic review and meta-analysis.

BACKGROUND: Psychotic disorders are a major contributor to global disability, yet prevalence data from South Asia which inhabits a quarter of the world's population, remain limited. Reliable estimates are essential for health service planning, policy, and closing the substantial treatment gap. This review provides the first comprehensive synthesis of psychosis prevalence across South Asia. METHODS: We searched PubMed, Embase, Web of Science, Global Health, and Medline to 18 December 2024 for DSM- or ICD-based prevalence studies in Afghanistan, Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka. Cross-sectional and longitudinal studies in community or clinical populations were included. Study quality was assessed using the Joanna Briggs Institute checklist. Random-effects meta-analyses estimated pooled prevalence using the logit transformation. Heterogeneity was explored with meta-regression of key methodological variables (publication year, diagnostic system, residential setting). FINDINGS: Thirty-one studies from five countries were included. Among community-dwelling adults, pooled point prevalence was 0.85% and lifetime prevalence was 1.40%, with inter-country differences (India 1.18%, Pakistan 2.13%, Nepal 2.90%). Clinical samples showed substantially higher proportions of individuals with psychosis in service settings (11.44%), reflecting concentration of cases in treatment-seeking samples. Data for children and adolescents were limited and summarised narratively. Heterogeneity was high across meta-analyses, and exploratory meta-regression did not identify any significant moderators. INTERPRETATION: Psychosis prevalence estimates in South Asia appear higher than global averages but should be interpreted cautiously due to substantial heterogeneity and methodological variation; nevertheless, they highlight the need for culturally sensitive screening, improved detection, and strengthened mental health services.

Humans

Psychedelic-induced hypomania and mania: a systematic review and meta-analysis.

Serotonergic psychedelics are increasingly investigated as treatments for affective disorders. Concerns persist regarding their potential to induce hypomania or mania, particularly in individuals with bipolar spectrum vulnerability. Whether these substances precipitate transient mood switches or contribute to persistent bipolar illness or diagnostic transition remains unclear. We conducted a systematic review of human studies examining manic or hypomanic symptoms following exposure to serotonergic psychedelics (psilocybin, LSD, mescaline, DMT/ayahuasca) or MDMA (CRD420251160656). Databases and trial registries were searched through January 26, 2026. Eligible designs included randomized and non-randomized clinical studies, registry-based cohorts, cross-sectional surveys, and longitudinal observational studies. Outcomes included dysphoria/euphoria, manic or hypomanic symptoms and transition to bipolar disorder. Risk of bias was assessed using ROBINS-I, ROB2 or NIH tools. Twenty-three studies met inclusion criteria, four contributing to meta-analysis. Rates of psychedelic-associated dysphoria/euphoria, hypomania or mania ranged from 5.8% in controlled trials of psilocybin-assisted psychotherapy for major depressive disorders to 30% in naturalistic studies of individuals with bipolar disorder. When present, manic symptoms were typically acute and self-limited. Observational studies identified higher risks among individuals with bipolar I disorder, familial vulnerability, polysubstance use, and unsupervised or illegal use. Registry-based cohorts examining diagnostic transitions showed a prevalence of subsequent transition to bipolar disorder of 4% (95% CI 2-8%; N&#x2009;=&#x2009;7478; I&#xb2;&#x2009;=&#x2009;32.1%), with little evidence for a hallucinogen-specific signal. Overall, serotonergic psychedelics appear to pose a low but clinically meaningful relative risk of transient mood-related symptoms in susceptible individuals while remaining relatively safe in controlled clinical settings. Long-term outcomes and repeated exposure remain insufficiently studied, underscoring the need for rigorous longitudinal research.

Humans

Hyperbaric oxygen for the treatment of traumatic incomplete spinal cord injury: a systematic review and meta-analysis of randomized controlled trials.

The therapeutic efficacy of hyperbaric oxygen therapy for traumatic incomplete spinal cord injury remains a subject of debate. To comprehensively evaluate the impact of hyperbaric oxygen on motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury, we conducted a systematic review and meta-analysis. We performed a comprehensive search across PubMed, Embase, the Cochrane Library, Web of Science, and major Chinese databases for randomized controlled trials published through June 2025. A total of 15 randomized controlled trials were included. The pooled results indicated that hyperbaric oxygen therapy significantly improved the American Spinal Injury Association motor score (mean difference = 10.30, 95% confidence interval: 7.70-12.90), the total American Spinal Injury Association sensory score (mean difference = 29.29, 95% confidence interval: 18.82-39.75), the American Spinal Injury Association light touch score (mean difference = 9.84, 95% confidence interval: 6.15-13.53), and the American Spinal Injury Association pinprick score (mean difference = 8.75, 95% confidence interval: 4.40-13.11). Furthermore, hyperbaric oxygen therapy was associated with significant enhancements in the Barthel Index (mean difference = 16.60, 95% confidence interval: 10.51-22.68) and the Functional Independence Measure (mean difference = 17.41, 95% confidence interval: 10.83-23.98). In conclusion, adjunctive hyperbaric oxygen therapy appears to improve motor function, sensory function, and activities of daily living in patients with traumatic incomplete spinal cord injury compared to conventional treatments alone. However, due to methodological limitations and potential publication bias in the included studies, these findings should be interpreted with caution, and further high-quality, multi-center randomized controlled trials are warranted.

Humans

Epigenetic Clocks of Biological Aging and Cognitively Healthy Longevity: The Women's Health Initiative Memory Study.

BACKGROUND: Little is known about whether epigenetic age acceleration (EAA) clocks are capable of predicting exceptional longevity with or without preserved cognitive function. METHODS: We examined 5844 women from the Women's Health Initiative Memory Study. Fifteen epigenetic clocks were measured at baseline (1996-1999). Longevity outcomes were defined as: 1) survival to age 90 with preserved cognition (n&#x2009;=&#x2009;1726, 29.5%); or 2) survival to age 90 with cognitive impairment (n&#x2009;=&#x2009;956, 16.4%); vs. 3) death before age 90 (n&#x2009;=&#x2009;2611, 44.7%). Logistic regression models examined associations between the 15 clocks and survival to age 90 (vs. death before age 90), adjusting for covariates. Multinomial logistic regression models examined associations with survival to age 90 without cognitive impairment and survival to age 90 with cognitive impairment (each vs. death before age 90), also adjusting for covariates. RESULTS: Each standard deviation increase in EAA for the first-generation clocks was associated with 7%-18% reduced odds of survival to age 90 vs. earlier death. Stronger associations were observed for second- and third-generation clocks, including AgeAccelGrim2 (OR&#x2009;=&#x2009;0.66; 95% CI 0.61-0.71), PCGrimAge (OR&#x2009;=&#x2009;0.64; 95% CI 0.59-0.69), PCPhenoAge (OR&#x2009;=&#x2009;0.73; 95% CI 0.68-0.78) and DunedinPACE (OR&#x2009;=&#x2009;0.77; 95% CI 0.72-0.82). None of the clocks was more strongly associated with survival to age 90 with preserved cognition than with survival to age 90 with cognitive impairment, relative to death before age 90. CONCLUSION: All epigenetic clocks were associated with exceptional longevity, but none were associated with cognitive healthspan. Developing clocks that can differentiate long survival with and without preserved cognitive function is critical.

Healthspan

Excimer laser angioplasty for acute coronary occlusion: a stratified meta-analysis of efficacy against aspiration thrombectomy and conventional PCI.

Primary percutaneous coronary intervention (PCI) achieves epicardial reperfusion in most STEMI patients, yet microvascular obstruction persists in up to 60% of patients. Excimer laser coronary angioplasty (ELCA) vaporizes thrombus in situ and may reduce distal embolization, but the evidence base has not been systematically synthesized. This systematic review and meta-analysis (PROSPERO CRD420261422463) included comparative studies of adjunctive ELCA versus aspiration thrombectomy (Stratum A) or PCI alone (Stratum B) in acute coronary occlusion. Primary outcomes were final TIMI-3 flow and myocardial blush grade (MBG) 3; secondary outcomes were short-term mortality, MACCE, and slow-flow/no-reflow. A random-effects model with Hartung-Knapp-Sidik-Jonkman confidence intervals was applied to all outcomes. Certainty was assessed with GRADE. Ten studies (1 RCT, 9 observational) were included, from a total enrolled population exceeding 3,500. In Stratum A, no outcome reached significance: MBG-3 (OR 3.57, 95% CI 0.07-185.10), mortality (OR 0.31, 0.02-4.04), MACCE (OR 0.22, 0.04-1.26), TIMI-3 flow (OR 1.58, 0.67-3.75) and slow-flow/no-reflow (OR 0.78, 0.22-2.78). In Stratum B, using each study's propensity-matched data, no outcome differed significantly (TIMI-3 OR 0.88, 0.38-2.03; MBG-3 OR 1.06, 0.13-8.43; slow-flow/no-reflow OR 0.93, 0.29-3.02; mortality OR 0.44, 0.05-3.80). Composite endpoints were not pooled across incompatible follow-up horizons, and all outcomes were of very low certainty. Adjunctive ELCA-containing strategies during primary PCI were not associated with improved angiographic or short-term clinical outcomes against either comparator. Multicenter randomized trials are required before recommending clinical adoption.

Humans

Biologic-biologic and biologic-JAK inhibitor combination therapy in refractory systemic autoinflammatory diseases.

OBJECTIVES: Systemic autoinflammatory diseases (SAIDs) arise from genetic defects in innate immunity, leading to dysregulated activation of inflammatory pathways, including interleukin (IL)-1, IL-6, TNF, and JAK/STAT. Clinical manifestations range from recurrent fever to severe complications such as encephalitis and AA amyloidosis. Management aims to control inflammation using immunosuppressive agents and targeted monotherapies (biologics or JAK inhibitors). Advanced combination therapy (ACT), defined as the use of biologics and/or JAK inhibitors in combination, has emerged as a strategy for refractory disease. METHODS: In this observational retrospective longitudinal cohort study, patients with SAIDs treated with ACT were included. Demographic, clinical, treatment, and safety data were collected. Treatment response was assessed using a composite outcome incorporating corticosteroid dose, C-reactive protein (CRP), and clinical improvement and categorized as non-response, partial response, or complete response. RESULTS: Thirty-eight patients (median age 30 years [range 4-76]) were included. The most common indications for ACT were pyogenic arthritis, pyoderma gangrenosum and acne (PAPA), mevalonate kinase deficiency (MKD), and undifferentiated SAIDs. Most patients had disease-related complications and were dependent on glucocorticoids and/or opioids to control inflammation and pain, respectively. Following multiple ACT trials, complete response was observed in 21 patients (55.3%), partial response in 12 (31.6%), and no response in 5 (13.1%). Overall, 65 ACT regimens were administered, most commonly combining IL-1 and TNF inhibitors. Thirty-nine regimens were discontinued because of lack of efficacy, secondary loss of response, or adverse events. At the final follow-up, 26 patients (68%) remained on ACT, with a median treatment duration of 60 months (range, 11-186). CONCLUSIONS: ACT offers significant clinical benefits for patients with difficult-to-treat SAIDs, though challenges such as secondary loss of efficacy and infection risks remain.

Humans

Effectiveness of high-power laser use in the removal of esthetic restorations: a systematic review.

This systematic review aimed to evaluate the effectiveness of high-power lasers in the removal of esthetic restorations compared with conventional methods. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) and registered in PROSPERO (registration number: CRD420251055736). A comprehensive electronic search was performed in MEDLINE, Scopus, Embase, Web of Science, and the Cochrane Library. Study selection, data extraction, and methodological quality assessment were independently performed by four reviewers using QUIN tool for in vitro studies. A total of 2.384 records were identified, of which 19 in vitro studies conducted on extracted human permanent teeth met the eligibility criteria and were included in the qualitative synthesis. The included studies evaluated different high-power laser systems, predominantly Er: YAG and Er, Cr: YSGG lasers, as well as CO&#x2082; lasers. Five studies were classified as high quality, whereas the remaining fourteen studies were classified as moderate quality. Available laboratory evidence suggests that laser-assisted techniques may represent a potential alternative approach for removing esthetic restorations, with advantages including conservative tissue removal, reduced damage to underlying tooth structures, and intrapulpal temperature increases within acceptable limits. The Er: YAG laser was the most frequently investigated system, with power settings ranging from 1.5 to 5.9&#xa0;W, showing particularly favorable laboratorial performance in the removal of lithium disilicate restorations, especially in thinner substrates. Within the limitations of the available evidence, high-power lasers appear to be a promising and minimally invasive alternative to conventional methods for the removal of esthetic restorations. However, the predominance of in vitro studies highlights the need for well-designed clinical trials to confirm these findings and support their clinical application.

Humans

Genetic evidence for a causal relationship between melatonin metabolism and depression.

To investigate the causal relevance of melatonin metabolism, which provides the biological basis for circulating melatonin levels, to specific depression symptom subtypes, we performed a targeted systematic review of melatonin metabolism pathways in the human brain and liver. Using two-sample Mendelian randomization (MR), we assessed the causal effects of metabolism pathways and/or individual genes on major depressive disorder (MDD) and nine symptom subtypes derived from Patient Health Questionnaire-9 (PHQ-9). Instrumental variables (IVs) were expression quantitative trait loci (eQTL) for eight individual genes, one synthesis route, and three degradation routes. Results were assessed using Bayesian colocalization and phenome-wide association analyses. At the pathway-level, the genetically proxied synthesis-route signal was associated with PHQ-9 Assessment 5 (PHQ9A5, OR: 0.89, 95% CI: 0.85-0.93), but sensitivity analyses suggested this association was primarily driven by TPH1 and may reflect serotonin-related biology. In contrast, higher brain melatonin degradation raised the risk of both PHQ9A1 (OR: 1.03, 95% CI: 1.02-1.04) and PHQ9A7 (OR: 1.03, 95% CI: 1.02-1.03). Within degradation, up-regulation of the kynurenine sub-pathway increased the odds of PHQ9A3 (OR: 1.05, 95% CI: 1.02-1.07), PHQ9A4 (OR&#xa0;=&#xa0;1.04, 95% CI: 1.02-1.06) and PHQ9A7 (OR: 1.05, 95% CI: 1.02-1.07). Gene-level analyses were largely concordant, except for SULT1A1, whose higher expression was genetically protective for PHQ9A3 but risk-increased for PHQ9A1 and PHQ9A4. Overall, these results demonstrate that melatonin metabolism exerts symptom-specific and pathway-specific causal effects on depression. A stratified view of melatonin's role may help optimize the application of exogenous melatonin supplementation.

Melatonin

Long-term efficacy of cognitive behavioural therapy for insomnia (CBT-I) on depressive symptoms: A systematic review and meta-analysis of randomised controlled trials.

Depressive symptoms are common in individuals with persistent insomnia. Previous meta-analyses of randomised controlled trials (RCTs) showed that cognitive behavioural therapy for insomnia (CBT-I) can reduce depressive symptoms at post-treatment. However, the long-term maintenance of these improvements has never been systematically examined. To fill-in this gap, we conducted a systematic review and meta-analysis of the long-term (&#x2265;3 months) effects of CBT-I on depressive symptoms. The review was registered in PROSPERO (CRD420251146061). Only RCTs in adults with insomnia were considered. Pubmed, Scopus, Psycinfo, CINAHL, and Medline were searched up to 12 September 2025 with no predefined time constraints. From 5359 records initially retrieved, we included 53 articles reporting on 13,608 individuals. After outliers removal, random effects meta-analysis showed that CBT-I was superior to control conditions in reducing depressive symptoms at 3 [k&#x202f;=&#x202f;29, d&#x202f;=&#x202f;-.35, [95% CI: -.49 to -.21], p&#x202f;<&#x202f;.001], 6 [k&#x202f;=&#x202f;29, d&#x202f;=&#x202f;-.32, [95% CI: -.59 to -.05], p&#x202f;=&#x202f;.018], and 12 [k&#x202f;=&#x202f;10, d&#x202f;=&#x202f;-.25, [95% CI: -.39 to -.12], p&#x202f;<&#x202f;.001] months follow-ups. Results demonstrate that the effects of CBT-I on depressive symptoms are sustained throughout the year following treatment, although effects may decline over time.

Humans

Treatment-related associations of nucleus accumbens connectivity within mesocorticolimbic circuits in depression.

Pharmacological treatment remains a mainstay in managing depression, yet the neural correlates associated with treatment response remain incompletely understood. This study used multimodal neuroimaging to examine nucleus accumbens (NAc)-centered structural and functional alterations associated with fluoxetine and Shugan Jieyu Capsule (SG), a traditional Chinese medicine, in patients with mild-to-moderate depression (MMD). Sixty patients were randomized to an 8-week course of fluoxetine or SG. Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HAMD-24), and structural and functional MRI scans were acquired at baseline and endpoint. Both treatments were associated with significant symptom improvement. Neuroimaging analyses revealed structural and functional alterations involving the NAc. Changes in NAc-amygdala connectivity showed an exploratory association with symptom improvement in the SG group, whereas changes in NAc-rostral anterior cingulate cortex connectivity were associated with symptom improvement in the fluoxetine group and remained significant after correction for multiple comparisons. In addition, remitters exhibited stronger baseline connectivity between the NAc and ventral tegmental area and between the NAc and middle frontal gyrus compared with non-remitters. These findings suggest that NAc-centered connectivity may be relevant to treatment-related neural changes in depression and may inform future research on imaging-based candidate markers of treatment response and personalized treatment approaches. TRIAL REGISTRATION: The study is registered in https://www.chictr.org.cn/ with a registration number ChiCTR1900024988 (date: 08.06.2019).

Humans

Fractional laser therapy versus microneedling for non-acne scars and scar-like dermal fibrotic lesions.

BACKGROUND: Scarring caused by trauma, burns, surgery, and other dermal fibrotic conditions can lead to functional limitation and cosmetic distress. The comparative effectiveness of fractional laser therapy and microneedling for non-acne scars remains uncertain. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials comparing fractional laser therapy with microneedling for non-acne scars and scar-like dermal fibrotic lesions. Following a PROSPERO-registered protocol and PRISMA guidelines, we searched PubMed, EMBASE, Web of Science, Cochrane Library, and CNKI from inception to May 2026 without language restrictions. Parallel-group and split-body randomized trials were eligible. Random-effects models were used to calculate standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes. RESULTS: Nine randomized controlled trials were included. Fractional laser therapy showed a statistically significant advantage over microneedling in scar scores (SMD = -0.99, 95% CI [-1.83, -0.15], P&#x2009;=&#x2009;0.02) and collagen fiber regeneration (SMD = -2.14, 95% CI [-3.57, -0.72], P&#x2009;=&#x2009;0.03). No statistically significant differences were found between the two interventions for elastic fiber improvement, epidermal thickness, or adverse events. Subgroup analyses did not show clear or consistent significant differences according to laser type, including comparisons between traditional and non-traditional fractional lasers and between CO&#x2082; and non-CO&#x2082; fractional laser systems. Substantial heterogeneity was observed across several outcomes, indicating considerable between-study variability. CONCLUSION: Based on currently available randomized evidence, fractional laser therapy may provide superior improvement in overall scar severity and collagen fiber regeneration compared with microneedling for non-acne scars and scar-like dermal fibrotic lesions. However, no clear differences were observed for elastic fiber improvement, epidermal thickness, or adverse-event incidence. Given the substantial heterogeneity, limited sample sizes, and possible reporting bias, these findings should be interpreted cautiously. Further large, standardized trials with longer follow-up are needed.

Humans

Prospective Longitudinal Associations Between Adverse Childhood Experiences and Adult Mental Health Outcomes: Systematic Review and Meta-Analysis.

Research suggests a strong, dose-response relationship between adverse childhood experiences (ACEs) and poor adult mental health outcomes. This systematic review and meta-analysis aimed to systematically investigate the existence and strength of prospective associations between ACEs and adult mental health outcomes: anxiety, depression, psychotic-like experiences, post-traumatic stress disorder (PTSD), self-harm, and suicidality. We searched 12 electronic databases for publications after 1990. A narrative synthesis of included studies and random-effects meta-analyses with moderation were completed for all outcomes, excluding self-harm. In total, 62 studies from 15 countries were included. Most studies were from the United States; 95% of publications (N&#x2009;=&#x2009;59) came from high-income countries (HICs) and 5% (N&#x2009;=&#x2009;3) from upper-middle-income countries. Pooled associations between ACEs and adult mental illness were strongest for PTSD (OR&#x2009;=&#x2009;2.26; 95% CI [1.75, 2.77]), followed by anxiety (OR&#x2009;=&#x2009;1.78; 95% CI [1.45, 2.11]), depression (OR&#x2009;=&#x2009;1.61; 95% CI [1.45, 1.76]), psychotic-like experiences (OR&#x2009;=&#x2009;1.34; 95% CI [1.13, 1.54]), and suicidality (OR&#x2009;=&#x2009;1.28; 95% CI [1.13, 1.43]). Moderation analyses suggested ACEs with a violence or maltreatment component were significant risk factors for adult depression compared to household ACEs, and that study location was a significant moderator in the depression, anxiety, and PTSD models. Further moderation effects will be discussed. Findings confirm ACEs are a significant risk factor for mental ill-health in adulthood. Our review highlights the urgent need for research exploring associations between ACEs measured in childhood and adult mental illness outside of HIC settings.

Humans