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Diagnostic and Predictive Value of Circulating and Exosomal microRNAs in Ferroptosis-Associated Neurological Conditions: A Systematic Review and Meta-analysis.

Circulating microRNAs (miRNAs) have emerged as potential non-invasive markers for intracranial pathology, yet their diagnostic accuracy and relationship with ferroptosis-mediated neuronal damage remain poorly defined. The primary objective of this study was to evaluate the diagnostic and predictive potential of circulating and exosomal miRNAs across ferroptosis-associated neurological conditions and to explore their associations with ferroptosis-related pathways. Following PRISMA-DTA guidelines, a systematic literature search was conducted across PubMed, Scopus, Cochrane, and ScienceDirect, identifying 205 records. After screening for human clinical cohort validation, 7 studies were included in the qualitative synthesis and 5 in the quantitative meta-analysis. Pooled Area-under-the-Curve (AUC) was calculated using a random-effects inverse-variance model, while prognostic correlation coefficients (r) were synthesized using Fisher's Z-transformation. Methodological quality was assessed via QUADAS-2. Analysis of 7 clinical cohorts provided heterogeneous evidence on the diagnostic and prognostic potential of miRNAs. Random-effects pooling of the two eligible diagnostic AUC estimates yielded an exploratory pooled AUC of 0.87 (95% CI, 0.79-0.94; I2 .90%). Prognostic synthesis of Group 2 identified an exploratory association between miRNA levels and clinical severity scales (exploratory pooled correlation coefficient of 0.67 (95% CI: 0.56-0.76; I2 .714.4%). Selected miRNAs were mapped to ferroptosis-associated regulators, including SLC7A11, ABCB8, and SLC40A1. Exosomal miRNAs hold potential to indicate disease-associated molecular information, although comparative clinical evidence remains yet to be explored. Circulating and exosomal miRNAs show promising diagnostic and prognostic potential across selected neurological conditions. These findings highlight a potential mechanistic association between miRNA expression and ferroptosis-mediated neuronal injury.

Humans

Granger connectivity and graph-theoretical analysis of scalp EEG across the preictal to ictal transition for presurgical evaluation.

OBJECTIVE: To assess the feasibility of estimating lateralization and localization of the epileptogenic zone (EZ) in temporal and extratemporal lobe epilepsy by combining Electric Source Imaging (ESI) with functional connectivity analysis of high-density EEG from the preictal to the ictal phase. METHODS: Adults with drug-resistant focal epilepsy and at least one recorded seizure during 40- or 64 channels EEG monitoring were retrospectively included. Granger causality and hubness centrality were computed over the 10-s preictal interval and the first 5 s of the ictal period, with ictal onset defined as the first EEG change identified by experienced epileptologists. The reference standard for EZ localization was based on resective surgical outcome or stereo-EEG findings. RESULTS: Thirteen patients (7 females; median age 35 years) were included. Connectivity analyses showed higher concordance with clinical findings during the preictal phase than during the ictal phase for both lateralization (91% vs 46%) and localization (73% vs 27%). Performance was highest in temporal (7/7 lateralization; 6/7 localization) and frontal lobe epilepsy (2/2 for both), and lower in parieto-occipital epilepsy (1/2 and 0/2, respectively). In two cases with poor surgical outcome or no surgical indication, connectivity findings were discordant with clinical estimates. CONCLUSIONS: Connectivity analysis across the preictal to ictal transition provides relevant lateralizing and localizing information, particularly in temporal and frontal lobe epilepsy, and may reveal clinically meaningful discordance. SIGNIFICANCE: Integrating high-density EEG, ESI, and functional connectivity during the phase preceding the first EEG change may support non-invasive presurgical evaluation.

Humans

Hemotropic mono- and coinfections in Colombian ruminants: descriptive occurrence and host-related factors associated with coinfection in cattle.

Hemotropic pathogens such as Anaplasma, Babesia, Mycoplasma, and Trypanosoma are endemic to cattle and can cause coinfections, complicating disease dynamics and control. However, the host-related factors influencing these infections under tropical conditions remain poorly understood. This study aimed to investigate the occurrence of hemotropic monoinfections and coinfections in ruminants tested for hemotropic pathogens and to identify host-related factors associated with coinfection in cattle under field conditions in Colombia. A total of 104 animals were included: 91 cattle, 10 buffaloes, and 3 goats. Among the cattle, 34 (37.4%) exhibited monoinfections, 47 (51.6%) had coinfections, and 10 tested negative. In buffaloes, seven (70%) presented monoinfections, and two (20%) presented coinfections; in goats, one had a monoinfection, and one had a coinfection, most frequently involving Mycoplasma spp. The predominant coinfection patterns were Anaplasma&#x2009;+&#x2009;Mycoplasma and Mycoplasma&#x2009;+&#x2009;Trypanosoma, particularly in Bos indicus cattle. Bivariate and multivariable analyses revealed that breed was the strongest predictor of coinfection, with animals of less common breeds showing 93% lower odds (aOR&#x2009;=&#x2009;0.07; 95% CI: 0.02-0.30; p&#x2009;<&#x2009;0.001). Bos taurus individuals also tended toward lower odds of coinfection in the multivariable model, although this trend did not reach statistical significance. Our findings demonstrate a high frequency of hemotropic coinfections in cattle, particularly those involving Mycoplasma spp., and highlight the influence of host-related factors on infection dynamics. These results underscore the importance of integrating demographic and genetic information into surveillance and prevention strategies to improve the management of hemotropic infections in tropical livestock systems.

Animals

Menopause in the All of Us Research Program: a descriptive summary of electronic health record and survey response across sociodemographic characteristics.

OBJECTIVES: Menopause is a significant physiological transition with implications for health outcomes (eg, cardiometabolic disease), yet gaps remain in understanding this transition, including how menopause timing and type influence health outcomes. Large-scale cohort studies in midlife (age=40-60) females, including the All of Us Research Program (AoURP), provide opportunities to study menopause across diverse populations and data modalities. We characterized menopause-related data in AoURP, focusing on age distributions and concordance between electronic health record (EHR) diagnosis codes and survey responses. METHODS: We analyzed menopause-related surveys, EHR diagnostic codes, and genomic data among ~396,000 AoURP female participants. We summarized menopause-related variables across data sources, evaluated overlap between survey, EHR, and genomic data sets, and described age distributions overall and across sociodemographic characteristics. RESULTS: Among ~396,000 females, survey responses captured ~193,000 menopause observations, nearly seven times more than EHR diagnoses (~28,000), suggesting under-ascertainment in EHR data. Nearly all females (~99%) with an EHR menopause diagnosis reported menopause in the survey. Approximately 22,000 participants had overlapping menopause-related EHR, survey, and genomic data. Survey age patterns matched expectations, with participants predominantly <40 years reporting premenopausal status and those >60 years reporting postmenopausal status. A small subset with age >70 years (N&#x2248;1,700; 4%) reported no menopause, suggesting response or recall bias. EHR menopause codes were concentrated after age 45 years, with a notable spike at age 65. Modest differences in survey-based menopause age distributions were observed across sociodemographic characteristics (eg, race and ancestry). CONCLUSIONS: These findings inform sampling strategies, power calculations, phenotype definition, and study design for menopause research using AoURP data.

Age

An integrated multiscale air quality modelling framework for industrial park pollution: Linking local emissions to regional transport.

Capturing the spatiotemporal distribution of pollutants in industrial parks remains challenging for regional air quality models because of their coarse resolution (3 km), resulting in uncertainties in local emission quantification. To address this, we developed the Integrated Multiscale Air Quality Modelling System for Industry (IAQMS-Industry), coupling the regional Nested Air Quality Prediction Modelling System (NAQPMS) with a city-scale chemical transport model. This framework integrates point-source locations and Gaussian plume dispersion to simulate particulate matter with a diameter smaller than 2.5 micrometres (PM2.5) at 100 m resolution. Applied to the Beijing Yi Zhuang and Tangshan industrial parks and evaluated against observations. The coupled model achieved a normalized mean bias (NMB) ranging from 3.1 % to 6.2 %, improving upon NAQPMS (-16.9 % to -7.7 %). Spatial analysis revealed that coarse regional grids underestimated the PM2.5&#x200b; concentrations at industrial sites by smoothing gradients, whereas IAQMS-Industry successfully resolved spatial patterns. Industrial point emissions accounted for 22.9 %-26.4 % of PM2.5 in the coupled model, which was significantly greater than the regional model estimates of 1.6 %-13.7 %. These findings indicate that regional models overestimate pollutant dispersion processes in industrial parks while underestimating local industrial impacts. By explicitly resolving point-source dynamics and linking them to regional transport, IAQMS-Industry provides a robust tool for designing targeted emission controls in industrial cities and balancing local air quality improvements with minimized regional pollution outflow. This study underscores the necessity of multiscale modelling for accurate source apportionment and informed environmental governance in industrial zones.

Air Pollution

Hope is linked with more favorable tumor molecular signatures in serous ovarian cancer.

INTRODUCTION: Hope has been associated with improved quality of life and lower mortality in cancer, but the underlying biological mechanisms are poorly characterized. We previously reported that hope was associated with less inflammation and more normalized diurnal cortisol pre-treatment among women with ovarian cancer. We also reported associations of socio-environmental factors with pro-metastatic processes. Here, we used genome-wide transcriptional profiling to quantify associations between hope and tumor molecular signatures reflecting invasiveness, inflammation, and cellular immunity. METHOD: Participants were 74 women with serous ovarian cancer who provided demographic information and completed surveys pre-surgery. Hope was assessed using a face-valid item from the Center for Epidemiological Studies Depression Scale (CES-D). Depression was assessed using the full CES-D without the hope item. Illumina HT12 microarrays were used to assay tumor RNA, and associations between hope and tumor gene expression were quantified, adjusting for depression, age, BMI, grade, and stage. RESULTS: Adjusting for covariates, hope was associated with multiple favorable differences in RNA expression, including lower levels of mesenchymal differentiation (p&#x202f;=&#x202f;0.008) and pro-inflammatory gene regulation (NF-&#x3ba;B: p&#x202f;<&#x202f;0.001; IRF1: p&#x202f;=&#x202f;0.024; STAT: p&#x202f;=&#x202f;0.018), elevated epithelial differentiation (p&#x202f;=&#x202f;0.011), and elevated activity of the IRF7 transcription factor which promotes cellular immunity (p&#x202f;=&#x202f;0.016). CONCLUSIONS: These data suggest that hope is associated with an ovarian tumor gene expression profile characterized by reduced epithelial-mesenchymal transition (EMT) and inflammatory activity, and increased activity of a transcription factor promoting cellular immunity. These findings highlight potential biological implications of a resilience factor such as hope, but need replication with more robust assessments of hope.

Epithelial mesenchymal transition

Continuous Intravenous Lidocaine for Refractory Cancer Pain in Palliative Care: A Multicenter Feasibility Study.

ObjectivesTo assess the feasibility and tolerability of continuous low-dose intravenous lidocaine infusion in patients with opioid-refractory cancer pain receiving palliative care, and to explore its potential impact on pain outcomes in real-world clinical conditions.MethodsWe conducted a multicenter, randomized, double-blind, placebo-controlled feasibility study in palliative care units to evaluate continuous intravenous lidocaine infusion in patients with opioid-refractory cancer pain. Patients were randomized to receive lidocaine (5&#x2005;mg/kg/day, increased to 8&#x2005;mg/kg/day if pain reduction was <30% after 24&#x2005;h) or placebo for 48&#x2005;h. Pain intensity was assessed using the Numeric Pain Intensity Scale, with a clinically meaningful response defined as a&#x2009;&#x2265;30% reduction from baseline at 40&#x2005;min. Secondary outcomes included pain evolution over time, neuropathic pain, symptom burden, and tolerability.ResultsThirty-five patients were included in the final analysis (18 lidocaine, 17 placebo). No significant difference was observed between lidocaine and placebo for the primary endpoint or for secondary pain outcomes. Reductions in pain intensity were observed in both groups. In the lidocaine group, 61% of patients required dose escalation to 8&#x2005;mg/kg/day. Continuous intravenous lidocaine infusion was generally well tolerated, with mostly mild adverse events and no unexpected toxicity.ConclusionIn this multicenter feasibility study, continuous low-dose intravenous lidocaine did not demonstrate a clinically meaningful analgesic benefit over placebo. As the planned sample size was not reached, the study was underpowered. These findings highlight the challenges of randomized trials in palliative care and may inform future feasibility-oriented designs.

Humans

Cognitive-metabolic relationship in temporal lobe epilepsy: A systematic review.

OBJECTIVE: To summarize the current literature on neurometabolic dysfunction identified through brain imaging and its cognitive correlates in temporal lobe epilepsy (TLE). BACKGROUND: Cognitive decline contributes to chronic disability in TLE. The pathophysiology of cognitive decline in TLE is poorly understood, limiting therapeutic advances. Characterizing metabolic changes in patients with TLE and cognitive impairment may identify biomarkers and inform new treatment strategies. DESIGN/METHODS: We conducted a systematic review of five major databases, gathering studies published through December 2024, in accordance with PRISMA guidelines. We included all observational studies describing associations between metabolic imaging findings and cognitive measures in TLE. RESULTS: Of 1449 reports, 38 met the inclusion criteria, encompassing 1161 patients with TLE aged 5-66&#xa0;years. Twenty-two studies applied fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) to assess interictal brain glucose metabolism. Two studies utilized PET with other tracers to assess more specific metabolic aspects. Fourteen studies used proton magnetic resonance spectroscopy (1H-MRS) to quantify local concentrations of brain metabolites. Impairment of verbal memory was consistently associated with left temporal lobe metabolite changes. Non-memory cognitive impairments correlated with changes in glucose metabolism, N-acetylaspartate, and gamma-aminobutyrate in both temporal and extratemporal areas. CONCLUSION: 18F-FDG PET remains the most widely used imaging modality to assess cognitive-metabolic correlates in TLE, while other PET tracers and 1H-MRS are potentially underexplored. Verbal memory impairment correlates robustly with left temporal dysmetabolism. Cognitive impairment in TLE is multifaceted and correlates with measurable changes in metabolism in both temporal and extratemporal regions. While our synthesis was restricted by some methodological limitations, these neurometabolic signatures may hold promise as potential biomarkers for identifying risk of cognitive decline and highlight avenues for future research.

Humans

Exploratory proteomic and metabolomic profiling of pleural effusions identifies histone H4 and alanine as promising complementary markers for pleural tuberculosis.

The diagnosis of pleural tuberculosis (Pl-TB) remains challenging. Histopathological analysis and pathogen detection in pleural biopsies are informative but limited. We investigated differentially expressed proteins and metabolites in pleural effusions from patients with Pl-TB, malignancies, and other pathologies. A proteomic analysis of pooled pleural effusions identified 45 proteins exclusively detected or upregulated in Pl-TB samples, many linked to infectious processes. Conversely, 18 proteins were uniquely found or upregulated in malignant pleural effusions, mainly associated with detoxification and hemostasis. To validate these findings, we employed targeted proteomics in individual samples. Eight proteins were validated: S100-A9, histone H4, insulin-like growth factor-binding protein 2, fibrinogen beta chain, ficolin-3, immunoglobulin heavy constant alpha 1, sulfhydryl oxidase 1, and histidine-rich glycoprotein. Additionally, NMR-based metabolomics identified 13 metabolites with differential abundance between Pl-TB and non-TB samples. Notably, N-acetyl-glycoprotein and the branched-chain amino acids, alanine and lysine differed between groups. Proteomic and metabolomic analyses revealed distinct molecular profiles between Pl-TB and non-TB patients, despite intra-group variability. To address this, we applied classification models. Histone H4 and alanine consistently emerged as discriminative features. Overall, this study provides novel insights into the molecular landscape of Pl-TB. The combined quantification of proteins and metabolites may improve differential diagnosis, although should be further validated in larger, independent cohorts before clinical application.

Humans

Anabolic androgen therapy in critically ill adults: A systematic review and meta-analysis.

Critical illness is characterized by a catabolic, proinflammatory state. Anabolic agents, such as testosterone, have therefore been proposed as therapeutic targets. Our objectives were to assess the effects of testosterone in critically ill populations on patient-important outcomes and identify design limitations to inform future studies. We searched for randomized control trials (RCTs) through Medline, Embase, and EBM Reviews databases from inception through February 24, 2026, including English language articles enrolling adults (&#x2265;18&#xa0;years) admitted to ICU where anabolic androgen therapies (AAT) were compared with placebo or standard of care. Studies had to report at least one of: mortality, ICU and hospital lengths of stay, or duration of mechanical ventilation. We extracted data independently using a standardized data extraction tool, and feedback was received from all co-authors to ensure agreement. For each outcome, we performed meta-analyses using a random-effects model with inverse variance weighting in RevMan. We used the GRADE approach to assess certainty in pooled estimates of effect. Of 1325 screened articles, we found 4 that fit our inclusion criteria. Together, we judged risk of bias as 'some concerns' in 3 trials and 'high' in the final trial, and ultimately found that the effects of anabolic-androgen therapy on patient-important outcomes uncertain. With the uncertainty of current evidence for the effects of anabolic-androgen therapy in critically ill adults, there is insufficient support for its routine use. Future randomized evidence is needed to determine whether anabolic-androgen therapy improves clinically-important outcomes and better define its safety profile in critically ill adults.

Humans

The Impact of Video Game Experience on Surgical Performance: A Systematic Review.

OBJECTIVE: To assess whether video gaming experience is associated with improved surgical performance in the surgeon population across laparoscopic, robotic, and other surgical modalities, and evaluate its implications on surgical training and education. METHODS: A structured literature search was conducted across five databases on 29th November 2024 in adherence to PRISMA guidelines. Comparative studies evaluating surgical performance outcome data between surgeons with differing video game experience were eligible for inclusion. Outcomes evaluated were time to complete task, error rate, accuracy, economy of motion, and overall score. Included studies were assessed for risk of bias using ROBINS-I and RoB 2. RESULTS: 15 studies involving 641 participants were included, comprising one randomized controlled trial and 14 nonrandomized studies. All nonrandomized studies were judged to be at moderate or serious risk of bias, and the single randomized controlled trial was judged to be at serious risk of bias. Differences in study design and outcome measures meant that quantitative synthesis could not be performed. Across laparoscopic studies, video gaming experience was associated with improved overall score and time to task completion predominantly in the period prior to structured training interventions, with accuracy findings consistently favoring gamers in the two studies reporting this outcome. Error rate and economy of motion findings were inconsistent or predominantly nonsignificant. No meaningful association was identified across nonlaparoscopic modalities. CONCLUSIONS: Video gaming may be associated with improved surgical performance in surgeons, though this appears restricted to laparoscopic tasks and the pretraining intervention period. As a low-cost and accessible activity, video gaming may represent a practical informal adjunct to formal surgical training to help ease the transition into structured technical training. Surgical program directors need not alter existing selection criteria or training modules based on the available literature.

Video Games

Costs of surgeries in low- and middle-income countries: a systematic literature review.

BACKGROUND: Surgical care is essential for achieving global health equity, yet low- and middle-income countries (LMICs) face major gaps in access and planning, partly due to limited evidence on the costs and resource requirements of surgical interventions. Understanding these costs is vital for designing efficient and equitable health systems. METHODS: We conducted a systematic literature review (covering MEDLINE, EMBASE, Global Health, EconLit and grey literature) to identify studies reporting the costs of surgeries in LMICs from January 2000 to June 2023. Minor and major surgical procedures were considered, focusing on therapeutic procedures (excluding diagnostic interventions). Studies that clearly identified, quantified and costed hospital resources and services deployed in the provision of surgical care, and included at least two of the surgical production factors (ie, consumables, diagnostics, personnel, infrastructure and overhead) in the costing were included. Costs were standardised to 2023 International dollars (I$) for comparability. RESULTS: A total of 74 studies from 29 countries met the inclusion criteria, with 210 cost estimates across 65 procedure groups. Costs varied widely: from I$1.54 for a caesarean section in Tanzania to I$618 098 for paediatric cataract surgery in Zambia. Full costing studies reported higher estimates than partial costing studies. Most studies (60%) originated from upper-middle-income countries, with limited data (10%) from low-income settings. CONCLUSION: This review provides a reference list of surgical procedure costs across LMICs, highlighting considerable cost variation by procedure, specialty and country. The findings underscore the need for better-quality, standardised cost data-especially from low-income countries-to inform national surgical plans, universal health coverage benefit packages and reimbursement policies.

Developing Countries

The Addition of Concurrent Immune Checkpoint Inhibitors for Chemoradiotherapy With Consolidative Immune Checkpoint Inhibitors in Unresectable Cancers: A Systematic Review and Meta-Analysis.

Following the success of chemoradiotherapy (CRT) combined with consolidative immune checkpoint inhibitors (ICIs) in locally advanced tumors, over 30 ongoing randomized controlled trials (RCTs) are investigating the potential benefits of adding concurrent ICIs. To investigate the differences in efficacy and safety between adding and not adding concurrent ICIs to CRT followed by consolidative ICIs, a literature search was conducted in PubMed, Embase, and the Cochrane Library, incorporating RCTs comparing CRT combined with consolidative ICIs versus CRT alone, or CRT with both concurrent and consolidative ICIs versus CRT alone. The primary outcomes were overall survival (OS) and progression-free survival (PFS). To reduce potential bias, an additional mirror-design analysis was performed through network meta-analysis. A total of 13 RCTs comprising 6868 patients and 14 cohort studies comprising 4724 patients were included. While patients treated with CRT and consolidative ICIs demonstrated significantly superior OS and PFS to patients treated with CRT alone in RCTs (HR of OS, 0.743, 95% CI, 0.654-0.843; HR of PFS, 0.674, 95% CI, 0.577-0.786), CRT and concurrent-plus-consolidative ICIs did not improve OS and PFS compared with CRT alone (HR of OS, 0.942, 95% CI, 0.782-1.134; HR of PFS, 0.880, 95% CI, 0.752-1.030). Significant differences were detected in OS (p&#x2009;=&#x2009;0.038) and PFS (p&#x2009;=&#x2009;0.017) between CRT combined with consolidative ICIs treatment versus CRT combined with concurrent and consolidative ICIs treatment from RCTs. In conclusion, adding concurrent ICIs may dampen the survival benefits of CRT combined with consolidative ICIs. This evidence informs future RCT design strategies.

Humans

Willingness to switch to long-acting regimens among people with HIV: a systematic review and meta-analysis.

OBJECTIVES: Long-acting regimens (LARs) offer promising alternatives for people with HIV, enhancing autonomy and convenience. Understanding preferences for LAR is essential to guide policy and implementation. DESIGN: This systematic review and meta-analysis examined willingness among adults with HIV to switch from daily oral antiretroviral therapy (ART) to LAR. METHODS: Following PRISMA guidelines, we included studies of adults with HIV using daily oral ART reporting willingness to switch to existing or hypothetical LAR. The primary outcome was the proportion willing to switch. Articles were searched in PubMed and Embase up to October 2024. Risk of bias was assessed using the RoB-PrevMH tool. A random-effects meta-analysis with a generalized linear mixed model synthesized willingness for LAR. Subgroup analyses explored heterogeneity. Alternative LAR were summarized descriptively. RESULTS: Searches identified 2038 records, of which 22 studies were included. Most studies were conducted in Europe or North America (96%). Willingness to switch to any LAR was 70% [95% confidence interval (95% CI): 59-79; I2 &#x200a;=&#x200a;97.9%]. Furthermore, two-monthly intramuscular injections were the most frequently investigated LAR, with a pooled willingness of 60% (95%CI: 42-76; I2 &#x200a;=&#x200a;97.5%). No study-level characteristics explained heterogeneity. Limited studies investigated willingness for alternative LAR. CONCLUSION: The majority of people with HIV expressed willingness to switch to LAR, with two-monthly intramuscular injections being the most commonly investigated formulation. Substantial heterogeneity persisted, suggesting that LAR preferences are highly context dependent. Evidence on alternative LAR, including tablets, implants and intravenous infusions, is limited. Low and middle-income countries were underrepresented, highlighting the need for geographically diverse research to better understand context-specific preferences and thereby inform treatment policy.

Humans

Clinical and psychological characteristics of adolescents at risk of mood disorders compared with adolescents with suicidal behavior.

Suicide is one of the leading causes of death among adolescents, yet little is understood about the biopsychosocial factors related to suicidality. The demographic, clinical, and biological characteristics of adolescents with and without psychiatric histories may help inform mechanistic approaches to treatment of mood disorders and suicidality. The 'characterizing the inflammatory profile and suicidal behavior in adolescents' and 'RAD arm of the Texas Resilience Against Depression' studies aimed to characterize the clinical and biological profiles of youth with suicidal behavior and youth at risk for mood disorders, compared to healthy adolescents (n&#xa0;=&#xa0;75 in each group). Here, we report the descriptive baseline clinical and psychological characteristics of adolescents at risk of mood disorders and those with suicidal behavior. The adolescents with suicidal behavior reported 3.53 lifetime suicidal events on average, predominantly reported moderate to very severe depression (34.7%, 24%, to 9.3%), moderate to severe anxiety (58.6%), low optimism (91.9%), and mild (39.2%) to moderate (28.4%) degree of hopelessness. The at-risk adolescents predominantly reported no depression (60%) or anxiety (68.9%), moderate optimism (50%), and a positive outlook (85.7%). Healthy adolescents predominantly reported no depression (88.3%) or anxiety (93.2%), moderate optimism (59%), and a positive outlook (87%). The adolescents with suicidal behavior and those at risk of mood disorders exhibited significantly higher irritability and borderline personality disorder features (uncorrected p&#xa0;=&#xa0;0.02 to p&#xa0;<&#xa0;0.001) and lower resilience compared to healthy adolescents. Ongoing investigations using the longitudinal clinical and biological data will help identify the immune biosignatures of suicidality in youth.

Humans

New Evidence in Heart Failure: 2026 Update.

Heart failure (HF) remains a major cause of morbidity, mortality, impaired quality of life and healthcare expenditure worldwide. The global burden of HF continues to increase due to population aging, improved survival, and the growing prevalence of cardiovascular, renal, and metabolic comorbidities. Simultaneously, the pace of scientific progress in HF has accelerated considerably. Recent advances have refined our understanding of HF epidemiology, prognosis, and disease trajectories, including emerging concepts of HF improvement, remission, and recovery. The Second Universal Definition of HF has also updated the classification framework, moving beyond the traditional ejection fraction-based categories. HF is now broadly classified into two major phenotypes: heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Novel mechanistic insights highlight the role of inflammation, immune activation, metabolic dysfunction, mitochondrial biology, and multisystem interactions in HF progression. There has also been significant progress in the characterization and management of major comorbidities, including chronic kidney disease (CKD), diabetes, obesity, atrial fibrillation (AF), pulmonary hypertension, frailty, malnutrition, and cancer. Diagnostic innovations include novel biomarkers, multi-omics technologies, artificial intelligence-based approaches, advanced imaging techniques, congestion assessment tools, and emerging digital health solutions. Important advances have occurred in specific HF aetiologies, including cardiomyopathies, cardiac amyloidosis (CA), myocarditis, arrhythmia-induced cardiomyopathy (AiCM), and Chagas cardiomyopathy. Therapeutic developments continue to reshape HF management across the spectrum of left ventricular ejection fraction. Recent evidence has focused on optimization of guideline-directed medical therapy in HFrEF, expansion of evidence-based therapies in HFpEF, and growing roles for sodium-glucose cotransporter-2 inhibitors, finerenone, incretin-based therapies, and transcatheter valve interventions. Collectively, these advances support the transition from a predominantly phenotype-based approach towards a more personalized and biologically informed model of HF care, with the potential to further improve outcomes across the entire HF spectrum.

Journal Article

Assessing perinatal depression identifying abilities among maternal and child health workers in rural China using smartphone-based virtual patients: a multi-center cross-sectional study.

OBJECTIVE: To assess rural maternal and child health (MCH) workers' virtual patients (VPs)-assessed performance in identifying perinatal depression (PND) using smartphone-based VPs, and to identify factors associated with this performance in rural Hunan, China. METHODS: A multicentre cross-sectional study was conducted in Hunan Province, China. A standardized questionnaire collected demographic and work-related characteristics of rural MCH workers. Smartphone-based VPs were used to assess PND identification performance in a simulated clinical scenario. An overall score &#x2265;60 was used as a prespecified operational benchmark across consultation, ancillary assessment, diagnosis, management, and health education domains. Data were analyzed using SPSS 26.0. RESULTS: A total of 375 rural MCH workers participated, yielding an effective response rate of 90.4%. Only 25.9% met the prespecified operational benchmark for VP-assessed PND identification performance. The mean accuracy scores for consultation, ancillary assessment, diagnosis, management, and health education were 94%, 48%, 64%, 58%, and 74%, respectively. Complete consultation accuracy was higher among MCH workers from township health centers than among those from county-level MCH hospitals. MCH workers aged 18-39 years showed higher odds of complete diagnostic accuracy for PND than those aged &#x2265;40 years. CONCLUSIONS: Smartphone-based VP assessment was feasible in rural MCH settings and revealed suboptimal PND identification performance. Mobile VPs may help identify frontline performance gaps and inform targeted training, but further validation against real-world clinical performance, or standardized patient encounters is needed before large-scale implementation. These findings may support targeted capacity-building for rural MCH workers and more equitable perinatal mental health care.

Humans

Effect of cognitive enhancement therapy for early course schizophrenia on gray matter volume: A confirmatory multisite randomized clinical trial.

BACKGROUND: Cognitive Enhancement Therapy (CET) is an evidence-based cognitive remediation intervention for early course schizophrenia with established benefits for cognition. CET may protect against broad temporolimbic gray matter volume loss associated with cognitive improvement, but this finding has yet to be replicated. This research reexamined if CET protects against temporolimbic gray matter volume loss in an independent and larger multisite early course sample, and if this neuroprotective effect predicts cognitive and social adjustment improvement. METHODS: Ninety-nine participants with early course schizophrenia completed MRI, cognitive, and social adjustment assessments at baseline, 9 (mid-treatment), and 18 (end of treatment) months. Linear mixed-effects models examined the differential impact of CET (n&#x202f;=&#x202f;56) compared to Enriched Supportive Therapy (n&#x202f;=&#x202f;43) on temporolimbic gray matter volume in regions-of-interest (ROIs) that previously demonstrated CET-related neuroprotection (primary ROIs), as well as frontotemporal ROIs outlined in the first trial (secondary ROIs). RESULTS: The right rostral anterior cingulate was the only primary ROI to demonstrate a significant group&#x202f;&#xd7;&#x202f;time interaction, but was unrelated to cognitive and social adjustment change. No secondary ROIs exhibited a differential treatment effect. CONCLUSION: This confirmatory trial did not recapitulate the observed broad pattern of CET-related temporolimbic gray matter volume neuroprotection. Consistent with the larger literature demonstrating limited evidence of cognitive remediation effects on the brain in schizophrenia, these findings underscore the need for continued investigation of CET-related changes with other neuroimaging modalities, especially given its established cognitive benefits. Such information is critical for cognitive remediation optimization based on validated therapeutic mechanisms.

Humans