Foundation models represent a new frontier in ophthalmic artificial intelligence, enabling learning of transferable features from large unlabelled imaging datasets for flexible application to varying downstream tasks. We systematically analyze the evolution of ophthalmic foundation models across 12 distinct models developed between 2022 and July, 2025. We examine advances in modality integration (unimodal, multimodal to vision-language), pretraining objectives (generative versus contrastive approaches) and supervision strategies (image and text guided). Emerging techniques such as imaging modality agnostic encoders, synthetic data augmentation, and computationally efficient architectures improved model performance and generalisability. Overall, we observed a clear shift from domain-specific unimodal approaches towards modality-agnostic foundation models guided by clinical text. Future directions include wider modality integration, higher dimensional inputs (spatially and temporally), diverse pretraining, and standardised benchmark datasets. In synthesizing these trends, this review offers the conceptual and technical grounding to support both clinicians and researchers in ophthalmic foundation model design, selection, and application.

Firearm injuries are prevalent among children in the United States and induce significant psychological distress. This study aims to identify clinical predictors for developing mental health disorders (MHD) and substance use disorders (SUD) after firearm injury withi1n the pediatric population.

The National Readmissions Database was queried from 2016-2022 for patients ≤18 years old with hospital admissions for firearm injuries. The primary outcome was the presence of new MHD or SUD during hospital readmissions. Multivariable regression analysis was used to test the independent association of medical and surgical complications with MHD and SUD while controlling for confounders, including the presence of MHD and SUD at index admission.

There were 35,733 hospital admissions, with a mortality rate of 6.4%. Survivors were mostly male (86%), with a median age of 17 years [IQR 15, 18]. Patients were most commonly from the lowest income quartile (57%). Baseline MHDs or SUDs were present in 20% of the population, and these patients suffered worse injuries and more complicated hospital courses. New MHDs or SUDs occurred in 2.2% of the population. Females, those with self-inflicted injuries, those who underwent surgical procedures, and those with medical/surgical complications are at increased risk of developing new MHDs or SUDs. Within the same calendar year, 11% of patients were readmitted, and 33% of patients requiring readmission presented to a different hospital.

MHD and SUD are prevalent after pediatric firearm injuries in the United States. Children with complicated hospital courses after firearm injury may benefit from early mental health screening and intervention.

IV STUDY TYPE: Retrospective cohort analysis.

The rise of electronic cigarettes (e-cigarettes) has attracted both former smokers and teenagers looking for an alternative nicotine source. This study aimed to assess the prevalence of e-cigarette use, the determinants associated with its use, dependence, and the impact of e-cigarette use on physical activity and mental health among the Saudi population.

A cross-sectional study was conducted from September 27, 2024, to October 21, 2024. We used Penn State Nicotine Dependence Index, the Kessler Psychological Distress Scale, and the Global Physical Activity Questionnaire. Convenience and snowball sampling methods were used to recruit participants using an electronic survey questionnaire and face-to-face interviews.

Among 3092 participants, the prevalence of e-cigarette use was 9.8%.Nicotine dependence was notable among users, with 41.7% exhibiting medium dependence and 22.2% reporting high dependence. Physical activity levels varied: 22.3% engaged in high activity, 34.1% in moderate, and 24.3% in low activity. Regarding mental health, 42.2% experienced high psychological distress. Participants with high physical activity had significantly higher odds of e-cigarette use [crude odds ratio (cOR) = 1.79, 95% confidence interval (CI): 1.29-2.49], while those with high distress had lower odds [cOR = 0.27, 95% CI: 0.19-0.39]. Path analysis revealed that mental distress positively predicted e-cigarette dependence (β=0.118), whereas physical activity showed a small positive association with dependence (β=0.209).

E-cigarette use in this population is significantly influenced by socio-demographic factors, physical activity levels, and mental health status. The complex relationship observed, where high physical activity is associated with use and mental distress is protective against initiation but predictive of dependence, highlights the need for integrated public health strategies. Interventions should focus on high-risk groups and address the dual role of lifestyle and psychological factors in both prevention and dependence management.

People living with HIV and hospitalised with sepsis in Africa are at risk of death due to tuberculosis but diagnostics for tuberculosis might be delayed or inaccessible for people presenting for critical care. We aimed to compare the effects of immediate empirical and high-dose antituberculosis therapy on 28-day mortality in adult people living with HIV with sepsis in east Africa.

ATLAS was a phase 3, open-label, randomised, controlled, 2 × 2 factorial, superiority trial conducted at four hospitals in Tanzania and Uganda. Participants were aged 18 years or older, living with HIV, and had been admitted to hospital with sepsis with two or more modified quick Sequential Organ Failure Assessment score criteria. Exclusion criteria were active tuberculosis or receipt of antituberculosis therapy within 6 months of hospitalisation, pregnancy or lactation, allergies to antituberculosis therapy, another investigational drug within the past month, chronic liver disease, heavy alcohol use, positive serum cryptococcal antigen, or anticipated significant drug-drug interaction with rifampicin. A computer-generated permuted-block algorithm with allocation concealment and random block sizes of four and eight randomly assigned participants (1:1) to receive either immediate or diagnosis-dependent antituberculosis therapy, and (1:1) to receive either high-dose or conventional WHO-recommended weight-based dose antituberculosis therapy. Allocation was stratified by country and the presence of altered mental status at the time of randomisation. Participants randomly assigned to conventional-dose antituberculosis therapy received fixed-dose combination tablets of rifampicin approximately 10 mg/kg, isoniazid approximately 5 mg/kg, pyrazinamide, and ethambutol, plus pyridoxine 50 mg orally. Participants randomly assigned to receive high-dose antituberculosis therapy received rifampicin approximately 30 mg/kg and isoniazid approximately 7·5 mg/kg as a combination of single formulation tablets and fixed-dose combination tablets that included WHO-recommended weight-based doses of pyrazinamide and ethambutol, plus pyridoxine. Participants continued immediate antituberculosis therapy for 28 days. All medications were administered daily. Participants in the diagnosis-dependent antituberculosis therapy groups received treatment based on a clinical or microbiological diagnosis of tuberculosis. All participants received 2 g intravenous ceftriaxone daily for 7 days. The primary endpoint was 28-day mortality analysed in the modified intention-to-treat population and in the subgroup with later confirmed tuberculosis. We defined the survival time for each participant as the time from randomisation until death, discharged (alive) by day 28, or censored (alive) at day 28. We graded adverse events according to recommendations from the National Institutes of Health Division of AIDS. This study was registered with ClinicalTrials.gov, NCT04618198, and is completed.

Between Jan 5, 2022, and Dec 9, 2024, 707 people were screened for eligibility and 437 were randomly assigned (110 to immediate conventional-dose, 112 to immediate high-dose, 107 to diagnosis-dependent conventional-dose, and 108 to diagnosis-dependent high-dose antituberculosis therapy). 395 patients (226 [57%] of whom were female and 169 [43%] were male; all participants were Black) received study intervention and were analysed for the primary outcome of 28-day mortality. We confirmed tuberculosis in 204 (52%) patients. There was no evidence of differences in 28-day mortality in immediate antituberculosis therapy groups (50 deaths [25%] in 198 patients) compared with diagnosis-dependent groups (50 deaths [25%] in 197 patients; adjusted hazard ratio [aHR] 0·99 [95% CI 0·67-1·46]; p=0·95), or in high-dose antituberculosis therapy groups (51 deaths [26%] in 199 patients) compared with conventional-dose groups (49 deaths [25%] in 196 patients; aHR 1·07 [0·72-1·59]; p=0·73). In patients with microbiologically confirmed tuberculosis, the 28-day mortality relative to the diagnosis-dependent conventional-dose group (18 deaths [34%] in 53 patients) was lower for the immediate conventional-dose group (six deaths [12%] in 51 participants; aHR 0·32 [95% CI 0·13-0·82]; p=0·015); for the diagnosis-dependent high-dose group (11 deaths [20%] in 56 patients) was 0·51 (0·24-1·08; p=0·79); and for the immediate high-dose group (11 deaths [26%] in 43 patients) was 0·63 (0·29-1·36; p=0·24). No significant differences in adverse events occurred between treatment groups but numerically more events of drug-induced liver injury occurred in the immediate high-dose group compared with any other group.

Among all participants with HIV-related sepsis, 28-day mortality was not significantly reduced with immediate or high-dose antituberculosis therapy. In the subgroup with later confirmed tuberculosis, immediate conventional-dose antituberculosis therapy significantly reduced 28-day mortality, suggesting, as in other forms of bacterial sepsis, that hours to active treatment might determine survival.

US National Institutes of Health.

Opioid analgesia and adverse outcomes vary across individuals. We show that runt-related transcription factor 1 (Runx1) modulates the microglial transcriptome and is a genetic determinant of opioid antinociceptive responses and withdrawal. In mice, Runx1 deletion in microglia produces distinct ultrastructural and transcriptomic signatures, reducing morphine potency despite no prior opioid exposure. These mice also require greater post-operative morphine and display exacerbated morphine-induced hyperalgesia and withdrawal. Single-cell RNA sequencing (scRNA-seq) and chromatin immunoprecipitation sequencing (ChIP-seq) analyses reveal a unique microglial state, with Runx1 regulating inflammatory signaling and key microglial functions. In humans, association analyses link RUNX1 variants to inter-individual differences in perioperative opioid requirement and withdrawal severity. Identifying RUNX1 susceptibility genotypes may be important for understanding individual variability in opioid responses, with potential relevance for future personalized approaches.

This exploratory study tested the hypothesis that Huntington's disease (HD) is characterized by distinct abnormalities in resting-state electroencephalographic (rsEEG) rhythms compared to Alzheimer's disease (AD).

Clinical and rsEEG data were collected from 35 patients with HD, 81 patients with AD, and 102 healthy controls (HC). The rsEEG cortical source activations from 30 electrodes were estimated using eLORETA and were harmonized across clinical sites.

Compared to the HC group, both the HD and AD groups showed widespread increases in rsEEG delta source activation and decreases in alpha source activation, with the HD patients exhibiting the most pronounced frontal effects. In patients with HD, those abnormal rsEEG source activations were associated with cognitive, motor, and functional deficits.

Patients with HD were characterized by a particular slowing of frontal rsEEG rhythms associated with clinically relevant variables.

A topographically widespread slowing of cortical oscillatory activity was observed in both HD and AD groups, with a particularly pronounced frontal effect in HD, which may predict a greater impact on the sleep-wake cycle. These observations should be considered exploratory and need validation in future studies with enhanced vigilance monitoring during longer rsEEG recordings.

Exercise is a potent modulator of mental health, with accumulating evidence highlighting its ability to produce structural and functional changes in the brain. This review synthesizes findings across neurobiological, molecular, and systemic domains to explain how exercise improves outcomes in mood, anxiety, and stress-related disorders. We examine how exercise stimulates brain-derived neurotrophic factor (BDNF), regulates monoaminergic systems (serotonin, dopamine, norepinephrine), modulates inflammatory and oxidative stress pathways, and promotes neurogenesis and synaptic plasticity. The review also explores systemic mechanisms including the gut-brain axis, myokine signaling (e.g., irisin, cathepsin B), and the regulation of the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, we discuss how exercise influences key psychological mechanisms, including emotion regulation, self-efficacy, and cognitive reappraisal, offering a translational bridge between physiology and psychotherapy. Understanding these overlapping mechanisms can guide clinicians in prescribing exercise as an evidence-based adjunct or standalone therapy for mental health disorders. This model of exercise as medicine has the potential to enhance both accessibility and efficacy of mental health care. Implications for clinical integration, mechanistic research, and policy development are discussed.

Childhood trauma (CT) has widespread adverse effects on individual's cognitive and emotional problems; however, little is known about the underlying psychological mechanisms. This study aimed to examine the relationship between CT, inhibitory dysfunction, and emotion processing, as well as to explore potential differences in these associations across groups with different levels of social anhedonia.

We administered a set of self-reported measures to capture CT, pleasure experiences, emotion regulation as well as executive dysfunction to 1622 healthy participants. Partial correlation network and nodal centrality were estimated. The mediation effect of inhibitory dysfunction on the relationships between CT and emotion processing was examined. Furthermore, participants were divided into three groups (i.e., high, middle and low) according to their social anhedonia (SoA) levels, network comparison tests and mediation effect analysis in each group were performed.

Network analysis showed that CT was negatively associated with cognitive reappraisal (CR) and pleasure experiences, and positively associated with expressive suppression. Inhibitory dysfunction significantly mediated the relationship between CT and emotion regulation. Subgroup analysis showed that significant mediation effect of inhibitory dysfunction on the association between CT and CR was only found in low SoA group, but not in middle and high SoA groups.

Our study suggested that inhibitory dysfunction plays an important role between CT and emotion regulation, which is disrupted in individuals with middle to high levels of social anhedonia. These findings highlight the necessity of considering inhibitory function when developing interventions for trauma-related emotional problems.

Mental disorders and chronic pain frequently co-occur. The prevalence of this comorbidity varies widely across investigations and is certainly overestimated using screening self-reports. The main aim of this cross-sectional research was to calculate prevalence rates of mental disorders in a chronic pain population during their first consultation in an Italian specialized pain clinic using the narrow diagnostic criteria of the DSM-5. Additionally, we examined the relationship between this psychiatric comorbidity and a broad range of socio-demographic and clinical parameters related to chronic pain.

174 participants were enrolled in the Pain Therapy Service at the Parma University Hospital. They completed the Structured Clinical Interview for DSM-5 mental disorders (SCID-5) and the Brief Pain Inventory (BPI). Associations between psychiatric comorbidity and other parameters were explored using regression analyses.

57 (32.7%) subjects with chronic pain had DSM-5 psychiatric comorbidity, particularly major depression and anxiety disorders. This comorbid psychopathology showed significant associations with BPI pain severity and interference scores, as well as with the presence of widespread chronic pain (including fibromyalgia) and the prescription of anti-neuropathic medication at entry. Notably, only a minority (n = 18; 31.6%) of these participants with current comorbid mental disorders were treated in psychiatric services.

A large portion of chronic pain patients with comorbid psychiatric syndromes remain undiagnosed and undertreated. The presence of mental health operators in multidisciplinary chronic pain teams is justified and recommended.

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder characterized by persistent intrusive thoughts and repetitive behaviors, significantly impacting patients' quality of life, social functioning, and overall well-being. Recent advances in neuroimaging techniques, particularly the development and application of the Human Brainnetome Atlas (BNA), have provided precise structural and functional subdivisions of the human brain, greatly enhancing the understanding of OCD neuropathology. This review comprehensively summarizes the latest applications of BNA in OCD research, specifically emphasizing detailed analyses of structural and functional connectivity abnormalities within neural circuits, their associations with clinical symptoms, and potential mechanisms underlying these abnormalities. Additionally, the utility of BNA in classifying patient subtypes based on distinct neurobiological profiles and its role in facilitating early diagnostic interventions are discussed. Methodological limitations are also addressed, underscoring the necessity of controlling confounding variables, such as pharmacological treatments and clinical heterogeneity, to strengthen research outcomes. Finally, future research directions are proposed, including the integration of BNA with advanced technologies such as artificial intelligence, multimodal imaging methods, and individualized neuromodulation strategies, to further refine and expand precision medicine approaches in OCD management.