This review aimed to map the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on gout-related and cardiometabolic outcomes in patients with type 2 diabetes mellitus (T2DM) and gout.

A scoping review was conducted following the Joanna Briggs Institute methodology and the PRISMA-ScR checklist. Searches were performed in PubMed, EMBASE, Scopus, Web of Science, LILACS/BVS, and gray literature sources. Eligible studies included patients with T2DM and gout treated with SGLT2i, assessing outcomes such as mortality, gout flares, serum uric acid (SUA) levels, emergency care visits, and hospitalizations due to gout. The PRISMA-ScR checklist is provided in Additional file 1, and the full search strategy in Additional file 2.

Of 282 articles initially identified, 22 met the inclusion criteria. Most studies were retrospective cohort studies (n = 12) or post hoc analyses (n = 8). Only three studies evaluated patients with both T2DM and gout exclusively. The main findings included reductions in SUA levels (n = 8), incidence of gout (n = 12), gout flares (n = 8), initiation of urate-lowering therapy or colchicine (n = 8), and gout-related emergency care or hospital visits (n = 1). Reductions in all-cause (n = 5) and cardiovascular (CV) mortality (n = 4) were also reported. Across the included studies, SGLT2i were frequently associated with favorable effects on the analyzed outcomes.

SGLT2i appears to be associated with multiple favorable effects in patients with T2DM and gout, including urate-lowering effects, reduced gout flares, and lower mortality (all-cause and CV-related). Although limited by the small number of studies focusing specifically on this population, these findings support the potential therapeutic relevance of SGLT2i in patients with coexisting T2DM and gout, contributing to the management of both conditions and the reduction of CV-related events associated with them.

Myocardial infarction (MI) triggers persistent inflammatory dysregulation, wherein macrophages undergo glycolytic reprogramming and adopt an inflammatory phenotype that impairs cardiac repair. However, the specific metabolic drivers underlying post-MI macrophage dysfunction remain unclear. Here, we identify enolase 1 (ENO1)-a glycolytic enzyme up-regulated in post-MI macrophages-as a critical regulator of macrophage metabolic fate and inflammatory function. To intervene, we engineered an acid-responsive nanocarrier (PECS) that externalizes phosphatidylserine within the acidic infarct microenvironment, facilitating selective macrophage uptake. Intracellular delivery of siENO1 suppressed glycolytic flux, thereby curbing lactate accumulation and relieving its metabolic inhibition of KLF4, which initiated anti-inflammatory reprogramming. In vivo, PECS-loaded siENO1 (siENO1@PECS) treatment attenuated infarct size, fibrosis, and cardiomyocyte apoptosis while improving ventricular function. Collectively, these findings identify ENO1 as a critical metabolic checkpoint in post-MI macrophage regulation and demonstrate a bioresponsive nanocarrier strategy for precise gene modulation to enhance cardiac repair.

Following the publication of the above paper, it has been drawn to the Editor's attention by a concerned reader that, for the immunohistochemical images shown in Fig. 3 on p. 1070, the 'SOCS3/HD/16W' and 'SOCS3/CD/28W' images were apparently the same, albeit with differently coloured shading, suggesting that this figure had been assembled incorrectly. In addition, upon analyzing the data in this paper independently in the Editorial Office, it came to light that one of the histological images featured in Fig. 2A (the 'Oil Red O/12W' image) apparently reappeared in a paper written by different authors at different research institutes in the journal Redox Biology several years after the publication of this article, albeit the image in that paper did not feature the same level of clarity. The authors have been contacted by the Editorial Office to offer an explanation for the apparently incorrect assembly of the data in Fig. 3, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office conitnues to investigate this matter further. [International Journal of Molecular Medicine 31: 1066‑1074, 2013; DOI: 10.3892/ijmm.2013.1323].

Understanding the influence of cardiovascular diseases (CVD) on human regulatory functions is a major challenge in modern healthcare. This study explores whether the autonomic response to sleep arousals can serve as a diagnostic marker of the health of physiological networks. We introduce a novel method for the robust calculation of information transfer, based on the optimization of embedding parameters for transfer entropy (TE) calculation. Using this approach, we analyzed the information transfer dynamics of 8,136 sleep arousals from 1,956 subjects from the SHHS follow-up visit. Compared to three state-of-the-art approaches, our newly introduced method, max. TE, achieved a 17.9% more stable TE estimate than the second-best approach. Our results indicate a significantly ( p < 0.001 ) lower TE in patients with CVD ( 85.4 ± 0.8  mnats) than that in healthy controls ( 87.9 ± 0.5  mnats), indicating an impairment of regulatory control mechanisms. Furthermore, the TE decreases linearly with increasing age and shows significant differences between sleep stages, with the highest TE occurring during REM sleep ( p < 0.001 ) . These findings demonstrate that sleep arousals, as a physiological stimulus, can reveal sleep stage- and disease-related changes in cardiovascular networks and that our approach provides a robust group-level embedding strategy for physiological information-transfer analysis.

With the rapid advancement of China's aging population, the mental health problems of the elderly, especially depression, have become an important concern in the field of public health. However, research on the combined effect of education level and widowhood on depression is still relatively limited. The aim of this study is to explore the association between education level, widowhood status, and depression symptoms among elderly people in China, and further analyze the moderating effects of health status, demographic characteristics, and behavioral variables in this association. Data from the 2018 China Health and Retirement Longitudinal Study were used. A total of 3243 participants aged 50 and above were analyzed. A simplified 10 item CES-D scale was used to assess depression. Logistic regression models were used to examine the independent and interactive effects of education level and widowhood on depression, while adjusting for demographic variables (age, gender, type of residence), health status (chronic disease, self-rated health), and behavioral factors (physical activity, smoking). Even after controlling for confounding factors, lower levels of education were significantly associated with a higher risk of depressive symptoms (odds ratio [OR] = 1.52, P < .01). Widowhood is also a strong predictor of depression (OR = 1.79, P < .01), especially in women. Interaction analysis indicates that poor self-rated health and a sedentary lifestyle exacerbate the negative impact of low education and widowhood on depression. In addition, rural residents and individuals with lower socioeconomic status face a higher risk of depression symptoms. Low education level and widowhood are independent factors contributing to the high incidence of depression among elderly people in China. Health status and lifestyle factors play a crucial mediating role in this association. These findings emphasize the necessity of targeted intervention measures, such as community-based education programs, sports promotion, and strengthening social support networks, to reduce the risk of depression among vulnerable elderly people in China.

Training mental health clinicians to conduct standardized clinical assessments is challenging due to a lack of scalable, realistic practice opportunities. Traditional methods often fail to prepare trainees for the variability and complexity of real-world patient interactions, potentially impacting data quality in clinical trials. This paper introduces a novel approach to address this training gap using large language model (LLM)-based interview simulations.

This study aimed to develop and validate a voice-enabled virtual patient simulation system as a proof of concept. We described the development of the system and evaluated whether it could generate virtual patients that (1) accurately adhered to predefined clinical profiles, (2) maintained a coherent and consistent narrative, and (3) produced dialogue that is perceived as realistic.

We implemented a system that used an LLM to simulate patients with specified symptom profiles, demographic backgrounds, and distinct communication styles. The system's performance was analyzed through a mixed methods evaluation, which included a formal assessment by 5 experienced clinical raters who conducted simulated structured Montgomery-Åsberg Depression Rating Scale (MADRS) interviews with 4 virtual patient personae, scored them on the scale, and provided qualitative feedback on the system's clinical plausibility, narrative cohesion, and dialogue realism.

Across 20 interviews, the virtual patients demonstrated reasonable adherence to their configured clinical profiles, with human rater scores falling near their predefined score configurations. The mean item difference between MADRS rater scores and configured scores was 0.52 (SD 0.75); interrater reliability for the total score was 0.90 (95% CI 0.68-0.99). Expert raters consistently gave average ratings of "agree" to "strongly agree" when asked to evaluate the qualitative realism and cohesion of the virtual patients.

LLM-powered virtual patient simulations offered a promising, scalable tool for training clinicians in standardized clinical assessment. This pilot study provides initial evidence for the system's ability to produce clinically relevant practice scenarios with reasonable fidelity.

Globally, the mental health of children and adolescents is a public health concern. Schools are a primary access point for youth mental health support, yet traditional delivery models remain constrained by limited resources, shortage of specialised professionals, and high counsellor caseloads. Digital mental health interventions may help address these gaps by offering scalable, accessible, and less-stigmatising support.

This review aimed to map and characterise school-based digital mental health interventions for children and adolescents by examining intervention characteristics, implementation, and intervention outcomes.

A comprehensive search of peer-reviewed studies (2008-2025) was conducted across PsycNet, ERIC, and PubMed, using the PRISMA-ScR Checklist. Eligible studies evaluated a digital mental health intervention delivered in a school setting among K-12 students and reported at least one implementation and/or mental health outcome.

Across 40 studies, most were conducted in high-income countries and used randomised designs. Web-based, structured cognitive behavioural therapy (CBT) modules in classroom settings predominated. Intervention delivery ranged from teacher-led to self-directed use, with some hybrid clinician-supported models. Findings were heterogeneous for internalising symptoms (e.g., depression and anxiety), with evidence of benefit in some CBT-oriented interventions but mixed effects in universal programmes. In contrast, mental health literacy, stigma, and well-being outcomes showed more consistent positive effects. Engagement and implementation quality appeared closely linked to effectiveness.

School-based digital mental health interventions can improve mental health literacy and stigma-related outcomes when grounded in CBT. Future research should prioritise standardised outcome measurement (e.g., fidelity, adoption), theory-to-component linkages, co-design elements, and hybrid effectiveness-implementation, particularly in low-and middle-income settings.

While there is much research on stigma toward marginalized populations, public perceptions regarding deservingness of basic human and civil rights of these groups have not been examined in a nationwide sample of US adults.

To understand the US public's perceptions regarding deservingness of basic human and contested civil rights for people with severe physical disabilities (SPDs), severe mental illness (SMI), and substance use disorders (SUDs).

This cross-sectional study was a nationwide US internet-based quota panel survey of US adults (aged ≥18 years) who completed the survey. Responses were collected from January 17 to February 12, 2025.

Participants rated their support for 5 human rights (adequate standard of living, high standards of health, legal capacity, freedom from torture, living independently) and 3 civil rights (being a parent, running for political office, owning a gun) for people with SPDs, SMI, and SUDs using a 5-point Likert scale, with marginalized subgroups presented to participants in randomized order. McNemar test for paired binary data was used to examine differences in mean support across subgroups, and linear probability regression models were used to identify demographic variables associated with support.

In this survey of 1442 US adult participants (849 female [58.9%]; 588 male [40.8%]; 3 nonbinary [0.2%]; and 2 preferred not to say [0.1%]), the SPD subgroup received significantly higher support across all 5 human rights and 3 civil rights compared with SMI and SUD subgroups. For example, 79.0% (95% CI, 76.9%-81.2%) of participants supported the right to live independently for people with SPDs, while 67.0% supported this right for those with SMI (95% CI, 64.6%-69.5%) and 68.4% supported this right for those with SUDs (95% CI, 66.0%-70.9%). Civil rights received lower support across all 3 subgroups; for example, 40.1% (95% CI, 37.5%-42.6%) supported the right to run for political office for those with SMI and 41.4% (95% CI, 38.8%-44.0%) for those with SUDs compared with 62.7% (95% CI, 60.1%-65.2%) for those with SPDs. Democratic affiliation and lived experience with behavioral health care were associated with higher support for human rights (eg, among those with SUDs, up to 17.1 and 14.2 percentage points higher support, respectively). Male sex and younger age (18-24 years) were associated with greater support for civil rights (eg, male sex with 17.9 percentage points higher support for gun ownership among those with SPDs and age 18-24 years with a 27.1 percentage-point difference among those with SMI).

These findings contribute important evidence to the existing literature on stigma, highlighting discrepancies in public support for basic human and contested civil rights across marginalized subgroups, which can inform interventions to address public attitudes toward people with behavioral health conditions.

Hepatocellular carcinoma (HCC) is a cancer with rising incidence and economic burden. However, evidence on healthcare resource utilization (HCRU) and associated costs is scarce in Europe. This study aims to determine HCRU and costs of HCC from a German third-party payer's perspective.

This longitudinal claims study (BARMER statutory health insurance) included patients with HCC (ICD-10-GM C22.0; 2016-2020). HCRU and costs within 2 years after diagnosis were analyzed descriptively and reported per patient (PP) and per patient per month (PPPM).

The cohort included 2778 patients. Mean age was 71.9 years (SD ±9.7); 69% were male. Total cost within 2 years after diagnosis was approximately €105 million, with mean cost PP of €37,970 (SD ±€43,840), primarily due to inpatient stays (67%). Median costs PP were highest for patients receiving liver transplantation (€126,943; interquartile range [IQR]: €104,340-€167,205) and lowest for patients without any tumor-specific therapy (€10,132; IQR: €5875-€19,663). Considering the observation period, costs PPPM were lowest for liver resection (€2434; IQR: €1282-€5425) and thermal ablation (€2349; IQR: €1233-€4316), whereas costs PPPM were highest for patients without tumor-specific HCC treatment (€5984; IQR: €2764-€10,908). Similar patterns were observed in the HCRU assessment.

In this German claims data analysis, PP costs and HCRU in patients with HCC were higher among those who underwent liver transplantation and lower among those without tumor-specific treatment. However, after adjustment for follow-up duration, the high costs PP among patients receiving curative-intent treatments were significantly relativized. These findings support structured HCC surveillance to potentially improve clinical and economic outcomes.

Burning mouth syndrome (BMS) is a chronic orofacial neuropathic pain disorder, occurring in the absence of clinically evident mucosal lesions or identifiable oral pathology that can explain the symptoms. A significant proportion of patients experience uncontrolled symptoms despite multiple therapies. OnabotulinumtoxinA (onaBoNT/A) is used in neuropathic pain, as clinical trials have shown benefits in peripheral and central neuropathic pain management with its application. We present an exploratory case series of four patients with refractory BMS treated with intradermal onaBoNT/A injections.

Four patients with refractory BMS were included in this study. OnaBoNT/A intradermal injections were performed in the inner labial mucosae and tip of the tongue. We assessed pain intensity before the procedure and after 15 days, adverse effects, time to symptom recurrence, cumulative effects with multiple procedures, and patients' global impression of change.

All patients reported the procedure was quick and well tolerated. No immediate adverse effects were identified. All patients had significant pain reduction at 15-day follow-up assessment. Regarding adverse effects, one patient reported transient lower lip asymmetry in one procedure, and another reported transient mild mouth closure impairment. Symptoms recurred between 2.5 and 3.0 months after the first procedure. Three patients desired to continue the treatment. One patient reported no symptom recurrence after four procedures with three-month intervals; after four procedures, the treatments were suspended, and she remained asymptomatic until the end of follow-up. One patient reported incremental benefit from repeated procedures. All patients reported the treatment had a meaningful impact on their daily life.

Our results suggest that intradermal onaBoNT/A injections may constitute an effective and durable treatment option for patients with BMS refractory to conventional therapies. Despite these favourable outcomes, adverse events were noted in procedures targeting the labial mucosa. In future applications, we aim to examine technical variations between sessions associated with and without adverse effects, to optimise safety and refine the technique.