Toxoplasma gondii (T. gondii) is a prevalent zoonotic parasite that has been implicated in influencing human psychiatric disorders and risk-taking behaviors. Using genome-wide association study (GWAS) data, we selected 25 and 76 single-nucleotide polymorphisms as instrumental variables for anti-T. gondii IgG seropositivity and anti-T. gondii IgG levels, respectively, and conducted two-sample Mendelian randomization (MR) analyses across 18 GWAS datasets to investigate potential causal effects on addiction, bipolar disorder, obsessive-compulsive disorder, schizophrenia, and risk-taking behavior in European populations. Contrary to previous epidemiological evidence, our MR analyses do not support a significant causal association between T. gondii infection and any of the studied psychiatric disorders or risk-taking behavior. Collectively, these results establish that any true causal effect of genetic liability to T. gondii infection is likely to be small (OR < 1.18 for schizophrenia, < 1.29 for bipolar disorder) and below the effect sizes typically reported in observational seroepidemiological studies, although small or infection-phase-specific effects cannot be excluded.

Chronic kidney disease (CKD) is a growing global health issue that significantly impairs quality of life (QoL), particularly among patients undergoing dialysis. This study examines the relationships between e-health literacy, self-efficacy, and QoL in this vulnerable population.

To examine associations among e-health literacy, self-efficacy, and health-related quality of life (HRQoL) among patients receiving hemodialysis in Northern Jordan.

A cross-sectional study was conducted among 184 adult HD patients recruited from four hospitals in Northern Jordan. Data were collected using validated Arabic versions of the eHealth Literacy Scale (eHEALS), the Self-Efficacy for Managing Chronic Disease Scale (SEMCD-6), and the Kidney Disease Quality of Life-36 (KDQOL-36). Spearman correlation was used to examine associations between variables. Multiple linear regression was performed to identify independent predictors of KDQOL-36 total scores.

Among 184 participants (mean age 49.9 years, 65% male), the mean self-efficacy score was 25.52 (SD = 1.8) and the mean e-health literacy score was 3.62 (SD = 0.58). The mean KDQOL‑36 total score was 105 ± 17, with domain scores of 39 ± 7 for Symptoms/Problems, 25 ± 6 for Effects of Kidney Disease, 11 ± 3 for Burden of Kidney Disease, 29 ± 5 for Social Function, 12 ± 3 for the Physical Component Summary, and 21 ± 4 for the Mental Component Summary. Multivariable regression identified independent predictors of higher quality of life: graduate-level education (B = 8.06, 95% CI: 2.32-13.80, p = 0.006) and employment (B = 7.14, 95% CI: 2.10-12.20, p = 0.006). Diabetes was independently associated with lower quality of life (B = -5.92, 95% CI: -10.90 to -0.95, p = 0.020). Although significant in unadjusted analyses, e-health literacy and self-efficacy were not independent predictors after adjustment for socioeconomic and clinical factors.

Health-related quality of life among HD patients appears to be influenced primarily by socioeconomic and clinical factors, particularly educational attainment, employment status, and diabetes mellitus. Although e-health literacy and self-efficacy were associated with HRQoL in unadjusted analyses, these associations were attenuated after adjusting for socioeconomic and clinical characteristics. Interventions that address educational disparities, support patient engagement, and optimize comorbidity management may improve health outcomes among patients receiving hemodialysis.

Sleep disturbances, particularly insomnia, are increasingly recognized as behavioral determinants of type 2 diabetes (T2DM). However, their contribution to validated diabetes risk scores beyond traditional sociodemographic and lifestyle factors remains insufficiently explored.

To examine the association between insomnia severity, sociodemographic variables, lifestyle habits, and estimated T2DM risk using three validated non-invasive risk assessment scales.

A cross-sectional study was conducted among 84,898 Spanish workers aged 18-69 years undergoing occupational health evaluations (2021-2024). Sociodemographic and behavioral data were collected through standardized questionnaires, including adherence to the Mediterranean diet (MEDAS-14), physical activity (IPAQ-SF), and smoking status. Insomnia was assessed using the Insomnia Severity Index (ISI). Diabetes risk was estimated using three validated non-invasive risk-assessment tools: the Finnish Diabetes Risk Score, the QDScore/QDiabetes, and the Trinidad Risk Assessment Questionnaire for Type 2 Diabetes Mellitus. As these instruments were developed and validated in different populations, comparisons of absolute risk categories across scales should be interpreted with caution. Multivariable logistic regression models adjusted for age, sex, social class, smoking, diet, and physical activity were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).

Severe insomnia was associated with approximately 2.1-2.6-fold higher odds of high estimated diabetes risk across all three scales in the pooled analyses, with significant trends across categories of insomnia severity (all P for trend <0.001). This association persisted across sex and activity strata. Adding ISI modestly improved model discrimination (ΔAUC ≈ +0.015; P≤0.003) and reclassification (continuous net reclassification improvement [NRI], 6.5%-8.1%).

Insomnia severity was independently associated with higher estimated risk of T2DM beyond measured sociodemographic and lifestyle determinants. Incorporating sleep health-via brief tools such as the ISI-into diabetes risk assessment could enhance early prevention strategies in clinical and occupational settings.

Compound birth-death processes are widely used to model the age-incidence curves of many cancers. There are efficient schemes for directly computing the relevant probability distributions in the context of linear multi-stage clonal expansion (MSCE) models. However, these schemes have not been generalised to models on arbitrary graphs, forcing the use of either full stochastic simulations or mean-field approximations, which can become inaccurate at late times or old ages. Here, we present a numerical integration scheme for directly computing survival probabilities of a first-order birth-death process on an arbitrary directed graph, without the use of stochastic simulations. As a concrete application, we show that this new numerical method can be used to infer the parameters of an example graphical model from simulated data.

All individuals with colorectal cancer (CRC) should undergo genetic cancer risk assessment given its implications for personalized treatment, surveillance, risk-reduction strategies, and cascade testing. Universal screening using immunohistochemistry (IHC) for mismatch repair (MMR) proteins in tumor tissue, when combined with clinical criteria, is essential for identifying individuals at higher risk for carrying germline pathogenic variants (PVs) in resource limited countries.

The spectrum of PVs in cancer susceptibility genes was characterized using NGS multigene panel assays among selected patients with CRC at two centers in Mexico. Germline genetic testing was used as the reference standard to evaluate the diagnostic accuracy of the referral criteria.

From September 2018 to October 2024, 208 patients were enrolled. The median age at diagnosis was 45.0 years; 52.4% were women, 48.6% had deficient-MMR CRC, and 38.0% reported family history of CRC. Germline PVs were identified in 32.2% (n = 67); of these, 77.6% (n = 52) had Lynch syndrome (30 MLH1, 14 MSH2, 6 MSH6, and 2 PMS2), while 22.4% (n = 15) harbored PVs in other genes (4 ATM, 3 BRCA1, 3 CHEK2, 2 TP53, 1 BRCA2, 1 BRIP1, and 1 PALB2). Additionally, one individual harbored a monoallelic PV in MUTYH. The Amsterdam II criteria demonstrated the highest specificity (Sensitivity 56.0%, Specificity 91.9%), while the revised Bethesda criteria (Sensitivity 98.1%, Specificity 19.9%) and IHC for MMR proteins (Sensitivity 91.2%, Specificity 68.7%) exhibited high sensitivity. The area under the ROC curve for PREMM5 was 0.822 (95% CI 0.746-0.898).

PREMM5, Revised Bethesda criteria and IHC for MMR proteins effectively prioritized patients eligible for germline genetic testing in resource-limited settings. The performance of PREMM5 in this Mexican cohort was comparable to findings reported in validation studies within other populations. Considering the spectrum of PVs identified, employing a multigene panel test is recommended for Mexican patients with CRC.

Previous studies indicate that preoperative chronic steroid use is associated with an increased risk of postoperative pulmonary embolism (PE) in adult patients undergoing tumor craniotomy. We aimed to evaluate whether the platelet-to-white blood cell (PLT/WBC) ratio may partially explain the association. This retrospective study involved a secondary analysis of data from the American College of Surgeons National Surgical Quality Improvement Program database, encompassing 15,274 patients who underwent tumor craniotomy. Multivariable logistic regression was performed to assess the association between preoperative chronic steroid use and 30-day postoperative PE. Furthermore, a mediation analysis was performed to explore the role of the PLT/WBC ratio in this association. Preoperative chronic steroid use was present in 15.18% (n = 2,319) of patients, and the rate of postoperative PE was 1.41% (n = 215), with a higher rate in chronic steroid users compared to non-users (2.37% vs. 1.24%). Multivariable analysis revealed a positive association between preoperative chronic steroid use and postoperative PE (OR = 1.90, 95% CI: 1.24, 2.90). Mediation analysis demonstrated that the PLT/WBC ratio significantly explained part of the association between chronic steroid use and postoperative PE (P = 0.006). Our findings further supported the association between preoperative chronic steroid use and elevated odds of postoperative PE in adults undergoing tumor craniotomy. Additionally, our analysis revealed that preoperative PLT/WBC ratio potentially acts as a partial linking factor in this association. Future studies are required to substantiate these findings.

Incidentalomas-unexpected neoplastic lesions discovered during imaging for unrelated complaints-represent a growing clinical and ethical challenge in emergency medicine. Their detection has increased due to widespread use of advanced imaging, particularly in patients who may otherwise escape thorough diagnostic evaluation.

We sought to determine the frequency, anatomical distribution, and clinical management gaps of neoplastic incidentalomas observed in patients presenting with non-specific, low-severity complaints at the emergency department (ED). (In this paper, neoplastic incidentalomas include both lesions discovered incidentally during imaging for unrelated conditions and newly diagnosed malignancies plausibly related to the patient's presenting symptoms,) METHODS: Data collection covered the period January 1-December 31, 2023. We conducted a retrospective observational study of all adult patients presenting to the ED of P.O. Anastasia Guerriero University Hospital in Marcianise, Italy. Incidentalomas were identified through discharge summaries and classified by imaging modality, anatomical site, and triage code. We analyzed data using descriptive and inferential statistics.

Among 35,081 ED visits, 53 neoplastic incidentalomas were identified (1.52 per 1,000). The majority occurred in females (69%) and elderly (> 65 years) patients (61%), who often presented with minor complaints such as abdominal pain (38%) or anemia (15%). Most incidentalomas were gastrointestinal (31%) or pulmonary (23%) and primarily detected via computed tomography (51%). Notably, 100% of cases were triaged as non-urgent. Based on established guidelines, up to 20% of cases may represent potential overdiagnosis. The next most common modalities of detection were ultrasound (28%) and chest radiograph (22%).

Neoplastic incidentalomas are not rare in the ED setting, even among patients who present with low-severity symptoms. Our findings underscore the importance of structured follow-up protocols and integration of guideline-based reporting to avoid diagnostic delays, overdiagnosis, and unnecessary interventions. Emergency physicians should maintain diagnostic vigilance and consider incidental findings in clinical workflows.

Lung squamous cell carcinoma (LUSC) is a difficult cancer to treat, with few targeted therapies to improve its poor prognosis. The goal of this study was to use a drug repurposing strategy to evaluate and compare drug sensitivities using 2D adherent and 3D spheroid models of NCI-H2170 LUSC cells. Both 2D adherent and 3D spheroid models were used to grow NCI-H2170 lung squamous cell carcinoma cells and evaluate their sensitivity to a large library of food and drug administration (FDA)-approved drugs, including many not typically used as anti-cancer agents. Cell death was assessed in the 2D adherent models, and for the top drugs half maximal effective concentration (EC50) values were determined. For the 3D spheroid models, drugs reducing spheroid size after 4 days of treatment were identified. There were 263 drugs that reduced the cell viability to <20% when cells were grown in 2D in 10 µM drug. When grown in 3D the cells were generally more drug resistant, with 87 drugs capable of reducing spheroid volume when grown over 4 days in 10 µM drug. Interestingly, 60 drugs proved effective in both model systems including many drugs that typically associated with anti-cancer properties. Of these 60, four were further found to have selective effects towards metastatic NCI-H2170 cells as compared to a much less metastatic matched cell line expressing the metastasis suppressor CREB3L1, in both 2D and 3D model systems. These included the hypoxia-inducible factor 1-alpha (HIF-1α inhibitor 2-methoxyestradiol, and three anti-infection agents (cetylpyridinium chloride, chlorhexidine-2HCl, zinc pyrithione).

These results suggest that the HIF-1α inhibitor 2-methoxyestradiol, and three anti-infection agents (cetylpyridinium chloride, chlorhexidine-2HCl, zinc pyrithione) may be effective for metastatic LUSCs.

Basal cell carcinoma (BCC), the most common skin cancer, is driven by UV-induced DNA damage and shaped by immune surveillance. Although GWAS has identified over 140 risk loci, their cell-type-specific effects remain obscured by tissue-level averaging.

We integrated BCC GWAS summary statistics from a UK-based cohort (17,416 cases, 375,455 controls) with single-cell expression quantitative trait locus (sc-eQTL) data from 12 immune cell types in the OneK1K resource. Using the OTTERS framework combined with ACAT-O, we performed single-cell transcriptome-wide association analysis (scTWAS); bulk TWAS using GTEx whole blood served as a conventional tissue-averaged benchmark for comparison, rather than a definitive gold standard. Functional enrichment was conducted via Gene Ontology (GO).

Bulk TWAS using GTEx whole blood identified 35 BCC-associated genes (FDR < 0.05), including MC1R and CASP8. In contrast, single-cell transcriptome-wide association study (scTWAS) across 12 OneK1K cell types revealed 207 non-redundant susceptibility genes, predominantly in CD4ET, MONOC, and BIN. Functional enrichment uncovered cell-type-specific programs: MHC class II antigen presentation (CD4ET), PRR-mediated innate immunity (MONOC), and pro-inflammatory secretion (BIN)-all absent in bulk results.

Our exploratory scTWAS using healthy donor PBMC-derived eQTLs uncovered cell-type-specific BCC associations missed by bulk analyses, providing hypothesis-generating insights into immune-related genetic effects in BCC. This underscores how single-cell resolution can overcome signal dilution from cellular heterogeneity, though validation in tumor-derived immune populations is warranted.

The COVID-19 pandemic highlighted a critical need for effective population mental health approaches to target the most prevalent disorders (eg, depression) during periods of elevated community distress. The effectiveness of remotely delivered and web-based interventions should be investigated to identify and innovate high-quality models for population mental health service delivery.

The primary objective investigated the effectiveness of adding Mindfulness-Based Cognitive Therapy for Resilience (MBCT-R)-a live, online, synchronous, remotely delivered, group-based intervention-to Cambridge Health Alliance MindWell (CHA-MW), a web-based population health screening and stratified support program, compared with CHA-MW alone, on depression symptom severity. The secondary objective evaluated adding internet Cognitive Behavioral Therapy (iCBT)-an asynchronous, web-based, individual, digital intervention-to CHA-MW, compared with CHA-MW alone.

Participants (N=97) were randomized in a 2:2:1 ratio to receive MBCT-R+CHA-MW (n=37), iCBT+CHA-MW (n=41), or CHA-MW alone (n=19) in a 3-arm randomized clinical trial, from May 2021 to September 2022 in an urban public safety net hospital outpatient setting. CHA-MW served as a low-intensity control condition. For the MBCT-R+CHA-MW arm, MBCT-R was an 8-session program mildly adapted from MBCT to address COVID-19-related risks for depression. For the iCBT+CHA-MW arm, iCBT was a 6-session curriculum added to CHA-MW. All study procedures, including regular mental health symptom screenings, were conducted remotely or via a web-based platform. The primary outcome was change in depression symptom severity during the 24-week study period using an intention-to-treat approach that used generalized linear mixed-effects models to evaluate the comparative effectiveness of MBCT-R+CHA-MW vs CHA-MW over time. A secondary analysis compared iCBT+CHA-MW vs CHA-MW on depression severity. Completer analyses were conducted (per-protocol 6+ sessions). The secondary outcome was mental health visit utilization frequency during the study period.

Both MBCT-R+CHA-MW (mean difference -14.1, 95% CI -21.0 to -7.2) and CHA-MW (mean difference -15.2, 95% CI -21.8 to -8.6) had significant reductions in depression symptom severity, with no statistically significant between-group differences. iCBT+CHA-MW (mean difference -12.7, 95% CI -17.4 to -8.1) also reduced depression symptoms but without between-group differences when compared with CHA-MW. Intervention completion rates were low (MBCT-R: 30% and iCBT: 24%), and completers demonstrated significantly greater reductions in depression severity than noncompleters (mean difference -8.5, 95% CI -16.2 to -0.8). Overall mental health clinician visits by group had no statistically significant differences. CHA-MW had the largest increase in participants with new psychopharmacology treatment visits during the 24-week study (CHA-MW +21%, MBCT-R +10%, and iCBT -5%).

MBCT-R+CHA-MW, iCBT+CHA-MW, and CHA-MW were each effective in treating depression, without any intervention demonstrating superiority in intention-to-treat analyses. CHA-MW was as efficacious during the COVID-19 pandemic as more resource-intensive interventions that demanded greater time and effort from participants. Low completion rates for MBCT-R and iCBT during the COVID-19 pandemic may have contributed to these results.