Despite significant advances in breast cancer therapy, resistance to apoptosis remains a major obstacle to successful treatment. Lifeguard (LFG), an antiapoptotic membrane protein, has been implicated in breast cancer progression; however, its role in endoplasmic reticulum (ER) stress-associated molecular responses and apoptosis-related gene regulation remains incompletely understood.

This study aimed to investigate molecular changes associated with LFG-targeted siRNA treatment and reduced LFG mRNA expression in human breast cancer cells.

The triple-negative breast cancer cell line MDA-MB-231 and the non-tumorigenic mammary epithelial cell line MCF10A were transfected with LFG-specific siRNA. LFG mRNA expression was analyzed by quantitative RT-PCR. Furthermore, ER stress- and apoptosis-related gene expression was examined using an RT² Profiler PCR Array, and intracellular calcium-associated fluorescence was assessed by fluorescence-based calcium imaging. LFG mRNA expression was markedly reduced following LFG-specific siRNA treatment in MDA-MB-231 cells, whereas a more moderate reduction was observed in MCF10A cells. LFG-targeted siRNA treatment was associated with altered intracellular calcium-associated fluorescence and differential expression of several ER stress- and apoptosis-related genes, including upregulation of CREB3L3, SREBF1, and INHBE, as well as downregulation of EDEM1, HSPA2, and RRM2.

These findings demonstrate that LFG-targeted siRNA treatment and reduced LFG mRNA expression are associated with changes in intracellular calcium-related responses and ER stress- and apoptosis-associated gene expression, particularly in MDA-MB-231 cells. Further studies are required to determine the underlying mechanisms and establish the functional role of LFG in these cellular responses.

Vitamin C, a classical antioxidant, is increasingly recognized as a key regulator of cellular signaling networks, epigenetic, and post-translational regulation. As a cofactor of Fe²⁺/2-oxoglutarate-dependent dioxygenases, vitamin C promotes epigenomic changes by enhancing TET-dependent DNA demethylation and the activity of Jumonji-C domain-containing histone demethylase, thereby influencing key cellular processes including pluripotency, reprogramming, and differentiation. Recent studies have also uncovered a direct role for vitamin C in proteome regulation by modifying lysine residues, to generate vitcyl-lysine (a process termed as Vitcylation), opening new avenues for its therapeutic applications. These lesser-understood functions of vitamin C underpin its context-dependent roles in cancer and other disease states. Future mechanistic studies identifying targets of vitamin C-dependent protein modification and their consequences on epigenome regulation will be critical for advancing its therapeutic applications.

Trans-endothelial migration (TEM) is a critical rate-limiting barrier in tumor metastasis, yet its mechanistic basis remains poorly defined. Here we show that α-ketoglutarate (α-KG) and its metabolic enzyme glutamate dehydrogenase 1 (GLUD1) constitute a pivotal regulatory axis governing this process. Mechanistically, GLUD1 translocates to the nucleus, where α-KG binds to its non-catalytic site (K147) to induce a conformational change that stabilizes the GLUD1-SNAIL interaction, promoting assembly of a nuclear ternary complex. Notably, this complex is preferentially enriched in tumors, and specific blockade of K147 disrupts this assembly and abrogates metastatic effects. Our findings reveal a non-canonical role for GLUD1 and α-KG in transcriptional regulation and propose a therapeutic paradigm that selectively interferes with metabolite-dependent complex formation rather than enzymatic activity, offering a precise strategy to target TEM-driven metastatic cells.

Brain cancer mortality trends in the United States may be affected by deaths recorded as unspecified brain malignancies, affecting epidemiological interpretation. We aimed to evaluate the impact of unspecified brain malignancies on overall brain cancer mortality trends patterns over time.

Mortality data were extracted in June 2026 from the CDC WONDER as multiple causes of deaths with ICD- 10 codes (C71.9 and C71), respectively, from 1999 to 2024. The age-adjusted mortality rate (AAMR) per 100,000 persons, by sex, race, census, 2013 urbanization, state, and place of death, as well as the (CMR) by age, were reported and analyzed using Joinpoint regression software to evaluate (APC) and (AAPC) and corresponding 95 % confidence intervals (CIs).

From 1999 to 2024, 359,859 deaths occurred among patients with unspecified brain malignancies and overall brain cancer. The overall AAMR declined from 6.53 per 100,000 in 1999 to 5.69 per 100,000 in 2024. The largest decline was observed between 2015 to 2024, corresponding to APC of -1.1657 (95% CI: -1.42 to -0.91; p < - 0.000001). The AAPC throughout the period was -0.516 (95% CI: -0.34 to-0.64; p < 0.000001). Men (7.55) had higher average AAMRs than women (4.95), adult aged >75+ years had a higher burden (CMR:19.41), Non-Hispanic whites had highest mortality (7.02) while, Non-Hispanic Asian or Pacific islander had the lowest mortality (2.81). Midwest had the greatest mortality (6.45) and the Northeast had the lowest (5.87). Non-metropolitan areas showed average higher AAMR then the Metropolitan areas (6.60 vs 6.13). South Dakota was highest mortality state during 2019-2020, while Vermont was highest mortality state during 2021 to 2024.

Analysis reported higher burden of brain malignancy among the males, older ages, and Non-Hispanic white populations, Midwest, Non metropolitan areas highlighting diagnostic precision and targetted intervention.

Lower respiratory tract infection (LRTI) is a major cause of hospitalisation in older adults with Parkinson's disease (PD), but it remains uncertain whether PD-related measures provide clinically relevant information beyond general vulnerability and acute infection severity.

We conducted a single-centre retrospective cohort study of patients aged ≥65 years with neurologist-diagnosed PD who were hospitalised for LRTI between 2018 and 2025. The primary outcome was a composite of intensive care unit admission, invasive mechanical ventilation, or in-hospital death. Documented readmission to the index hospital within 90 days among survivors was analysed as a secondary exploratory outcome. Multivariable logistic and Cox regression models evaluated clinical factors associated with these outcomes. A hierarchical extension added Hoehn-Yahr stage and pre-admission wheelchair- or bed-bound status to the base clinical model. Calendar-period analyses and bootstrap internal validation were performed.

Among 246 patients, 62 (25.2%) experienced the composite in-hospital outcome. In the PD-specific extended model, higher Charlson Comorbidity Index (adjusted odds ratio [OR] per 1-point increase 1.19, 95% confidence interval [CI] 1.00-1.42), hypoxaemia (OR 2.00, 95% CI 1.01-3.96), serum albumin <35 g/L (OR 3.18, 95% CI 1.65-6.14), sepsis or septic shock (OR 2.41, 95% CI 1.17-4.98), and pre-admission wheelchair- or bed-bound status (OR 2.08, 95% CI 1.08-4.01) were associated with the outcome. Hoehn-Yahr stage, PD duration, tube feeding, and antiparkinsonian medication burden were not independently associated. Among 228 patients discharged alive, 74 (32.5%) had a documented readmission to the index hospital. Hypoalbuminaemia (adjusted hazard ratio [HR] 1.82, 95% CI 1.12-2.95) and non-home discharge (HR 1.96, 95% CI 1.19-3.24) were among the factors associated with documented same-hospital return. Bootstrap-corrected discrimination was 0.81 for the extended logistic model and 0.70 for the Cox model.

Severe in-hospital deterioration was associated mainly with general physiological vulnerability, acute infection severity, and pre-admission mobility dependence, whereas most other available PD-specific measures showed no clear independent association. These findings support integrated clinical assessment but not a validated PD-specific prediction strategy; the post-discharge analysis reflects documented return to the index hospital rather than complete population-level readmission.

Novel influenza A viruses (NIAV) infection is a zoonotic acute respiratory disease. The H5N1 and H7N9 subtypes cause high mortality, posing major public health threats. This study aimed to establish rapid, field-deployable subtype-specific nucleic acid detection assays for H5 and H7 by integrating reverse-transcription enzymatic recombinase amplification (RT-ERA) with CRISPR/Cas12a. Two separate reactions are required per sample.

Conserved hemagglutinin (H) sequences were retrieved from the NCBI database, and primers, probes, and crRNAs were designed using Primer Premier 5 and Primer-BLAST. The sensitivity of RT-ERA alone was compared with that of the ERA-CRISPR/Cas12a using serially diluted virus strain nucleic acid. The specificity was verified against other respiratory pathogens with similar clinical manifestations.

The optimal primers were F1R2 for H5 and F2R3 for H7. The limit of detection (LOD) of RT-ERA alone was 2.63×10³ copies/µL for H5 and 1.86×10³ copies/µL for H7; the ERA-CRISPR/Cas12a assay improved the LOD to 2.63×10¹ copies/µL for H5 and 1.86 copies/µL for H7, representing 100-fold and 1000-fold enhancements in sensitivity, respectively. Specificity testing showed that the assay exclusively detected H5N1 and H7N9 with no cross-reactivity to other tested pathogens.

The ERA-CRISPR/Cas12a method exhibits enhanced sensitivity for H5 and H7 subtypes detection, along with high specificity, rapidity, and minimal equipment requirements. It offers a promising screening tool for NIAV infections.

To investigate test-retest reliability, measurement error (standard error of measurement [SEM] and minimum detectable difference [MDD]), and the learning effect of the Modified Shuttle Test (MST) in children with asthma.

Multicenter cross-sectional study including clinically stable children aged 6-12 years with asthma. Lung function and exercise capacity were assessed using MST. Intraclass Correlation Coefficient (ICC) was calculated to assess test-retest reliability. The first and second tests were compared using the paired Student's t-test to assess differences between tests. SEM and MDD were calculated to quantify measurement error.

One hundred and twenty three children were included (71 boys [57%]; median age 9 [7-10] years). The mean distance covered in the best MST was 611 ± 214 meters (confidence interval [95% CI] = 573-649meters). The MST showed an excellent test-retest reliability (ICC = 0.96; 95% CI: 0.95-0.97). Distance was significantly lower in the second test than in the first (574 ± 218 vs. 601 ± 216 m; p = 0.0001). Learning effect was -27 ± 79 (4% ± 14%), the SEM was 56 meters (9.5%), and the MDD was 156 m (26.6%).

The MST demonstrated excellent test-retest reliability and acceptable measurement error for assessing exercise capacity in children with asthma. Although a systematic difference was observed between tests, there was no evidence of a consistent learning effect, with individual variability in repeated performance.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide and is increasingly recognized as a major contributor to liver-related and cardiometabolic morbidity. In people living with HIV (PLWH), the burden of MASLD is disproportionately high and continues to rise in the era of effective antiretroviral therapy (ART). The recent redefinition of MASLD underscores a paradigm shift toward metabolic dysfunction as a central driver of disease pathogenesis, a concept that is particularly relevant in the context of HIV infection. In PLWH, MASLD may represent a distinct immunometabolic condition in which conventional metabolic risk factors interact with chronic immune activation, persistent inflammation, ART exposure, and gut-liver axis dysfunction. These factors may contribute to steatosis and fibrosis and complicate conventional obesity-based screening and risk stratification. This narrative review summarizes the disease burden, immunometabolic mechanisms, diagnosis, and management of MASLD in PLWH and identifies priorities for research and clinical care. Management requires integrated assessment of metabolic dysfunction, persistent inflammation, cumulative ART exposure, and cardiovascular risk rather than reliance on obesity-based screening alone.

The triglyceride-glucose (TyG) index and its derivatives are cost-effective markers of insulin resistance and cardiovascular risk. However, the comparative predictive value of baseline levels, cumulative exposure, and annual mean changes in TyG-related indices remains unclear. This study aimed to systematically compare the predictive performance of multiple dimensions of TyG-related indices for cardiovascular events in rural older adults with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3.

This cohort study enrolled 4,169 participants aged ≥65 years with no history of cardiovascular events. Longitudinal data from annual standardized health examinations under the National Basic Public Health Services Project were used to calculate baseline, cumulative exposure, and annual mean change values of TyG-related indices. Associations, dose-response relationships, and predictive performance were assessed via accelerated failure time models, restricted cubic spline analyses, time-dependent receiver operating characteristic analyses, and model fit statistics. Linear mixed-effects models were applied to delineate longitudinal trajectories of these indices. Sensitivity analyses were further conducted to verify the robustness of the main findings.

During 6 years of follow-up, 822 cardiovascular events were documented. Cardiovascular risk increased progressively with advancing CKM syndrome stages (P = 0.004). Baseline and cumulative TyG-WC and TyG-WHtR were consistently and strongly associated with incident cardiovascular events (all P < 0.001), with cumulative measures demonstrating slightly stronger associations. Dose-response analyses revealed a linear relationship between TyG and cardiovascular events, whereas TyG-BMI, TyG-WC, and TyG-WHtR exhibited nonlinear associations. In terms of association strength, most annual mean change measures were not significantly associated with outcomes, only TyG-BMI showed a weak association(P = 0.033) and was the only indicator with a statistically significant time-to-CVD interaction in longitudinal trajectory analysis. Nevertheless, all annual mean change indicators generally demonstrated poorer predictive performance than baseline and cumulative indicators for cardiovascular events. Among all indices, baseline and cumulative TyG-WC showed the optimal predictive performance across follow-up periods, and baseline TyG-WC had predictive utility comparable to cumulative TyG-WC. Sensitivity analyses further confirmed the robustness of these key findings.

Baseline and cumulative TyG-related indices demonstrated stronger associations with cardiovascular events compared with annual mean changes, suggesting that sustained metabolic exposure is more clinically informative than short-term fluctuation. Baseline and cumulative TyG-WC demonstrated relatively better predictive performance and, especially baseline measure, may serve as a simple and low-cost auxiliary tool for cardiovascular risk stratification in resource-constrained primary care settings, though it should not replace conventional cardiovascular risk-assessment instruments.

Anomia is a common linguistic consequence of post-stroke aphasia. Widely used confrontation-naming measures were developed primarily in English-speaking populations, and item familiarity may not transfer to Arabic speakers. We developed the Arabic Naming Test (ANT) as a culturally grounded picture-naming task and examined its preliminary clinical feasibility in Saudi Arabic-speaking adults.

In this cross-sectional convenience-sample study, 75 neurotypical native Arabic-speaking adults and 30 adults with post-stroke aphasia completed a 90-item picture-confrontation naming task. Accuracy and response latency were recorded; participants with aphasia also completed a sequential semantic-phonemic cueing protocol. Welch tests and age-adjusted sensitivity analyses compared groups.

The aphasia group had lower ANT scores than neurotypical peers (M = 49.50, SD = 31.66 vs. M = 87.55, SD = 3.48; Welch's t(29.3) = -6.57, p < 0.001; Hedges' g = -2.21) and slower mean response latency per item (M = 1.80 s vs. M = 1.06 s; Welch's t(29.8) = 3.77, p < 0.001; Hedges' g = 1.24). These group differences remained statistically significant in age-adjusted sensitivity analyses. Sequential semantic-phonemic cueing analyses of 30 participants showed reductions in description, miscellaneous, no-response, and semantic errors after adjustment for multiple comparisons. On average, 17.17 items (SD = 18.46) were named correctly after phonemic cueing and 2.90 items (SD = 3.32) after semantic cueing alone.

In this preliminary convenience sample, the ANT showed substantial known-groups differences between Saudi Arabic-speaking neurotypical adults and adults with post-stroke aphasia and generated descriptive cueing and error-profile observations. These findings support continued development of a culturally grounded Arabic naming measure; however, larger, demographically balanced multi-site studies are needed before formal reliability, psychometric validation, diagnostic accuracy, or clinically meaningful thresholds can be established.