Molecular signatures are increasingly recognized as pivotal factors in therapy selection for lung adenocarcinomas (LUAD). A developing therapeutic approach focuses on targeting metabolic dependencies within cancer cells. ERCC6L, a vital protein involved in chromosome separation during cell mitosis, emerges as a compelling subject concerning its impact on LUAD tumorigenesis and progression. Our investigation uncovered elevated levels of ERCC6L in LUAD, significantly associated with unfavorable patient outcomes. Functional analyses elucidate ERCC6L's role in promoting LUAD cell proliferation, migration, and invasion by inducing glycolysis and stemness characteristics. Mechanistically, our data reveal ERCC6L's involvement in upregulating aerobic glycolysis through the induction of hypoxia-inducible factor-1α (HIF-1α) expression and transcriptional activity in LUAD cells. Furthermore, ERCC6L stabilizes HIF-1α by inhibiting its hydroxylation and ubiquitin-mediated degradation. The ERCC6L/HIF-1α axis plays a crucial functional role in enhancing cancer stemness and LUAD progression both in vitro and in vivo. Hence, our findings underscore the significance of the ERCC6L/HIF-1α axis in regulating aerobic glycolysis in LUAD cells, suggesting its potential as a biomarker and therapeutic target for LUAD patients.

Chloride channel accessory 1 (CLCA1) is considered a potential prognostic biomarker for colon adenocarcinoma (COAD). The objective of this research was to develop two pathomics models to predict CLCA1 expression from hematoxylin-eosin (H&E) stained pathological images and to investigate the biological mechanisms linked to pathomics features by associating the pathomics model with transcriptomic data. The prognostic value of CLCA1 in COAD was assessed based on gene transcriptome expression data. The two pathomics models were constructed to predict CLCA1 expression in COAD based on pathological image features using the random forest (RF) and XGBoost machine learning algorithms. The RF pathomics model demonstrated superior predictive performance, achieving area under the curve (AUC) values of 0.846 and 0.776 in the training and validation cohorts, respectively, and was selected for further analysis. The ability of the pathomics model to predict overall survival (OS) in COAD was determined using univariate and multivariate Cox regression analyses. The possible biological mechanisms behind the pathomics model were explored by conducting gene set variation analysis (GSVA), immune infiltration assessment, and somatic mutation analysis. CLCA1 expression was downregulated in COAD patients and was associated with a poor prognosis (P = 0.008). Participants were categorized into high- and low-risk score groups based on the critical value of the risk score. High-risk scores were protective for OS in COAD in both univariate and multivariate Cox regression analyses. Meanwhile, GSVA enrichment analysis unveiled notable enrichment of pathways such as the epithelial-mesenchymal transition and vascular endothelial growth factor (VEGF) signaling in the low-risk score group. Two pathomics-based machine learning models were developed to predict CLCA1 expression from H&E stained images of COAD. A theoretical basis for interpreting the disease model was developed by comprehensively analyzing the pathomics-based models and transcriptomic data, facilitating further hypothesis-driven experimental research.

Vimentin is a type III intermediate filament (IF) protein that is induced in a large number of solid tumours. A single cysteine at position 328 in vimentin plays a crucial role in assembly, organisation, and stability of IFs. However, its exact function during epithelial-mesenchymal transition (EMT) and cancer progression has not been investigated. To investigate this, we have transduced wildtype (WT) and C328S vimentin separately in MCF-7 cells that lack endogenous vimentin. The expression of C328-VIM impacted vimentin-actin interactions and induced EMT-like features that include enhanced cell proliferation, migration, and invasion accompanied by reduced cell adhesion when compared to the wildtype cells. Functional transcriptomic studies confirmed the upregulation of EMT and mesenchymal markers, downregulation of epithelial markers, as well as acquisition of signatures associated with cancer stemness (CD56, POU5F1, PROCR, and CD49f), thus transforming MCF-7 cells from oestrogen-positive to triple-reduced (ESR1, PGR, and HER2) status. We also observed a stark increase in the expression of long non-coding RNA, XIST, in MCF-7 cells expressing C328-VIM. Targeting the mutant vimentin or XIST by RNA interference partially reversed the phenotypes in C328-VIM-expressing MCF-7 cells. Furthermore, the introduction of C328-VIM cells into nude mice promoted tumour growth by increasing cancer stemness in an oestrogen-independent manner. Altogether, our studies provide insight into how cysteine 328 in vimentin dictates mechano-transduction signals to remodel actin cytoskeleton and protect against EMT and cancer growth via modulating lncRNA XIST. Therefore, targeting vimentin and/or XIST via RNA interference should be a promising therapeutic strategy for breast cancer treatment.

Total pelvic exenteration (TPE) is widely regarded as the most effective intervention for the management of primary locally advanced rectal cancer and locally recurrent rectal cancer. However, TPE presents several challenges, including the potential for failing to achieve R0 resection, high incidence of complication, decreased postoperative quality of life, and the possible overtreatment in patients without carcinomatous adhesions or with only inflammatory adhesions, as well as in those who achieve pathological complete response after neoadjuvant therapy. In the context of precision medicine, further investigation is necessary to enhance the accuracy of preoperative diagnoses of extrarectal cancer invasion and to explore the comprehensive application of genetic molecular typing methods alongside innovative neoadjuvant treatment strategies. Such research should aim to enhance the R0 resection rate of TPE, minimize surgical complications and mortality, improve postoperative quality of life, and achieve an optimal balance between radical resection and the preservation of organ function.

Triple-negative breast cancer (TNBC) is a molecular subtype of breast cancer characterized by the absence of estrogen and progesterone receptors and the lack of HER2 overexpression. TNBC is highly heterogeneous, complicating the identification of new therapeutic targets. However, the expression of the androgen receptor (AR) in the luminal androgen receptor (LAR TNBC) subgroup has opened the door to alternative therapeutic approaches. This study aimed to assess AR expression and correlate it with clinicopathological factors in 160 early-stage TNBC patients treated from February 2015 to February 2017. Our findings reveal that AR expression is observed in 16.87% (27/160) of ≥1% AR positivity cases. Moreover, a significant 12.5% (20/160) was found in ≥10% AR positive cases. Positive AR expression was inversely correlated with a high Ki-67 proliferation index and with the basal immunophenotype. The five-year survival rate for our cohort was 83.12%, and no significant association between AR expression and overall survival was observed (p = 0.77). The study highlights the potential role of AR expression in TNBC and its implications for therapeutic strategies, although no significant association with overall survival was found.

The COVID-19 pandemic precipitated unprecedented disruptions across global healthcare systems, with nursing education being particularly affected. In addition to the challenges encountered during the height of the crisis, the aftermath of the pandemic has continued to impose significant difficulties on nursing students, especially within clinical learning environments. Despite the breadth of emerging literature, a notable gap persists in studies explicitly examining the post-pandemic experiences of nursing students in these settings. Moreover, the present study is a qualitative study with the content analysis in Iran from October 2024 to February 2025. Twenty- two nursing students participated in this study. Data were collected from individual, and semi-structured interviews. Data analysis was conducted using the qualitative content analysis method proposed by Graneheim and Lundman (2004).

The analysis yielded three overarching themes, each encompassing specific subthemes: (1) lack of clinical competence (insufficient clinical knowledge, deficiency in clinical skills, and poor clinical judgment.) (2), psychological challenges (the quagmire of hopelessness, emotional exhaustion, and lack of self-efficacy) and (3) disruption in professional interactions (lack of mutual respect and absence of a team-oriented spirit).

Not applicable.

Interstitial lung disease (ILD) and pulmonary sarcoidosis (PS) constitute major global health challenges, characterized by progressive respiratory symptoms and diverse epidemiological trends. Although the incidence and mortality rates of ILD and PS have increased following the COVID-19 pandemic, comprehensive research examining their burden and associated risk factors remains limited. Therefore, the present study aimed to analyze the spatiotemporal distribution, gender-specific and age-related disparities, and sociodemographic determinants of ILD and PS from 1990 to 2021 to facilitate evidence-based targeted interventions.

By using data from the Global Burden of Disease 2021 database, we analyzed age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and age-standardized disability-adjusted life year rate (ASDR) across 204 countries/regions. Temporal trends were evaluated using average annual percentage change (AAPC), age-period-cohort (APC), and Bayesian APC (BAPC) models. Decomposition analysis and Pearson's correlation analysis were conducted to assess the impact of aging, population growth, and sociodemographic index (SDI). Joinpoint regression was used to identify inflection points in trends. Future disease burdens (2021-2050) were projected through BAPC modeling.

Global ILD and PS cases increased from 157,441.17 in 1990 to 390,267.11 in 2021, with an annual increase in ASIR, ASMR, and ASDR by 0.61%, 1.32%, and 0.83%, respectively. High-SDI regions exhibited the highest ASIR (71.4/100,000) and ASMR (25.5/100,000). Males exhibited greater disease burdens than females ASDR 57.79/100,000 vs. 39.49/100,000 in 2021), with a peak incidence in the 70-74 age group. SDI showed positive correlations with ASIR and ASMR, exhibiting U-shaped relationships in certain regions. Projections indicated stable ASMR but increasing ASIR and ASDR by 2050, particularly among males.

The global burden of ILD and PS has increased markedly since 1990, influenced by population aging, industrial development, and socioeconomic disparities. Prioritizing early screening (e.g., high-resolution computed tomography and serum biomarkers), minimizing environmental and occupational exposures, and implementing gender-/age-specific interventions are critical measures. Strengthening healthcare infrastructure in low-SDI regions and integrating advanced diagnostic technologies are crucial for reducing future disease burdens.

Data in Ethiopia on the epidemiology of Respiratory Syncytial Virus (RSV) and subtypes among influenza-like illness (ILI) and severe acute respiratory infections (SARI) cases is limited. Here, we assessed the epidemiology of RSV and its subtypes among the pediatric and adult ILI /SARI cases in Ethiopia.

We conducted prospective, multicenter facility-based study from May 2023 to April 2024. Respiratory swab specimens, epidemiological and clinical data were collected from participants of all age groups, and both hospitalized and non-hospitalized individuals who met the World Health Organization (WHO) case definition for ILI/SARI and provided informed consent. Laboratory investigation was performed using reverse transcription polymerase chain reaction (RT-PCR). Data were analyzed using SPSS V29. Descriptive statistics were used to summarize frequencies and ratios, and multivariable logistic regression model was employed to assess factors associated with RSV positivity.

In total, 4170 participants were enrolled, the majority (57.9%) of whom were cases from children under five and SARI (76.5%). RSV was detected in 654 cases (15.7%; 95% CI: 14.6-16.8). RSV subtyping was carried out for 475 (72.6%) of 654 RSV positive samples. The finding revealed that both RSV-A and RSV-B subtypes were co-circulating in Ethiopia, with predominance of RSV-B (68.8%). Age group, season and timing of sample collection were factors independently associated with RSV positivity. Accordingly, children aged < 2 years (AOR: 8.20, 95% CI: 3.57-18.81) and 2-4 years (AOR: 5.01, 95% CI: 2.15-11.67), autumn (AOR: 5.89, 95% CI: 3.79-9.17) and winter (AOR: 3.27, 95% CI: 2.07-5.16) seasons, and case whose samples were collected within three days of symptom onset (AOR: 1.76, 95% CI: 1.09-2.84) were significantly associated with RSV positivity.

The study provides evidence of RSV circulation among ILI/SARI cases in Ethiopia. It also revealed that RSV-B was the predominant subtype circulating in the country. The age-specific and temporal patterns of RSV positivity identified in this study contribute to the understanding of RSV and its subtypes epidemiology in Ethiopia. The findings provide valuable evidence to inform implementation of RSV vaccine introduction programs, particularly targeting high-risk populations during periods of peak transmission. Future research focusing on RSV genomic analysis and disease burden is needed to better understand RSV viral evolution, transmission dynamics and public health impacts in Ethiopia.

Due to modern lifestyles, physical activity (PA) has decreased at a population level, resulting in health concerns worldwide. Increased level of PA can reduce mortality and morbidity in pulmonary diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Many previous studies on the association between pulmonary function and PA assessed PA by questionnaires. We aimed to study the cross-sectional association between pulmonary function and objectively measured PA and sedentary behavior (SB) in population-based data. A total of 4729 subjects participated in the Health 2011 survey, which represents the Finnish adult population. Of these, 1511 completed spirometry and the required 4-day accelerometer wear time. Spirometry values of forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) were determined. We compared the differences in daily PA measured with triaxial accelerometer between those with obstructive or restrictive spirometry results (defined as FEV1/FVC < -1.65 z-score, lower limit of normal [LLN] and FVC < -1.65 z-score, respectively) and those with FEV1 < -1.65 z-score to those with normal spirometry in adjusted logistic regression analysis. Airway obstruction, pulmonary restriction, and FEV1 < LLN were associated with less time spent in moderate (adjusted odds ratio [OR] 0.63, 95% confidence interval [CI] 0.40-0.99; OR 0.65, 95% CI 0.43-1.00; OR 0.58, 95% CI 0.39-0.87, respectively) and moderate-to-vigorous level of PA (OR 0.65, 95% CI 0.43-0.98; OR 0.63, 95% CI 0.42-0.94; OR 0.56, 95% CI 0.38-0.82, respectively). Those with restrictive spirometry had greater time spent sedentary and a lower daily step count when compared to those with normal spirometry. Respective ORs with 95% CIs were 1.09 (1.01-1.19) and 0.85 (0.75-0.96). Our results show the association between impaired pulmonary function and measured lower level of daily PA. Restriction associated with greater time spent sedentary and a lower daily step count when compared with those with normal spirometry, airway obstruction, and FEV1 < LLN.

The COVID-19 pandemic has been associated with increased neuropsychiatric conditions in children and youths, with evidence suggesting that SARS-CoV-2 infection may contribute additional risks beyond pandemic stressors. This study aims to assess the full spectrum of neuropsychiatric conditions in COVID-19 positive children (ages 5-12) and youths (ages 12-20) compared to a matched COVID-19 negative cohort, accounting for factors influencing infection risk. Using EHR data from 25 institutions in the RECOVER program, we conduct a retrospective analysis of 326,074 COVID-19 positive and 887,314 negative participants matched for risk factors and stratified by age. Neuropsychiatric outcomes are examined 28 to 179 days post-infection or negative test between March 2020 and December 2022. SARS-CoV-2 positivity is confirmed via PCR, serology, or antigen tests, while negativity requires negative test results and no related diagnoses. Risk differences reveal higher frequencies of neuropsychiatric conditions in the COVID-19 positive cohort. Children face increased risks for anxiety, OCD, ADHD, autism, and other conditions, while youths exhibit elevated risks for anxiety, suicidality, depression, and related symptoms. These findings highlight SARS-CoV-2 infection as a potential contributor to neuropsychiatric risks, emphasizing the importance of research into tailored treatments and preventive strategies for affected individuals.