Determinants of telemedicine applications use by general practice patients with chronic respiratory diseases are not yet fully known. The aim of this study was twofold: (a) to assess facilitators and barriers for the use of digital home spirometers in primary care, and (b) to evaluate parameters for process quality in implementing guideline-recommended care in daily practice. The study was evaluated using a mixed-methods design. Patients with bronchial asthma or chronic obstructive pulmonary disease were instructed to take daily measurements using a digital home-spirometry device. Primary care physicians regularly controlled spirometry data using a digital monitoring portal. Telephone interviews were conducted with patients and healthcare professionals. Qualitative analysis of the transcripts was based on content analysis. Quantitative data included the assessment of quality indicators in the beginning (t0) and at the end (t1) of each individual's participation in the study, the Patient Assessment of Chronic Illness Care Short-Version (t0) and reasons for use/non-use of the spirometer (t1). Logistic regression was performed to determine predictors of use according to instructions. Altogether, 127 patients participated in the study; the average age was 59 years, 61% (n = 78) of participants were female. 21 telephone interviews with patients and healthcare professionals were conducted. Facilitators included: sense of obligation, habituation, visualization of progression, self-efficacy, physician contacts, remote treatment, and positive aspects of integration into daily practice. Barriers included: understanding of the disease, dyspnea, as well as project and technical requirements. Care providers considered time-consuming procedures and clinical assessability as barriers. At t0 and t1, approximately one third of respondents (33% resp. 36%) stated that they had received disease-specific training, and 57% stated in both cases that they had gotten the annual influenza vaccination. Logistic regression revealed that duration of disease (OR 0.96; CI 95% 0.93; 0.99), a daily measurement being too strenuous (OR 0.165; CI 95% 0.04; 0.076), and the fact that measurements could not be taken while away from home (OR 0.235; CI 95% 0.07; 0.75) to be negative predictors of use according to instructions. For the patients in the study, digital applications improved self-efficacy and self-control. However, a better understanding of these applications and additional medical feedback could be helpful for the patients using such digital applications. The evaluation of process quality parameters showed potential for improving rates of disease-related education and influenza vaccination.
Non-randomized studies of interventions (NRSIs) provide important evidence on harms, especially for rare adverse events that randomized controlled trials (RCTs) are often underpowered to detect. Evidence synthesis is therefore needed to integrate findings across study designs and to inform a comprehensive assessment of harms. However, synthesizing evidence from RCTs and NRSIs remains methodologically challenging. We examined how evidence from RCTs and NRSIs is synthesized in practice and how conclusions were drawn when findings conflict. The meta-epidemiological study included systematic reviews indexed in PubMed between 1 January 2017 and 31 December 2024 that synthesized evidence from both RCTs and NRSIs for the same outcome. We evaluated methodological practices across four synthesis scenarios. For reviews that combined RCTs and NRSIs in a meta-analysis, we assessed key methodological components of the review process. For reviews that meta-analyzed RCTs and NRSIs separately, we assessed qualitative agreement between RCTs and NRSIs based on the magnitude, direction, and statistical significance of the estimates. When qualitative disagreement was observed, we further evaluated whether the review conclusions were reasonable, taking into account the certainty of evidence and the heterogeneity of the estimates. Of 42,341 records screened, 195 systematic reviews were included. 49 (25.1%) conducted only qualitative syntheses of both RCTs and NRSIs. 11 (5.6%) meta-analyzed only RCTs, with NRSIs synthesized qualitatively; and 7 (3.6%) meta-analyzed only NRSIs, with RCTs synthesized qualitatively. Among the 91 reviews (46.7%) that combined RCTs and NRSIs in a single meta-analysis, important methodological gaps were identified: 72.5% included NRSIs at moderate or high risk of bias, 49.5% used unadjusted estimates, and 53.8% did not conduct subgroup analyses by study design. Separate meta-analyses for RCTs and NRSIs were conducted in 37 reviews (19.0%), of which 67.6% showed qualitative disagreement between the two study designs, and 20.0% were judged to have inappropriate conclusions according to our assessment criteria. Systematic reviews synthesizing RCTs and NRSIs for harms frequently overlook essential methodological considerations and often draw conclusions without adequately addressing conflicting findings across study designs. These practices risk compromising the credibility of harm assessments used in clinical, regulatory, and policy decision-making.
Twenty-first-century skills-such as critical thinking, problem solving, leadership, digital literacy, and innovation-are among the core competencies required for future health managers to function effectively within the complex and technology-driven structure of modern healthcare systems. The purpose of this study was to determine the 21st-century skill levels of undergraduate Health Management students in Türkiye and to examine whether these skills significantly differ according to demographic (gender, age, year of study) and academic (academic achievement and accreditation status) variables. This study employed a cross-sectional descriptive design. Data were collected via an online survey from 565 undergraduate Health Management students across Türkiye. The Multidimensional 21st Century Skills Scale, consisting of five subdimensions, was used as the data collection instrument. Descriptive statistics, independent samples t-test, one-way analysis of variance (ANOVA), and multiple regression analysis were performed to analyze the data. A significance level of p < .05 was adopted. The overall 21st-century skill levels of the students were found to be above average. The highest mean scores were observed in the Career Consciousness and Information and Technology Literacy dimensions, whereas the lowest means were obtained in the Entrepreneurship and Innovation and Critical Thinking and Problem Solving subdimensions. Regarding gender, a significant difference was found only in the Career Consciousness dimension in favor of female students (p < .05). In general, increases in age and year of study were associated with higher 21st-century skill levels. Academic achievement produced significant differences particularly in Information and Technology Literacy and Critical Thinking skills. While no significant differences were found regarding the official accreditation status of universities, students' perceived accreditation revealed significant differences in certain skill dimensions. Multiple regression analysis indicated that age and perceived accreditation were significant predictors of overall 21st-century skills. Health Management students demonstrated strong profiles in career awareness and digital competencies, yet showed areas for development in critical thinking, innovation, and leadership. The findings suggest the importance of revising Health Management curricula in alignment with 21st-century skills, expanding experiential and project-based learning opportunities, and designing educational strategies that foster students' innovation and entrepreneurship capacities.
Smokeless tobacco products and areca nut, widely used in Uttar Pradesh, are strongly associated with oral cancer, which ranks among the top three cancers in India. Data from the Population-Based Cancer Registry, Varanasi, highlights one of the highest oral cancer burdens across India. Despite the availability of national guidelines, frontline health workers (ASHAs) remain underutilised for tobacco cessation counselling and oral cancer symptom-based screening. This study assessed the impact of a structured training intervention on their knowledge, practices, and legal awareness. A pre-post intervention study was conducted in one rural block of Varanasi district between January and May 2023. A total of 202 ASHAs were enrolled through purposive sampling. The one-day training, based on Government of India modules, covered epidemiology, clinical features, determinants of tobacco use, cessation counselling, symptom-based oral cancer screening, and relevant legislation. Data were collected using a validated questionnaire before and after training. Descriptive statistics, Stuart-Maxwell tests, and Spearman's correlations were applied for analysis. Baseline scores revealed substantial knowledge and practice gaps: 45.6% of ASHAs had poor epidemiological awareness, 56.9% poor clinical knowledge, and 81.7% poor understanding of determinants of tobacco use. Only 19.8% reported routinely performing symptom-based screening for oral cancer, and while 64.8% "always" provided counselling, legal literacy was limited (only 38.1% aware of the COTPA Act). Following the intervention, significant improvements were observed across all domains (p < 0.01). Post-intervention most ASHAs reported willingness for oral cancer screening (64.8%) and provide tobacco cessation counselling (75.7%). Awareness of the COTPA Act increased to 65.4%. Strong positive correlations were observed between knowledge domains, suggesting synergistic gains. A structured, government-endorsed training programme significantly improved ASHAs' knowledge, attitudes, and practices related to tobacco cessation and oral cancer screening, demonstrating the feasibility of leveraging frontline workers for community-based cancer prevention. However, achieving higher competency levels requires more intensive, competency-based training with supportive supervision. Integration within routine health systems and further research on long-term impact are warranted. Trial registration Clinical Trials Registry India CTRI/2021/02/031306. Date of registration 16/02/2021.
Prompt diagnosis of bloodstream infections (BSIs) is critical for antimicrobial stewardship but hindered by blood culture delays of 48 h or more. We developed and validated a deep learning model to predict BSI risk from standard 12-lead electrocardiograms (ECGs). This study adhered to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines. In this retrospective, multi-center study, we trained a deep learning model to predict clinically significant BSIs (excluding common contaminants) using ECGs from adult emergency department (ED) patients at an academic medical center in Taiwan (April 2012 to March 2022; total N = 163,826) and validated it in three independent cohorts: internal (n = 22,205), external (n = 22,709), and MIMIC-IV (n = 66,937). For the MIMIC-IV cohort, BSI was identified using the derived suspicion of infection framework with a positive blood culture flag. The model achieved AUCs of 0.821 (95% CI 0.804-0.838), 0.800 (0.782-0.818), and 0.756 (0.743-0.768) across the three test cohorts, respectively. At a high-sensitivity rule-out threshold the model classified 19-25% of patients as low risk (negative predictive value [NPV] 99.8%); at the Youden point, the sensitivity and specificity were 73.2% and 76.8% in the internal test set, with an NPV of 99.2%. The model showed superior discrimination compared with XGBoost and logistic regression baselines. Decision-curve analysis showed net benefit over heart rate alone and the default treat-all and treat-none strategies across the clinically relevant low-threshold range. Exploratory analyses indicated that the ECG-derived risk signal was elevated across Gram-positive, Gram-negative, and fungal infections; pathogen-specific prediction will require a dedicated model (Supplementary Figure S3). The primary model stratified 90-day mortality risk among infected patients (adjusted HR 3.43 [1.93-6.09] for high- vs. low-risk). Deep learning analysis of standard 12-lead ECGs obtained at ED triage can predict clinically significant BSI with discrimination superior to conventional ECG parameters. The model discriminated best (highest AUC) in patients with low clinical suspicion (qSOFA = 0), although its incremental value in this low-prevalence subgroup is modest. Prospective validation is needed before clinical implementation.
Despite effective antiretroviral therapy (ART), a subset of people living with HIV(PLWH)experiences low-level viremia(LLV), yet its impact on subsequent virologic failure (VF) and immunologic failure (IF) remains unclear. This study aims to elucidate the effect of LLV on the risk of VF and IF. This retrospective cohort study included PLWH aged ≥ 18 years who initiated ART in Qinzhou City, Guangxi, China, from 2005 to 2023. Participants were categorized into mutually exclusive viral load categories: undetectable viral load (≤ 50 copies/mL) and LLV (51-999 copies/mL). Time-updated Cox proportional hazards models were used to evaluate the association between LLV and the risk of VF and IF. A total of 4,274 participants were followed for 12,288.35 person-years, with a median follow-up of 3.03 years. Among these participants, 11.16% experienced at least one LLV event. Compared to those with an undetectable viral load, individuals with LLV had a significantly higher risk of VF (adjusted hazard ratio [aHR] = 5.23, 95% CI: 3.48-7.85), with intermittent low-level viremia (ILLV) showing the strongest association (aHR = 7.34, 95% CI: 4.92-10.94). Conversely, LLV was associated with a lower risk of IF compared with an undetectable viral load (aHR = 0.59, 95% CI: 0.37-0.92), a finding consistent with the reduced risk observed in the ILLV subgroup (aHR = 0.56, 95% CI: 0.33-0.96). Patients with LLV had an increased risk of subsequent VF, emphasizing the need for close monitoring of viral load and potential treatment adjustments to optimize long-term ART outcomes.
The role of adjuvant systemic therapy after resection following conversion therapy in patients with hepatocellular carcinoma (HCC) rendered resectable by transarterial therapy combined with systemic therapy remains unclear. This study aimed to evaluate the impact of adjuvant systemic therapy on survival outcomes in real-world practice. We retrospectively analyzed patients with initially unresectable HCC who underwent curative-intent resection after successful first-line transarterial therapy combined with systemic therapy between January 2018 and December 2023. Postoperative management included either adjuvant systemic therapy or active surveillance. Propensity score matching (1:2) was applied to balance baseline characteristics. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using Kaplan-Meier methods and compared by log-rank tests. Subgroup and recurrence pattern analyses were also performed. Among 496 eligible patients, 120 received adjuvant systemic therapy and 376 underwent active surveillance. After matching, 326 patients were included (116 vs. 210). Adjuvant systemic therapy was associated with significantly improved OS (HR 0.58, 95% CI 0.38-0.89; p = 0.01) and RFS (HR 0.64, 95% CI 0.48-0.84; p = 0.002). Survival benefit of adjuvant systemic therapy was observed in patients with BCLC stage C disease (OS: HR 0.53, 95% CI 0.31-0.90, p = 0.02; RFS: HR 0.61, 95% CI 0.43-0.87, p = 0.007) and in those with BCLC stage A or B disease exceeding the up-to-seven criteria (OS: HR 0.46, 95% CI 0.22-0.95, p = 0.03; RFS: HR 0.56, 95% CI 0.34-0.91, p = 0.02). Multivariable analysis identified adjuvant systemic therapy as an independent predictor of improved OS and RFS. In patients undergoing resection following conversion therapy for initially unresectable HCC, adjuvant systemic therapy was associated with improved survival, particularly among those with high-risk disease features.
Transhumeral amputations often result in significant functional limitations. Multiarticulated myoelectric prostheses for individuals with transhumeral amputations are often unreliable because of limitations in signal quality and challenges with accurately detecting motion intent from the available musculature in the residual limb, leading to high prosthesis rejection rates. Surgical approaches like targeted muscle reinnervation have been proposed to mitigate these challenges by biologically amplifying motor signals but are not suitable for all individuals. There is intriguing evidence that distinct muscle activation patterns associated with voluntary mobilization of the phantom limb may be produced in the residual limb after transhumeral amputation even without surgical intervention. However, this phenomenon has not been sufficiently investigated. This study explores the potential of ultrasound imaging to visualize muscle activity associated with phantom hand movements in an individual with transhumeral amputation who has not undergone targeted muscle reinnervation. We demonstrate that ultrasound imaging can capture these patterns, with each tested phantom movement corresponding to unique residual limb muscle activity. The activation patterns for each motion showed greater consistency across repetitions (correlation range: 0.41-0.86) compared to their average similarity with other motions (correlation range 0.06-0.32). These findings provide preliminary imaging evidence suggesting functional innervation of the residual upper arm muscles with digit-level specificity after transhumeral amputation. We recommend further research into modalities that can sense phantom limb mobilization to improve prosthesis control after transhumeral amputation.
Philosophical counselling creates a dialogical space for exploring existential questions arising from serious illness, confrontation with mortality, bereavement, and caregiving. Although philosophy has long engaged with mortality and existential concerns, philosophy in form of philosophical counselling is not established in palliative care and has seldom been empirically studied. This study examines the views and experiences of individuals who engaged in philosophical counselling in palliative care-related contexts. Nine counselling processes were completed; post-counselling interviews were obtained from eight guests and analysed. Purposive sampling identified practitioners via professional associations in Austria, Germany, and Switzerland; guests were recruited by these practitioners in naturalistic practice settings. A qualitative content analysis was used to identify categories and subthemes. Through iterative, interpretive analysis, we generated four main categories: distinctive features of philosophical counselling; how guests perceived the philosophical practitioner; perceived effects; and strengths and limits. Participants valued freedom to explore open-ended questions without pressure to act or solve problems. Conversations were described as inspiring and created space for a "stepping out"-being seen as a person rather than only as affected. We interpreted philosophical curiosity as a grounding stance toward mortality. At the same time, critical questioning could become destabilizing, underscoring the need for calibrated movement between personal involvement and abstract reflection within an empathetic dialogical relationship. Philosophical counselling seems to offer a space for reflective depth and existential inquiry in palliative care, fostering curiosity, wonder, and connectedness. It is described as offering intellectual freedom and an open, goal-free space. Practice implications include preserving this space, resisting help-driven agendas and didactic, overly abstract lecturing, and calibrating critical inquiry within empathetic dialogue. Philosophical counselling may contribute to facets of death literacy. Our findings indicate that end-of-life themes are already being addressed within philosophical counselling and offer guidance for introducing practice in palliative care contexts.
Feedback is considered a fundamental component of motor skill learning, yet evidence comparing the effectiveness of visual, verbal, and combined feedback modalities in youth gymnastics remains limited. This study examined the effects of mixed (visual + verbal), visual, and verbal feedback on the acquisition of selected gymnastics skills using two-dimensional kinematic analysis. Sixty female gymnasts aged 7-11 years were randomly assigned to mixed feedback (n = 20), visual feedback (n = 20), or verbal feedback (n = 20) groups. Participants completed an 8-week gymnastics training program. Performance in the Front Scale, Back Scale (Knee-Knee), Back Scale (Shoulder-Knee), and Split Jump was assessed at pre-test, mid-test, and post-test using Kinovea-based kinematic analysis. A mixed-design ANOVA was conducted to evaluate the effects of feedback modality, time, and the Group × Time interaction. Bonferroni-adjusted post hoc comparisons were performed where appropriate. Significant Group × Time interactions were observed for the Back Scale (Knee-Knee) (F = 3.375, p = .020, η2 = .106), Back Scale (Shoulder-Knee) (F = 32.662, p < .001, η2 = .534), and Split Jump (F = 3.510, p = .023, η2 = .110), indicating that performance improvements differed across feedback conditions. Mixed feedback generally led to greater improvement than visual or verbal feedback for these skills. In contrast, although Front Scale performance improved over time, the Group × Time interaction was not statistically significant (F = 1.680, p = .160), suggesting that improvement patterns did not differ significantly among feedback modalities for this skill. Across all analyses, verbal feedback alone tended to produce smaller improvements than mixed or visual feedback. The findings indicate that the effectiveness of feedback modalities may depend on the specific gymnastics skill being learned. Mixed feedback appears particularly advantageous for skills requiring greater coordination and postural control, whereas no clear superiority of any feedback modality was observed for Front Scale performance. Integrating visual demonstrations with verbal instruction may therefore represent an effective strategy for enhancing motor skill acquisition in youth gymnastics. ClinicalTrials.gov (NCT07082647). Registered retrospectively on July 15, 2025.
The cross-modal correlations between radiomics and pathomics, as well as their clinical translational applications in oral tumors and cysts, remain unclear. Here, we proposed a novel radiomic feature selection strategy guided by radio-pathomic correlations in Ameloblastoma (AM) and Odontogenic Keratocyst (OKC) to enhance their preoperative differentiation. We automatically extracted radiomic and pathomic features from CBCT scans and multi-resolution (25, 50, 100, 200 μm) whole slide image-derived cell density maps, respectively. Subsequently, radio-pathomic associations were evaluated by correlation analysis at two levels, directly between features, and between latent factors derived from features via factor analysis, separately in AM and OKC. Additionally, we compared the diagnostic performance of machine learning models using our proposed pathomics-guided feature selection strategy against traditional selection approaches. At the feature level, correlation analysis identified one and seven significant feature pairs in AM and OKC, respectively (all |ρ| > 0.50, q < 0.05), suggesting that radiomic morphological feature weres strongly correlated with pathomic textural features reflecting tissue complexity. At the factor level, one significant factor pair was revealed in AM (ρ = 0.50, q = 0.007) and another in OKC (ρ = - 0.41, q = 0.04). Additionally, classification performance was enhanced by our proposed strategy across all six models, with an average area under the receiver operating characteristic curve (AUROC) improvement of 0.036 and individual gains ranging from 0.016 in Logistic Regression to 0.063 in Lasso. Significant cross-modal correlations between radiomic and pathomic features were identified in AM and OKC. Leveraging these associations, our proposed pathomics-guided radiomics showed the potential to improve the accuracy of preoperative differentiation between the two lesions, although these improvements reached statistical significance only in some models and still require further validation before clinical translation.
Arterial stiffness (AS) is a critical pathological basis for major cardiovascular diseases (CVD), with its progression closely associated with modifiable risk factors such as hypertension and dyslipidemia. Remnant cholesterol (RC), a key dyslipidemia indicator, is increasingly recognized for its cardiovascular risk predictive value independent of low-density lipoprotein cholesterol (LDL-C). This study explored the independent and additive interactive associations of hypertension and RC with AS in a Chinese middle-aged and elderly population, so as to provide evidence-based support for the prevention and management of cardiovascular diseases in this high-risk population. A retrospective cohort study was conducted on 6,886 middle-aged and elderly participants (≥ 45 years) who underwent health examinations at the Health Management Center of Zigong Fourth People's Hospital from January to December 2023. All participants completed measurements of brachial-ankle pulse wave velocity (baPWV) for AS assessment, blood pressure, blood lipids, and other biochemical indicators. Participants were stratified into the AS group (baPWV ≥ 1800 cm/s) and normal group (baPWV < 1800 cm/s). Multiple analytical approaches were used to analyze the relationship between hypertension, RC and AS: multivariable logistic regression models (adjusted for age, gender, BMI, smoking history, drinking history, diabetes, and other confounding factors) were applied to evaluate their independent and joint effcets with AS; participants were further divided into four subgroups (low RC without hypertension, high RC without hypertension, low RC with hypertension, high RC with hypertension) to assess the interaction of the two factors on AS risk; additive interaction models were constructed to quantify their additive interaction; restricted cubic spline (RCS) models were used to explore the non-linear relationship between blood pressure and AS risk and to identify apparent inflection points within the study population. Of the 6,886 participants, 4,702 (68.3%) were identified with AS. Both hypertension and elevated RC were independently associated with an increased odds of AS (P < 0.001). Participants with both hypertension and high RC exhibited the highest risk of AS (OR = 3.50, 95% CI: 2.66-4.61) compared to the low RC without hypertension. A additive interaction between hypertension and elevated RC on AS was observed, with the relative excess risk due to interaction (RERI) = 1.21 (95% CI: 0.13-2.23). The RCS model identified apparent inflection points around 127 mmHg for systolic blood pressure (SBP) and 84 mmHg for diastolic blood pressure (DBP), where the risk of AS appeared to increase more rapidly within the study population. This study identified an additive interaction between hypertension and elevated RC in relation to AS among middle-aged and elderly Chinese adults. These findings suggest that the integrated assessment of hypertension and RC may provide complementary information for identifying individuals at increased risk of AS.
This study examined the relationship between medical artificial intelligence readiness and AI-related anxiety among nursing students following surgical nursing education. A descriptive cross-sectional study was conducted with 252 nursing students from two universities who had completed surgical diseases nursing courses. Data were collected between February and July 2024 using the Artificial Intelligence Anxiety Scale and the Medical Artificial Intelligence Readiness Scale. Group comparisons, correlation analyses, and hierarchical regression analysis models were performed. Our findings indicate a notable "awareness-apprehension paradox": higher ability (technical readiness) was associated with lower learning anxiety (B = - 0.25, p < .01), whereas higher ethics (ethical readiness) was associated with greater concerns regarding job replacement (B = 0.41, p < .001) and anxiety. Female students had significantly higher anxiety scores, and regular AI use was associated with greater readiness. AI utilization and sociotechnical perceptions together accounted for variance in readiness outcomes. Higher levels of medical AI readiness were not uniformly associated with lower anxiety; instead, increased readiness coexisted with elevated concerns in specific anxiety dimensions, indicating a complex association between technological preparedness and psychological adaptation. The results suggest that developing technical competence alone may not be sufficient to align with confident technology adoption. They further indicate that, in the absence of corresponding organizational safeguards, ethical awareness may function more as a "cognitive demand" than as a resource. The study adds to the Job Demands-Resources (JD-R) framework by illustrating the dual nature of AI readiness. Nursing education programs may therefore benefit from integrating ethical reflection, critical technological awareness, and psychological preparedness alongside AI skill development to support sustainable implementation of AI-supported clinical practice.
The efficacy of oncolytic adenoviruses (ADVs) in colorectal cancer (CRC) is limited by their inability to effectively expand CD4+ T cells within the tumor microenvironment (TME). This study aimed to elucidate the underlying mechanism and overcome this bottleneck through viral engineering. We constructed an oncolytic adenovirus expressing inducible T cell co-stimulator ligand (ICOSL), designated ADV-ICOSL, based on the backbone virus ADV-NC. Its antitumor efficacy, safety, and ability to induce immunological memory were systematically evaluated in MC38 and CT26 murine colorectal cancer (CRC) models. The mechanism of action was investigated using flow cytometry, co-culture assays, RNA sequencing, and specific pathway inhibitors. The synergistic potential with anti-PD-1 or chimeric antigen receptor T cell (CAR-T) therapy was assessed. Furthermore, a humanized ICOSL-expressing virus (ADV-hICOSL) was developed and validated in cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. We initially discovered that ADV-NC treatment led to decreased ICOSL levels in the TME, resulting in insufficient co-stimulation for CD4+ T cells. In contrast, ADV-ICOSL significantly elevated ICOSL expression and demonstrated superior antitumor efficacy and the capacity to induce long-term immune memory. Mechanistic studies revealed that ADV-ICOSL, via elevating ICOSL, activated the PI3K/Akt-NF-κB signaling axis in CD4+ T cells, promoting their secretion of IL-2. IL-2, in a non-contact-dependent manner, potently enhanced the proliferation and cytotoxicity of CD8+ T cells. This process was strictly dependent on CD4+ T cells. Furthermore, ADV-ICOSL exhibited significant synergistic effects when combined with either anti-PD-1 or CAR-T therapy. Importantly, ADV-hICOSL effectively increased the infiltration of CD4+ T and GZMB+ CD8+ T cells in CDX/PDX models, exerting potent antitumor effects. Our study not only reveals that the suboptimal efficacy of conventional oncolytic adenovirus is associated with ICOSL downregulation and impaired CD4+ T cell help, but also successfully develops ADV-ICOSL to reverse this limitation. This study provides a novel combinatorial strategy and a solid experimental foundation for oncolytic virotherapy in CRC.
Heart failure (HF) is accompanied by chronic inflammation and metabolic stress, but the relationship between HF severity and the oral microbial ecosystem remains incompletely understood. This study aimed to investigate bacterial, fungal, and predicted functional alterations in supragingival plaque from patients with HF. This case-control study enrolled 63 patients with HF and 31 healthy controls (HC). Supragingival plaque samples were profiled by 16S rRNA and ITS sequencing. Community structure, differential amplicon sequence variants (ASVs), bacterial-fungal co-abundance networks, HF severity-associated ASVs and predicted MetaCyc pathways were analyzed using QIIME2, SparCC, weighted LASSO regression, and PICRUSt2. Pathway-ASV correlations were further assessed to explore links between taxonomic and predicted functional shifts. HF status and NYHA class were among the strongest explanatory factors for oral bacterial and fungal community variation. Differential abundance analysis identified 102 bacterial and 68 fungal ASVs between HF and control groups. Weighted LASSO analysis retained six ASVs associated with the NYHA III-IV phenotype: ASV586 (Geotrichum candidum), ASV238 (Nectriaceae), and ASV182 (Neisseria bacilliformis) showed positive coefficients, whereas Haemophilus (ASV1), Streptococcus (ASV0), and Pseudopropionibacterium (ASV148) showed negative coefficients. A combined 6-ASV score discriminated HF from controls with an AUC of 0.804 and NYHA III-IV from the remaining cohort with an AUC of 0.842. PICRUSt2 identified 165 pathways differing between HF and controls. TCA cycle I was enriched in HF and positively correlated with NYHA class, whereas pyruvate fermentation to butanoate, a butyrate-related fermentative pathway, was enriched in controls and negatively correlated with NYHA class. Robust pathway-ASV correlations linked HC-enriched oral biofilm taxa with HC-enriched functional modules, suggesting functional uncoupling of the supragingival plaque ecosystem in more severe HF. HF severity is associated with oral bacterial-fungal dysbiosis, characterized by enrichment of opportunistic pathogens, depletion of commensal biofilm organisms and predicted functional shifts involving microbial TCA cycle and fermentative capacity. These findings support an "oral-heart axis" in HF and warrant validation by longitudinal multi-omics studies.
Immediate extubation following cardiac surgery is rarely performed, largely due to concerns over hemodynamic instability, respiratory compromise, and potential postoperative complications. Most centers limit immediate extubation to low-risk patients, leaving its broader applicability less understood. This study utilized a standardized anesthetic procedure to implement immediate extubation in a diverse cardiac surgical population with varying risk profiles based on a single-center case series. We retrospectively reviewed the medical records of 34 cardiac surgery patients (congenital, valve, aortic, and coronary artery bypass grafting) from May 2024 to January 2025. A standardized, 10-step perioperative procedure was employed to facilitate immediate extubation. The effects of immediate extubation were assessed by extubation time, intensive care unit (ICU) length of stay, hospital length of stay, and postoperative complications. This study included 34 patients (73.5% male, mean age 55.9 ± 16.1 years), predominantly New York Heart Association class II (55.9%) and American Society of Anesthesiologists class IV (52.9%). Most completed preoperative pulmonary training with nebulization, and 88.2% maintained negative fluid balance pre-surgery. Valve replacements comprised 67.6% of cases, followed by coronary artery bypass grafting (17.6%) and congenital cardiac defect repairs (11.8%). Immediate extubation was achieved in 97.1% of patients (33/34), with mean extubation time of 5 ± 4.7 min post-operation. Mean ICU stay was 4 ± 4.1 days and postoperative hospitalization 14 ± 5.9 days. Acute kidney injury represented the most common complication (33.3%), followed by delirium (18.2%) and 24-hour reintubation (9.1%). Most perioperative complications remained manageable within standard protocols. Immediate extubation appears feasible in a carefully selected cohort of predominantly minimally invasive cardiac surgery patients managed under a standardised perioperative protocol, with an immediate extubation success rate of 97.1%. Larger, prospective, risk-stratified studies are needed before immediate extubation can be recommended as a broadly safe strategy across all cardiac surgical subgroups.
Cancer stem cells (CSCs) and normal stem cells share key properties such as self-renewal and differentiation capacity, yet the microRNAs (miRNAs) that are differentially expressed between them remain poorly characterized. This study aimed to identify such miRNAs, with a focus on microRNA-204 (miR-204), and to investigate its functional role and regulatory mechanisms in gastric cancer. Using miRNA microarray data from public databases (GEO and TCGA), we identified miR-204 as a stemness-related miRNA. Its expression was validated in clinical gastric cancer tissues and cell lines. Functional assays, including colony formation, Transwell, tumorsphere formation, and extreme limiting dilution analysis, were performed to assess the effects of miR-204 on proliferation, metastasis, and stemness. Luciferase reporter assays confirmed direct targeting of CD44 and EPCAM. The role of TP53 in miR-204 maturation was investigated using TP53-knockout mice and TP53 overexpression cell models. miR-204 was identified as a crucial miRNA, upregulated in normal stem cells but significantly downregulated in CSCs and multiple human cancers, including gastric cancer. Low miR-204 expression correlated with advanced TNM stage and poor overall survival in gastric cancer patients. Restoring miR-204 expression potently inhibited gastric cancer cell proliferation, metastasis, and stemness properties. Mechanistically, miR-204 directly targeted and suppressed the expression of two key CSC regulators, CD44 and EPCAM. Furthermore, we discovered that TP53 mutation is a major cause of miR-204 downregulation, and demonstrated that TP53 promotes the maturation of miR-204 rather than its primary transcription. Our study unveils miR-204 as a pivotal tumor suppressor that distinguishes CSCs from normal stem cells. It functions by targeting the CD44/EPCAM axis to inhibit gastric cancer stemness, a process governed by a novel TP53-miR-204 regulatory circuit. These findings position miR-204 as a promising prognostic biomarker and therapeutic target for eradicating CSCs in gastric cancer.
The efficacy and safety of pharmaceutical products are critically dependent on maintaining appropriate storage temperatures throughout the supply chain, from manufacturer to end-user. In veterinary medicine, this includes storage within clinics and during ambulatory services. The Federal Capital Territory (FCT) of Nigeria experiences high ambient temperatures, posing a significant risk to drug stability. This study aimed to investigate drug storage temperatures in veterinary clinics that also dispense and retail veterinary pharmaceuticals within the FCT and to assess their compliance with manufacturers' recommended storage conditions. A cross-sectional study was conducted across 23 veterinary clinics in four Area Councils of the FCT (AMAC, Bwari, Gwagwalada, Kuje). A structured questionnaire was used to gather data on storage infrastructure, including refrigerator use, alternative power supply, and temperature monitoring devices. The temperature of drug storage areas was recorded over two weeks (March 1st-15th, 2025) using an HTC-2 thermometer (Guangdong, China). Data were analyzed using descriptive statistics. While all 23 (100%) clinics possessed a refrigerator, only 60% had an alternative power supply. Critically, 60.9% (n = 14) of clinics lacked any form of temperature monitoring device in their storage areas. The mean ambient storage temperatures in all clinics exceeded the recommended maximum of 30 °C for pharmaceuticals stored in cabinets, with some clinics recording temperatures above 36 °C. During ambulatory services, 87% of Clinicians used drug storage boxes, but 30% parked their vehicles in areas without shade, potentially exposing drugs to high temperatures during transport. This study reveals a significant gap in compliance with manufacturer drug storage temperature recommendations among veterinary clinics in the FCT. The lack of temperature monitoring and exposure to excessive ambient temperatures may compromise drug quality and pose a risk to patient safety and treatment efficacy.
Professional identity (PI) is essential for nurses' commitment, job performance, and retention. There is, however, limited evidence on the psychological and contextual pathways through which perceived organizational support (POS) influences PI. This study analyzed the associations between POS and PI among Chinese nurses in public hospitals, and studied the mediating role of self-efficacy, which also included the moderating role of organizational culture, based on the Social Exchange Theory and Social Cognitive Theory. A study was conducted among 624 nurses in public hospitals in Shandong Province, China. Data were gathered from validated instruments on POS, PI, SE, and OC. The proposed model of mediation and moderation was tested using structural equation modeling (SEM) and bootstrapping analysis. POS was positively associated with both PI (β = 0.410, p < 0.001) and self-efficacy (β = 0.596, p < 0.001). Self-efficacy was also positively related to PI (β = 0.553, p < 0.001). The mediation analysis showed a partial mediation effect of self-efficacy between POS and PI (β = 0.330, p < 0.001). There are two ways in which nurses' PI is influenced by POS, one direct and the other indirect. The results indicate that supportive organizational practices and psychological empowerment are important factors to enhance the nurse's PI. Healthcare managers should establish a positive working culture and interventions that strengthen the self-efficacy of nurses to ensure the sustainability of the nursing workforce and nursing profession.
Comprehensive dental care includes health education strategies that highlight the importance of disease prevention and reach as many people as possible. Bacteria are central to most oral diseases, yet few studies have explored the impact of including specifics of microbial pathogenesis on oral health education. Therefore, the objectives of this study were to determine if oral hygiene instructions (OHI) provided to undergraduate students in a group-setting positively impacted oral health knowledge and beliefs, and whether integration of microbiology-focused instructions and activities further improved these oral health measures. A pre-test/post-test experimental study was conducted among undergraduate life-science students. Participants were allocated to the control group, (n=35) receiving Standard OHI (SD-OHI) and the experimental group (n=40) receiving Microbiology-focused OHI (MICRO-OHI). Each group completed questionnaires before and after the educational intervention for measurement of changes in oral health knowledge, beliefs, and behaviors. Descriptive statistics were conducted on the pre-test/post-test responses for SD-OHI and MICRO-OHI. Both groups showed improved responses on items related to oral health knowledge and beliefs and high agreement with statements on intention to adhere to routine oral hygiene practices. Microbiology-related items had significant improvement in the MICRO-OHI group compared to the SD-OHI group (p<0.05). Qualitative analysis of responses to "Why should we brush our teeth?" revealed that a higher percentage of MICRO-OHI responses added emphasis on bacteria/biofilm removal compared to SD-OHI. Both methods of group-based instruction increase health-promoting responses and the addition of microbiology-focused instructions has the potential to uniquely augment comprehensive oral healthcare strategies.