International consensus guidelines have informed the management of intraductal papillary mucinous neoplasms (IPMNs) and introduced high risk stigmata and worrisome features that risk stratify lesions beyond only cyst size. In this study, we sought to understand whether these clinical considerations have impacted surgical selection criteria at United States hospitals.

The National Cancer Database (2004-2021) was queried to identify all patients that underwent resection for non-invasive and invasive IPMNs. Patients with missing cyst size data were excluded. The cohort was divided into time periods reflecting the succession of IAP guidelines: Pre-Fukuoka (2004-2011), Fukuoka (2012-2016), Revised Fukuoka (2017-2021).

Of 3,580 resected IPMNs, invasive pathology was identified in 44% of all lesions, increasing to 48% when applying the Revised Fukuoka guidelines (Fukuoka 40%, Pre-Fukuoka 43%, p<0.001). While median cyst size of all resected IPMNs remained similar throughout the three eras, median size of non-invasive lesions progressively increased (2.6cm to 3.0cm, p=0.001), and that of invasive IPMNs decreased over time (3.1cm to 2.8cm, p<0.001). The proportion of resected non-invasive cysts ≥3cm increased over time (46%-52%-55%, p<0.001); however, the opposite was true for invasive lesions (57%-50%-48%, p=0.013). These trends were agnostic to hospital type (academic vs. non-academic), and non-academic hospitals had a greater proportion of non-invasive IPMNs ≥3cm (55% vs. 49%, p=0.026).

The size of resected noninvasive IPMNs has increased over time, whereas the size of invasive lesions has progressively decreased. This trend may reflect improved, guideline concordant recognition of malignant risk features, including reduced reliance on cyst size alone.

The characterization of human papillomavirus (HPV) infection in oropharyngeal carcinomas is prognostically relevant, but there may be discordance between p16 expression and molecular detection of viral DNA.

Retrospective study of 620 patients with squamous cell carcinoma of the oropharynx treated between 1991 and 2024 with joint determination of HPV by PCR and p16. Epidemiological, clinical, and therapeutic characteristics were analyzed according to HPV status, as well as specific, overall, and recurrence-free survival.

Overall, 74.0% of tumors were PCR-/p16-, 19.4% were PCR+/p16+, and 6.6% were discordant (3.9% PCR+/p16-; 2.7% PCR-/p16+). Five-year specific survival was significantly higher in the PCR+/p16+ group (P = 0.0001). No differences in survival were observed between the discordant and double-negative groups (P = 0.311). In the multivariable analysis, considering PCR+/p16+ patients as the reference category, the risk of death from tumor was 4.97 times higher in PCR+/p16-, 5.42 times higher in PCR-/p16+, and 3.63 times higher in PCR-/p16-. Similar findings were obtained in the cohort treated with radical intent. The prognostic differences remained for deaths from oropharyngeal tumor, second neoplasm, or non-oncological causes.

Only double-positive tumors (PCR+/p16+) show the prognostic benefit of HPV-related oropharyngeal carcinomas. Discordant tumors had a similar outcome to double-negative tumors. The combination of PCR and p16 improves prognostic accuracy and allows for the adequate identification of patients who are candidates for specific therapeutic strategies.

Desmoid tumors (DT) are rare fibroblastic neoplasms characterized by local aggressiveness, absence of metastatic potential, and heterogeneous clinical behavior. During the last decade, management has shifted from routine upfront surgery toward active surveillance and selective systemic therapy. We evaluated temporal changes in management and surgical outcomes within a multicenter real-world cohort.

We retrospectively reviewed consecutive patients with histologically confirmed DT managed between January 2015 and January 2026 across four tertiary hospitals in Madrid, Spain. Treatment-era analyses compared 2015-2019 with 2020-2026. Local recurrence-free survival (RFS) after surgery was estimated using the Kaplan-Meier method.

Eighty-two patients were included. Initial management was available for 79 patients: surgery in 48, active surveillance in 17, and systemic therapy in 14. Among 77 patients with an assignable treatment era, upfront surgery decreased from 24/30 (80.0%) in 2015-2019 to 24/47 (51.1%) in 2020-2026 (Fisher p = 0.015), while active surveillance and systemic therapy increased. Fifty-three patients underwent surgery during follow-up. Local recurrence occurred in 11/51 patients with evaluable postoperative follow-up. R1 resection was associated with a higher unadjusted risk of local recurrence than R0 resection (40.0% vs 3.8%; conditional OR 15.84, exact 95% CI 1.92-751.38; Fisher p = 0.002).

Contemporary recommendations have been progressively incorporated into routine practice, with reduced reliance on upfront surgery. Surgery remains important in selected patients. The observed association between R1 margins and local recurrence is unadjusted and should be interpreted cautiously given the limited number of events and potential residual confounding.

Follicular fluid (FF) constitutes the natural microenvironment of the ovarian follicle and contains numerous biologically active compounds, including hormones, cytokines, growth factors, and metabolites. Increasing evidence suggests that FF may be involved in carcinogenesis not only within the female reproductive system but also in distant tissues. The aim of this study was to evaluate the influence of ovarian follicular fluid on the proliferation of normal human skin fibroblasts (HSF), rat glioma cell line (C6), and human cancer cell lines, including human colon adenocarcinoma (LS180), human breast cancer (T47D), and human glioblastoma multiforme (T98G).

Cell proliferation was assessed using the MTT assay after 96 h of exposure to FF at concentrations ranging from 0.5% to 10%.

Low concentrations of FF stimulated or did not affect HSF proliferation, whereas higher concentrations exerted inhibitory effects depending on the individual FF sample. In contrast, significant anti-proliferative effects were observed in all examined cancer cell lines, particularly following treatment with FF1.

These findings indicate that follicular fluid contains components with selective anti-proliferative activity against cancer cells.

The association between obesity and asthma in children has been reported. However, despite its clinical and public health significance, the relationship between longitudinal body mass index standard deviation score (BMI-SDS) trajectories in early life and development of childhood asthma in Japan remains to be elucidated.

This study used fixed data on 11,433 parent-child pairs from the Japan Environment and Children's Study, an ongoing national birth cohort study. Information on bronchial asthma was collected from the caregiver-reported questionnaire. The association between body mass index standard deviation score (BMI-SDS) trajectories during the first 3 years of life and the risk of bronchial asthma was examined using multivariate logistic regression analysis.

Children with sustained above-average growth had a higher risk of bronchial asthma at 3 years of age, compared with those with a normative BMI-SDS trajectory (adjusted odds ratio [aOR] 1.31, 95% confidence interval [CI] 1.11-1.55, p = 0.001). At 3 years of age, the association between a persistently high BMI-SDS trajectory and bronchial asthma was more pronounced in boys than in girls (boys: adjusted OR [aOR] 1.39, 95%CI 1.12-1.73, p = 0.003 vs. girls: aOR 1.24, 95%CI 0.96-1.61, p = 0.100). At 4 years of age, similar associations were observed, while the association was stronger in boys, it was significant in girls as well.

The significance of this study is that it captures changes in BMI-SDS over time, rather than at a single point in time, our findings suggest that maintaining a normal BMI-SDS trajectory during childhood may be beneficial for asthma prevention.

Mycoplasma pneumoniae (MP) is a key pathogen causing pediatric community-acquired pneumonia. Increasing macrolide resistance poses considerable clinical challenges. This study investigated MP epidemiology and macrolide resistance in children aged 0-14 years in Southwest China from 2021-2025.

Retrospective analysis of MP antibody, nucleic acid, and resistance gene detection data. MP infections were categorized into macrolide-resistant (MRMP) and macrolide-sensitive (MSMP) groups. Clinical information was collected and compared.

Positive rates for MP-RNA, DNA, IgM, and total antibodies were 12.43%, 9.82%, 30.19%, and 49.82%, respectively. Infections predominantly affected children aged 2-8 years. The macrolide resistance rate was 87.87%. Compared with the MSMP group, the MRMP group had longer hospital stays (+0.74 days), higher rates of fiberoptic bronchoscopy (+19.6%), and a significantly higher initial macrolide treatment failure rate, leading to increased doxycycline use (+20.8%).

MRMP infections are highly prevalent in Southwest China and are associated with more complex clinical conditions and worse outcomes. Early resistance gene detection is recommended for hospitalized children with suspected MP infection during epidemic seasons. For children aged 2-8 years with persistent high fever and imaging findings of lung consolidation or mucus plugs, high suspicion of MRMP is warranted, and timely fiberoptic bronchoscopy should be considered.

Newly diagnosed tuberculosis (TB) patients frequently experience psychological distress, stigma, and concerns regarding treatment duration, side effects and social consequences, which may negatively affect adherence. Psychosocial counselling has been proposed as a patient-centred strategy to address these challenges; however, evidence regarding its effectiveness among newly diagnosed TB patients in primary care settings remains limited. This study aims to evaluate the effectiveness of a psychosocial counselling intervention in improving treatment adherence and psychosocial outcomes among newly diagnosed TB patients receiving care in primary healthcare centres (PHCs).

This study will employ a two-arm, parallel, cluster-randomised controlled trial involving 10 PHCs in Semarang City, Indonesia. PHCs will serve as clusters and will be randomly allocated in a 1:1 ratio to either the intervention or control arm (n=5 PHCs per arm) to minimise treatment contamination. An independent researcher will perform computer-generated randomisation. A total of 108 newly diagnosed pulmonary TB patients will be recruited. Participants in the intervention group will receive a structured psychosocial counselling programme in addition to standard TB care, while participants in the control group will receive standard TB care alone per national guidelines. Data will be collected at baseline (T₀), immediately after the intervention (T₁) and 2 months after treatment initiation (T₂). The primary outcome is treatment adherence during the intensive phase of treatment. Secondary outcomes include psychological distress, TB-related stigma, TB knowledge and treatment self-efficacy. Data will be analysed using descriptive statistics, mixed-effects models and multilevel logistic regression analyses that account for clustering at the PHC level.

Ethical approval has been obtained from the Ethics Committee of the Faculty of Public Health, Diponegoro University (304/EA/KEPK-FKM/2026). Written informed consent will be obtained from all participants prior to enrolment. Study findings will be disseminated through peer-reviewed scientific journals.

ClinicalTrials.gov (NCT07703696). Protocol V.2.0 (15 September 2026).

Prolonged public crises challenge leaders to make high-stakes decisions under conditions of uncertainty while sustaining organisational performance and public trust. Understanding how leaders navigate these complex demands is essential for strengthening health system preparedness and resilience.

The goal was to explore and unpack lived leadership experiences during a public crisis situation and to unpack how contextual factors shape their behaviours under uncertainty and prolonged disruption.

This study was conducted in Canada during the middle phases of the COVID-19 pandemic (October 2020-March 2021). Canada's healthcare system operates within a federal-provincial framework, with public health responsibilities spanning national, provincial and local levels. 16 senior leaders with provincial or national responsibilities across healthcare delivery, government, academia and research participated in the study. Purposive sampling was used to achieve variation across organtional and geographic regions. A qualitative case study design was employed, with semistructured interviews serving as the primary data collection method and thematic analysis used to analyse the data. The analysis was informed by Sriharan et al's Crisis Leadership Framework and reported in accordance with the Standards for Reporting Qualitative Research.

Videoconference interviews (40-50 min) explored leadership challenges, decision-making under uncertainty, communication, and contextual enablers and constraints. Transcripts were analysed using Braun and Clarke's six-phase approach with triangulation and reflexive documentation to enhance rigour.

Leaders described multifaceted roles that spanned clinical, administrative and advisory functions. Six leadership domains emerged from the analysis: adaptive leadership, learning-oriented leadership, systems thinking, psychological stewardship, implementation agility and strategic communication. Leadership enactment was shaped by structural integration and centralisation, which enabled real-time situational awareness and coordinated resource deployment. Rapid cycle decision-making was supported by emergency legislative flexibility, multidisciplinary evidence synthesis structures and peer learning networks. Constraints included systemic fragmentation, bureaucratic inertia, data sharing limitations and sustained workforce fatigue, all of which influenced leaders' ability to enact these domains under pressure.

Effective crisis leadership depended less on static competencies and more on dynamic enactment shaped by structural, operational and relational mechanisms. The findings extend the crisis leadership framework towards Dynamic Capability Leadership for Learning Health Systems, positioning leadership as a strategic capacity to sense emerging challenges, seize opportunities through rapid and accountable decision pathways and transform processes to sustain performance under uncertainty. These capabilities were enacted through adaptive and learning-oriented leadership, implementation agility, systems thinking, psychological stewardship and strategic communication, all amplified by structural integration and evidence-synthesis infrastructures. Overall, the findings highlight crisis leadership as a system property shaped by context, coordination and the ability to translate evolving knowledge into timely action.

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease closely associated with aging, yet the contribution of cellular senescence to fibrotic remodeling and its therapeutic implications remain incompletely understood. Syringin, a phenylpropanoid glycoside derived from Acanthopanax senticosus, has been reported to possess anti-inflammatory and antioxidant activities, but its role in IPF has not been elucidated. In this study, bulk lung transcriptomic data from the GTEx project and nine IPF cohorts were integrated with IPF scRNA-seq data to characterize senescence-associated fibrotic programs. A systems-level compound prioritization strategy incorporating reversed gene expression scoring, network proximity analysis, drug-likeness and toxicity evaluation was applied to identify candidate molecules. The results revealed a pronounced aging-associated transcriptomic profile in IPF lungs, with strong concordance between age-related and IPF-related gene programs. Single-cell analyses further identified senescent fibroblast populations as key cellular hubs characterized by elevated expression of SASP factors. Syringin was subsequently validated in TGFβ1-stimulated fibroblasts, and a murine model of bleomycin-induced pulmonary fibrosis. Syringin consistently attenuated fibroblast activation, cellular senescence markers, and pulmonary fibrosis in vivo and in vitro. Mechanistically, syringin markedly reversed the activation of replication stress-associated signaling pathways. Molecular docking and CETSA suggested a potential interaction between syringin and CHK1. Furthermore, CHK1 knockdown partially abrogated the regulatory effects of syringin on the ATR/CHK1-p53 signaling cascade, supporting CHK1 as a functional mediator of syringin activity. Collectively, these findings identify syringin as a natural small molecule with anti-senescent and anti-fibrotic properties, and may represent a potential therapeutic strategy for IPF.

To identify barriers and facilitators to the timely detection and optimal management of chronic wet cough (CWC) in children from the perspective of health care providers (HCPs) across primary care clinics providing services to Australian Aboriginal people in multiple, diverse communities.

Qualitative participatory action research study.

Eight Australian primary care clinics across three states and territories. Semi-structured interviews and focus groups were conducted with 83 HCPs from eight primary care clinics across metropolitan, regional and remote health service settings between May 2021 and July 2023.

Barriers to, and facilitators of, detection and optimal management of CWC in Aboriginal children in primary care settings.

Key barriers identified included limited condition-specific knowledge, time constraints and competing priorities. HCPs identified key facilitators, such as the need for additional training, educational resources and various modifications to clinic systems. Barriers and facilitators were similar across settings. Proposed solutions varied and were based on several factors, such as community size, availability of existing infrastructure and local preferences. In addition, HCPs highlighted the importance of a culturally secure environment in fostering engagement and communication with Aboriginal families.

Although the barriers and facilitators to the detection and management of CWC in Aboriginal children were largely consistent across settings, solutions must be tailored to each community's unique circumstances. A comprehensive approach is required to overcome barriers and deliver the intervention within a culturally secure framework.