• Noncoding RNAs as mechanistic regulators and therapeutic modulators of YAP/TAZ signaling in colorectal cancer.
    3 months ago
    Colorectal cancer (CRC) continues to represent a significant global health challenge due to its high incidence and mortality rates. Among the signaling pathways implicated in CRC, the Hippo pathway has gained considerable attention for its evolutionarily conserved role in regulating cellular proliferation, programmed cell death, and organ size control. The recent studies have revealed that alterations in this pathway contribute not only to tumor initiation but also to metastasis and therapy resistance. Emerging evidence underscores the pivotal involvement of noncoding RNAs (ncRNAs)-including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs)-in modulating this pathway, particularly through the regulation of its core effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ). The intricate crosstalk between ncRNAs and Hippo signaling components suggests a multilayered regulatory mechanism that warrants further investigation. This review provides mechanistic insights into the dynamic crosstalk between ncRNAs and the YAP/TAZ axis, highlighting their roles in tumor progression, metastasis, and chemoresistance. Considering these intricate interactions, this review further emphasizes the emerging therapeutic and biomarker potential of ncRNAs, offering novel perspectives for both targeted intervention and early diagnosis in CRC management.
    Cancer
    Policy
  • Spontaneous Splenic Hemorrhage Leading to Diagnosis of Metastatic Adenocarcinoma of Unknown Origin.
    3 months ago
    Spontaneous splenic hemorrhage is a rare initial presentation of malignancy. The objective of this case report is to elucidate the complexities of early diagnosis of splenic metastases and the complications associated with advanced malignancies of the spleen. It is also a reminder to consider splenic metastases and hemorrhage in the differential diagnosis for nonspecific presentations, such as acute abdomen, in adults.

    A 58-year-old female with 1 month of vague, worsening systemic symptoms and computed tomography findings suspicious for a subcapsular splenic hematoma was found to have splenic rupture. After undergoing emergency laparotomy with splenectomy, pathological samples revealed metastatic poorly differentiated adenocarcinoma of unknown origin. During a subsequent admission, she was found to be hemodynamically unstable, deemed a poor candidate for inpatient chemotherapy, and elected to proceed with comfort measures after which she died from multiorgan failure 3 weeks after initial presentation.

    Spontaneous (nontraumatic) splenic hemorrhage secondary to metastasis should remain a differential diagnosis for patients with acute abdomen and associated risk factors for primary malignancies.
    Cancer
    Advocacy
  • Serious bacterial infections in infants younger than 90 days of age with acute bronchiolitis.
    3 months ago
    Although acute bronchiolitis is primarily caused by viral infections, antibiotics are often administered to children with acute bronchiolitis. Due to concerns about serious bacterial infections (SBI), neonates and young infants are particularly prone to antibiotic overuse. This study aimed to identify the clinical characteristics and prevalence of SBI in neonates and infants aged < 90 days with acute bronchiolitis. We retrospectively reviewed the medical records of 651 neonates and infants aged < 90 days hospitalized with acute bronchiolitis between September 2015 and August 2024. Demographic and clinical data were analyzed to assess their clinical characteristics and the prevalence of SBI. Of the 651 infants, 230 (35.3%) had fever, and 485 (74.5%) received antibiotics. Blood cultures were performed in 646 (99.2%) infants; 52 (8.0%) yielded bacterial growth, but 50 were skin contaminants and one (Enterococcus faecium from an afebrile infant) was considered clinically insignificant. Only one (0.2%) infant had a probable true bacteremia caused by methicillin-susceptible Staphylococcus aureus. Among 621 (95.4%) infants who underwent urine cultures, seven (1.1%) had both bacteriuria and pyuria. Among them, only one (0.2%) infant had fever, which was deemed to have clinically significant urinary tract infection. Cerebrospinal fluid cultures in 31 infants were all negative.

    SBI were rare in neonates and infants aged < 90 days hospitalized for acute bronchiolitis. This suggests that routine sepsis workups and empirical antibiotic therapy are not necessary for most of these patients. A selective approach to bacterial testing and antibiotic therapy is strongly justified.

    •Empirical antibiotics are commonly used in infants aged ‹90 days with acute bronchiolitis due to concerns about concurrent serious bacterial infections.

    •Serious bacterial infections are extremely rare in infants aged ‹90 days hospitalized with acute bronchiolitis, regardless of fever.
    Chronic respiratory disease
    Access
    Care/Management
    Advocacy
  • IFNGR1, IRF8 genetic polymorphisms modulate the susceptibility of non-tuberculous mycobacteria pulmonary disease and influence the patients' treatment outcomes and immune status.
    3 months ago
    To investigate the association of genetic polymorphisms in MB21D1 (Mab-21 domain-containing 1), TMEM173 (Transmembrane Protein 173), IFNB1 (Interferon beta 1), IFNGR1 (Interferon gamma receptor 1), IFNGR2 (Interferon gamma receptor 2), IRF3 (Interferon Regulatory Factor 3), and IRF8 (Interferon Regulatory Factor 8) with susceptibility to non-tuberculous mycobacteria pulmonary disease (NTM-PD) as well as their correlation with the treatment outcomes and immune status of patients.

    Forty-four tagSNPs from the candidate genes were genotyped in a 2-phase cohort study including an initial discovery phase involving 707 NTM-PD patients and 726 healthy controls and a replication phase involving 357 NTM-PD patients and 400 controls. The frequencies and distributions of genotypes were compared between the case and control groups. Treatment success rates, sputum culture conversion rates, imaging characteristics, and peripheral blood immunological indices were compared among patients with different genotypes.

    Individuals with the IFNGR1 rs2234711 A/A genotype were more susceptible to MAC-PD compared to those with the G/G genotype (discovery phase OR = 1.752, P.adj = 0.025; replication phase OR = 2.143, P.adj = 0.019). Patients with the rs2234711 A/A genotype exhibited significantly lower treatment success rates and sputum culture conversion rates, along with elevated levels of peripheral blood heparin-binding protein (HBP), erythrocyte sedimentation rate, and interleukin-10, but significantly decreased interleukin-1β levels (all P < 0.05). Individuals with the IRF8 rs2280378 A/A genotype were more susceptible to MAB-PD (discovery phase OR = 2.302, P.adj = 0.014; replication phase OR = 2.465, P.adj = 0.015). Compared to G/G genotype patients, those with the rs2280378 A/A genotype exhibited lower treatment success rates and sputum culture conversion rates, were more likely to develop pulmonary cavities and multiple lung field involvement, and showed elevated levels of peripheral blood HBP and C-reactive protein, along with significantly reduced levels of serum interleukin-12 P70, tumor necrosis factor-α, and CD8 + T lymphocytes (all P < 0.05).

    In the Chinese Han population, IFNGR1 genetic polymorphisms are closely associated with MAC-PD susceptibility, while IRF8 genetic polymorphisms are associated with MAB-PD susceptibility. Variants in IFNGR1 and IRF8 significantly affect the immune status and treatment outcomes of MAC-PD and MAB-PD patients, respectively.
    Chronic respiratory disease
    Access
    Care/Management
  • A Complex Intervention to Strengthen Person-Centered Care and Leadership in Residential Care Facilities (the PERLE Study): Protocol for a Development and Implementation Study.
    3 months ago
    Although the benefits of person-centered care (PCC) are widely recognized, there is a lack of empirical research on how PCC is best developed and implemented by the leaders responsible for driving such initiatives. To achieve meaningful change and ensure the sustainability of PCC practices, it is crucial to understand how leaders can foster care environments rooted in person-centered values while managing operational challenges. This knowledge gap highlights the need for an in-depth exploration of the conceptual foundations, experiences, mechanisms, strategies, and outcomes of person-centered leadership (PCL) to design an intervention for strengthening such leadership.

    The Person-Centered Care and Leadership in Residential Care Facilities (PERLE) study aims to (1) explore and develop tools to measure PCL; (2) develop, test, implement, and investigate the effects of an intervention to strengthen PCL in residential care facilities (RCFs) for older people; and (3) generate knowledge about the process of development and implementation of the intervention.

    The PERLE study builds on the Medical Research Council framework for the development of complex interventions. It includes several studies with exploratory, descriptive, correlational, and quasi-experimental designs and is based on the research group's previous research on PCL. The project is composed of 5 work packages (WPs). Each WP includes research questions with different samples; data collection; and methodological approaches, such as qualitative, mixed methods, and quantitative studies. As this project involves sensitive issues, a high level of ethical awareness was maintained throughout. The primary challenge is the possible interference with participants' work time, which could otherwise be devoted to supporting older people and staff. Nevertheless, the involvement of leaders and staff can lead to valuable knowledge that can improve the quality of PCC. Participants will be provided with both oral and written information about the study and assured of their right to withdraw at any time without providing a reason.

    As of July 2025, 6 studies in WP I have been conducted, and one is in progress. The conducted studies address leaders' understanding of PCC, the meaning of PCL in RCFs from the perspective of leaders, the ethical challenges in providing PCC during the COVID-19 pandemic, and the cultural adaptation of the aged care clinical leadership qualities framework.

    This project aims to provide new insights into the support that first-line managers need to advance PCC in RCFs, highlight their specific challenges, and create tailored support measures for the implementation of PCL. The intervention could potentially reduce staff turnover and related costs while supporting leadership training and education to benefit future leaders in aged care, which may be important from an international perspective.

    DERR1-10.2196/76185.
    Chronic respiratory disease
    Access
    Care/Management
  • Post-infection Symptomatology of Human Metapneumovirus Infection.
    3 months ago
    Though there has been much discussion about post-acute sequelae of SARS-CoV-2 infection, there has been limited study on symptoms following infection with other respiratory viruses.

    In this retrospective chart review, we reviewed the medical records of 92 patients admitted to the hospital with a diagnosis of human metapneumovirus for 17 of the common symptoms associated with post-acute sequalae of SARS-CoV-2 that were either new or worse than baseline in the time frame of 90 to 270 days after diagnosis.

    Of those patients hospitalized with human metapneumovirus, 55.4% had at least 1 new or worsening symptom more than 3 months after diagnosis. The most common symptoms noted were shortness of breath (29.3%) followed by fatigue and cough (17.3% each).

    Our data suggest that other respiratory viruses - not just SARS-CoV-2 - may carry a significant burden of post-infection sequelae.
    Chronic respiratory disease
    Access
    Advocacy
  • [Phenomenology of Redeployed Psychiatric Nurses].
    3 months ago
    The global coronavirus outbreak posed a threat to healthcare providers. This study explored how psychiatric nurses (PNs) perceived their redeployment experiences.

    Using a phenomenological approach, semi-structured interviews were conducted with PNs deployed to care for COVID-19 patients.

    Our findings suggest that three themes emerge from the data: (1) Awareness of the mental health perspective, as a reference (2) Operating inside the community as opposed to maximizing functioning (3) Professional understanding of evidence.

    To enhance future healthcare responses, it's vital to recognize psychiatric nurses' expertise in managing mental health crises, delirium, and altered mental states, ensuring comprehensive emergency care.
    Chronic respiratory disease
    Mental Health
    Access
    Care/Management
    Advocacy
  • An Integrated and Coherent Framework for Point Estimation and Hypothesis Testing With Concurrent Controls in Platform Trials.
    3 months ago
    A platform trial with a master protocol provides an infrastructure to ethically and efficiently evaluate multiple treatment options in multiple diseases. Given that certain study drugs can enter or exit a platform trial, the randomization ratio is possible to change over time, and this potential modification is not necessarily dependent on accumulating outcomes data. It is recommended that the analysis should account for time periods with different randomization ratios, with possible approaches such as inverse probability of treatment weighting or a weighted approach by the time period. To guide practical implementation, we specifically investigate the relationship between these two estimators, and further derive an optimal estimator within this class to gain efficacy. Practical guidance is provided on how to construct estimators based on the observed data to approximate this unknown weight. The connection between the proposed method and the weighted least squares is also studied. We conduct simulation studies to demonstrate that the proposed method can control type I error rate with a reduced estimation bias, and can also achieve satisfactory power and mean squared error with computational efficiency. Another appealing feature of our framework is the ability to provide consistent conclusions for both point estimation and hypothesis testing. This is critical to the interpretation of clinical trial results. The proposed method is further applied to the Accelerating COVID-19 Therapeutic Interventions and Vaccines platform trial.
    Chronic respiratory disease
    Access
    Care/Management
    Advocacy
  • Financial burden of productivity loss in severe asthma and impact of biologic therapy.
    3 months ago
    Severe asthma leads to considerable productivity loss; however, patients' financial impact and the potential reversal through biologic therapy remain unexplored.

    What is the financial burden of productivity loss among employed individuals with severe asthma, and does it change during biologic therapy?

    Employed individuals from the Danish Severe Asthma Register (2016-2022) were included. Salary data were sourced from national registries, while productivity loss was measured using the Workplace Productivity and Activity Impairment (WPAI) Questionnaire at baseline and after a minimum of four months of biologic therapy.

    A total of 132 employed individuals (mean age 47.9 years, 39% female, mean annual salary € 74,646) were included. Before biologic therapy, productivity impairment was 39.1%. presenteeism and absenteeism rates were 35.8% and 11.3%, respectively, equating to annual productivity losses of € 28,880 per individual.On treatment, overall impairment was 17.6%, with significant reductions in both presenteeism and absenteeism, corresponding to annual loss reductions of € 16,506 per individual.

    The financial burden of productivity loss in severe asthma is substantial, primarily due to presenteeism. Biologic therapy significantly enhances productivity, suggesting that much of the individual financial burden can be reversed.
    Chronic respiratory disease
    Access
    Care/Management
    Advocacy
  • Implementation of a mindfulness campaign to reduce nurse burnout: A quality improvement project.
    3 months ago
    Nurse burnout in the ICU is driven by long hours, a high-pressure environment, and overwhelming workloads, which were exacerbated by the COVID-19 pandemic. This quality improvement project aimed to decrease burnout among ICU nurses by implementing a mindfulness campaign. Pre- and post-intervention surveys, utilizing the Maslach Burnout Inventory (MBI), were conducted to measure changes in burnout levels. Participants engaged in the 5-4-3-2-1 mindfulness method, designed to reduce stress through sensory engagement, and received badge cards for easy reference during their shifts. Results showed a small effect size in all three MBI subcategories, with a nonsignificant decrease in emotional exhaustion scores. Although the mindfulness intervention provided a helpful stress management tool, a significant reduction in burnout requires institution-level changes to address systemic stressors and promote nurse retention.
    Chronic respiratory disease
    Access
    Advocacy
    Education