Dual targeting macrophages and microglia is a therapeutic vulnerability in models of PTEN-deficient glioblastoma.

Tumor-associated macrophages and microglia (TAMs) are critical for tumor progression and therapy resistance in glioblastoma (GBM), a type of incurable brain cancer. We previously identified lysyl oxidase (LOX) and olfactomedin like-3 (OLFML3) as essential macrophage and microglia chemokines, respectively, in GBM. Here, single-cell transcriptomics and multiplex sequential immunofluorescence followed by functional studies demonstrate that macrophages negatively correlate with microglia in the GBM tumor microenvironment. LOX inhibition in PTEN-deficient GBM cells upregulates OLFML3 expression via the NF-κB-PATZ1 signaling pathway, inducing a compensatory increase of microglia infiltration. Dual targeting macrophages and microglia via inhibition of LOX and the CLOCK-OLFML3 axis generates potent anti-tumor effects and offers a complete tumor regression in more than 60% of animals when combined with anti-PD1 therapy in PTEN-deficient GBM mouse models. Thus, our findings provide a translational triple therapeutic strategy for this lethal disease.

Exploring the association between internet addiction and time management among undergraduate nursing students.

BACKGROUND: Modern undergraduate nursing students face unique challenges as digital natives balancing internet activities with the substantial academic demands of nursing studies. Given the detrimental effects of internet addiction on students' academic performance and well-being, having time management skills is crucial. AIMS: To assess the prevalence and levels of internet addiction and time management and their association among undergraduate nursing students. DESIGN: A cross-sectional, survey-based research design was used. SETTING: The Faculty of Nursing at Alexandria University in Egypt. SUBJECTS: A stratified random sample consisting of 825 undergraduate nursing students. TOOLS: The internet addiction test and time management questionnaire were utilized to collect data. FINDINGS: Internet addiction was prevalent among 98.8% of students, with 56.0% exhibiting mild levels, 40.0% showing moderate levels, and 2.8% having severe levels. A statistically significant negative correlation was found between students' internet addiction and overall time management (r= - 0.387, p < 0.001). CONCLUSION: A considerable level of internet addiction was revealed among the great majority of undergraduate nursing students; however, many students also demonstrated strong time management skills. Furthermore, internet addiction and overall time management were negatively associated, indicating that students with higher levels of internet addiction tend to have poorer time management abilities. RECOMMENDATIONS: Individual counseling and educational training programs should be developed to teach nursing students how to manage time and effectively plan internet usage.

Functional Neuroligin-2-MDGA1 interactions differentially regulate synaptic GABAARs and cytosolic gephyrin aggregation.

Neuroligin-2 (Nlgn2) is a key synaptic adhesion protein at virtually all GABAergic synapses, which recruits GABAARs by promoting assembly of the postsynaptic gephyrin scaffold. Intriguingly, loss of Nlgn2 differentially affects subsets of GABAergic synapses, indicating that synapse-specific interactors and redundancies define its function, but the nature of these interactions remain poorly understood. Here we investigated how Nlgn2 function in hippocampal area CA1 is modulated by two proposed interaction partners, MDGA1 and MDGA2. We show that loss of MDGA1 expression, but not heterozygous deletion of MDGA2, ameliorates the abnormal cytosolic gephyrin aggregation, the reduction in inhibitory synaptic transmission and the exacerbated anxiety-related behaviour characterizing Nlgn2 knockout (KO) mice. Additionally, combined Nlgn2 and MDGA1 deletion causes an exacerbated layer-specific loss of gephyrin puncta. Given that both Nlgn2 and the MDGA1 have been correlated with many psychiatric disorders, our data support the notion that cytosolic gephyrin aggregation may represent an interesting target for novel therapeutic strategies.

Effect of Adding Integrated Core and Graduated Upper Limb Exercises to Inpatient Cardiac Rehabilitation on Sternal Instability After Coronary Artery Bypass Grafting: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the effect of adding integrated core and graduated resistance upper limb exercises to an inpatient cardiac rehabilitation program in patients with acute sternal instability after coronary artery bypass grafting (CABG). DESIGN: This was a single-center, randomized, controlled, parallel-group intervention study. SETTING: This study was conducted at the National Heart Institute. PARTICIPANTS: Forty patients with post-CABG with sternal instability aged 50-60 years completed this study and were randomized into 2 groups: an intervention group (n=20) and an active control group (n=20). INTERVENTION: The intervention group (A) received a routine inpatient rehabilitation program from the first postoperative day plus integrated core and graduated resistance upper limb exercises, which started from the seventh postoperative day for approximately 4 weeks, whereas the control group (B) received only the routine inpatient rehabilitation program. MAIN OUTCOME MEASURES: Sternal separation measured by ultrasonography, visual analog scale for measuring pain, and activities of daily living (ADL) index were main outcome measures. RESULTS: Patients in the intervention group (A) showed a significant reduction in sternal separation from the supine and long sitting positions, whereas those in the control group (B) showed a significant increase in sternal separation (P=.0001). Both groups showed a reduction in pain, and an increase in the ADL score was observed in group A. There was a significant interaction between the time and group effects (P=.0001). CONCLUSION: Adding integrated core and graduated upper limb exercises to inpatient cardiac rehabilitation for patients with sternal instability after coronary artery bypass grafting significantly improved sternal healing, pain, and ADL.

Transcriptomic profiling of the oocyte-cumulus-granulosa cell complex from estrogen receptor ß knockout mice.

OBJECTIVE: To study the role of estrogen receptor ß in follicle development and maturation and the response to gonadotropin stimulation aiming at superovulation. DESIGN: Experimental study and transcriptomic analysis. SETTING: Karolinka Institutet, medical university. ANIMAL(S): Healthy wild-type (WT) and estrogen receptor ß knockout (Esr2-KO) female mice undergoing superovulation at 4 weeks, 7 weeks, and 6 months of age. INTERVENTION(S): Not applicable. MAIN OUTCOME MEASURE(S): Oocyte yield after superovulation, transcriptomic profiling of cumulus-granulosa cell complexes and oocytes, and immunohistochemical analyses. RESULT(S): Superovulation of estrogen receptor ß (ERß) knockout mice resulted in reduced oocyte yield at 6 months of age compared with WT mice, but younger mice had similar yields. RNA-seq analysis of cumulus cells from superovulated WT and Esr2-KO mice identified genes and pathways associated with among others adhesion, proliferation, Wnt-signaling, and placed ERß in bipotential granulosa cell cluster. Loss of ERß increased expression of the other estrogen receptors Esr1 and Gper1. CONCLUSION(S): Our results show that ERß has an important role in regulating ovulation in response to exogenous gonadotropins in 6-month-old mice, but not in younger mice. Our transcriptomic and immunohistochemical observations suggest a dysregulation of the granulosa cell communication and lack of tight coordination between granulosa cell replication and antrum expansion. A significant upregulation of other estrogen receptors may support a compensatory mechanism sustaining fertility during younger age in Esr2-KO mice.

ERß mediates sex-specific protection in the App-NL-G-F mouse model of Alzheimer's disease.

Menopausal loss of neuroprotective estrogen is thought to contribute to the sex differences in Alzheimer's disease (AD). Activation of estrogen receptor beta (ERß) can be clinically relevant since it avoids the negative systemic effects of ERα activation. However, very few studies have explored ERß-mediated neuroprotection in AD, and no information on its contribution to the sex differences in AD exists. In the present study we specifically explored the role of ERß in mediating sex-specific protection against AD pathology in the clinically relevant App NL-G-F knock-in mouse model of amyloidosis, and if surgical menopause (ovariectomy) modulates pathology in this model. We treated male and female App NL-G-F mice with the selective ERß agonist LY500307 and subset of the females was ovariectomized prior to treatment. Memory performance was assessed and a battery of biochemical assays were used to evaluate amyloid pathology and neuroinflammation. Primary microglial cultures from male and female wild-type and ERß-knockout mice were used to assess ERß's effect on microglial activation and phagocytosis. We find that ERß activation protects against amyloid pathology and cognitive decline in male and female App NL-G-F mice. Ovariectomy increased soluble amyloid beta (Aß) in cortex and insoluble Aß in hippocampus, but had otherwise limited effects on pathology. We further identify that ERß does not alter APP processing, but rather exerts its protection through amyloid scavenging that at least in part is mediated via microglia in a sex-specific manner. Combined, we provide new understanding to the sex differences in AD by demonstrating that ERß protects against AD pathology differently in males and females, warranting reassessment of ERß in combating AD.

Epigenetic regulation of tumor immunity.

Although cancer has long been considered a genetic disease, increasing evidence shows that epigenetic aberrations play a crucial role in affecting tumor biology and therapeutic response. The dysregulated epigenome in cancer cells reprograms the immune landscape within the tumor microenvironment, thereby hindering antitumor immunity, promoting tumor progression, and inducing immunotherapy resistance. Targeting epigenetically mediated tumor-immune crosstalk is an emerging strategy to inhibit tumor progression and circumvent the limitations of current immunotherapies, including immune checkpoint inhibitors. In this Review, we discuss the mechanisms by which epigenetic aberrations regulate tumor-immune interactions and how epigenetically targeted therapies inhibit tumor progression and synergize with immunotherapy.

Hemophagocytic lymphohistiocytosis in Egyptian children: diagnosis, treatment challenges, and outcome.

BACKGROUND: Hemophagocyticlymphohistiocytosis (HLH) is a spectrum of immune activation which could be genetically determined, or secondary to an underlying illness. Our aim was to present the clinico-genetic aspects of HLH among Egyptian children and to evaluate the patterns of reactivation and outcome with illustrations of overlap manifestations. RESEARCH DESIGNAND METHODS: We retrospectively collected the data of 55 patients with HLH, registered at Ain Shams University Children's Hospital,Cairo, Egypt. RESULTS: Median age at diagnosis was 19 months (range 2-180), 33 patients (60%) fulfilled the diagnostic HLH criteria at presentation. Fourteen (25.45%) patients had secondary HLH, 15 (27.27%) patients had genetically documented familial HLH (11 had variants in UNC13D gene and one in PRF1 gene), 3 had Griscelli and Chediak-Higashi syndromes. Sixteen patients (29.1%) had reactivations, 8 (50%) of them had molecularly confirmed HLH. We report the death of 40 patients, the median duration from the diagnosis to death of 5 months mostly due to disease activity. CONCLUSIONS: This study confirms that the nonspecific signs and symptoms of HLH are challenging. Genetic testing, though expensive and sophisticated, is integral for the diagnosis. The difficulty in finding non-related donors for stem cell transplantation and the early reactivations are the causes of the inferior outcome.

Deciphering the influence: academic stress and its role in shaping learning approaches among nursing students: a cross-sectional study.

BACKGROUND: Nursing education presents unique challenges, including high levels of academic stress and varied learning approaches among students. Understanding the relationship between academic stress and learning approaches is crucial for enhancing nursing education effectiveness and student well-being. AIM: This study aimed to investigate the prevalence of academic stress and its correlation with learning approaches among nursing students. DESIGN AND METHOD: A cross-sectional descriptive correlation research design was employed. A convenient sample of 1010 nursing students participated, completing socio-demographic data, the Perceived Stress Scale (PSS), and the Revised Study Process Questionnaire (R-SPQ-2 F). RESULTS: Most nursing students experienced moderate academic stress (56.3%) and exhibited moderate levels of deep learning approaches (55.0%). Stress from a lack of professional knowledge and skills negatively correlates with deep learning approaches (r = -0.392) and positively correlates with surface learning approaches (r = 0.365). Female students showed higher deep learning approach scores, while male students exhibited higher surface learning approach scores. Age, gender, educational level, and academic stress significantly influenced learning approaches. CONCLUSION: Academic stress significantly impacts learning approaches among nursing students. Strategies addressing stressors and promoting healthy learning approaches are essential for enhancing nursing education and student well-being. NURSING IMPLICATION: Understanding academic stress's impact on nursing students' learning approaches enables tailored interventions. Recognizing stressors informs strategies for promoting adaptive coping, fostering deep learning, and creating supportive environments. Integrating stress management, mentorship, and counseling enhances student well-being and nursing education quality.

Effect of Buerger-Allen exercise on wound healing in patients with diabetic foot ulcers: a randomised controlled trial.

OBJECTIVE: A diabetic foot ulcer (DFU) is a complication of type 2 diabetes that is difficult to treat. Buerger-Allen exercise has shown effectiveness in improving foot circulation and neuropathy in several studies; however, to the best of our knowledge, no randomised controlled study has investigated its effectiveness for DFU healing. Therefore, this study aimed to assess the effects of Buerger-Allen exercise on the healing of DFUs in patients with type 2 diabetes. METHOD: This is a parallel-group randomised controlled trial (RCT). Of 50 patients with neuropathic DFUs, 41 completed the study. They were assigned randomly to a study group (n=21) and a control group (n=20). Patients in the study group received the standard medical treatment and semi-supervised Buerger-Allen exercise for three sessions per week for four weeks, while patients in the control group only received the standard medical treatment. The outcome measures were: ankle-brachial pressure index (ABPI); ulcer size; ulcer depth; SINBAD score; and ulcer risk for poor outcomes (based on the SINBAD score). RESULTS: The study group's mean age was 49.48±6.45 years and the control group's mean age was 49.15±5.85. The study group's ABPI increased significantly compared to the baseline (1.17±0.04 versus 1.11±0.05, respectively; p<0.001) and the control group (1.17±0.04 versus 1.14±0.05, respectively; p=0.04) post-intervention. Ulcer size also reduced significantly in the study group compared to the baseline (2.63±2.0 versus 7.48±5.55cm2, respectively; p<0.001) and the control group (2.63±2.0 versus 6.43±4.45cm2, respectively; p<0.001) post-intervention. Ulcer depth decreased significantly in the study group compared to the baseline (1.71±1.05 versus 4.19±1.74mm, respectively; p<0.001) and the control group (1.71±1.05 versus 2.80±1.57mm, respectively; p=0.01) post-intervention. Furthermore, the SINBAD score in the study group decreased significantly compared to the baseline (1.38±0.86 versus 2.14±1.06, respectively; p<0.001) and the control group (1.38±0.86 versus 2.0±0.79, respectively; p=0.02) post-intervention. Moreover, the ulcer risk for poor outcomes, based on the SINBAD score, reduced significantly only in the study group, compared to the baseline (p=0.041). The control group showed non-significant changes compared to the baseline in all outcome measures (p>0.05). CONCLUSION: From the findings of this RCT, Buerger-Allen exercise, in combination with standard wound care, may help accelerate the healing of neuropathic DFUs in patients with type 2 diabetes, and could be suggested as part of the management plan for such conditions as an easy-to-perform offloading exercise intervention.

Lactate dehydrogenase A regulates tumor-macrophage symbiosis to promote glioblastoma progression.

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase inhibitor stiripentol emerges as the top hit. Combined profiling and functional studies demonstrate that lactate dehydrogenase A (LDHA)-directed extracellular signal-regulated kinase (ERK) pathway activates yes-associated protein 1 (YAP1)/ signal transducer and activator of transcription 3 (STAT3) transcriptional co-activators in glioblastoma cells to upregulate C-C motif chemokine ligand 2 (CCL2) and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.

Epigenetic regulation of tumor-immune symbiosis in glioma.

Glioma is a type of aggressive and incurable brain tumor. Patients with glioma are highly resistant to all types of therapies, including immunotherapies. Epigenetic reprogramming is a key molecular hallmark in tumors across cancer types, including glioma. Mounting evidence highlights a pivotal role of epigenetic regulation in shaping tumor biology and therapeutic responses through mechanisms involving both glioma cells and immune cells, as well as their symbiotic interactions in the tumor microenvironment (TME). In this review, we discuss the molecular mechanisms of epigenetic regulation that impacts glioma cell biology and tumor immunity in both a cell-autonomous and non-cell-autonomous manner. Moreover, we provide an overview of potential therapeutic approaches that can disrupt epigenetic-regulated tumor-immune symbiosis in the glioma TME.

Psychosocial and mental profile of children with sickle cell disease and their caregivers.

Sickle cell disease (SCD), a chronic debilitating disorder that may negatively affect health-related quality-of-life (HRQoL). In this observational, case-control study, we aim to assess the prevalence of impaired psychosocial profile and poor HRQoL among SCD patients and their caregivers as well as to determine the association of such impairment with parameters of disease severity. Sixty-five children and adolescents with SCD and 65 age- and sex-matched healthy controls and their caregivers were recruited. Demographic and clinical characteristics were collected, and a thorough clinical and psychiatric assessments and HR QoL were conducted. Recruited children and adolescents with SCD were 34 (52.3%) boys and 31 (47.7%) girls, and their mean age was 11.40 ± 3.55. Most of them (n = 44, 67.7%) had sickle HbSß+, and vaso-occlusive crises were the most common causes for hospital admission (n = 24, 36.9%). Children with SCD and their caregivers had depression and anxiety symptoms scores higher than reported in the control group. Children with SCD had significantly less self-esteem and less QoL scores with the least scores were in the communication domain. This adverse psychological profile was significantly negatively correlated with the age of the child, duration of illness, number and duration of hospitalizations, disease severity score, and occurrence of complications. We conclude that HRQoL of children suffering from SCD, and their caregivers are adversely affected necessitating implementation of interventions which focus on reducing depressive symptoms, enhancing self-esteem and QoL.

Health Problems of Increasing Man-Made and Climate-Related Disasters on Forcibly Displaced populations: A Scoping Review on Global Evidence.

Forcibly displaced populations are among the most vulnerable groups in disasters. They experience poorer health conditions compared with nondisplaced individuals. However, a clear picture is lacking regarding the overall health problems encountered by disaster-induced mid- to long-term displaced people. This study investigated these disorders prevalence and identified their correlates among long-settled displaced populations worldwide. The current scoping review follows the PRISMA-ScR guidelines; a systematic search was conducted on PubMed, Web of Science, and CINAHL and included original peer-reviewed studies, commentary, reviews, and grey literature published in English between January 1990 to June 2022. In the thematic and content analysis, the authors applied the narrative review approach to identify themes and sub-themes. Forty-eight documents were identified as fully relevant to this study. The largest number of published papers were from Asia, followed by the Middle East, the United States, and Europe. IDPs in developed countries were the most researched populations. Human-made disasters were addressed by 89% of the included studies. The four main thematic categories included were "physical health," "mental health," "inadequate facilities," and "lack of healthy behaviour." The worsening of noncommunicable diseases had the highest prevalence, followed by communicable diseases. Due to their condition, forcibly displaced migrants face a triple burden of communicable diseases and noncommunicable diseases such as mental health issues. Health-related research and policy need to consider the links among disasters, health problems, and forced migration as a determinant of health in the new era of climate change-driven displacements.

Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma.

Glioblastoma (GBM) is a hypoxic and "immune-cold" tumor containing rich stromal signaling molecules and cell populations, such as proteases and immunosuppressive tumor-associated macrophages (TAMs). Here, we seek to profile and characterize the potential proteases that may contribute to GBM immunosuppression. Legumain (LGMN) emerges as the key protease that is highly enriched in TAMs and transcriptionally upregulated by hypoxia-inducible factor 1-alpha (HIF1α). Functionally, the increased LGMN promotes TAM immunosuppressive polarization via activating the GSK-3ß-STAT3 signaling pathway. Inhibition of macrophage HIF1α and LGMN reduces TAM immunosuppressive polarization, impairs tumor progression, enhances CD8+ T cell-mediated anti-tumor immunity, and synergizes with anti-PD1 therapy in GBM mouse models. Thus, LGMN is a key molecular switch connecting two GBM hallmarks of hypoxia and immunosuppression, providing an actionable therapeutic intervention for this deadly disease.

LDHA-regulated tumor-macrophage symbiosis promotes glioblastoma progression.

Abundant macrophage infiltration and altered tumor metabolism are two key hallmarks of glioblastoma. By screening a cluster of metabolic small-molecule compounds, we show that inhibiting glioblastoma cell glycolysis impairs macrophage migration and lactate dehydrogenase (LDH) inhibitor stiripentol (an FDA-approved anti-seizure drug for Dravet Syndrome) emerges as the top hit. Combined profiling and functional studies demonstrate that LDHA-directed ERK pathway activates YAP1/STAT3 transcriptional co-activators in glioblastoma cells to upregulate CCL2 and CCL7, which recruit macrophages into the tumor microenvironment. Reciprocally, infiltrating macrophages produce LDHA-containing extracellular vesicles to promote glioblastoma cell glycolysis, proliferation, and survival. Genetic and pharmacological inhibition of LDHA-mediated tumor-macrophage symbiosis markedly suppresses tumor progression and macrophage infiltration in glioblastoma mouse models. Analysis of tumor and plasma samples of glioblastoma patients confirms that LDHA and its downstream signals are potential biomarkers correlating positively with macrophage density. Thus, LDHA-mediated tumor-macrophage symbiosis provides therapeutic targets for glioblastoma.

Pediatric COVID-19: Correlations between Clinical and Imaging Perspectives.

Background: Although SARS-CoV-2 infection primarily affects adults, the increasing emergence of infected pediatric patients has been recently reported. However, there is a paucity of data regarding the value of imaging in relation to the clinical severity of this pandemic emergency. Objectives: To demonstrate the relationships between clinical and radiological COVID-19 findings and to determine the most effective standardized pediatric clinical and imaging strategies predicting the disease severity. Patients and Methods. This observational study enrolled eighty pediatric patients with confirmed COVID-19 infection. The studied patients were categorized according to the disease severity and the presence of comorbidities. Patients' clinical findings, chest X-ray, and CT imaging results were analyzed. Patients' evaluations using several clinical and radiological severity scores were recorded. The relations between clinical and radiological severities were examined. Results: Significant associations were found between severe-to-critical illness and abnormal radiological findings (p = 0.009). In addition, chest X-ray score, chest CT severity score, and rapid evaluation of anamnesis, PO2, imaging disease, and dyspnea-COVID (RAPID-COVID) score were significantly higher among patients with severe infection (p < 0.001, <0.001, and 0.001) and those with comorbidities (p = 0.005, 0.002, and <0.001). Conclusions: Chest imaging of pediatric patients with COVID-19 infection may be of value during the evaluation of severe cases of infected pediatric patients and in those with underlying comorbid conditions, especially during the early stage of infection. Moreover, the combined use of specific clinical and radiological COVID-19 scores are likely to be a successful measure of the extent of disease severity.

Effect of fetuin-A on adenine-induced chronic kidney disease model in male rats.

Objectives: This study aimed to investigate the possible effects of fetuin-A on an adenine-induced chronic kidney disease (CKD) model in male rats. Materials and Methods: Rats were divided into three groups: group A included rats fed a normal diet; group B included rats fed a normal diet with 220 mg/kg adenine daily for 21 days; group C included rats fed a normal diet with 220 mg/kg adenine daily for 21 days and intraperitoneally administered with 5 mg\kg fetuin-A every other day for 2 weeks. Serum samples were assayed for serum creatinine, urea, sodium, potassium, calcium, phosphorus, tumor necrosis factor (TNF), interleukin-6 (IL-6), and estimated glomerular filtration rate (eGFR), and immunohistochemical staining was performed. Results: Group B showed a significant increase in serum creatinine, urea, phosphorus, potassium, TNF, and IL-6 and a significant decrease in serum sodium, calcium, and eGFR compared with group A. Regarding immunohistochemistry, group B showed increased apoptosis. In group C, fetuin-A reduced the urea, creatinine, and phosphorus levels, and in group C, fetuin-A decreased inflammation and apoptosis by reduction of caspase-3 staining. Conclusion: Fetuin-A improved kidney function in CKD due to its anti-inflammatory and anti-fibrotic role.

Enabling Transformational Leadership to Foster Disaster-Resilient Hospitals.

Hospitals' operational performance during disasters varies from failing, to being responsive and resilient, to dealing with disruption and surprise. Transformational leaders enable continuously learning hospitals that are resilient in the face of disasters by adapting regeneratively and evolving beyond undertaking conventional lesson-learning after each disaster. However, learning from successful transformational leaders in healthcare is still ad hoc with a lack of guidance on how to develop such leaders. Hence, this study sought to identify key competencies of transformational leaders by exploring hospital leaders' actions in dealing with disasters, considering the disaster cycle of prevention, preparedness, response, and recovery (PPRR). A qualitative case-study design was adopted comprising in-depth semi-structured interviews with twelve senior hospital staff with operational leadership experience with disasters. Three significant categories (themes) and seven key component competencies (sub-themes, in brackets) of transformational leaders were revealed through the analysis of transcripts: (1) 'Governance and leadership' ('transformative agency' and 'decisive accountability'); (2) 'Planning and risk assessment' ('risk navigation', 'disaster attunement', and 'planning agility'); and (3) 'Communication and network engagement' ('communication accelerator' and 'collaboration innovator'). The authors propose a transformational leadership model for hospital disaster resilience and an assessment checklist for leaders' self-reflection to support hospitals in their transition to resilient operations.