Staff Publication

Utilising research management technology to streamline and integrate pharmacy clinical trial processes within a multi-disciplinary research team: a service evaluation (2025)

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Type of publication:

Conference abstract

Author(s):

*Essra Y.; *Angela Y.; *Rachel R.;

Citation:

International Journal of Pharmacy Practice. Conference: Royal Pharmaceutical Society Annual Conference, RPS 2025. London United Kingdom. 33(Supplement 1) (pp i17), 2025. Date of Publication: 01 Nov 2025

Abstract:

Introduction: Clinical trials are the gold standard for testing pharmacological, behavioural and policy interventions [1]. In hospital settings, trial setup can be complex, requiring coordination across multiple teams, specialties, and environments. For trials involving InvestigationalMedicinal Products (IMPs), pharmacy departments must align their processes with other research teams in a transparent, efficient, and standardised manner [2]. One approach to achieving this is using a research management system. Aim(s): To evaluate the implementation of a digital research management system (EDGE) in streamlining and standardising the setup of clinical trials involving pharmacy and other departments. Methodology: As this was a service evaluation, ethical approval was not required. Retrospective quantitative data from between 01 May 2022- 28 May 2025 were extracted from the research management system at a single NHS hospital trust. Data were analysed to assess the number of pharmacy workflows set up, turnaround times and the range of clinical trials supported. Qualitative stakeholder feedback on experiences of implementation were also sought from research nurse colleagues and the trust governance and quality assurance lead. Result(s): Between 2022-2025, four pharmacy-specific workflows were developed and implemented. These were: Expression of interest/feasibility; Amendment implementation; Pharmacy site file audit and Trial closure and archiving. A total of 161 workflows were completed across 62 different clinical trials. Notably 67% of pharmacy workflows were completed ahead of their target timelines. Feedback from research nurses and the trust research and governance lead was positive. The implementation of the pharmacy workflows provided greater transparency for pharmacy set-up and management of clinical trials facilitating better collaborative relationships between the team. Use of the workflows also lead to reduction in e-mail correspondence with better ability to track progress with different tasks and provide visibility to obstacles and blockers. Discussion(s): The implementation of a research management system significantly improved the efficiency, transparency, and coordination of pharmacy workflows in clinical trial setup and management. Positive stakeholder feedback and early completion of most workflows suggest that digital tools can enhance interdisciplinary collaboration in research settings. A key limitation is this evaluation was limited to a single NHS trust and relied on retrospective data and informal stakeholder feedback, which may not fully capture the broader impact or generalisability of the findings.

DOI: 10.1093/ijpp/riaf093.092

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Double jeopardy: Escalating mortality trends and disparities in lung cancer patients with sepsis - A retrospective epidemiological study (2025)

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Type of publication:

Conference abstract

Author(s):

Hemida M.F.; Sarfraz M.R.; Khan T.; Mushtaq I.; Ibrahim A.A.; Chandak V.; Al-Saadi M.; Sharhiar Z.; *Ali A.

Citation:

Thorax. Conference: British Thoracic Society Winter Meeting 2025. Westminster . 80(Supplement 2) (pp A249-A250), 2025. Date of Publication: 01 Nov 2025

Abstract:

Background Lung cancer (LC) remains the leading cause of cancer-related mortality globally. Studies indicate LC patients with sepsis have significantly lower survival rates, yet the temporal trends and disparities in mortality remain unexplored. We examined mortality trends and disparities of LC complicated by sepsis across different sociodemographic strata. Methods This retrospective study analysed death certificate data from the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database from 1999-2023, for individuals >=25 years with multiple causes of death listed as lung/bronchus cancer (ICD-10: C34) with sepsis. Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated and stratified by sex, race/ethnicity, and geographic region, with Joinpoint regression analysis to determine the change in mortality trends. Results From 1999-2023, 103,907 deaths were attributed to LC with co-existing sepsis, demonstrating increasing mortality trends throughout the study period. AAMRs rose significantly from 1.61 in 1999 to 2.07 in 2023 (AAPC: 1.32%; p<0.000001). Sex-stratified analysis revealed men had consistently higher overall AAMRs (2.32/100,000) with an AAPC of 0.49% (95% CI: -0.12 to 1.12; p=0.12) compared to women (1.37/100,000) with an AAPC of 1.94% (95% CI: 1.74 to 2.14; p<0.000001). Patients aged >=65 years exhibited the highest mortality rates (6.59%). Racially, non-Hispanic (NH) Black individuals had the highest overall AAMRs with increasing mortality patterns (AAMRs: 2.57/100,000; AAPC: 0.32%; 95% CI: 0.045 to 0.599; p=0.02), while Hispanic populations recorded the lowest AAMR (1.01/100,000; AAPC: 0.61%; 95% CI: 0.156 to 1.068; p=0.01). Regionally, the South demonstrated the highest mortality (AAMRs: 2.04), followed by the Northeast (AAMRs: 1.78), Midwest (AAMRs: 1.75), and West (AAMRs: 1.42). Most deaths occurred in inpatient medical facilities (90,425 deaths; 87%). Conclusion Mortality rates increased significantly over the study period with a significant increase during recent years. Notable disparities across sex, race/ethnicity, and geographic regions were observed, with NH Black populations and Southern states showed highest mortality rates. These findings highlight the urgent need for targeted sepsis prevention protocols in LC patients, enhanced surveillance systems for high-risk demographics, and comprehensive region-specific interventions to address underlying healthcare disparities and improve clinical outcomes across all populations.

DOI: 10.1136/thorax-2025-BTSabstracts.358

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Epidemiology of cystic fibrosis-related deaths in the united states, 1999-2023: A CDC WONDER-based study (2025)

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Type of publication:

Conference abstract

Author(s):

Mushtaq I.; Sarfraz M.R.; Hemida M.F.; *Ali A.; Ibrahim A.A.; Patel K.; Saghir M.; Sharhiar Z.; Ahmad H.M.; Chaudhry Z.J.

Citation:

Thorax. Conference: British Thoracic Society Winter Meeting 2025. Westminster . 80(Supplement 2) (pp A55-A56), 2025. Date of Publication: 01 Nov 2025.

Abstract:

Background Cystic fibrosis (CF) is a hereditary multisystem disorder predominantly affecting the respiratory system, contributing significantly to morbidity and mortality in the developed nations, despite advancement in treatments. Characterizing mortality patterns across demographic and geographic populations is essential for developing targeted prevention and management strategies. Therefore, we analyzed temporal mortality trends in cystic fibrosis across diverse populations in the United States from 1999-2023. Methods Data were extracted from the CDC WONDER database (1999-2023) to identify mortality rates among individuals aged >=1 year with CF listed as the underlying cause of death (ICD-10: E84.0, E84.1, E84.8, E84.9). Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated and stratified by sex, age group, race/ethnicity, geographic region, and place of death. Temporal trends were analyzed using Joinpoint regression to estimate average annual percent change (AAPC). Results From 1999-2023, 11,997 deaths were reported among individuals with CF across all age groups (<1 to >=65 years). The AAMR decreased significantly from 0.19 in 1999 to 0.09 in 2023 (AAPC: -3.1%; p<0.000001), with accelerated decline in recent years. Both sexes demonstrated comparable average AAMRs (0.15), though with different rates of decline: men (AAPC: -2.7%; 95% CI: -4.17 to -1.29; p=0.0002) and women (AAPC: -2.9%; 95% CI: -4.19 to -1.66; p=0.000008). By race/ethnicity, non-Hispanic populations exhibited higher overall AAMRs compared to Hispanics (0.18 vs. 0.06), with incongruent trends observed among non-white races and Hispanic populations. Regionally, the Midwest recorded the highest AAMR (0.17), followed by the South (0.16), Northeast (0.15), and West (0.13). Age-stratified analysis revealed peak mortality in the 15-34 years group (0.32/100,000), followed by the 35-64 years group (0.12/100,000). Most deaths occurred in inpatient medical facilities (8,260 deaths; 68.8%). Conclusion CF mortality rates declined significantly over two decades, with comparable reductions in both sexes. However, substantial disparities persist, with young adults (15-34 years) experiencing high mortality rates and notable racial/ethnic differences. Regional disparities were evident across geographic areas. While these findings suggest improved CF management and care, they underscore the critical need for targeted interventions addressing persistent demographic and geographic disparities to ensure equitable outcomes across all populations.

DOI: 10.1136/thorax-2025-BTSabstracts.79

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Eosinophilic phenotype and bacterial load in hospitalised patients with exacerbations of COPD (2025)

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Type of publication:

Conference abstract

Author(s):

*Thumbe A.; *Ahmad N.

Citation:

Thorax. Conference: British Thoracic Society Winter Meeting 2025. Westminster . 80(Supplement 2) (pp A122), 2025. Date of Publication: 01 Nov 2025.

Abstract:

Background COPD is a heterogenous disease, and the eosinophilic phenotype is now well recognised as a treatable trait. However, it is less well known as to what extent bacterial infections affect this group of patients.1 Aim Our primary aim was to look at the incidence of bacterial growth in eosinophilic and the non-eosinophilic phenotype within our cohort of patients with COPD. Method A retrospective analysis was conducted on patients coded has having been admitted to our Trust with COPD exacerbations from October 2020 to April 2021. Historic sputum culture results were collected from our web-based patient portal. Patients were included in the analysis if they had a sputum culture showing bacterial growth at any time. Eosinophilic phenotypes (EP) were defined as having a blood eosinophil count >=0.3×109/L and non-eosinophilic phenotypes (NEP) as having a blood eosinophil count<0.3×109/L. Results In the study period, 337 unique patients were admitted with COPD exacerbations. They had a mean age (SD) of 73 (9) years, 49.6% (167/337) were female and 64.1% (216/337) were EP. 47% (n=157/337) patients had at least one positive sputum culture. Of these, 68.8% (n=108/157) were classified as EP. 72%(n=108/150) of EP had a positive sputum culture compared to 70% (n=49/70) of NEP; Odds Ratio 1.10 (95% CI 0.59-2.06); Chi-Square 0.021; p=0.88. When compared, NEP had higher burden of H. Influenzae, Strep Pneumoniae and Moraxella (59%, 20% and 20% vs 55%, 19% and 15%, respectively) whereas EP had a higher burden of Coliforms, Pseudomonas sp and S.aureus (32%, 30% and 15% v 25%, 25% and 8%, respectively). Conclusion Our findings suggest that in COPD patients requiring hospital admission, there is no significant difference between the bacterial burden of EP and NEP. Hence, future treatments of EP should not only include biologics but also focus on the role of bacteria in preventing exacerbations.

DOI: 10.1136/thorax-2025-BTSabstracts.179

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Two decades, two destinies: When chronic obstructive pulmonary disease hearts beat differently - The divergent mortality trajectories of atrial fibrillation vs other arrhythmias (2025)

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Type of publication:

Conference abstract

Author(s):

Sarfraz M.R.; Hemida M.F.; *Ali A.; Ishtiaq S.; Patel K.; Hussein M.; Tabasum P.; Basit Kayani A.; Mehmood H.; Mushtaq I.; Rehman S.;

Citation:

Thorax. Conference: British Thoracic Society Winter Meeting 2025. Westminster . 80(Supplement 2) (pp A71-A73), 2025. Date of Publication: 01 Nov 2025.

Abstract:

Background While arrhythmias are recognized as potential causes of death in chronic obstructive pulmonary disease (COPD) patients. However, temporal trends in arrhythmia-related mortality among COPD patients remain unexamined. Therefore, we conducted a comparative study evaluating mortality trends between atrial fibrillation (AF) and other arrhythmias in COPD patients. Methods A retrospective analysis of was conducted from 1999-2023, using the CDC WONDER database comparing COPD patients with AF (ICD-10: I48) versus other arrhythmias (ICD-10: I47, I49). Age-adjusted mortality rates (AAMRs) per 100,000 population were stratified by demographic variables for adults >=25 years. Joinpoint regression estimated average annual percent changes (AAPC) in mortality trends. Results From 1999-2023, 537,088 COPD-AF deaths were recorded (280,378 Men; 256,710 Women). AAMRs increased significantly from 5.55 to 13.66 (AAPC: +3.87%). Conversely, 168,770 COPD patients with other arrhythmias died (96,472 Men; 72,298 Women), with AAMRs declining significantly from 5.19 to 2.04 (AAPC: -3.56%). Men consistently showed higher mortality rates in both COPD with AF and other arrhythmias. In COPD-AF, AAMRs increased significantly for both genders (p<0.000001): men (7.96 to 16.95; AAPC: +3.23%) and women (4.17 to 11.19; AAPC: +4.18%). Conversely, in the COPD with other arrhythmias cohort, mortality rates decreased significantly (p<0.000001) for both men (AAMR: 7.68 to 2.67; AAPC: -4.05%) and women (AAMR: 3.58 to 1.52; AAPC: -3.16%). Inpatient medical facilities were the most common place of death for both groups, though COPD-AF patients had fewer inpatient deaths (59,284) than those with other arrhythmias (190,982). Both cohorts showed a notable shift toward increased home deaths over the study period. Racially, Whites had the highest AAMRs in both groups (AF: 11.04; other: 3.32), followed by American Indians (AF: 8.18; other: 2.78). Regionally, the Midwest showed highest mortality with opposing trends: upward for AF (AAPC: +4.89%) and downward for other arrhythmias (AAPC: -3.30%) p<0.000001. At state level, Vermont had the highest COPD-AF mortality (AAMR: 16.33), while Ohio had the highest AAMR for other arrhythmias (5.20). Conclusion COPD-AF mortality increased dramatically while other arrhythmia mortality declined significantly. Men showed consistently higher mortality with notable demographic disparities. These opposing trends suggest AF represents an emerging threat requiring targeted interventions.

DOI: 10.1136/thorax-2025-BTSabstracts.104

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Hypertonic saline in chronic lung disease: A local experience to suggest usefulness? (2025)

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Type of publication:

Conference abstract

Author(s):

*Johnson J.; *Ahmad N.;

Citation:

Thorax. Conference: British Thoracic Society Winter Meeting 2025. Westminster . 80(Supplement 2) (pp A151-A152), 2025. Date of Publication: 01 Nov 2025.

Abstract:

Background 7% Hypertonic saline (HTS) is increasingly being used as a mucolytic therapy in patients with chronic respiratory conditions, particularly those with mucus retention and impaired airway clearance. Despite its widespread use, data on the effectiveness of HTS and its potential impact on healthcare utilisation remain sparse. Understanding its role in symptom relief and hospital admission rates is critical in optimising treatment. Aim The primary outcome was to observe an improvement in symptoms. The secondary outcome looked at reduction in hospital admissions comparing 12 months before HTS initiation with 12 months post-initiation. Method This was a retrospective cohort study from March 2023 to February 2025. We identified patients initiated on HTS, through a logbook maintained by specialist respiratory nurses. Improvement in symptoms meant improved cough, ease of mucus expectoration and change in mucus colour, which was reported in clinic letters. We also collected data of their highest Blood eosinophil count (BEC) during this period. We used MS Excel and Vassar stats (vassarstats.net) for calculations. Results A total of 36 patients were initiated on HTS, of which 42% (n=15) had Bronchiectasis, 8% (n=3) had COPD, 22% had Asthma (n=8), 11% had Asthma-COPD overlap (4) and 17% were labelled as others (n=6). Mean Age was 65 years (SD 10) with 56% females. 67% had BEC >0.3 x109/L. 72% (n=26) reported symptomatic improvement of which notably 42% (n=11) had Bronchiectasis, 27% had Asthma (n=7) and 15% (n= 4) had Asthma-COPD. 25% (n=9) noted no benefit and 1 patient's data was not found. Subjects showing symptom improvement had a higher mean BEC (0.45×109/L v .27×109/L, p=0.01) when compared with those who did not show any improvement. Our secondary outcome measure showed no effect on hospital admissions following initiation of HTS. However, 4 of 6 patients who were hospitalised over the next 12 months reported a symptomatic improvement. Conclusion Majority of patients with Bronchiectasis, Asthma and Asthma-COPD overlap derive symptomatic benefit from HTS treatment. Improvement in patients with BEC>0.3 was statistically significant, suggesting higher degree of mucus impaction in this group. HTS probably does not affect hospital admissions; but requires further validation.

DOI: 10.1136/thorax-2025-BTSabstracts.219

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Mortality from tibial shaft fractures in the elderly (MTFE)-a multicentre study of management outcomes (2025)

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Type of publication:

Journal article

Author(s):

Azhar M.S.; Selim A.; Daoub A.; Farhan-Alanie M.M.; Shah R.

Citation:

Injury. 56(12) (no pagination), 2025. Article Number: 112806. Date of Publication: 01 Dec 2025.

Abstract:

Introduction The mortality rate for tibial shaft fractures in the elderly is comparable to that of hip fractures, yet there is considerable variation in their management. Operative treatment allows for earlier weight-bearing and reduces potential complications of prolonged immobilization; however, it carries risks for this comorbid cohort. The main objective of this study was to assess the difference in 1-year mortality between operative and non-operative management. Methods A multicentre study was conducted across six trusts in England, including eight acute hospitals: three major trauma centres and five district general hospitals (DGHs). Data were collected retrospectively, covering a 5-year period from January 2017 to December 2021. The study included all patients aged 65 and over with diaphyseal tibial fractures (AO42). Patients with non-acute (>3 weeks), periprosthetic, pathological, or multiple lower limb fractures were excluded. Results A total of 171 patients were identified, comprising 38 % males and 62 % females. Of these, 59.6 % were managed operatively, while 40.4 % were managed non-operatively. The median length of stay was similar between groups (8 days non-operative vs. 8.5 days operative, p = 0.87). Non-union (21.7 % vs. 6.3 %, p < 0.001) and malunion rates (27.7 % vs. 4.6 %, p = 0.001) were significantly higher in the non-operative group. One-year mortality was also higher in the non-operative group (38.3 % vs. 12.1 %, p < 0.001). Univariate and multivariate analyses showed an odds ratio of 4.5 and 4.7 for one-year mortality with non-operative treatment, with p -values of <0.001 and 0.005, respectively. Conclusion This study demonstrated that non-operatively treated tibial shaft fractures in the elderly are associated with significantly higher rates of non-union, malunion, and 1-year mortality. Therefore, we recommend an expedited multi-disciplinary approach to managing these patients, including surgical treatment and unrestricted weight bearing where possible, to optimize outcomes. Level of Evidence Level III.

DOI: 10.1016/j.injury.2025.112806

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The spiked helmet sign in severe sepsis: an unusual electrocardiographic finding in a critically ill patient (2025)

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Type of publication:

Journal article

Author(s):

Manea, Hashim; Alhatemi, Ahmed Qasim Mohammed; Al-Ghuraibawi, Mohammedbaqer Ali; *Alhumairi, Ghaith Asaad; Al-Shammari, Ali Saad; Al-Ibraheem, Abdullah Muataz Taha; Ahmad, Ibrar; Abdulammer, Hussein Safaa.

Citation:

Oxford Medical Case Reports. 2025(11):omaf232, 2025 Nov.

Abstract:

Background: The 'spiked helmet' sign is a rare electrocardiographic (ECG) phenomenon characterized by transient ST-segment elevations mimicking an acute coronary syndrome, typically seen in critically ill patients. While often associated with severe physiological stress, its presence in sepsis is particularly uncommon.

Case Presentation: A 68-year-old male with a history of hypertension and diabetes mellitus presented to the emergency department with fever, altered mental status, and hypotension. Initial workup revealed severe sepsis secondary to pneumonia. His ECG showed pronounced ST-segment elevations in leads II, III, and aVF, with a distinctive 'spiked helmet' pattern. Troponin levels were mildly elevated, raising concerns for concurrent myocardial ischemia. However, the patient denied chest pain, and further cardiac evaluation, including echocardiography, showed no evidence of ischemia or infarction. Intensive care management included broad-spectrum antibiotics, intravenous fluids, and vasopressors. Despite the severity of his illness, the patient's condition gradually improved, and repeat ECGs showed resolution of the ST-segment elevations. The 'spiked helmet' sign was attributed to severe sepsis-induced autonomic dysfunction rather than primary cardiac pathology.

Conclusion: This case highlights the importance of recognizing the 'spiked helmet' sign as a marker of severe stress in critically ill patients, which may mimic myocardial ischemia on ECG. Prompt differentiation between this sign and true ischemia is crucial to avoid unnecessary interventions and focus on managing the underlying critical illness.

DOI: 10.1093/omcr/omaf232

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Bridging Communication Gaps to Enhance Patient Safety: A Quality Improvement (QI) Project on the Role of Abbreviations, Their Risks, and Pathways to Change (2025)

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Type of publication:

Journal article

Author(s):

*Talha, Saarah; *Smith, Ben; *Khan, Ayesha; Gaddoura, Zaina.

Citation:

Cureus. 17(10):e95843, 2025 Oct.

Abstract:

Introduction Effective communication within the multidisciplinary team (MDT) is critical to safe patient care. Whilst electronic health records have improved legibility, the widespread use of non-standardised abbreviations continues to cause misinterpretation, risking delays, errors, and compromised patient safety. Abbreviations are often used for efficiency, yet their meanings vary between specialties, creating barriers for rotating staff, cross-disciplinary colleagues, and patients reviewing discharge summaries. Quality improvement project We conducted a closed-loop quality improvement (QI) project structured around the SQUIRE 2.0 guidelines for QI initiatives. The project took place in a UK district general hospital to assess and improve understanding of commonly used ear, nose, and throat (ENT) specialty abbreviations. Eighty-two common abbreviations were identified and used in a written expansion test. In cycle one (n = 45), mean accuracy was 24.3%, with no participant exceeding 77%. Following targeted interventions (educational seminars and a printed reference guide displayed in shared spaces), a second assessment cycle was conducted with a new cohort. Post-teaching scores improved by a relative 40% to a mean of 35% (range 24%-52%). Mann-Whitney U testing confirmed statistical significance (p < 0.05). Implications and discussion Findings revealed a substantial baseline knowledge gap, highlighting a safety risk. Low-cost, high-visibility measures, such as reference posters and induction-based teaching, improved comprehension and could be readily adopted in other departments. However, residual gaps suggest the need for upstream interventions, including integration of documentation clarity training into medical education and continued departmental reinforcement. Conclusion Clinicians' baseline abbreviation comprehension was poor, but targeted education significantly improved understanding. Whilst no participant achieved complete proficiency, results show that simple, resource-light strategies can enhance communication clarity and support safer care. Broader adoption, alongside curricular change, offers a sustainable path to reducing abbreviation-related risks.

DOI: 10.7759/cureus.95843

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Hologenomic analysis of rectal mucus sampling for detection of adenomatous polyps and colorectal cancer (2025)

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Type of publication:

Journal article

Author(s):

Tock, Andrew J; Patel, Kamrun S; Morales-Walker, Emma; Zhang, Linglan; Orthodoxou, Chris; MacRitchie, Alasdair D; Njoroge, Stephen; Olaniru, Oladapo E; Mozolowski, Guy; Mendes, Ines; Baker, Dave J; Siew, Malvin; Humphrey, Hannah N; Walker-Davies, Eleanor T; McDermott, Frank; Spencer, Sue; Bird, Susan; Savva, Katerina-Vanessa; Cunningham, Christopher; Rottenburg, Hannah; Sisodia, Heena; Battersby, Nick J; *Jones, Gareth A R; *Lacy-Colson, Jon; Baggaley, Alice E; Peters, Christopher J; Dodd, Andrew; Kang, Kiran; Hamon, Chris; Crespillo-Casado, Ana; Law, Erica; Sands, Megan; Lywood, Hugo; Page, Andrew J; Daniels, Ian; Wise, Daniel.

Citation:

Nature communications . 16(1):10876, 2025 Dec 04.

Abstract:

Colorectal cancer (CRC) is the fourth most common cancer and the third leading cause of cancer-related mortality worldwide, with incidence rising among younger populations. The significant clinical and economic burden highlights the need for minimally invasive technologies capable of detecting pre-malignant and early-stage disease. Although liquid biopsy approaches have advanced, they have not achieved sufficient performance for clinical adoption when compared with colonoscopy, the current diagnostic gold standard. CRC is a mucosal pathology, yet current diagnostic methods have not leveraged mucosal biology. Here we demonstrate the clinical utility of rectal mucus specimens, collected using a minimally invasive device in an outpatient setting, without bowel preparation. Through a hologenomic approach integrating host and microbial genomics, we identify genetic and epigenetic aberrations and perturbations in microbial communities that drive the detection of adenomatous polyps and CRC in rectal mucus. Hologenomic integration enables superior stratification of CRC by disease site and stage compared with single-omics methods. In summary, we demonstrate the clinical utility of rectal mucus sampling combined with hologenomic analysis as a translatable prospective tool for diagnostic application.

DOI: 10.1038/s41467-025-66006-1

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