bluuebunny/crossref_metadata_2025 huggingface dataset:
‘Stuck in catch-22’: a qualitative study of perceived work ability and decision-making about employment in severe asthma
Authors: Mackiewicz P. , Hussein H. , Mansur A. H. , Krishna M. T. , Walters G. I.
Published: February 2025

Background

Severe asthma (SA) is characterised by persistent asthma symptomatology despite adherence to intensive treatment and control of asthma triggers. It is estimated that approximately 50% of individuals with SA have current employment, considerably less than rates in the general population. Poor physical and mental health status have been suggested as a potential explanation for this, but the relationship has not been investigated in depth. We investigated how bio-psycho-social and cultural factors influence work ability and employment in SA patients.

Methods

Participants were recruited from the Birmingham Regional NHS Severe Asthma Service via opportunity sampling, with the exclusion criteria being individuals who had never been employed, currently in full-time education, or non-English speakers. Subsequently, men and those with minority-ethnic backgrounds were purposefully selected to gain a balanced sample. Interviews were performed either face-to-face, online or via telephone, transcribed using software and edited manually. Data were analysed using Reflexive Thematic Analysis.

Results

The study included 12 participants (9 females and 3 males). Four major themes were constructed: impact of patients’ asthma control on work, psychological burden of living with SA, costs and benefits of being in employment, and adaptations and strategies for remaining in employment.

Conclusions

Our findings highlight the potential for physical, occupational, psychological, and social support to address the diverse job-related difficulties experienced by people with SA. Additionally, national policy reforms should be considered to improve work capacity and promote employment opportunities.
The design, performance and organizational impact of a point-of-care ultrasound (POCUS) elective for internal medicine residents
Authors: Kuperstein Harry , Alam Werda , Paroya Azzam , Patel Kinner , Ahmad Sahar
Published: February 2025

Background

An educational gap for point-of-care-ultrasound (POCUS) training exists within Internal Medicine (IM) residency programs in that there is currently no standardized training paradigm. To address this need, we designed and implemented a five-day (one work week) elective for POCUS training intending to target IM resident POCUS knowledge and skills. This course integrates self-directed learning and supervised hands-on practice to deliver effective resident education in POCUS.

Methods

IM residents completed the five-day POCUS elective. Residents who took the elective were given an elective evaluation survey, written POCUS knowledge exams at a pre-course and post-course timepoint, as well as a post-course skills assessment exam.

Results

45 IM residents completed the elective in total. 47% (N = 21) of all participating residents completed the evaluation survey. 94% of those who responded to the evaluation survey reported above average or outstanding satisfaction with all aspects of the elective, including hands-on teaching and materials provided. Written knowledge exams results showed a significant increase in POCUS knowledge scores, with pre-test and post-test scores increasing from 39 to 66%, respectively (N = 30, p < 0.001). Overall, on a skills evaluation of tested residents (N = 20), 45% were deemed to acquire images independently while 40% could interpret independently, with all learners deemed able to do both with some level of supervision. Overall use of POCUS by IM residents as measured by saved ultrasound studies increased after the implementation of the elective, suggesting institutional impact.

Discussion

POCUS training is a recognized need for IM residency programs. While existing POCUS training programs vary in both length of course and depth of material to suit different educational objectives, we have presented a well-received and effective POCUS training paradigm aimed at achieving knowledge acquisition for clinical practice. This POCUS elective rotation, which is integrated into trainee’s patient care experiences, circumvents several known barriers to POCUS education including work-hour limitations and limited trainee hands-on experience opportunities. We propose that our elective serves as a model for IM residencies which have similar needs with respect to POCUS education.
National eHealth strategies: a comparative study of nine OECD health systems
Authors: Palm Klas , Brantnell Anders , Peolsson Michael , Özbek Nurgül , Hedström Gustaf
Published: February 2025

Background

The development of effective eHealth strategies is critical to enhancing healthcare systems’ efficiency and outcomes. However, there is limited comparative analysis of eHealth strategies across health systems, particularly in terms of their vision, objectives, implementation methods, and follow-up processes. This study compares the eHealth strategies of nine health systems, focusing on three key dimensions: vision and objectives, means to achieve objectives, and structures for follow-up.

Methods

A comparative qualitative analysis was conducted using publicly available eHealth strategy documents from nine health systems: Australia, Denmark, Estonia, Finland, Norway, Sweden, the UK (NHS England), Catalonia (Spain), and the USA (Veterans Affairs). The analysis mapped these systems’ visions, objectives, implementation methods, and follow-up structures.

Results

Findings show that most systems articulate clear visions and strategic goals. However, there is considerable variability in the level of detail regarding the means of achieving objectives and structures for follow-up. Australia and Estonia present the most comprehensive strategies, with clear tasks, responsibilities, timelines, and follow-up mechanisms. In contrast, countries like Sweden and Catalonia provide less detailed strategic plans, particularly in terms of follow-up processes.

Conclusions

While most studied health systems include clear visions and strategic goals, there is variability in the detail and comprehensiveness of their implementation and evaluation frameworks. Strategies with detailed implementation plans and follow-up processes, such as those from Australia and Estonia, offer valuable models. Further research is recommended to explore the practical impact of these strategies on healthcare delivery, patient outcomes, and system efficiency. Additionally, the role of stakeholder involvement in shaping these strategies warrants further investigation.
Göttingen minipigs present with significant regeneration kinetics after sphincter injury compared to German landrace gilts; a feasibility study
Authors: Knoll Jasmin , Harland Niklas , Amend Bastian , Stenzl Arnulf , Aicher Wilhelm K.
Published: February 2025

Background

Animals serve as important models for exploring the pathology, diagnosis, and therapy of different diseases and injuries. While smaller animals are preferred for bulk cohort studies, larger animals offer opportunities to investigate surgical procedures at proportions close to the human situation. Therefore, in a feasibility study, we investigated urethral sphincter deficiency in German landrace gilts and Göttingen minipigs to develop a model of urinary incontinence as a basis for future preclinical studies of incontinence therapies. Urethral sphincter deficiency was induced surgically by transurethral electrocautery and balloon dilatation, and the deficiency was determined by urodynamics after injury and during follow-up. In cryosections, sphincter injury was visualized by histochemistry.

Results

Sphincter deficiency was induced in two cohorts and groups of four female Göttingen minipigs each (total n = 20) by two different treatments. One cohort of minipigs showed an initially significant urethral sphincter deficiency (treatment 1; n = 16, p < 0.001). However, spontaneous sphincter regeneration was observed within one to two weeks. The other cohort of minipigs (treatment 2; n = 4) displayed a non-significant reduction of urethral sphincter pressure and an increase in muscle strength over time as well. In contrast, German landrace gilts presented immediately after treatment with significant sphincter deficiency (treatment 1; n = 6, 21%, p < 0.001) and suffered from significant loss of sphincter function for at least five weeks (67%, p < 0.01).

Conclusion

Göttingen minipigs inherit significantly superior sphincter regeneration capacities compared to landrace pigs. This difference may bias preclinical studies in urology and other fields and explain in part seemingly contradictory results from different animal studies.
Updated insights into the impact of adjuvant chemotherapy on recurrence and survival after curative resection of liver or lung metastases in colorectal cancer: a rapid review and meta-analysis
Authors: Tatsuta Kyota , Sakata Mayu , Kojima Tadahiro , Booka Eisuke , Kurachi Kiyotaka , Takeuchi Hiroya
Published: February 2025

Background

Colorectal cancer (CRC) frequently metastasizes to the liver and lungs, leading to poor prognosis. Advances in chemotherapy, minimally invasive surgery, and perioperative care have expanded adjuvant chemotherapy (AC) regimens and eligibility for AC. However, the impact of AC after curative resection of distant metastases on recurrence and prognosis remains uncertain. This study evaluated the role of AC in CRC liver and lung metastases, focusing on cases with curative resection based on the latest studies published in the past five years.

Methods

This systematic review followed PRISMA guidelines. Literature searches of Medline and Cochrane Library (2019–2023) identified studies on AC or observation after curative resection of CRC metastases, reporting outcomes such as overall survival (OS) and disease-free survival (DFS). Data analysis was performed using Review Manager and R software, with results expressed as hazard ratios (HR) and 95% confidence intervals (CI).

Results

Seven studies met the eligibility criteria, including one randomized controlled trial and six retrospective studies, encompassing 1580 patients who underwent curative resection (R0) for CRC metastases. This meta-analysis showed a positive trend in OS for the AC group compared to that for the surgery-alone group (HR 0.86, 95% CI: 0.73–1.01; p = 0.06), but the difference was insignificant. AC significantly improved DFS (HR 0.81, 95% CI: 0.66–0.99; p = 0.04). Subgroup analysis indicated that AC significantly improved DFS and tended to improve OS for liver metastasis. In contrast, AC did not improve OS in cases of lung metastasis.

Conclusions

This meta-analysis suggests that AC demonstrated significant positive effects on DFS. Moreover, AC could contribute to improvements in OS. These findings, supported by the latest research, reinforce the recommendation of AC as a valuable strategy for improving both recurrence and survival outcomes in patients with curatively resected distant CRC metastases.
Ferroptosis emerges as the predominant form of regulated cell death in goat sperm cryopreservation
Authors: Hai Erhan , Li Boyuan , Song Yukun , Zhang Jian , Zhang Jiaxin
Published: February 2025

Background

Freezing-induced sperm damage, often associated with oxidative stress, can result in regulated cell death. Given that oxidative stress can trigger various forms of regulated cell death, the prevailing form during sperm cryopreservation remains unknown. Our study aimed to investigate this issue using cashmere goats as a model.

Results

We found a significant increase in lyso-phospholipids in frozen-thawed sperm suggested ferroptosis. Assessment of cryopreserved sperm, with or without prior treatment with ferroptosis or apoptosis inhibitors, demonstrated the significant efficacy of ferroptosis inhibitors in reducing freezing damage. This implicates ferroptosis as the primary form of regulated cell death induced during sperm cryopreservation. Additionally, the positive rate of transferrin receptor protein 1 was significantly lower in fresh live sperm (47.8%) than in thawed live sperm (71.5%), and the latter rate was lower than that in dead sperm (82.5%). By contrast, cleaved caspase-3 positivity showed no significant difference between fresh live sperm and thawed live sperm but was notably lower in thawed live sperm than in dead sperm.

Conclusions

Our findings establish ferroptosis as the dominant regulated cell death form during goat sperm cryopreservation, providing novel insights into freezing-induced sperm damage mechanisms. These findings have significant implications for optimizing cryopreservation protocols and enhancing sperm viability after freezing-thawing.

Graphical Abstract
Quasi-static analysis of soft rock failure characteristics targeted to cyclic direct shear test
Authors: Hidaka Kosuke , Ishimaru Makoto , Okada Tetsuji , Sekiguchi Akira , Sawada Takaaki , Yokota Katsuya , Matsui Nobuaki , Mazda Taiji
Published: February 2025

In Japan, the disastrous effects of the 2011 Tohoku Earthquake has affected seismic design. Furthermore, there is an increasing need for dynamic nonlinear analysis that can consider large strain levels in assessing the seismic resilience of essential structures such as nuclear power plants. However, the applicability of dynamic nonlinear analysis methods to rock masses has not yet been fully evaluated. Their applicability needs to be confirmed by dynamic phenomena, such as shaking table tests. Herein, as a preliminary step, quasi-static analyses of cyclic direct shear tests were conducted to validate the constitutive model. Soft rock samples with relatively few fractures were used as the testing material. In the tests, the load was applied in multiple steps by increasing the loading amplitude at each step, with a loading frequency of 0.1 Hz. The quasi-static analyses revealed that, although an existing constitutive model generally reproduced the shear load–displacement relationship obtained in the tests from small displacement levels to peak strength, discrepancies emerged beyond peak strength. Therefore, we focused on the post-failure history damping characteristics of the soft rocks and added a damping constant after rock failure to the existing constitutive model. Consequently, the accuracy of the values of the stress history beyond peak strength was improved by more than 10%, and the reproducibility of the shear load–displacement relationship improved. Therefore, the applicability of the improved constitutive model was confirmed for conditions of quasi-static cyclic loading of soft rock with few fractures, from small displacement levels to beyond peak strength.
CaEch1-mediated mitophagy regulates vegetative growth, conidiation, appressorium formation, and pathogenicity in Colletotrichum camelliae
Authors: Meng Shuai , Xiong Meng , Cheng Longjun , Wang Li , Chen Ya , Luo Chaoxi , Chao Shufen
Published: February 2025

Anthracnose, caused by Colletotrichum camelliae, poses a significant threat to the yield and quality of Camellia oleifera. Mitophagy, a selective form of autophagy, is crucial in maintaining mitochondrial quality and intracellular homeostasis. To date, an optimized experimental system for studying mitophagy in C. camelliae has yet to be established, and the role of mitophagy in the pathogenesis of C. camelliae remains unclear. Here, we characterized the function of CaEch1, a homolog of Magnaporthe oryza MoEch1, in the anthracnose fungus C. camelliae. Our findings indicate that mitochondria-localized CaEch1, plays a vital role for mitophagy in C. camelliae. Also, the CaEch11-29-GFP could serve as a reliable marker for monitoring mitophagy in C. camelliae. Additionally, the knockout of CaECH1 resulted in defects in fungal growth, conidiation, and appressorium formation. Pathogenicity assays further revealed that knockout of CaECH1 significantly reduced the virulence of C. camelliae. In summary, our research underscores the importance of CaEch1 in growth, conidiation, appressorium formation, and virulence in C. camelliae. This suggests its potential as a marker for mitophagy and provides valuable insights for developing new fungicides targeting anthracnose.
Physical, psychological, and sexual violence as risk factors for social phobia in a sample of Moroccan students
Authors: Belaatar Mohjat , Najdi Adil , Louajri Adnane , Ammouri Adil El , Fadila Bousgheiri , Senhaji Meftaha
Published: February 2025

Background

Social phobia is one of the most widespread mental disorders among young people, especially students. It may be due to several factors, the most important of which is violence and its various subtypes.

Aim

The main objective of the study was to identify the subtypes of violence that might be considered risk factors for social phobia.

Methods

In this descriptive study, the participants were students at different institutions of Abdelmalek Essaâdi University in Morocco. In total, we interviewed 1191 students of which 1154 are aged between 18 and 28, 34 between 29 and 39, 2 students are 44, and only 1 is 64, using the M.I.N.I. questionnaire, along with a background questionnaire that contains questions about childhood information and risk factors such as exposure to violence.

Results

The prevalence of social phobia among the students in this study was 27% (321 students) of whom 138 students (44.7%) had experienced physical violence, 108 (42.5%) had experienced psychological violence, and only 52 (36.9%) had experienced sexual violence.

Conclusions

The Moroccan population, despite its diversity, customs, and education, remains similar to other populations in terms of mental health and mental disorders.
Knowledge management enablers and innovative capabilities: the mediating role of knowledge transfer—insights from telecom industry in Egypt
Authors: Hameed Marwa Mohamed Abdel , Hashem Abd Elazez Abd Eltawab , Ali Tarek Mohamed
Published: February 2025

Purpose

This study aims to investigate the mediating role of knowledge transfer (KT) in explaining the interdependencies between Knowledge Management Enablers (KMEs) and Innovation Capabilities (ICs) within Egypt’s Telecom industry.

Design/methodology/approach

Using a cross-sectional survey, the authors collected data from 315 employees working at the leading four Telecom Companies in Egypt. The hypothesized model was analyzed using the partial least square structural equation modeling technique. Semi-structured interviews were conducted with 40 key positions and mirrored against the quantitative data. The qualitative data were analyzed using the thematic analysis technique.

Findings

The results indicate a significant positive effect of the KM enablers of T-shaped skills and leadership-style on workers’ ICs. The KMEs dimensions of organization culture, structure, IT-Support-T-shaped skills and leadership-style explain the KT mechanism. The relationship between the KM enablers of (organization culture, structure, IT-Support, and leadership-style) and workers’ ICs is mediated by the KT mechanism. The relationship between T-shaped skills and ICs is not mediated by KT.

Research limitations/implications

Limited attention, until now, is given to the KMEs, KT and ICs interdependencies. This study bridges this research gap by exploring how KM enablers (i.e., organization culture, organization structure, IT infrastructure, T-shape skills, and leadership-style) shape the mechanism of transferring knowledge within the organization, which generates ICs for organizations operating in dynamic environment.

Practical implications

The results provide managers with applicable recommendations for fostering KMEs, encouraging KT mechanisms, and enhancing workers’ ICs.

Originality/value

This research is among the first to significantly contribute to understanding how KT mechanism, as mediator, explain the interdependencies between KMEs and ICs in ever-changing business environment.
Sacroiliitis and endocarditis in the absence of fever: an unusual clinical presentation following diarrhea in a young patient
Authors: Kiskani Amin Karimzadeh , Hassanaghaei Tarlaan , Banestani Nazanin Sanjari , Salajegheh Faranak , Rukerd Mohammad Rezaei Zadeh , Ziaadini Bentolhoda
Published: February 2025

We present a case of a 23-year-old woman who developed afebrile left-sided sacroiliitis and tricuspid valve endocarditis caused by Staphylococcus aureus, one week after experiencing a bout of diarrhea. The patient presented with bilateral lower extremity weakness and left sacroiliac joint pain, without fever. Diagnostic workup, including laboratory tests, imaging studies, and synovial fluid analysis, confirmed the diagnosis of S. aureus septic arthritis. The patient subsequently developed tricuspid valve endocarditis, diagnosed by transthoracic echocardiography. Management involved a prolonged course of intravenous clindamycin, as the patient had an allergic reaction to vancomycin. This case highlights the importance of considering infectious etiologies in patients presenting with musculoskeletal complaints, even in the absence of fever, and underscores the potential for hematogenous spread of infection from one site to another. Further research is needed to elucidate the pathophysiological mechanisms underlying afebrile presentations of serious infections and to identify risk factors for atypical clinical manifestations.
Final overall survival and new ctDNA analysis in MET-driven advanced papillary renal cancer (CALYPSO).
Authors: Jackson-Spence Francesca , Larkin James , Patel Poulam , Valderrama Begoña P. , Rodriguez-Vida Alejo , Mendez-Vidal Maria Jose , Childress Merrida , Li Wenshu , Boyle Patrick , Gasco Amaya , Markovets Aleksandra , Hartmaier Ryan James , Ackerman Charlotte , Szabados Bernadett Emma , Priyadarshini Garima , Jamal Fahmida , Powles Thomas , Suárez Cristina
Published: February 2025

444

Background:
Phase II data from the CALYPSO study (NCT02819596) has shown activity for durvalumab (PD-L1 inhibitor) plus savolitinib (MET inhibitor) (D+S) in MET-driven advanced papillary renal cancer (aPRC), resulting in the ongoing randomised phase III study, SAMETA (NCT03091192). Here we present the final efficacy and new ctDNA analysis.
Methods:
The aPRC cohort was a single arm study of D+S in both untreated and previously treated disease. Efficacy endpoints include response rates (RR) as per RECIST 1.1, progression-free survival (PFS) and overall survival (OS). PD-L1, TMB and MET status were analysed. Safety was assessed via CTC criteria. FoundationOne CDx was used to profile tissue in 41 patients. Plasma was collected for ctDNA analysis (FoundationOne Tracker analysis; n=21) at baseline (pre-treatment) and sequential time points on treatment. MET mutations were also tracked using F1 Tracker following identification by the F1CDx assay.
Results:
At 41 months follow-up, the RR in the Intention to Treat (ITT) aPRC population (n=41) was 34% (95% CI, 20-51) and 59% (95% CI, 33-82) in MET-driven patients (n=17). The median PFS was 8.4 months (95% CI, 3.0-13.9) in the ITT population and 16.7 months (95% CI, 5.1-31.4) in MET-driven patients. The median OS was 18.3 months (95% CI, 7.3-30.6) in the ITT population and 27.4 months (95% CI, 9.3-51.6) in MET-driven patients. The hazard ratio (HR) for PFS and OS in MET-driven vs non-MET-driven in PRC cohort was 0.36 (p=0.02) and 0.76 (p=0.43), respectively. 66% of patients were PD-L1+, and 32% were both MET-driven/PD-L1+. The PD-L1 biomarker did not enrich for responders. 27% patients had tissue TMB >median (2.52mut/Mb). TMB was not associated with outcome. 10/16 (63%) were ctDNA positive at baseline, which was associated with a shorter median OS of 7.3 vs 36.4 months (HR 3.91, p=0.02). The mean reduction in Variant Allele Frequency (VAF) was 43% with therapy. For patients with pre- and on-treatment ctDNA, those with CR/PR had ctDNA VAF reduction while those with SD/PD had ctDNA VAF increase (p=0.05). ctDNA clearance was associated with improved PFS (p=0.04). Only 2 patients had MET mutations tracked. ctDNA positivity did not correlate with MET alterations, PD-L1 status or the presence of visceral metastases.
Conclusions:
D+S continue to show impressive efficacy in MET driven tumors, supporting the ongoing SAMETA trial. ctDNA monitoring on therapy holds promise as a prognostic and potentially predictive tool in this setting. Clinical trial information:
NCT02819596
.
Survival disparities by sex with contemporary advanced urothelial carcinoma (aUC) therapy: A real-world analysis.
Authors: Barsouk Adam , Elghawy Omar , Sussman Jonathan Henry , Xu Jessica , Mamtani Ronac , Mei Lin
Published: February 2025

670

Background:
Retrospective population data suggest poorer survival for female aUC patients. However, data on survival disparities in the era of immuno- and targeted therapies is limited.
Methods:
This cohort study used Flatiron Health’s nationwide de-identified electronic health record (EHR)-derived database. 7,244 patients (pts) were identified. Patients started on systemic therapy for aUC from 1/1/2017 to 5/1/2024, with reported sex, were included. Baseline demographics (including social determinants of health (SDOH) score), Eastern Cooperative Oncology Group performance status (ECOG PS), disease characteristics, treatment history, and clinical outcomes were abstracted. Progression free survival (PFS) and overall survival (OS) were compared between male and female patients, via Kaplan-Meier log-rank analysis and Cox proportional hazards models that included race, gender, and first-line therapy. Independent sample t-tests and chi-square analyses were used for univariate comparisons. P-values < 0.05 were considered statistically significant.
Results:
A total of 3,045 pts with aUC were identified. 762 were (25.0%) female. In 1L, 28% received immunotherapy (IO) monotherapy, 3.4% received enfortumab vedotin+pembrolizumab (EVP), 37% received carboplatin (carbo), 28% cisplatin (cis), and 6% other chemotherapy (p=0.814). Females were more like to have ECOG PS>1 at diagnosis (p=0.020). Greater SDOH score was not associated with sex (p>0.1). Female sex was associated with inferior 1L PFS (median 4.3 vs 4.6m; HR 1.14, p=0.04) but no difference in OS (6.4 vs 6.5m; HR 1.01, p=0.2). Females had inferior PFS to men on Cox multivariable analysis when adjusting for race and first line therapy (p=0.006). On Cox univariate analysis stratified by 1L treatment, PFS was comparable between sexes on carbo (n=1127; p=0.4), cis (n=856; p=0.2) and EVP (n=25, p= 0.7), but women had inferior PFS to men on IO (n=595, p= 0.01). Women had comparable OS to men among all 1L treatments.
Conclusions:
In a large real-world database, female aUC patients had inferior PFS but comparable OS to males. Among 1L treatments, only immunotherapy was associated with inferior PFS for females vs. males.

Baseline characteristics and survival in males vs. females.

Male (n=2283)
Female (n=762)
Sig (p)

Baseline Characteristics

ECOG PS

0-1 (%)
64.1
60.6

0.020

2-4 (%)
15.2
17.8

Treatment at Academic Center (%)
19.1
18.0
0.360

SDOH score
3.13
3.07
0.110

1L Treatment

IO (%)
27.7
28.1
0.814

EVP (%)
3.3
3.7

Carbo (%)
37.3
36.2

Cis (%)
27.5
28.9

Other (%)
6.6
6.1

Survival

mPFS (m)
4.6
4.3

0.040

mOS (m)
6.5
6.4
0.200

Sig. values in bold (p<0.05).
Missed opportunity: PROMs as primary endpoints in bladder cancer trials.
Authors: Harisingani Avi Ravi , Sukaina Mahnoor , Deshmukh Sameer S , Keen Mahnoor Asghar , Ahmad Zain , Zerin Annu , Kumar Madhan Srinivasan , Singh Gagandeep , Ansar Sadia , Madan Hritik , Naveed Maria , Jatwani Karan
Published: February 2025

682

Background:
Bladder cancer is the sixth most common malignancy in the United States. Recent advances in treatment paradigm have changed the landscape of bladder cancer. Patient-reported outcome measures (PROMs) are measures of symptom burden and health related quality of life (HRQoL) that come directly from the patient, without clinician interpretation. PROMs can be the intervention and/or the outcome in a trial. We aimed to evaluate the trends in the usage of PROs for patients with muscle invasive bladder cancer (MIBC) and locally advanced or metastatic bladder (mBC) cancer as a measure of endpoints across global clinical trial databases.
Methods:
We searched the clinicaltrials.gov database for phase III trials involving muscle invasive, locally advanced and metastatic bladder cancer patients from 1990 to 2024. The data extraction included primary and secondary endpoints, PROMs, PRO parameters, and clinical trial duration. Descriptive statistics derived were used to summarize the data.
Results:
Fifty-four trials were included in the analysis, out of which 64.8% (n=35) were for mBC and 35.1% (n=19) for MIBC. Twenty-nine trials (53.7%) included PROMs as endpoint measures, more than half in MIBC (n=16, 55%). Approximately one third (n=13/35) of mBC included PROMs in their trials (37.1%) whereas (84.2%) included PROMs in MIBC trials (n= 16/19). None of the studies reported PROs as a primary outcome measure, twenty-three studies (79%) reported PROs as a secondary outcome, and only one (3.4%) reporting it as both primary and secondary outcome measure. In mBC nine trials (56.25%) in the 1
st
line setting, six studies (37.5%) in the 2
nd
line setting and one trial (6.25%) labelled as adjuvant after radiation. In MIBC trials, three studies (23%) were in the adjuvant setting, five studies (38%) in the neoadjuvant setting and one trial (8%) involving both adjuvant & neoadjuvant, and four studies (31%) in the chemoradiotherapy setting. Eleven different symptom domains were utilized to measure PROs across both the groups. The European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ C30) and the EuroQOL 5-dimension 5-level Questionnaire (EQ-5D-5L) were the most frequently utilized PRO scales, being used in 62.5% and 37.5% of PRO reporting studies respectively.
Conclusions:
PROMs are increasingly used in bladder cancer trials, especially for MIBC. Approximately one-third of the trials included PROMs, yet none utilized them as primary endpoints, indicating a missed opportunity to truly understand treatment impact from the patient's perspective. Future research should prioritize PROMs as primary outcome measures to ensure patient-centered care and improve quality of life for bladder cancer patients. Further efforts are needed to standardize the current available scales to measure PROs.
Patient-reported outcome (PRO) assessment and reporting in first-line (1L) locally advanced or metastatic urothelial cancer (la/mUC) clinical trials: Results of a systematic literature review (SLR).
Authors: Kearney Mairead , Macmillan Tom , Poritz Julia , Schreiber-Gosche Sherrie , Musat Mihaela Georgiana
Published: February 2025

757

Background:
Although maintaining health-related quality of life (HRQOL) is a primary goal of advanced cancer care, HRQOL and PROs usually are not measured or reported as robustly as efficacy outcomes in clinical trials. One example is la/mUC, an aggressive and incurable disease with a profound effect on patient HRQOL and functioning. With its changing therapeutic landscape in which newer agents with various efficacy and toxicity profiles are incorporated into clinical care, more attention must be given to the optimal deployment of PRO measures (PROMs). Our aim was to conduct a critical evaluation of currently used PROMs in la/mUC 1L trials.
Methods:
A SLR was conducted using 5 online databases to identify publications up to May 29, 2024 and recent conference abstracts of phase 2 or 3 clinical trials and real-world evidence (RWE) studies reporting PROs in the treatment of la/mUC.
Results:
Forty-nine studies were identified in the SLR (37 clinical trials; 12 RWE studies). Of the 37 clinical trials, 18 were in the 1L population. The most common PROMs in 1L trials were the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 (n = 15) and the EuroQol-5D (n = 6). Other PROMs used were the Brief Pain Inventory–Short Form (n = 2), Functional Assessment of Cancer Therapy–Bladder (FACT-Bl; n = 1), National Comprehensive Cancer Network/FACT Bladder Symptom Index-18 (n = 1), and the Generic Quality of Life Inventory-74 (n = 1). PROMs were almost exclusively included as secondary endpoints (n = 16); only 2 trials included PROMs as exploratory endpoints. Prespecified analyses for HRQOL assessments were generally not stated in publications, and analytical methods and reporting varied. Of the 15 trials that used the EORTC QLQ-C30, 93% reported general health status/QOL, and 60% and 47% reported functional and symptom scales, respectively. Overall, HRQOL, functioning, and/or symptoms were maintained or improved, but meaningful changes in PRO scores reported were difficult to interpret due to the ways in which minimal clinically important difference thresholds were applied.
Conclusions:
Understanding the impact of various 1L treatment regimens on PROs relies on consistent assessment and transparent reporting. The findings of this SLR highlight the challenges in conducting cross-trial comparisons of PROs due to heterogeneity in study designs, patient characteristics, choice of PROMs, statistical analyses, and reporting of outcomes. To understand the symptom burden associated with novel therapeutics, it is recommended that the la/mUC research community develop a consensus regarding PRO development and implementation. This will facilitate interpretation of the patient experience, enhance clinical care, and guide informed treatment decision-making by clinicians and patients with la/mUC.
A multicenter, open-label phase 1/2 study of TYRA-300 in advanced urothelial carcinoma and other solid tumors with activating FGFR3 alterations (SURF301).
Authors: Hansen Aaron Richard , Zhang Alison Yan , Boni Valentina , Mantia Charlene , Yu Evan Y. , Weickhardt Andrew James , Robert Marie , Gupta Shilpa , Morales-Barrera Rafael , Hoimes Christopher J. , Berlin Jordan , Iyer Gopa , Millward Michael , Lihou Christine Francis , Loriot Yohan , Pouessel Damien , Mittal Kriti , Hill Andrew Graham , Racca Fabricio , Tran Ben
Published: February 2025

TPS904

Background:
Activating
FGFR3
gene alterations have been identified in up to 20% of advanced/metastatic urothelial cancers (mUC). The pan-FGFR inhibitor erdafitinib (erda) is approved for the treatment of mUC with susceptible
FGFR3
genetic alterations whose disease has progressed on or after at least one line of prior systemic therapy. Since pan-FGFR inhibitors target all four isoforms of FGFR (1-4), their lack of FGFR isoform specificity can lead to off-target toxicity (e.g., hyperphosphatemia, stomatitis, ocular toxicity, skin and nail toxicity) and loss of activity due to development of on-target resistance mutations (e.g., V555M/L gatekeeper). TYRA-300 has been designed to be more selective for FGFR3 over FGFR1/2/4 to minimize off-target toxicity and to avoid interactions with known
FGFR3
gatekeeper mutations. TYRA-300 is in development for the treatment of
FGFR3
+ mUC and other solid tumors (SURF301 - NCT05544552).
Methods:
SURF301 is a first-in-human, open-label, Phase 1/2 global study in several parts: dose escalation in participants with advanced malignancies, with/without
FGFR3
alterations (Phase 1, Part A); dose expansion in participants with
FGFR3
-activating mutations or fusions (Phase 1, Part B); and select tumor expansion cohorts with
FGFR3
activating mutations or fusions (Phase 2). The purpose of Phase 1 is to evaluate the safety, tolerability, pharmacokinetics (PK), preliminary antitumor activity of TYRA-300, and identify the recommended Phase 2 dose (RP2D). Phase 2 will enroll participants in
FGFR3
+ mUC and other tumor types to further explore the anti-tumor activity and safety of TYRA-300. SURF301 study began enrolling patients in November 2022 and is ongoing in Australia, the United States, France, and Spain. Clinical trial information:
NCT05544552
.
Phase 2 trial of immuno-ablation with intrabladder injection of N-803 or intravesical N-803 plus BCG for intermediate-risk non-muscle invasive papillary bladder cancer.
Authors: Reddy Sandeep Bobby , Kates Max , Huang Megan , Ravi Bhavya , Bhar Paul , Spilman Patricia R , Brown Bruce , Sender Leonard S. , Soon-Shiong Patrick
Published: February 2025

TPS905

Background:
Response rates (55-65%) with bacillus Calmette-Guerin (BCG) monotherapy in papillary non-muscle invasive bladder cancer (NMIBC) are lower than rates (70-75%) for carcinoma in situ (CIS) disease, pointing to an unmet need for efficacious treatment of papillary NMIBC. We previously reported a complete response (CR) rate of 71% with combined intravesical use of the interleukin-15 (IL-15) superagonist fusion molecule N-803 (nogapendekin alfa inbakicept, NAI; ANKTIVA) and BCG in QUILT 3.032 cohort A study participants with BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease and a disease-free survival (DFS) probability of 55.4% at 12 months for cohort B participants with BCG-unresponsive high-grade Ta/T1 papillary NMIBC. Based on these and other findings, the combination of N-803 plus BCG was recently approved by the FDA for BCG-unresponsive bladder CIS +/- Ta/T1 papillary disease. In a planned study, the efficacy of intrabladder N-803 immunoablative monotherapy by peritumoral injection of N-803 will be compared to intravesical N-803 plus BCG in patients with intermediate-risk BCG-naïve papillary NMIBC. The rationale for injection is based on findings from pre-clinical murine tumor models, the hypothesis that N-803 half-life will be extended by injection, and the suitability of injection for papillary disease.
Methods:
In the open-label phase 2 randomized study QUILT-215, adult participants with histologically-confirmed BCG-naïve intermediate-risk papillary Ta/T1 NMIBC will be enrolled into either Arm A or B. Up to 20 participants will be enrolled in each arm. In the first treatment period, Arm A participants will receive 400 µg N-803 monotherapy every 3 weeks by peritumoral intrabladder delivery and Arm B participants will receive 400 µg N-803 plus 50 mg BCG weekly for 6 weeks by intravesical delivery. The initial response assessment will be at 3 months. The second treatment period would commence at the end of month 3 and continue through month 15, with treatment depending upon the month 3 response. The primary endpoint is the CR (absence of any grade papillary NMIBC or CIS disease) rate at month 3 as determined by Investigator assessment of cystoscopy, cytology, and biopsy. The CR rate will be summarized by the number and percent and exact 95% CI using the Clopper-Pearson method. Secondary endpoints are progression-free survival (PFS), time to disease progression, overall survival (OS), disease-specific survival (DSS), duration of response (DOR) and cystectomy avoidance rate, to be analyzed using Kaplan-Meier methods. Safety will be assessed, including adverse events (AEs) and serious AEs (SAEs).
Embedding voices of under-served communities in Health Research Priority Setting in Thailand
Authors: Khirikoekkong Napat , Asarath Supa-at , Osterrieder Anne , Maung Lwin Khin , Cheah Phaik Yeong
Published: February 2025

Health research is needed to develop new treatments, diagnostic methods and prevention strategies for many diseases, but resources are limited particularly in low-and middle-income countries (LMICs). Our proposed project involves in-depth engagement with community advisory boards and existing community groups in healthcare research priority setting in Thailand. We will use Wellcome’s “Responsive Dialogues” engagement approach, focusing on “under-served” groups, as their voices are seldom heard in healthcare research priority setting. We estimate that we will engage with 6–8 community groups involving 48–80 participants. Our objectives are firstly, to contribute to the health research agenda setting in Thailand for government, non-governmental actors, academia, and others who conduct health research in the next 5 to 10 years. Secondly, we aim to identify ethical and practical issues related to healthcare research priority setting, specifically in relation to involving under-served communities.
Adverse effects of oral glucocorticoid therapy - a brief review of literature
Authors: Gruszka Marta , Polańska Paulina , Kubicka Maria , Zakrocka Martyna , Fick Jakub
Published: February 2025

Introduction and Objective: Glucocorticoids (GCs) are among the most commonly prescribed pharmaceuticals across various medical specialties. The purpose of this article is to provide an overview of the most common side effects of oral glucocorticoid therapy and to underline the importance of educating healthcare professionals and patients on this topic.
State of knowledge: Glucocorticoids are commonly used in a wide range of patients because of their anti-inflammatory and immunosuppressive properties. Oral glucocorticoids can lead to a greater number of side effects in comparison with other routes of administration due to their systemic action. Adverse effects of glucocorticoid therapy involve endocrine, cardiovascular, musculoskeletal and central nervous systems. Patients often present with elevated serum glucose levels caused by reduced insulin sensitivity and amplified hepatic glucose production. Moreover, hyperglycemia and hypertension increase the risk of ischemic heart disease and heart failure. GCs impede bone formation and escalate bone resorption, resulting in bone mass reduction and osteoporosis. Myopathy may occur as a result of intensified catabolic processes. Glucocorticoid therapy impacts the production of cortisol by the adrenal glands and can lead to adrenal insufficiency and even adrenal crisis. Characteristic changes in external appearance aggravate self-esteem and mental health of patients resulting in decreased quality of life. Another adverse effect described in literature is substantial cognitive decline.
Summary: Despite their multiple positive applications, glucocorticoids are associated with numerous side effects. It is imperative for medical professionals to ascertain that the disadvantages do not outweigh the advantages of glucocorticoid therapy. Further research is needed to ensure that patients are provided with the best possible care.
Rheumatologic Disorders and Their Ocular Manifestations – Clinical Insights and Therapeutic Approaches
Authors: Borowiec Agnieszka , Borowiec Kinga
Published: February 2025

Introduction and purpose: Rheumatic disorders, a broad group of conditions primarily affecting the joints, can have significant systemic manifestations that extend beyond musculoskeletal involvement. One such often-overlooked aspect of these diseases is the impact they can have on the eyes. Ocular symptoms are common in many rheumatic diseases and can range from mild irritation to severe sight-threatening complications. This article explores the range of ocular symptoms associated with rheumatic diseases, emphasizing their clinical presentations and the importance of early recognition and treatment. Materials and methods: A review was conducted in PubMed including publications regarding ocular manifestations of rheumatic diseases. Literature was searched using the following terms: “uveitis in rheumatic disorders”, “spondyloarthropathies”, “systemic lupus erythematosus”, “HLA B27 uveitis” and “treatment of rheumatic diseases”.Brief description of the state of knowledge: The eyes may be affected either directly through inflammation of various ocular structures or indirectly as part of the systemic manifestations of autoimmune processes. Conditions such as rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome and ankylosing spondylitis often present with ocular involvement including dry eye syndrome, uveitis, scleritis, episcleritis and retinal vasculitis. While some ocular findings may be asymptomatic others can lead to significant visual impairment if not properly managed.Conclusions: Rheumatic diseases are often associated with a range of ophthalmic complications which can sometimes develop before any other systemic signs of the rheumatic condition appear, making them crucial indicators of potential underlying disease. In many cases, the visual system may be the first to show signs of involvement and recognizing these symptoms early is essential for timely diagnosis and management.
Determinants of Original Local Government Revenue (PAD): Case Studies of 34 Provinces in Indonesia
Authors: A'yun Indanazulfa Qurrota , Vianti Wulan Okta , Zalina Zalina
Published: February 2025

Regional Original Revenue (PAD) is a fund received by the region from the existing resources in the area. PAD is regulated based on regional regulations in accordance with applicable laws. The higher the skill of the region in increasing regional original income, the greater the flexibility of the region to use PAD in accordance with the wishes, needs and priorities of regional development. This study aims to analyze the effect of independent variables, local taxes, regional levies, Gross Domestic Product (GRDP) and investment on PAD in 34 provinces in Indonesia from 2015 to 2018. This study uses a random effect regression analysis method and is analyzed using statistics. The results show that the variables of local taxes, regional levies and investment have a positive and significant impact on PAD in 34 provinces in Indonesia, while the variable Gross Domestic Product (GRDP) has a positive but not significant effect on PAD in 34 provinces in Indonesia.
How to be a Better Doctor: Recognizing How Cognitive Biases Shape—and Distort—Clinical Evidence
Authors: Baxendale Sallie
Published: February 2025

Rather than the absence of any harm, it is the expectation of an overall benefit of a medical treatment that is the foundation of the implicit doctor-patient contract. In the context of an expectation of efficacy, powerful cognitive biases can blind clinicians to obvious signs that a treatment is not helping, or may even be harming their patients. With examples from medical history and current clinical controversies, this paper examines how systematic psychological biases can distort not just individual decision making, but perceptions of the evidence base upon which clinical decisions are built. These distortions can perpetuate harmful practices in medicine long after the objective evidence points in a different direction. By becoming aware of these biases and the way they shape perceptions of the evidence base, doctors can reduce the negative impact they may have on the patients in their care.
Fassbinder's Simulations: Fascist Futures, Retro Entertainment, and Remediation in Welt am Draht (1973)
Authors: Henkel Brook
Published: February 2025

abstract: This article presents an historicized close reading of Rainer Werner Fassbinder's 1973 science fiction film Welt am Draht as an incisive critique of simulation, retro culture, and fascist futures. Overlooked in the film are numerous markers of German history on different levels of simulated reality which address the voiding of history by retro entertainment and construct provocative parallels between the late Weimar era and authoritarian tendencies in post-1968 West Germany. Reread alongside Jean Baudrillard's contemporaneous writings, Welt am Draht distinguishes itself for its attention to media difference and the politics of remediation as central to the film's critique of simulation.
Isotropic PSF modification for optimized optical lens design in image-matching tasks
Authors: Chen Bingkun , Ren Zheng , Zhou Jingwen , Li Haoying , Xu Hao , Xu Nan , Feng Huajun , Chen Shiqi
Published: February 2025

Image matching is widely used in many practical applications, such as high-precision map reconstruction, UAV localization, and autonomous driving. Since the optical lens directly influences the captured image, which in turn affects image-matching performance, designing optical lenses that are better suited for image-matching tasks under similar budget or size constraints is a highly valuable and practical problem. In this paper, based on the differentiable optics framework, we propose modifying the point spread function (PSF) of the optical lens to be isotropic across different fields of view (FoV) by introducing intuitive PSF-based loss functions. This modification benefits feature detection and description performance. Experimental results show that our method significantly improves the feature-matching performance of the given optical design, even though it does not achieve the highest image quality.