bluuebunny/crossref_metadata_2025 huggingface dataset:
Klebsiella pneumoniae Lung Abscess Due to Aspiration of Seawater During Recreational Free Diving
Authors: Paraz Carisa Mariella , Sandoval Mark Anthony , Cruz Enrick Joshua
Published: February 2025

Cough persisting for 5 wk, low-grade fever, and thick, pinkish to reddish, foul-tasting sputum made the doctors seeing this patient think of tuberculosis at first. However, a history of aspirating seawater during recreational free diving gave a clearer picture of how this patient got sick. Investigations later revealed a cavitary lesion in the right lung, and sputum culture grew Klebsiella pneumoniae, resulting in a diagnosis of lung abscess. This case is being reported to show this peculiar way that a bacterial pathogen entered the respiratory tree and that recreational free diving poses a health risk if done in a marine environment where this “survivor bacteria” thrives.
Physiological and fermentative performance of non-Saccharomyces yeasts isolated from kombucha for beer production
Authors: Silva de Souza Hygor Lendell , de Almeida Diego Pádua , dos Santos Alexandre Soares , Ramos Cíntia Lacerda
Published: February 2025

This study aimed to isolate, identify, and characterize kombucha yeasts for beer production. Nineteen yeasts were isolated, and the species Brettanomyces bruxellensis, Galactomyces candidum, Galactomyces sp., Pichia kluyveri, and Saccharomycodes ludwigii were identified. The strains B. bruxellensis L652, P. kluyveri L472, L231, L431, and L131, and S. ludwigii L331 present desired physiological properties for beer production, including tolerance to 6% ethanol, 100 mg/L of iso-α-acid and flocculation capacity. It was selected for wort fermentation at 10 °C and 20 °C. Beers with different chemical characteristics were produced when evaluated at 10 °C and 20 °C for all strains. Minor carbohydrate residuals and higher ethanol concentrations were observed in the beers fermented at 20 °C. All non- Saccharomyces yeasts evaluated produced alcohol-free beers (<0.5%) at 10 °C. At 20 °C, only the yeast P. kluyveri L431 produced non-alcoholic beer (0.24%). The yeasts P. kluyveri L131, L231, and L472 and B. bruxellensis L652 produced beers with reduced alcoholic content (0.6–1.4%), and the strains S. ludwigii L331 produced alcoholic beer (2.45%). Relating acetic acid, the strains P. kluyveri L431 and L472 presented higher concentrations (0.226 g/L and 0.264 g/L, respectively) at 10 °C, while S. ludwigii L331 showed the highest concentration (0.936 g/L) at 20 °C, demonstrating the potential to produce sour beers. These results indicate that evaluating the yeast strain according to the beer style is crucial.
Vital materiality and its constitution of knowing in craft practice
Authors: Li Mixue , Holstein Jeannie , Wedekind Volker
Published: February 2025

Recent scholarship has acknowledged the importance of materiality, body senses and sensible knowledge in understanding knowing in practice, although humans and their practices are still privileged. In response, we examine how vital materiality, or the capacity of things, constitutes the practice of knowing, including in relation to and with the body and bodily senses. This focus is relevant for management education and learning, sharpening our view of what practices and knowing matter most. Drawing on a study of 20 studio potters, involving observation, interviews, and participation in a pottery course, we reveal the agentic power of the material in constituting the practice of knowing, in the resistance of the material, the accidental and unpredictable encounters between material, and the loss of self in, and a subversion from, the material. We show what constitutes “embodied learning” for knowing in practice is the generation of a specific materialized sensitivity of—attunement, sensitivity to risk, and subversion—through the vitality of matter. Offering a stimulus to rethinking subjectivity and positionality in our pedagogy, we propose that to truly unsettle the human-centric practices of teaching and learning, we need to develop a specific “materialized sensitivity” in our pedagogic activities and entanglements.
Professional credibility cycles in education: Constructing trust and expertise in a regulated state school system
Authors: Americo Bruno Luiz , Clegg Stewart
Published: February 2025

Experts must adapt to immediate circumstances when managing impressions and be able to reassert credibility and exercise authority when performing professionalism. A credible professional is constructed, applied, and recognized locally as well as relationally, particularly within the context of careers in bureaucratic structures. Few studies investigate professional credibility through processual approaches assessing experts’ testimony and practice in situ as they manage their careers over a period of time. We examine the cycles of professional credibility in a rural elementary state school in Brazil, focusing on how credibility is constructed, applied, and recognized in highly regulated bureaucratic systems. We use the “credit cycle” framework from science and technology studies to analyze education professionals’ positions, career paths, and group dynamics. Our ethnographic approach included participant observation, document analysis, audio-visual data collection, and interviews with education workers. We used event-related phases and narrative analysis to analyze data and uncover insights into professional credibility, expanding the concept of the credit cycle beyond laboratories to include primary education professionals and managers. We consider how individual professional credibility is enacted by producing report cards and educational projects within what is a highly regulated educational system. What is “critical” in our research is a critique of the approach to the bureaucratization of professions that suggests that the outcome is “de-professionalization” or “proletarianization.” Our research findings highlight professional credibility’s relational, transactional, dynamic, and cyclical nature and offer practical insights for understanding and enhancing expertise in bureaucratic settings. Future studies should apply the credit cycle to other professional contexts.
Assessing FDM-printed thermoplastics for outdoor tactile graphics: Durability and performance analysis
Authors: Abellán-Nebot José V , Gual-Ortí Jaume , Serrano-Mira Julio , Tovar-Batista Berenice M , Leal-Cano David
Published: February 2025

This study investigates the feasibility of utilizing low-cost Fused Deposition Modeling (FDM) technology to produce durable Tactile Graphics (TG) for outdoor environments. Five common FDM thermoplastics—PLA, ABS, ASA, PET-G, and PP—were evaluated for printability, geometric quality, wear resistance, UV resistance, and chemical resistance. Results indicate that PLA offers high geometric precision and ease of printing, rendering it suitable for low-cost indoor applications. For outdoor environments, PET-G exhibited the best overall performance in wear and chemical resistance, while ASA demonstrated significant UV degradation. PP, although durable, presented challenges in printability. ABS and ASA exhibited a favorable trade-off between printing quality and environmental resistance. A multi-objective selection function was developed to guide material selection based on specific TG requirements. For indoor applications prioritizing quality and cost-effectiveness, PLA is recommended. For outdoor TGs requiring durability and chemical resistance, PET-G is preferred. ABS offers a balanced option with moderate durability and good geometric quality. This study provides a comprehensive framework for expanding FDM applications in accessible TG manufacturing for various environments and use cases.
Creep characteristics and cavitation mechanisms of AA2017
Authors: Alizadeh Mahdiye , Serajzadeh Siamak
Published: February 2025

In this work, the creep behavior of AA2017 and the governing cavitation processes were investigated at intermediate temperatures. Initially, the examined alloy was subjected to solution treatment at 495 °C and then over-aged at 210 °C. Afterward, the creep tests were performed over a temperature range of 120 °C to 210 °C and applied stress in the 120 MPa to 310 MPa range. The obtained results facilitated the analysis of the predominant creep mechanism and the impact of second-phase precipitations on cavitation nucleation and growth kinetics. Moreover, the morphology and the distribution of cavities were studied and the volume fraction of cavities was defined using optical metallography and scanning electron microscopy. The physical models of cavity growth were also utilized to justify the observed phenomena. It was found that the stress exponent varied between 3.4 and 9.8 at temperatures between 120 and 210 °C while the activation energy for creep was computed as 151.3 kJ/mol at the stress of 230 MPa. However, as the stress decreased to 180 MPa, the activation energy increased to about 194 kJ/mol. This suggests that dislocation climb is the dominant creep mechanism at lower temperatures while solute drag dominates the creep process at 210 °C. The examined alloy is susceptible to cavitation during creep testing. At the same time, the coalescence was observed at the high applied stress, particularly at the stress of 290 MPa at creep strains higher than 0.015.
What happens when you give an entrepreneur a camera? Illuminating spatial, embodied and affective aspects of entrepreneurship
Authors: Kars-Unluoglu Selen , Kevill Alex , Shortt Harriet
Published: February 2025

The use of video to unlock the minutiae of everyday entrepreneurship is growing in response to calls for more creative research methods in studying entrepreneurship. In this paper, we explore the value and relevance of participant-generated video diaries to the field. Drawing on data from a year-long empirical research project that used participant-generated video diaries, we evaluate the contribution of this method by contrasting it with adjacent and related video methods used by entrepreneurship scholars to-date. We find that it is the seemingly mundane and ordinary, the unromantic and commonplace, but powerfully intimate and otherwise invisible aspects of everyday entrepreneurial life that we get to see, efficiently and effectively, when we give an entrepreneur a camera. This, in turn, significantly enhances our understanding of the spatial, embodied and feeling-based experiences of entrepreneurs. Building on our experience, we provide suggestions for the design and execution of participant-generated video diaries in entrepreneurship research. We contribute to the field by guiding scholars to capitalize on the unique affordances of this method to broaden the methodological base of entrepreneurship research and to elicit new data about the minutiae of complex entrepreneurial experiences and practices.
Hamilton's fear: Republican judicial review and the separation of complicit powers
Authors: Sigalet Geoffrey
Published: February 2025

Recent republican debates about judicial review have focused on whether courts deliver legitimate forms of political contestation about rights. These ‘political constitutionalists’ frame the separation of powers as a matter of ‘friction’. The rival approach emphasizes whether the expertise and capacity of courts can ‘efficiently’ get certain jobs done to secure different ends. These rival approaches inform debates about judicial review and bills of rights. This article argues that emphasizing political contestation fails to address the problem of complicity between the branches. Judicial politics in the USA, Canada, the UK and New Zealand suggests that judicial complicity with the political branches lets political actors escape democratic accountability for policy choices related to rights. Courts enable this by abusing the power to interpret law to help political factions protect or reform the status quo. As such, liberty can have something to fear from the judiciary when it does not act alone.
Towards a wider adoption of EN 17037: A Scandinavian perspective
Authors: Rogers P , Rasmussen HF , Logadóttir Á , Hansen Hamre E , Vikberg H
Published: February 2025

The aim of the EN 17037:2018 Daylight standard is to ensure consistency of assessment method across Europe. It also provides recommendations as to levels of daylight which are considered to be acceptable. The lack of natural light common to Scandinavian winters provides a unique opportunity for application of the standard’s guidelines for daylight provision, yet across the region practical application has been limited. This paper examines the effect of the EN 17037 guidelines for daylight provision on the markets of Denmark, Sweden, Norway, Finland and Iceland, with particular focus on how these guidelines relate to national regulations. The challenges to adoption are unique to each country, but a recurring theme is that the minimum recommendations for daylight provision are widely considered to be too stringent. This holds particularly true for application to multifamily residential buildings in urban settings. In a number of the countries, the standard’s acceptance has been further hindered by the persistence of simplified compliance methods. This paper advocates for the standard’s minimum thresholds for daylight provision to be adjusted to better align with market conditions. If the EN 17037 is to fulfil its potential, we regard this to be a necessary step.
CACNA1S-associated triadopathy presenting with myalgia, muscle weakness, and asymptomatic hyperCKemia
Authors: Luo Si , Zhu Min , Tan Dandan , Qiu Yusen , Zhou Meihong , Hong Daojun
Published: February 2025

CACNA1S variants can alter the structure and function of the calcium channel, resulting in abnormal calcium influx and homeostasis. It is well established that pathogenic variants in CACNA1S can lead to hypokalemic periodic paralysis, malignant hyperthermia, and congenital myopathy. Nevertheless, the clinical presentations and disease progression of exertional myalgia and weakness associated with CACNA1S variants remain elusive. In this study, four affected individuals from an autosomal-dominant family were described, exhibiting symptoms of severe exertional myalgia, followed by flaccid weakness or rhabdomyolysis, along with asymptomatic hyperCKemia during the interictal period. Long exercise test showed a late decrease in compound muscle action potential amplitude. Muscle MRI revealed edema-like changes in the early stage, and fatty degeneration and substitution in prolonged disease courses, while closely aligned with the features of chronic myopathy. Ultrastructural examination revealed dilation of the sarcoplasmic reticulum and myofibrillar structural disarrangement. Genetic screening identified a c.3724A>G (p.Arg1242Gly) mutation in the CACNA1S gene. A literature review revealed that 15 patients exhibited the exertional myalgia and weakness phenotype associated with CACNA1S mutations, presenting similar clinical, electrophysiological, radiological, and pathological features. As the disease progressed, these patients developed severe muscle weakness, ultimately leading to wheelchair dependency. This exertional myalgia-weakness phenotype represented a unique CACNA1S-related phenotype that broadened the spectrum of CACNA1S-associated myopathy, bridging between periodic paralysis and congenital myopathies. The similarities between CACNA1S-associated myalgia-weakness and RyR1-associated myalgia-weakness underscored a shared pathogenesis of excitatory-contractile coupling at the triad of skeletal muscle.
A framework to standardize gait study protocols in Parkinson's disease
Authors: Mancini Martina , Hausdorff Jeffrey M , Pelosin Elisa , Bonato Paolo , Camicioli Richard , Ellis Terry D , Klucken Jochen , Gifford Larry , Fasano Alfonso , Nieuwboer Alice , Kopil Catherine , Klapper Katharina , Kirsch Leslie , Dexter David T , Fuest Rosie , Miller Vicki , Asis Angelica , Müller Martijn LTM , Stephenson Diane , Mirelman Anat
Published: February 2025

Background

Research over the past twenty years has shown that gait outcomes have a high sensitivity for diagnosing Parkinson's disease (PD), for detecting the effects of interventions, and for monitoring disease progression, even in early disease. However, the lack of standardization in protocols and reported gait measures is impeding data aggregation across study sites and contributes to heterogeneity in the results, thus limiting the adoption of gait outcomes in clinical trials.

Objective

To provide recommendations for a minimum set of gait measures to be adopted in projects evaluating people with PD to enhance standardization across the field.

Methods

The Gait Advisors Leading Outcomes for Parkinson's (GALOP) committee is an advisory committee for the MJFF. Based on a five-step approach, GALOP generated recommendations for standardizing protocols that assess quantitative gait measures, following expert consensus on best practices.

Results

Built on the literature and consensus amongst experts, we recommend a minimum set of meta-data to accompany gait protocols and a minimum gait assessment protocol to be performed at a comfortable speed. Suggestions on challenging testing are provided.

Conclusions

To support and empower the scientific community, we have generated recommendations to collect and share gait data gathered from people with PD using an open data repository. Standardizing gait protocols and outcomes in PD has the potential of accelerating research and clinical trials, harmonizing protocols across study sites, fostering collaborations, and in the long run, improving patient care and quality of life.
The Effects of Age on the Performance of Hotels: Does an Historical Effect Exist?
Authors: Tang Khoa D. B. , O’Neill John W.
Published: February 2025

This paper focuses on the relationship between hotel age and performance, challenging the prevailing theory that hotel performance uniformly declines with age. Using the most extensive dataset available, encompassing over 3,000 U.S. hotels over six recent years, we employ a mixed-methods approach to assess whether a U-shaped performance trend exists. Our analysis reveals a nuanced pattern wherein hotel performance declines during the initial years of operation but improves beyond a critical turning point at approximately 40 years old, particularly for hotels located in large metropolitan areas, and also based on hotel brand-affiliation status and class. The findings suggest that certain older hotels defy conventional depreciation models, experiencing a resurgence in performance. These insights have implications for hospitality researchers, as well as for practitioners, suggesting re-evaluating older hotels’ strategies and informing investment and taxation decisions.
Structuring and centralizing breast cancer real-world biomarker data from pathology reports through C-LAB® artificial intelligence platform
Authors: Le Borgne Florent , Garnier Camille , Morisseau Camille , Navarrete Yanis , Echeverria Yanina , Mir Juan , Calafell Jaume , Perennec Tanguy , Kerdraon Olivier , Frenel Jean-Sébastien , Raimbourg Judith , Campone Mario , Paz Maria Fe , Bocquet François
Published: February 2025

Purpose

To evaluate the effectiveness of C-LAB®, an artificial intelligence (AI) platform, in extracting, structuring, and centralizing biomarker data from breast cancer pathology reports within the challenging, heterogeneous dataset of the Institut de Cancérologie de l’Ouest (ICO).

Methods

C-LAB® was deployed at the ICO to analyze HER2 and hormonal receptor data from breast cancer pathology reports. During the development phase, 292 anatomic pathology reports were used to design and refine the rule-based extraction algorithm through an iterative process of monitoring and adjustments. After finalizing the algorithm, it was applied to a total of 2323 anatomic pathology reports. To evaluate the platform's accuracy, performance metrics could only be calculated for a subset of these reports that were also available in the structured National Epidemiological Strategy and Medical Economics (ESME) database. Out of the 2323 pathology reports belonging to 487 patients analyzed by C-LAB®, 666 corresponded to 97 patients present in the ESME database. These reports were used as the gold standard for performance assessment, as ESME provides structured data against which the outputs of the C-LAB® algorithm could be compared.

Results

C-LAB® achieved over 80% agreement with human extractions (precision, recall, and F1-score) in structuring biomarker data from complex, unstructured pathology reports, despite dataset variability and optical character recognition errors. While the ESME database served as a benchmark, its reliance on single manual data entry without secondary review introduces potential inaccuracies, suggesting the observed performance reflects close alignment between human and algorithmic extractions rather than absolute accuracy. C-LAB® demonstrates significant potential to reduce manual workload, centralize data, and enable scalable, real-time reporting.

Conclusion

AI technologies like C-LAB® show significant potential in creating accessible and actionable digital factories from complex pathology data, aiding in the precision management of diseases such as breast cancer diagnostics and treatment.
Radiomics analysis based on plain X-rays to detect spinal fractures with posterior wall injury
Authors: Liu Wangmi , Zhang Xiaxuan , Tang Ruofu , Yu Chengcheng , Sun Guofang
Published: February 2025

Purpose

Spinal fractures, particularly those involving posterior wall injury, pose a heightened risk of instability and significantly influence treatment strategies. This study aimed to improve early diagnosis and treatment planning for spinal fractures through radiomics analysis based on plain X-ray imaging.

Methods

This retrospective study analyzed plain X-rays of patients with spinal fractures at the thoracolumbar junction. Radiomic features were extracted from both anteroposterior and lateral plain spine radiographs to evaluate the utility of radiomics in detecting posterior wall injury. Diagnostic accuracy, sensitivity, and specificity of the radiomics models were assessed and compared with the performance of a spine surgeon.

Results

A total of 100 patients were included in the study, and four radiomic features were identified to construct radiomic signatures. In the training set, the RandomForest, ExtraTrees, and eXtreme Gradient Boosting (XGBoost) models achieved an area under the curve (AUC) of 1. In the validation set, the highest AUC value was 0.889, achieved by the RandomForest and XGBoost models. The diagnostic accuracy, sensitivity, and specificity of the radiomics models outperformed those of the spine surgeon.

Conclusions

Radiomics analysis based on plain X-ray imaging demonstrates significant potential for detecting posterior wall injury following spinal fractures. This approach offers a promising tool for early diagnosis and informed clinical decision-making in the management of spinal fractures.
“I Became Self-Motivated”: Investigating Chinese Students’ Motivation in Assessed Collaborative Writing Tasks
Authors: Chen Wenting , Chen Mingyue
Published: February 2025

While the existing literature on collaborative writing has implied the benefits of its implementation in second language (L2) classrooms for students’ language learning, the assessment of collaborative writing has received scant attention in both language assessment literature and L2 writing literature. This study proposes an assessment scheme considering both products and processes when assessing online writing undertaken collaboratively. It employs a case study approach to explore two pairs of Chinese students’ motivation toward assessed collaborative writing tasks. Drawing on data from participants’ reflections, pair interviews, stimulated recall interviews, online pair-talks, and revision histories, this study reveals that students with similar L2 proficiency may hold different motivations during product-graded, web-based collaborative writing assignments compared to product & process-graded assignments of the same nature. Additionally, this study finds that assessment can lead to changes in students’ motivations, which in turn affect learner participation in collaborative writing. The results can enhance our comprehension of the impact of assessment on learners’ motivation in computer-mediated collaborative writing tasks, offering fresh insights into strategies for strengthening learner motivation during the implementation of such tasks. The study suggests teachers should prioritize assessment as a pivotal element when incorporating computer-assisted collaborative writing, conscientiously consider students’ motivations in activity design, and recognize the growing significance of computer technologies in L2 learning.
Self-medication with NSAIDs and purchase of branded and over-the-counter medicines: Analysis of a national survey in Peru
Authors: Benites-Meza Jerry K , Pinedo-Castillo Liseth , Cabanillas-Lazo Miguel , Boyd-Gamarra María A , Herrera-Añazco Percy , Mougenot Benoit , Benites-Zapata Vicente A
Published: February 2025

Background:

This study aimed to determine the association between self-medications with nonsteroidal anti-inflammatory drugs (NSAIDs) and the purchase of branded and over-the-counter medications in Peru.

Design and methods:

This secondary analysis used a representative survey of Peru from 2014 to 2016. The exposure variable was self-medication with NSAIDs, defined as “the purchase of NSAIDs for oneself without a prescription.” The outcome was the purchase of branded and over-the-counter medications. Crude prevalence ratios (cPR) and adjusted prevalence ratios (aPR) with their respective 95% confidence intervals (95% CI) were calculated.

Results:

Of the total of 2158 participants, 52.80% were women with an average age of 40.24 years. The prevalence of self-medication with NSAIDs was 68.21%, whereas the rates of purchasing branded and over-the-counter medications were 63.78% and 13.16%, respectively. The adjusted Poisson regression analysis showed an association between self-medication with NSAIDs and the purchase of branded (aPR = 1.18; 95% CI: 1.12–1.25; p < 0.001) and over-the-counter (aPR = 2.38; 95% CI: 1.95−2.90; p < 0.001) medications.

Conclusions:

Approximately 7/10 users who self-medicate with NSAIDs chose branded medications, whereas nearly 1/5 opt for over-the-counter medications. Self-medication with NSAIDs was associated with a higher likelihood of purchasing branded and over-the-counter medications.
Implementation of the virtual transitional care stroke intervention for older adults with stroke and multimorbidity: A qualitative descriptive study
Authors: Markle-Reid Maureen , Fisher Kathryn , Walker Kimberly M. , Cameron Jill I. , Dayler David , Fleck Rebecca , Gafni Amiram , Ganann Rebecca , Hajas Ken , Koetsier Barbara , Mahony Robert , Pollard Chris , Prescott Jim , Rooke Tammy , Whitmore Carly
Published: February 2025

Background

Older adults with stroke and multimorbidity experience frequent care transitions, which are often poorly coordinated and fragmented. We conducted a pragmatic randomized controlled trial (RCT) to test the implementation and effectiveness of the Transitional Care Stroke Intervention (TCSI), a 6-month, multi-component, evidence-informed intervention to support older adults with stroke and multimorbidity using outpatient stroke rehabilitation services. The TCSI was designed to support self-management, improve health outcomes, and enhance the quality and experience of care transitions.

Objective

To explore the facilitators and challenges to implementing the TCSI, from the perspective of healthcare providers (HCPs) (n = 12) and Managers (n = 3).

Methods

Data collection and analysis were guided by the Consolidated Framework for Implementation Research (CFIR). Data were collected from study documents, individual and group interviews conducted with HCPs and a Care Coordinator, and surveys from managers. Data were analyzed using thematic analysis.

Results

Intervention implementation was facilitated by: a) strong collaborative and interdependent HCP team relationships, b) dedicated resources (funding, staffing) to support intervention delivery, c) training and ongoing support, customized to individual HCP needs, d) organizational readiness, strong leadership, and effective champions, e) structures to facilitate virtual information-sharing, and f) regular monitoring of intervention implementation. Implementation challenges included: a) COVID-19 related challenges (staff turnover, community service disruptions), b) poor communication with community service providers, c) documentation burden (intervention-related), and d) virtual care delivery.

Conclusions

This research enhances understanding of the diversity of factors influencing implementation of the TCSI, and the conditions under which implementation is more likely to succeed.
The MURANO study: final analysis and retreatment/crossover substudy results of VenR for patients with relapsed/refractory CLL
Authors: Kater Arnon P. , Harrup Rosemary Anne , Kipps Thomas J , Eichhorst Barbara , Owen Carolyn , Assouline Sarit E. , Lamanna Nicole , Robak Tadeusz , de la Serna Javier , Jaeger Ulrich , Cartron Guillaume , Montillo Marco , Mellink Clemens , Langerak Anton W. , Chyla Brenda , Popovic Relja , Jiang Yanwen , Millen Rosemary , Lefebure Marcus , Thadani-Mulero Maria , Boyer Michelle , Seymour John F
Published: February 2025

Fixed-duration venetoclax-rituximab (VenR) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) in the phase 3 MURANO trial (NCT02005471) resulted in superior progression-free survival (PFS) and overall survival (OS) vs bendamustine-rituximab (BR). We report the final analyses of MURANO (median 7 years follow-up). Patients were randomized to VenR (venetoclax 400 mg daily for 2 years plus monthly rituximab for 6 months; n = 194) or BR (6 months; n = 195). In a substudy, patients with progressive disease (PD) received VenR as retreatment or crossover from BR. At the final data cut (3 August 2022), median PFS with VenR was 54.7 vs 17.0 months with BR. Seven-year PFS with VenR was 23.0%. Seven-year OS was 69.6% and 51.0%, respectively. Among VenR-treated patients with undetectable (u) minimal residual disease (MRD) and no PD at end of treatment (EOT) (n = 83), median PFS from EOT was 52.5 vs 18.0 months in patients with MRD at EOT (n = 35; P < 0.0001). Fourteen patients had enduring uMRD. Three distinct mutations in BCL2 in four patients were identified. In the substudy, 25 patients were retreated with VenR and nine patients crossed over to VenR; median PFS was 23 and 27 months, and best overall response rate was 72% and 89%, respectively. At the end of combination treatment, following retreatment or crossover, eight and six patients achieved uMRD, respectively. No new safety findings were observed. Overall, these final MURANO analyses support consideration of fixed-duration VenR therapy for patients with relapsed/refractory CLL.
A First-in-Class JAK/ROCK Inhibitor, Rovadicitinib, for Glucocorticoid-Refractory or -Dependent Chronic GVHD
Authors: Zhao Yanmin , Luo Yi , Shi Jimin , Wang Shunqing , Wang Caixia xia , Jiang Erlie , Liang Chen , Zhu Xiaoyu , Zhang Xuejun , Meng Fankai , Jin Hua , Zhao Yeqian , Yu Jian , Lai Xiaoyu , Liu Lizhen , Fu Huarui , Ye Yishan , Zhang Congxiao , Wang Tao , Tu Lifan , Wang Xunqiang , Huang He
Published: February 2025

Rovadicitinib (TQ05105) is a novel, oral dual JAK1/2 and ROCK1/2 inhibitor targeting inflammatory and fibrotic components of chronic graft-versus-host disease (cGVHD). We aimed to evaluate the safety and efficacy of rovadicitinib for glucocorticoid-refractory or -dependent cGVHD. This phase 1b/2a, multicenter, open-label study (NCT04944043) enrolled patients with moderate or severe glucocorticoid-refractory or -dependent cGVHD. The study followed a 3+3 design with two escalating doses (rovadicitinib 10 and 15 mg twice daily) and a dose expansion cohort. Primary endpoints included safety and recommended phase 2 dose (RP2D); the best overall response (BOR) was the key secondary endpoint. Forty-four patients were enrolled, with 29 in the 10 mg twice-daily cohort and 15 in the 15 mg twice-daily cohort. Rovadicitinib was well tolerated without dose-limiting toxicity at both dosages, and no rovadicitinib-related AEs led to discontinuation. The most prevalent hematological AE was anemia (38.6%), with grade ≥ 3 of 4.6%. The RP2D was 10 mg twice daily. The BOR was 86.4% (95% confidence interval [CI], 72.6-94.8), with no difference between the two dosage cohorts. Besides, BOR achieved 72.7% (8/11) in the steroid-refractory cohort and 90.9% (30/33) in the steroid-dependent cohort. All affected organs exhibited responses regardless of prior therapy. The failure-free survival rate was 85.2% (95% CI, 64.5-94.3) at 12 months. Rovadicitinib treatment reduced the corticosteroid dose in 88.6% of patients. cGVHD-related symptoms were improved in 59.1% of patients. Rovadicitinib has favorable tolerability and notable clinical response rates, ameliorating the quality of life and reducing corticosteroid dose requirements in patients with glucocorticoid-refractory or -dependent cGVHD.
Integrated cross-linking by TG2 and FXIII generates hepatoprotective fibrin(ogen) deposits in injured liver
Authors: Wei Zimu , Boateng Nana Kwame Kwabi , Schmitt Lauren , Cline Holly , Fernandes Fonseca Maria Theodora , Newberry Ariana , Taylor Alicia , Adelmeijer Jelle , Poole Lauren , Stravitz R. Todd , Lee William M. , Lisman Ton , Hansen Kirk C , Luyendyk James P
Published: February 2025

The transglutaminase coagulation factor XIII (FXIII) is critical for the stability and function of intravascular fibrin clots. Pro-repair extravascular fibrin(ogen) deposits are potentially subject to crosslinking by FXIII as well as other transglutaminases not typically resident in plasma. However, the impact of these alternative modifiers on fibrin(ogen) structure and function is not known. We tested the hypothesis that tissue transglutaminase (TG2) modifies FXIII-directed fibrin(ogen) crosslinking in vitro and within injured tissue. Global proteomic analysis following experimental acetaminophen (APAP)-induced acute liver injury revealed that intrahepatic fibrin(ogen) deposition was associated with hepatic TG2 levels that exceeded that of FXIII. Mass spectrometry-based crosslink mapping of in vitro fibrin matrices uncovered the first evidence of synergistic fibrin(ogen) a-a crosslinking catalyzed by both transglutaminases. Fibrin(ogen) crosslinking was increased in livers from patients with APAP-induced acute liver failure. APAP-challenged TG2-/- mice displayed an altered pattern of FXIII-dependent fibrin(ogen)-g and fibrin(ogen)-a chain crosslinking aligned with the impact of TG2 on fibrin crosslinking in vitro. This shift in fibrin(ogen) crosslinking exacerbated pathologies including hepatic necrosis and sinusoidal congestion. The results are the first to indicate that TG2 impacts FXIII-directed fibrin(ogen) crosslinking, both in vitro and in vivo. The results suggest that TG2 functions to dynamically alter the structure of extravascular fibrin(ogen) to mitigate liver damage, a novel mechanism likely applicable across types of tissue injury.
A CEBPB/IL-1β/TNF-α Feedback Loop Drives Drug Resistance to Venetoclax and MDM2 Inhibitors in Monocytic Leukemia
Authors: Allen Basil , Bottomly Daniel , Köhnke Thomas , Wang Anthony , Lin Hsin-Yun , Johnson Kara , Kenna Isabel , Streltsova Anastatia , Martin Emma , Chen Reid , Savoy Lindsey , Long Nicola , Ryabinin Peter , Kurtz Stephen E , Eide Christopher A , Carlos Amy , Kaempf Andy , Liu Tingting , Tognon Cristina E. , Searles Robert , Piehowski Paul D. , Gosline Sara J.C. , Agarwal Anupriya , Chang Bill H , Barton Michelle , Druker Brian J , McWeeney Shannon K. , Majeti Ravindra , Tyner Jeffrey W. , Zhang Haijiao
Published: February 2025

MDM2 inhibitors are promising therapeutics for acute myeloid leukemia (AML) with wild-type TP53. Through an integrated analysis of functional genomic data from primary patient samples, we found that an MDM2 inhibitor idasanutlin, like venetoclax, is ineffective against monocytic leukemia (FAB M4/M5). To dissect the underlying resistance mechanisms, we explored both intrinsic and extrinsic factors. We found that monocytic leukemia cells express elevated levels of CEBPB, which promotes monocytic differentiation, suppresses CASP3 and CASP6, and upregulates MCL1, BCL2A1, and the IL-1/TNF-α/NF-κB pathway members, conferring drug resistance to a broad range of MDM2 inhibitors, BH3 mimetics, and venetoclax combinations. Additionally, aberrant monocytes in M4/M5 leukemia produce elevated levels of IL-1 and TNF-α, which promotes monocytic differentiation and upregulate inflammatory cytokines and receptors, thereby extrinsically protecting leukemia blasts from venetoclax and MDM2 inhibition. Interestingly, IL-1β and TNF-α only increase CEBPB levels and protect M4/M5 cells from these drugs, but not M0/M1 leukemia cells. Treatment with venetoclax and idasanutlin induces compensatory upregulation of CEBPB and the IL-1/TNF-α/NF-κB pathway, independent of FAB subtype, indicating a drug induced compensatory protection mechanisms. A combination of venetoclax/ idasanutlin with inhibitors that block IL-1/TNF-α pathway, demonstrate synergistic cytotoxicity in M4/M5 AML. As such, we uncovered a targetable positive feedback loop involving CEBPB, IL-1/TNF-α, and monocyte differentiation in M4/M5 leukemia, which promotes both intrinsic and extrinsic drug resistance, along with drug-induced protection against venetoclax and MDM2 inhibitors.
Healthcare professionals’ attitudes towards social prescribing in specialist children’s weight management services
Authors: Garside Megan , Homer Catherine , Dayson Christopher , Dowrick Lorna , Pickering Katie , Wright Neil
Published: February 2025

Background

Addressing increasing rates of childhood obesity is a global priority. High numbers of children and young people are living with obesity and experience significant physical and mental health impacts. Social prescribing research has shown it can help improve young people’s physical and mental health, meaning it may be a helpful way to provide additional, personalised support to young people who are living with obesity, and to help to address the health inequalities experienced by this group. This study aimed to provide an overview of the current understanding and use of social prescribing from healthcare professionals working in specialist weight management services in England, and to identify perceived benefits and barriers to future implementation of social prescribing in these services.

Methods

A national survey was distributed online between April and July 2023 to healthcare professionals working within specialist weight management clinics across England to gather information regarding their current use and understanding of social prescribing.

Results

Thirty-eight completed surveys were analysed, with good representation from services across England. Staff felt they had an understanding of what social prescribing is and were willing to use it. Anticipated benefits included improvements to wellbeing and providing opportunities for physical activity and family support. Reported barriers included limited capacity from staff and a need for more training around how to identify appropriate community-based services to link with.

Conclusion

Healthcare professionals working in children’s weight management services felt social prescribing could be beneficial for the families they worked with. However, to support implementation in their services, there is a need for further resource, such as staff time and training, to help develop relationships between clinical services and community-based services.
Renal disorders in Autoimmune Polyendocrinopathy Candidiasis Ectodermal dystrophy (APECED): a systematic review
Authors: Shafiei Mohammadreza , Hosseini Solale , Ghadimi Soodeh , Mirzaee Mahbubeh , Keikhah Mohammadamin , Ardalan Nastaran , Mohkam Masoumeh , Tamiji Mehrdad , Jamee Mahnaz
Published: February 2025

Background

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy (APECED), also known as autoimmune polyendocrine syndrome type I (APS-I) is an inborn error of immunity (IEI) with an immune dysregulation phenotype, mainly characterized by endocrine and non-endocrine manifestations including adrenal insufficiency, chronic mucocutaneous candidiasis, and ectodermal dystrophy. Renal disorders seem to be a significant morbidity in APECED patients, requiring further investigations.

Methods

The literature search was conducted in PubMed, Web of Science, and Scopus databases using relevant keywords, and included articles were systematically reviewed regarding the clinical and immunological features. APECED patients with at least one nephrological complication were included.

Results

Ninety-three APECED patients from 30 studies were identified. More than half of the patients (38,52%) presented nephrocalcinosis. The second and third most prevalent renal complications were tubulointerstitial nephritis (TIN) (23,31%), and hypertension (13,18%), respectively. Other less frequent renal disorders including renal tubular acidosis (RTA) glomerulonephritis were also reported among patients. Additionally urinary tract infections (UTI), were also common among cases (15,20.5%).

Conclusions

Renal complications in APECED represent a significant issue that should be monitored and considered in managing these patients to preserve renal function and improve patients’ outcomes.
Cisplatin-induced oxidative stress, apoptosis, and pro-inflammatory responses in chondrocytes through modulating LOX-1
Authors: Wu Chin-Hsien , Chou Wan-Ching , Jou I.-Ming , Tu Yuan-Kun , Ma Ching-Hou , Tsai Kun-Ling
Published: February 2025

Cisplatin is a potent and efficacious anticancer medication. In pediatric cancer, the height of the growth plate’s proliferating layer is known to be reduced by cisplatin, but researchers have not yet determined the specific mechanism behind this phenomenon. Lectin-like oxidized low-density lipoprotein receptor-1 is known to be involved in the development of osteoarthritis and atherosclerosis. The equilibrium of cartilage is regulated by LOX-1, but the function of LOX-1 in cisplatin-induced chondrocyte impairment remains unknown. Positive regulation of LOX-1 leads to increased cellular oxidative stress and cell damage. Research has shown that blocking of LOX-1 can reduce the chondrocyte damage and oxidative stress in cells induced by oxidized LDL treatment. However, the role of LOX-1 in cisplatin-mediated chondrocyte damage is still unclear. This study found that cisplatin increased ROS concentration and p38, ERK phosphorylation. Cisplatin activated NF-κB in chondrocytes. In addition, LOX-1 small interfering RNA transfection mitigated cisplatin-induced apoptosis in TC28a2 cells. Phosphorylated extracellular signal-regulated kinase and p38 were dose-dependently increased by administration of cisplatin. Silencing LOX-1 or MAPK inhibition reduces cisplatin-caused apoptosis. The findings suggest that cisplatin-induced growth plate dysfunction operates through the LOX-1/p38/NF-κB signaling pathway.
Exploring new frontiers in oncofertility preservation: a case of ovarian stimulation during pregnancy
Authors: Pirooznia Parisa , Meighani Esmat Mashhadi , Ghaffari Firouzeh
Published: February 2025

Background

The standard treatment for Pregnancy-Associated Breast Cancer (PABC) includes surgery and neoadjuvant chemotherapy, which can impair fertility, emphasizing the critical need for fertility preservation in these patients. This case report discusses a breast cancer patient who was found to be pregnant shortly after starting treatment. Despite the pregnancy and increased levels of βHCG and progesterone, the ovarian stimulation cycle yielded a satisfactory number of mature oocytes and high-quality embryos.

Case presentation

A 40-year-old woman, G1Ab1 (Gravida1Abortion1), who was diagnosed with Invasive Ductal Carcinoma with negative receptors (Estrogen Receptor, Progesterone Receptor, and Human Epidermal Growth Factor Receptor 2) was referred to the oncofertility unit of the Royan Infertility Center for fertility preservation prior to the commencement of chemotherapy. Following necessary consultations and procedures, and confirming a negative pregnancy test, a random start letrozole-based protocol was initiated for ovarian stimulation. During the cycle, a positive pregnancy test was encountered. Despite the positive test, the cycle continued, and on day 13 of the cycle, triggering was performed with a GnRH agonist. A puncture was performed 36 h later, yielding 12 oocytes and 8 embryos.

Conclusion

This case highlights the feasibility of adapting random-start ovarian stimulation protocols during pregnancy, warranting further investigation in similar clinical scenarios.
Cross-species imputation and comparison of single-cell transcriptomic profiles
Authors: Zhang Ran , Yang Mu , Schreiber Jacob , O’Day Diana R. , Turner James M. A. , Shendure Jay , Noble William Stafford , Disteche Christine M. , Deng Xinxian
Published: February 2025

Cross-species comparison and prediction of gene expression profiles are important to understand regulatory changes during evolution and to transfer knowledge learned from model organisms to humans. Single-cell RNA-seq (scRNA-seq) profiles enable us to capture gene expression profiles with respect to variations among individual cells; however, cross-species comparison of scRNA-seq profiles is challenging because of data sparsity, batch effects, and the lack of one-to-one cell matching across species. Moreover, single-cell profiles are challenging to obtain in certain biological contexts, limiting the scope of hypothesis generation. Here we developed Icebear, a neural network framework that decomposes single-cell measurements into factors representing cell identity, species, and batch factors. Icebear enables accurate prediction of single-cell gene expression profiles across species, thereby providing high-resolution cell type and disease profiles in under-characterized contexts. Icebear also facilitates direct cross-species comparison of single-cell expression profiles for conserved genes that are located on the X chromosome in eutherian mammals but on autosomes in chicken. This comparison, for the first time, revealed evolutionary and diverse adaptations of X-chromosome upregulation in mammals.
An influential study of a time-delayed epidemic model incorporating vaccination and treatment interventions
Authors: Pathak Sushil , Kota Venkata Ratnam
Published: February 2025

A mathematical model delineating the dynamics of infectious diseases under appropriate vaccination and treatment efforts is analyzed. The study thoroughly investigates the implications of time delays inherent in vaccine preparation and administration, the transition from treatment to recovery, and the timeline from exposure to infection. The model is strengthened by establishing essential mathematical properties such as nonnegativity, boundedness, existence of solutions, and equilibria. An estimate of the basic reproduction number is provided to facilitate a preliminary understanding of disease behavior. Furthermore, the local stability of disease-free and endemic equilibria is examined in relation to the basic reproduction number, highlighting the model’s capacity to predict disease dynamics. Moreover, the global stability of the equilibria is essential for understanding the ultimate impact of the disease, as the initial incidence may or may not continue its influence in the presence of counteracting effects such as vaccination and treatment throughout the system. Finally, the results are tested with parameters chosen from recently collected data on the dynamics of COVID-19, and numerical examples are presented to support the theoretical concepts proposed. Simulations visualize these numerical examples.