bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma
Authors: Sidana Surbhi , Patel Krina K. , Peres Lauren C. , Bansal Radhika , Kocoglu Mehmet H. , Shune Leyla , Atrash Shebli , Smith Kinaya , Midha Shonali , Ferreri Christopher , Dhakal Binod , Dima Danai , Costello Patrick , Wagner Charlotte , Reshef Ran , Hosoya Hitomi , Mikkilineni Lekha , Atanackovic Djordje , Chhabra Saurabh , Parrondo Ricardo , Nadeem Omar , Mann Hashim , Kalariya Nilesh , Hovanky Vanna , De Avila Gabriel , Freeman Ciara L. , Locke Frederick L. , Alsina Melissa , Wong Sandy , Herr Megan , Htut Myo , McGuirk Joseph , Sborov Douglas W. , Khouri Jack , Martin Thomas , Janakiram Murali , Lin Yi , Hansen Doris K. 
Published: October 2024

Abstract
Ciltacabtagene autoleucel (cilta-cel) was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 1 March 2022 and 31 December 2022 at 16 US academic medical centers were included. Overall, 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel, of which 54% would not have met CARTITUDE-1 eligibility criteria. In treated patients (N = 236), cytokine release syndrome was seen in 75% (grade ≥3, 5%), immune effector cell–associated neurotoxicity syndrome in 14% (grade ≥3, 4%), and delayed neurotoxicity in 10%. Overall and complete response rates were as follows: all patients who received cilta-cel (N = 236), 89% and 70%; patients receiving conforming cilta-cel (n = 191), 94% and 74%; and conforming cilta-cel with fludarabine/cyclophosphamide lymphodepletion (n = 152), 95% and 76%, respectively. Nonrelapse mortality was 10%, most commonly from infection. After a median follow-up of 13 months from cilta-cel, the median progression-free survival (PFS) was not reached, with 12-month estimate being 68% (95% confidence interval, 62-74). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior B-cell maturation antigen–targeted therapy (P = .08). Second primary malignancies excluding nonmelanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard-of-care cilta-cel in RRMM, despite more than half the patients not meeting the CARTITUDE-1 eligibility criteria.
Systemic pro-inflammatory response following bronchoscopic lung volume reduction using endobronchial valves
Authors: Hartman Jorine E. , van der Molen Marieke C. , Jonker Marnix R. , Posthuma Rein , Vanfleteren Lowie E.G.W. , Slebos Dirk-Jan , Pouwels Simon D. 
Published: October 2024

RationaleBronchoscopic lung volume reduction treatment using endobronchial valves (EBV) is an effective treatment for severe COPD patients by improving lung function and quality of life. However, little is known about its effects on systemic inflammation. Therefore, the aim of our study was to investigate whether EBV treatment impacts the inflammatory cytokine profile.MethodsThis study was a predefined substudy of the SoLVE trial (NCT03474471) that investigated the combination of EBV treatment with pulmonary rehabilitation (PR). The substudy included the collection of blood samples with assessment of 10 inflammatory markers prior to EBV treatment and 6 months after EBV or EBV+PR treatment.ResultsIn 66 patients, six months after treatment a pro-inflammatory cytokine profile was observed, with an increase in all pro-inflammatory markers and a decrease in the anti-inflammatory cytokine IL-10. The changes in plasma cytokine profile were not associated with changes in clinical outcomes such as lung function or exercise capacity.DiscussionIn conclusion, our study demonstrated an elevation in systemic pro-inflammatory cytokine levels following successful EBV-treatment, which was not associated with adverse clinical outcomes. It would be interesting to further explore, whether this increase is attributed to a foreign body response or if other factors contribute to this phenomenon.
The association between endothelial dysfunction and subclinical myocardial injury in male obstructive sleep apnoea patients
Authors: Cao Wenhao , Luo Jinmei , Hui Xinjie , Xiao Yi , Huang Rong 
Published: October 2024

BackgroundEndothelial dysfunction was shown to contribute significantly to the elevated cardiovascular risk observed in the general population. However, the relationship between endothelial dysfunction and subclinical myocardial injury in obstructive sleep apnoea (OSA) patients remains unclear.MethodsThis cross-sectional study recruited 165 consecutive male patients diagnosed with OSA. All participants underwent overnight polysomnography to confirm the diagnosis and assess the severity of OSA. Subclinical myocardial injury was evaluated using high-sensitivity cardiac troponin I (hs-cTnI) measurements, while endothelial dysfunction was assessed through the peripheral arterial tonometry.ResultsEndothelial dysfunction was present in 80 (48.5%) of the subjects and hs-cTnI was detectable in 147 (89.1%) of the participants. When compared with OSA patients without endothelial dysfunction, those with endothelial dysfunction exhibited significantly lower percentages of hypertension (23.8%versus43.5%, p=0.007) and abdominal obesity (76.3%versus88.2%, p=0.043). Patients with endothelial dysfunction frequently manifest a lower apnoea–hypopnoea index and oxygen desaturation index. Despite comparable median hs-cTnI levels, a higher proportion of subjects with detectable hs-cTnI levels was observed among those with endothelial dysfunction (95%versus83.5%, p=0.018). Logistic regression analysis indicated that endothelial dysfunction was significantly associated with a detectable level of hs-cTnI after adjustment for multiple confounders.ConclusionsIn male OSA patients, endothelial dysfunction appears to be potentially correlated with an increased risk of subclinical myocardial injury, as evidenced by the higher prevalence of detectable hs-cTnI levels. Further investigations are warranted to elucidate the role of endothelial dysfunction in predicting future cardiovascular mortality in this population.
Evaluating digital adherence support in asthma: The ADITION non-interventional study
Authors: Woehrle Holger , Driemert Jens , Jerrentrup Lukas , Schiefer Conrad , Bushart Gregor , Sauerbeck Inessa Schwab 
Published: October 2024

IntroductionPoor adherence to asthma maintenance therapy is associated with worse outcomes. A solution could be digital adherence support. This study evaluated asthma control and adherence in patients using mometasone furoate/indacaterol/glycopyrronium (MF/IND/GLY) with a digital support system, or using any inhaled corticosteroid/long-acting β2-agonist/long-acting muscarinic antagonist combination (ICS/LABA/LAMA) without support.MethodsThis prospective, non-interventional, multicentre, open-label study enrolled adults with asthma in Germany. Prior to inclusion, treatment was initiated with MF/IND/GLY with digital support, or with any ICS/LABA/LAMA without digital support. The primary endpoint was change in Asthma Control Test (ACT) at 6 months.ResultsOf 222 and 203 patients in the MF/IND/GLY plus digital support and ICS/LABA/LAMA groups, respectively, 76.1% and 74.9% completed follow-up. Baseline mean ACT total scores were 17.0 and 14.7, with mean changes from baseline at 6 months of 3.0 and 4.1; following propensity matching (N=92/group), mean (95% CI) changes were similar in the two groups, with overlapping CIs (2.9 [1.9, 3.9] and 4.0 [3.0, 5.1]). At enrolment, patients were overall moderately adherent to maintenance therapy, with limited changes over the study. The overall incidence of adverse events was similar in the two groups (29.5% and 27.3% patients).ConclusionsPatients using MF/IND/GLY with digital support had similar improvements in asthma control to those receiving ICS/LABA/LAMA alone, with minimal changes in adherence. These results illustrate the challenges in evaluating asthma control and adherence in non-interventional studies. Further studies are required to evaluate the value of digital support systems, and how they can be used to optimise inhaler adherence.
Establishing a rabbit model with massive supraspinatus tendon defect for investigating scaffold-assisted tendon repair
Authors: Huang Shuting , Tam Ming Yik , Ho Wai Hon Caleb , Wong Hong Ki , Zhou Meng , Zeng Chun , Xie Denghui , Elmer Ker Dai Fei , Ling Samuel KK. , Tuan Rocky S. , Wang Dan Michelle 
Published: October 2024

Abstract
Background
Shoulder pain and disability from rotator cuff tears remain challenging clinical problem despite advancements in surgical techniques and materials. To advance our understanding of injury progression and develop effective therapeutics using tissue engineering and regenerative medicine approaches, it is crucial to develop and utilize animal models that closely resemble the anatomy and display the pathophysiology of the human rotator cuff. Among various animal models, the rabbit shoulder defect model is particularly favored due to its similarity to human rotator cuff pathology. However, a standardized protocol for creating a massive rotator cuff defect in the rabbits is not well defined. Therefore, the objective of our study was to establish a robust and reproducible model of a rotator cuff defect to evaluate the regenerative efficacy of scaffolds.

Results
In our study, we successfully developed a rabbit model with a massive supraspinatus tendon defect that closely resembles the common rotator cuff injuries observed in humans. This defect involved a complete transection of the tendon, spanning 10 mm in length and encompassing its full thickness and width. To ensure stable scaffolding, we employed an innovative bridging suture technique that utilized a modified Mason-Allen suture as a structural support. Moreover, to assess the therapeutic effectiveness of the model, we utilized different scaffolds, including a bovine tendon extracellular matrix (ECM) scaffold and a commercial acellular dermal matrix (ADM) scaffold. Throughout the observation period, no scaffold damage was observed. Notably, comprehensive histological analysis demonstrated that the regenerative tissue in the tendon ECM scaffold group exhibited an organized and aligned fiber structure, indicating tendon-like tissue regeneration while the tissue in the ADM group showed comparatively less organization.

Conclusions
This study presents a comprehensive description of the implemented procedures for the development of a highly reproducible animal model that induces massive segmental defects in rotator cuff tendons. This protocol can be universally implemented with alternative scaffolds to investigate extensive tendon defects and evaluate the efficacy of regenerative treatments. The application of our animal model offers a standardized and reproducible platform, enabling researchers to systematically evaluate, compare, and optimize scaffold designs. This approach holds significant importance in advancing the development of tissue engineering strategies for effectively repairing extensive tendon defects.
Prevalence and factors associated with gestational diabetes mellitus in Malaysia: a population-based study comparing 2016 and 2022
Authors: Zulkiply Siti Hafizah , Ratnam Kishwen Kanna Yoga , Liew Siaw Hun 
Published: October 2024

Abstract
Background
Gestational diabetes mellitus (GDM) poses substantial health risks to both mothers and infants. Malaysia exhibits a heightened prevalence of GDM.

Objective
This study aims to examine the changes in the prevalence of GDM between 2016 and 2022 and its determining factors.

Methods
The data analysed in this study were derived from the National Health and Morbidity Survey (NHMS) 2016 and 2022, a nationwide study employing a two-stage stratified random sampling design in Malaysia. Changes in the prevalence were compared between data from NHMS 2016 and 2022, while factors were evaluated based on data from NHMS 2022. Descriptive statistics and multiple logistic regression analyses were performed using IBM SPSS version 27.

Results
The prevalence of GDM increased from 12.5% in 2016 to 27.1% in 2022. In both years, the prevalence was highest among those aged 44–49 years, those of Indian ethnicity, those in higher income groups and those with higher education levels. Advanced maternal age, high body mass index (BMI) and hypertension were associated with a greater risk of GDM.

Conclusion
The prevalence of GDM among the Malaysian population doubled from 2016 to 2022. The findings underscore the importance of implementing targeted programs for expectant mothers in high-risk groups to mitigate the incidence of GDM and its associated morbidities.
External validation of an artificial intelligence multi-label deep learning model capable of ankle fracture classification
Authors: Olczak Jakub , Prijs Jasper , IJpma Frank , Wallin Fredrik , Akbarian Ehsan , Doornberg Job , Gordon Max 
Published: October 2024

Abstract
Background
Advances in medical imaging have made it possible to classify ankle fractures using Artificial Intelligence (AI). Recent studies have demonstrated good internal validity for machine learning algorithms using the AO/OTA 2018 classification. This study aimed to externally validate one such model for ankle fracture classification and ways to improve external validity.

Methods
In this retrospective observation study, we trained a deep-learning neural network (7,500 ankle studies) to classify traumatic malleolar fractures according to the AO/OTA classification. Our internal validation dataset (IVD) contained 409 studies collected from Danderyd Hospital in Stockholm, Sweden, between 2002 and 2016. The external validation dataset (EVD) contained 399 studies collected from Flinders Medical Centre, Adelaide, Australia, between 2016 and 2020. Our primary outcome measures were the area under the receiver operating characteristic (AUC) and the area under the precision-recall curve (AUPR) for fracture classification of AO/OTA malleolar (44) fractures. Secondary outcomes were performance on other fractures visible on ankle radiographs and inter-observer reliability of reviewers.

Results
Compared to the weighted mean AUC (wAUC) 0.86 (95%CI 0.82–0.89) for fracture detection in the EVD, the network attained wAUC 0.95 (95%CI 0.94–0.97) for the IVD. The area under the precision-recall curve (AUPR) was 0.93 vs. 0.96. The wAUC for individual outcomes (type 44A-C, group 44A1-C3, and subgroup 44A1.1-C3.3) was 0.82 for the EVD and 0.93 for the IVD. The weighted mean AUPR (wAUPR) was 0.59 vs 0.63. Throughout, the performance was superior to that of a random classifier for the EVD.

Conclusion
Although the two datasets had considerable differences, the model transferred well to the EVD and the alternative clinical scenario it represents. The direct clinical implications of this study are that algorithms developed elsewhere need local validation and that discrepancies can be rectified using targeted training. In a wider sense, we believe this opens up possibilities for building advanced treatment recommendations based on exact fracture types that are more objective than current clinical decisions, often influenced by who is present during rounds.
Taurolidine-containing solution for reducing cardiac implantable electronic device infection-early report from the European TauroPace™ registry
Authors: Vonthein Reinhard , Baldauf Benito , Borov Stefan , Lau Ernest W. , Giaccardi Marzia , Assadian Ojan , Haddad Christelle , Chévalier Philippe , Bode Kerstin , Foley Paul , Thomas Honey , Campbell Niall G. , Fichtner Stephanie , Donazzan Luca , Pescoller Felix , Oberhollenzer Rainer , Cemin Roberto , Bonnemeier Hendrik 
Published: October 2024

Abstract
Introduction
Infection is a significant complication of cardiac implantable electronic device (CIED) therapy. The European TauroPace™ Registry investigates the safety and efficacy of TauroPace™ (TP), an antimicrobial solution containing taurolidine, designed to prevent CIED infections.

Methods
This multicenter study included patients undergoing CIED procedures at participating centers where TP was used as a disinfectant for external hardware surfaces and an antiseptic for irrigating surgical sites. All patients eligible for CIED placement with adjunctive TP as the standard of care were included. Other aspects of CIED procedures adhered to current guidelines. Data on CIED-related infective endocarditis, CIED pocket infection, device and procedure-related complications, adverse events, and all-cause mortality were prospectively collected for 12 months. In cases of revision, the previous procedure was censored, and a new procedure was created. Binomial and Kaplan–Meier statistics were employed to analyze event rates.

Results
From January 2020 to November 2022, TP was used in 822 out of 1170 CIED procedures. Among patients who completed the 3-month follow-up, no CIED pocket infections were observed, and one case of CIED-related infective endocarditis was reported. In the 12-month follow-up cohort, two additional local pocket CIED infections were observed, resulting in a total of three major CIED infections within 1 year after the CIED placement procedure. The 3-month and 12-month major CIED infection rates were 0.125% and 0.51%, respectively. During the observation a complication rate of 4.4% was reported. No adverse events related to TP were observed.

Conclusions
TP appears to be effective and safe in preventing CIED infections.
ClinicalTrials.gov Identifier: NCT04735666.
NAT10/ac4C/JunB facilitates TNBC malignant progression and immunosuppression by driving glycolysis addiction
Authors: Li Guozheng , Ma Xin , Sui Shiyao , Chen Yihai , Li Hui , Liu Lei , Zhang Xin , Zhang Lei , Hao Yi , Yang Zihan , Yang Shuai , He Xu , Wang Qin , Tao Weiyang , Xu Shouping 
Published: October 2024

Abstract
Background
N4-Acetylcytidine (ac4C), a highly conserved post-transcriptional mechanism, plays a pivotal role in RNA modification and tumor progression. However, the molecular mechanism by which ac4C modification mediates tumor immunosuppression remains elusive in triple-negative breast cancer (TNBC).

Methods
NAT10 expression was analyzed in TNBC samples in the level of mRNA and protein, and compared with the corresponding normal tissues. ac4C modification levels also measured in the TNBC samples. The effects of NAT10 on immune microenvironment and tumor metabolism were investigated. NAT10-mediated ac4C and its downstream regulatory mechanisms were determined in vitro and in vivo. The combination therapy of targeting NAT10 in TNBC was further explored.

Results
The results revealed that the loss of NAT10 inhibited TNBC development and promoted T cell activation. Mechanistically, NAT10 upregulated JunB expression by increasing ac4C modification levels on its mRNA. Moreover, JunB further up-regulated LDHA expression and facilitated glycolysis. By deeply digging, remodelin, a NAT10 inhibitor, elevated the surface expression of CTLA-4 on T cells. The combination of remodelin and CTLA-4 mAb can further activate T cells and inhibite tumor progression.

Conclusion
Taken together, our study demonstrated that the NAT10-ac4C-JunB-LDHA pathway increases glycolysis levels and creates an immunosuppressive tumor microenvironment (TME). Consequently, targeting this pathway may assist in the identification of novel therapeutic strategies to improve the efficacy of cancer immunotherapy.
Negotiating pricing and payment terms for insurance covered mHealth apps: a qualitative content analysis and taxonomy development based on a German experience
Authors: Freitag Bettina , Fehring Leonard , Uncovska Marie , Olsacher Alexandra , Meister Sven 
Published: October 2024

Abstract
Background
Germany was the first country worldwide to offer mobile digital health applications (mHealth apps, “DiGA”) on prescription with full cost coverage by statutory health insurances. Especially statutory health insurances criticize the current pricing and payment regulations in Germany due to “free and non-transparent” pricing in the first year and lack of cost use evidence. The study consists of two parts: The first part evaluates interests of digital health application providers and statutory health insurances in Germany to identify overlaps and divergences of interests. The second part includes the development of a comprehensive pricing and payment taxonomy for reimbursable mHealth apps in general.

Methods
Both parts of the study used the input from 16 expert interviews with representatives of digital health application providers and statutory health insurances in Germany. In part one the authors conducted a qualitative content analysis and in part two they followed the taxonomy development process according to Nickerson et al. (2013).

Results
A value based care model is expected to bring the greatest benefit for patients while statutory health insurances welcome the idea of usage based pricing. The final pricing and payment taxonomy consists of four design and negotiation steps (price finding, payment prerequisites, payment modalities, composition of negotiation board).

Conclusions
As healthcare resources are scarce and thus need to be optimally allocated, it is important to implement pricing and payment terms for reimbursable mHealth apps that result in the greatest benefit for patients. To the best of the authors’ knowledge, there has been no structured study yet that examines alternative pricing strategies for reimbursable mHealth apps.The developed pricing and payment taxonomy for reimbursable mHealth apps serves as planning and decision basis for developers, health policy makers and payers internationally.