bluuebunny/crossref_metadata_2025_split huggingface dataset:
Powerful together with diabetes, a group-based self-management intervention for patients with type 2 diabetes from lower educational groups: study protocol for a hybrid type 2 evaluation
Authors: Horreh Bedra , van Nassau Femke , Landais Lorraine , Vissenberg Charlotte , van Dongen Johanna M , van der Ploeg Hidde P , Stronks Karien 
Published: January 2025

IntroductionType 2 diabetes mellitus (T2DM) is a major burden on public health worldwide. To reduce adverse events and complications, effective T2DM self-management is required. Self-management and glycaemic control are generally poorer in lower educated people compared with higher educated people. This study aims to assess the (cost-)effectiveness and to conduct a process evaluation of a diabetes self-management programme, ‘Powerful Together With Diabetes’ (PTWD), which is specifically developed for patients from lower educational groups.Methods and analysisThe PTWD programme is focused on attaining basic knowledge and skills for effective diabetes self-management. In a previous study (the Diabetes in Social Context (DISC) study), lower-educated participants enjoyed the PTWD programme as well as improved their T2DM-related behaviours. The design of the study is an effectiveness-implementation hybrid type 2 trial. We will conduct mixed methods effectiveness, process and economic evaluations. To investigate the (cost-)effectiveness, a two-arm quasi-experimental trial will be conducted with a parallel mixed method process evaluation. The primary outcome of the study is change in haemoglobin A1c levels from baseline to 12 months. Secondary outcomes include use of primary and secondary care, medication use, blood biomarkers, T2DM self-management health behaviours, anthropometrics, and quality of life. Data will be collected with questionnaires, physical activity trackers and registration data from general practitioner registries. To see if the results are maintained, we will also measure the outcomes 24 months after baseline. Study participants are patients from lower educational groups living with T2DM between 35 and 70 years old. Participants will be recruited through general practices, and the intervention will be held in community centres. Our aim is to include 114 participants in the intervention group and 570 participants in the control group.Ethics and disseminationThis study has been approved by the Medical Ethics Committee of the Academic Medical Center in Amsterdam (#2021_222). Participants will sign an informed consent form prior to enrolment. Manuscripts with the results of the effectiveness, economic and process evaluations will be published in peer-reviewed journals.Trial registration numberISRCTN12982302ISRCTN registry (registered on 29 March 2022).
Product Market Competition, Corporate Social Responsibility Disclosure, and Sustainability Governance: Evidence from Australia
Authors: Li Zhongtian , Jia Jing , Chapple Ellie 
Published: January 2025

Synopsis The research problem We investigated the relationship between product market competition and the textual characteristics of corporate social responsibility (CSR) disclosures. Specifically, we investigated three textual characteristics: tone of optimism, tone of tangibility (matter-of-factness), and readability. Motivation or theoretical reasoning On the one hand, the three ways in which CSR disclosure can enhance corporate success in competitive product market situations are as follows: (1) More readable disclosures with more optimistic and matter-of-fact tones help firms attract new customers while enhancing customer loyalty and brand value. (2) Increased market competition is expected to encourage firms to provide more-readable CSR disclosures with optimistic and matter-of-fact tones to enhance their access to external financing at lower costs. (3) CSR disclosure may strengthen a firm’s connections with business stakeholders (e.g., employees and suppliers). These connections are conducive to corporate success in competitive product market situations. On the other hand, it is well established that firms find CSR disclosure to be costly. The test hypotheses A significant relationship exists between product market competition and the three textual characteristics of CSR disclosures, namely, tone of optimism, tone of tangibility (matter-of-factness), and readability. Target population Our sample comprised 2,018 firm-year observations (2002–2020) of listed firms in Australia. Findings Our study found that firms facing an increase in product market competition tend to publish less-readable CSR disclosures with less use of optimism and matter-of-fact tones of language, and vice versa. In practical terms, this indicates that firms fail to leverage CSR disclosure in managing their product market competition, even though CSR disclosure is recognized as an effective marketing and brand strategy. Therefore, our study examined whether or not the CSR committee, as a key sustainability governance mechanism on CSR disclosure, could contribute to mitigating this missed opportunity. We found that the negative relationship between the two variables is attenuated by the presence of a CSR committee and by the CSR committee’s effectiveness. Our study should be of interest to firms, users of CSR disclosures, and regulators.
Radius estimates for nearly stable H-hypersurfaces of dimension 2, 3, and 4
Authors: Tinaglia G. , Zhou A. 
Published: January 2025

In this paper, we study the geometry of complete constant mean curvature (CMC) hypersurfaces immersed in an [Formula: see text]-dimensional Riemannian manifold [Formula: see text] ([Formula: see text] and [Formula: see text]) with sectional curvatures uniformly bounded from below. We generalise radius estimates given by Rosenberg [Constant mean curvature surfaces in homogeneously regular 3-manifolds, Bull. Aust. Math. Soc. 74 (2006) 227–238] ([Formula: see text]) and by Elbert et al. [Stable constant mean curvature hypersurfaces, Proc. Amer. Math. Soc. 135 (2007) 3359–3366] and Cheng [On constant mean curvature hypersurfaces with finite index, Arch. Math. (Basel) 86 (2006) 365–374] ([Formula: see text]) to nearly stable CMC hypersurfaces immersed in N. We also prove that certain CMC hypersurfaces effectively embedded in [Formula: see text] must be proper.
Efficacy of the Protocol for Trauma Team Activation in Taipei: A Retrospective Study
Authors: Chen Wan-Lin , Ou Ju-Chi , Ko Shih-Yu , Li Wen-Ching , Ma Hon-Ping 
Published: January 2025

Introduction: Trauma triage is the use of trauma assessment for prioritizing patients for treatment or transport by injury severity. According to Taiwan Public Health Report, accidents and their adverse events were the sixth leading cause of death and accounted for over 7000 casualties in 2009. However, a lack of accuracy in identifying the severity of a patient’s injury and their prehospital information can result in inappropriate triage. This study evaluated the efficacy of field triage guidelines governing trauma team activation in Taipei and explored the characteristics of undertriaged and overtriaged patients.Methods: This study retrospectively observed all patients with trauma transported to the emergency department of a medical center by Taipei City public ambulance from January 1, 2016, to December 31, 2019. A total of 2217 patients were included. The Cribari matrix method was used to assess undertriage and overtriage. A logistic regression was employed to analyze the effect of risk factors in patients with major trauma.Results: In this study, 320 and 1897 patients with trauma had full and limited trauma team activation, respectively. Among them, 664 patients with trauma were older than 65 years, and most of them were injured in a traffic accident. Among patients with major trauma, 24, 214, and 156 patients were aged < 20, 20–65, and > 65 years, respectively. A logistic regression analysis revealed that patients with a Glasgow Coma Scale score of less than 13, with systolic blood pressure level of less than 90, and with respiratory rate over 30 breaths per minute was more likely to be appropriately triaged.Conclusion: The Taipei prehospital field triage guidelines are acceptable but not an ideal tool for identifying patients with major trauma, with an overtriage rate of 48.12% and an undertriage rate of 12.03%. To decrease undertriage or overtriage rates, emergency medical service providers should receive comprehensive training.
Functional Analysis of Complex Structural and Splice‐Altering Variants in the ARSB Gene Towards the Personalized Antisense‐Based Therapy for Mucopolysaccharidosis Type VI Patients
Authors: Bychkov Igor , Filatova Alexandra , Baydakova Galina , Sikora Nataliya , Garifullina Emiliya , Bykova Anna , Tabakov Vyacheslav , Skretnev Alexandr , Skoblov Mikhail , Zakharova Ekaterina 
Published: January 2025

Mucopolysaccharidosis Type VI (MPS VI) is a lysosomal storage disorder associated with biallelic pathogenic variants in the ARSB gene. Herein, we present three patients with biochemical and clinical pictures of MPS VI, for whom routine molecular genetic analysis using Sanger sequencing of ARSB failed to identify one or both causative variants. RNA analysis of patients’ samples revealed alterations of the wild‐type ARSB mRNA isoform in all cases, and one case required further analysis using whole genome sequencing. As a result, we identified one complex structural variant, which is a 52‐kb insertion of the LHFPL2 gene fragment in the ARSB Intron 4, derived from nonallelic homologous recombination and leading to premature transcription termination, a recurrent deep intronic variant leading to pseudoexon activation and an intragenic deletion altering the integrity and splicing of the ARSB Exon 2.Using a minigene‐based cellular model, we demonstrated that the identified pseudoexon can be efficiently blocked by antisense molecules incorporated into modified U7 small nuclear RNAs and circular RNAs. The same approach was used to block the overlapping polymorphic pseudoexon in the ARSB gene and increase the amount of wild‐type mRNA isoform approximately twofold.
Improving Patient Understanding of Glomerular Disease Terms With ChatGPT
Authors: Abdelgadir Yasir H. , Thongprayoon Charat , Craici Iasmina M. , Cheungpasitporn Wisit , Miao Jing 
Published: January 2025

Background: Glomerular disease is complex and difficult for patients to understand, as it involves various pathophysiology, immunology, and pharmacology areas.Objective: This study explored whether ChatGPT can maintain accuracy while simplifying glomerular disease terms to enhance patient comprehension.Methods: 67 terms related to glomerular disease were analyzed using GPT‐4 through two distinct queries. One aimed at a general explanation and another tailored for patients with an education level of 8th grade or lower. GPT‐4’s accuracy was scored from 1 (incorrect) to 5 (correct and comprehensive). Its readability was assessed using the Consensus Reading Grade (CRG) Level, which incorporates seven readability indices including the Flesch–Kincaid Grade (FKG) and SMOG indices. Flesch Reading Ease (FRE) score, ranging from 0 to 100 with higher scores indicating easier‐to‐read text, was also used to evaluate the readability. A paired t‐test was conducted to assess differences in accuracy and readability levels between different queries.Results: GPT‐4’s general explanations of glomerular disease terms averaged at a college readability level, indicated by the CRG score of 14.1 and FKG score of 13.9. SMOG index also indicated the topic’s complexity, with a score of 11.8. When tailored for patients at or below an 8th‐grade reading level, readability improved, averaging 9.7 by the CRG score, 8.7 by FKG score, and 7.3 by SMOG score. The FRE score also indicated a further improvement of readability from 31.6 for general explanations to 63.5 for tailored explanations. However, the accuracy in GPT‐4’s tailored explanations was significantly lower than that in general explanations (4.2 ± 0.4 versus 4.7 ± 0.3, p < 0.0001).Conclusion: While GPT‐4 effectively simplified information about glomerular diseases, it compromised its accuracy in the process. To implement these findings, we suggest pilot studies in clinical settings to assess patient understanding, using feedback from diverse groups to customize content, expanding research to enhance AI accuracy and reduce biases, setting strict ethical guidelines for AI in healthcare, and integrating with health informatics systems to provide tailored educational content to patients. This approach will promote effective and ethical use of AI tools like ChatGPT in patient education, empowering patients to make informed health decisions.
Phase I Trial of TTI-101, a First-in-Class Oral Inhibitor of STAT3, in Patients with Advanced Solid Tumors
Authors: Tsimberidou Apostolia M. , Vining David J. , Arora Sukeshi P. , de Achaval Sofia , Larson Jeffrey , Kauh John , Cartwright Carrie , Avritscher Rony , Alibhai Imran , Tweardy David J. , Kaseb Ahmed O. 
Published: January 2025

Abstract

Purpose:
Signal transducer and activator of transcription 3 is a transcription factor that is essential for the survival and immune sequestration of cancer cells. We conducted a phase I study of TTI-101, a first-in-class, selective small-molecule inhibitor of signal transducer and activator of transcription 3, in patients with advanced metastatic cancer.

Patients and Methods:
Patients were treated with TTI-101 orally twice daily in 28-day cycles at four dose levels (DL): 3.2 (DL1), 6.4 (DL2), 12.8 (DL3), and 25.6 (DL4) mg/kg/day (“3+3” design). Three TTI-101 formulations were used in a stepwise manner (NCT03195699).

Results:
Sixty-four patients were treated (median age, 63 years; male sex, 52%; median number of prior therapies, 3). No dose-limiting toxicities or fatal treatment-related adverse events (TRAE) were observed. Diarrhea (mostly grade 1/2) was the only TRAE observed in ≥30% of subjects. Five patients experienced grade 3 TRAEs that resolved. TTI-101 showed linear pharmacokinetics from DL1 to DL3, with the pharmacokinetics plateauing at DL3. The recommended phase II dose is 12.8 mg/kg/day (DL3). Of the 41 patients who were evaluable for response, five (12%) had confirmed partial responses (cPR) and 17 (41%) had stable disease. Three (18%) of the 17 patients with hepatocellular carcinoma had a cPR (median time to treatment failure, 10.6 months). Two other cPRs were noted in one patient with ovarian cancer and one patient with gastric cancer.

Conclusions:
TTI-101 was well tolerated. cPRs were observed across tumor types. The antitumor activity of TTI-101 monotherapy in patients with advanced, metastatic solid tumors is promising. A phase II study of TTI-101 in hepatocellular carcinoma is currently underway.
ctDNA: A Gateway for Personalized Risk Stratification in Surgically Resectable Hepatocellular Cancer
Authors: Pinato David J. , Lombardi Pasquale , D’Alessio Antonio , Torkpour Aria , Fulgenzi Claudia Angela Maria , Brunetti Leonardo 
Published: January 2025

Summary
Although deemed potentially curative, surgical resection of hepatocellular carcinoma is associated with &gt;70% risk of postoperative relapse. Recurrence is uniquely multifactorial in hepatocellular carcinoma, potentially stemming from metachronous reoccurrence of the original tumor or de novo cancerization. ctDNA may improve personalized risk stratification after resection, a setting where adjuvant immunotherapy has failed to provide survival benefit.
See related article by Hu et al., p. XX
Targeting P21‐Activated Kinase 2 as a Novel Therapeutic Approach to Mitigate Endoplasmic Reticulum Stress in Heart Failure With Preserved Ejection Fraction
Authors: Zhang Hongyuan , Xu Honglin , Zhou Fangchao , Azam Tayyiba , Samman Sultan , Binder Pablo , Nguyen Binh , Cartwright Elizabeth J. , Müller Oliver J. , Hille Susanne S. , Pu Fay , Green Darren , Liu Yanrong , Zi Min , Wang Xin 
Published: January 2025

Background
Heart failure with preserved ejection fraction (HFpEF) is linked to prolonged endoplasmic reticulum (ER) stress. P21‐activated kinase 2 (Pak2) facilitates a protective ER stress response. This study explores the mechanism and role of Pak2 in HFpEF pathology.

Methods and Results

The HFpEF mouse model was established using a high‐fat diet combined with the nitric oxide synthase inhibitor Nω‐Nitro‐
l
‐arginine methyl ester (high‐fat diet+Nω‐Nitro‐
l
‐arginine methyl ester). The model exhibited the typical characteristics of HFpEF (cardiac hypertrophy, diastolic dysfunction with preserved systolic function, and lung edema) as determined by echocardiography and hemodynamic analysis. Terminal deoxynucleotidyl transferase dUTP nick end labeling and dihydroethidium staining results showed that cell death and reactive oxygen species generation were higher in the high‐fat diet+Nω‐Nitro‐
l
‐arginine methyl ester–treated group. Transmission electron microscopy revealed disruption of the ER subcellular structures in the HFpEF mouse model, while western blot analysis confirmed reduced Pak2 phosphorylation and impaired inositol‐requiring enzyme 1/X‐box binding protein 1 splicing ER stress response signaling. Furthermore, H9c2 cells subjected to the palmitic acid–mediated metabolic stress developed temporal changes in unfolded protein response proteins and Pak2 activity. The inositol requiring enzyme 1/X‐box binding protein 1 splicing branch of unfolded protein response was impaired earlier than other branches. Overexpression of Pak2 by adenovirus in H9c2 cells sustained the activation of inositol requiring enzyme 1/X‐box binding protein 1 splicing. Pak2 deficiency in the mouse heart accelerated the HFpEF progression, and this phenomenon occurred as early as 10 weeks in Pak2 cardiomyocyte‐specific knockout mice. Conversely, adeno‐associated virus serotype 9–mediated Pak2 overexpression mitigated HFpEF symptoms, underscoring its protective role against HFpEF progression.

Conclusions
Pak2 prevents HFpEF progression, exerting cardioprotective effects against ER stress. These insights underscore the therapeutic value of Pak2 in HFpEF.
Contemporary Administrative Codes to Identify Pulmonary Vein Isolation Procedures for Atrial Fibrillation
Authors: Ferro Enrico G. , Reynolds Matthew R. , Xu Jiaman , Song Yang , Cohen David J. , Wadhera Rishi K. , d'Avila Andre , Zimetbaum Peter J. , Yeh Robert W. , Kramer Daniel B. 
Published: January 2025

Background
Use of pulmonary vein isolation (PVI) to treat atrial fibrillation continues to increase. Despite great interest in leveraging administrative data for real‐world analyses, contemporary procedural codes for identifying PVI have not been evaluated.

Methods and Results

In this observational retrospective cohort study, inpatient PVIs were identified among US Medicare fee‐for‐service beneficiaries using Current Procedural Terminology (CPT) code 93656 in Carrier Line Files. Each patient was matched with their claims from Medicare Provider Analysis and Review to compare CPT with
International Classification of Diseases
,
Tenth Revision
,
Procedure Coding System
(
ICD‐10‐PCS
) claims submitted by health care facilities to bill for PVIs. We performed the reverse for commonly matched
ICD‐10‐PCS
codes, to identify corresponding CPT‐billed procedures. Finally, we reviewed institutional cases for additional comparison of CPT and
ICD‐10‐PCS
assignation for PVI. We identified 25 617 inpatient PVIs from January 2017 to December 2021, of which 18 165 (71%) were linked to Medicare Provider Analysis and Review. Of these, 16 672 (92%) were billed as
ICD‐10‐PCS
02583ZZ: “Destruction of Conduction Mechanism, Percutaneous Approach.” The reverse process yielded heterogeneous results: among 75 003 procedures billed as
ICD‐10‐PCS
02583ZZ, only 15 691 (21%) matched with CPT 93656 (PVI), as several other unrelated procedures were billed under this
ICD‐10‐PCS
code. Institutional case review confirmed the greater specificity of CPT codes.

Conclusions

The
ICD‐10‐PCS
code associated with CPT‐billed PVI procedures actually referred to ablation of the atrioventricular junction. Yet this
ICD‐10‐PCS
code also matched with a wide range of other procedures distinct from PVI. We conclude that
ICD‐10‐PCS
codes alone are not sensitive nor specific for identifying PVI in claims and cannot be reliably used in isolation for health services research on this important procedure.
Eliciting and Improving the Causal Reasoning Abilities of Large Language Models with Conditional Statements
Authors: Liu Xiao , Yin Da , Zhang Chen , Zhao Dongyan , Feng Yansong 
Published: January 2025

Abstract
Causal reasoning, the ability to identify cause-and-effect relationships, is crucial in human thinking. Although large language models (LLMs) succeed in many NLP tasks, it is still challenging for them to conduct complex causal reasoning like abductive reasoning and counterfactual reasoning. Complex causal structures are rarely expressed explicitly in the text, which could make learning them challenging for LLMs. Given the fact that programming code may express causal relations more often and explicitly with conditional statements like if, we want to explore whether large language models of code (Code-LLMs) acquire better causal reasoning abilities, and whether code prompts better describe the causal structure than text prompts. Our experiments show that compared to general-purpose LLMs like Llama-2 and GPT-3, Code-LLMs like CodeLlama and Codex are significantly better in causal reasoning. Code prompts not only work well for Code-LLMs, but also help improve the performance of most general-purpose LLMs. To understand why code prompts are effective, we intervene on the prompts from different aspects, and discover that the programming structure is crucial in code prompt design, while models are more robust towards format perturbations.We further explore whether exposing models with more code with conditional statements aids in enhancing causal reasoning abilities. We finetune LLMs on such code corpus, and find their performance improves when prompted with either code prompts or text prompts.
Main Sequence of Human Luminance-evoked Pupil Dynamics
Authors: Coutinho Jonathan D. , Huang Jeff , Lefèvre Philippe , Blohm Gunnar , Munoz Douglas P. 
Published: January 2025

Abstract
Pupil responses are commonly used to provide insight into visual perception, autonomic control, cognition, and various brain disorders. However, making inferences from pupil data can be complicated by nonlinearities in pupil dynamics and variability within and across individuals, which challenge the assumptions of linearity or group-level homogeneity required for common analysis methods. In this study, we evaluated luminance evoked pupil dynamics in young healthy adults (n = 10, M:F = 5:5, age 19–25 years) by identifying nonlinearities, variability, and conserved relationships across individuals to improve the ability to make inferences from pupil data. We found a nonlinear relationship between final pupil diameter and luminance, linearized by considering the logarithm of luminance. Peak diameter change and peak velocity were nonlinear functions of log-luminance for constriction but not dilation responses. Across participants, curve fit parameters characterizing pupil responses as a function of luminance were highly variable, yet there was an across-participant linear correlation between overall pupil size and pupil gain (i.e., diameter change per unit log-luminance change). In terms of within-participant trial-by-trial variability, participants showed greater variability in final pupil size compared with constriction peak diameter change as a function of log-luminance. Despite the variability in stimulus–response metrics within and across participants, we found that all participants showed a highly stereotyped “main sequence” relationship between peak diameter change and peak velocity (independent of luminance). The main sequence relationship can be used to inform models of the neural control of pupil dynamics and as an empirical analysis tool to evaluate variability and abnormalities in pupil behavior.