bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial intelligence empowering rare diseases: a bibliometric perspective over the last two decades
Authors: Ou Peiling , Wen Ru , Shi Linfeng , Wang Jian , Liu Chen 
Published: September 2024

Abstract
Objective
To conduct a comprehensive bibliometric analysis of the application of artificial intelligence (AI) in Rare diseases (RDs), with a focus on analyzing publication output, identifying leading contributors by country, assessing the extent of international collaboration, tracking the emergence of research hotspots, and detecting trends through keyword bursts.

Methods
In this bibliometric study, we identified and retrieved publications on AI applications in RDs spanning 2003 to 2023 from the Web of Science (WoS). We conducted a global research landscape analysis and utilized CiteSpace to perform keyword clustering and burst detection in this field.

Results
A total of 1501 publications were included in this study. The evolution of AI applications in RDs progressed through three stages: the start-up period (2003–2010), the steady development period (2011–2018), and the accelerated growth period (2019–2023), reflecting this field’s increasing importance and impact at the time of the study. These studies originated from 85 countries, with the United States as the leading contributor. “Mutation”, “Diagnosis”, and “Management” were the top three keywords with high frequency. Keyword clustering analysis identified gene identification, effective management, and personalized treatment as three primary research areas of AI applications in RDs. Furthermore, the keyword burst detection indicated a growing interest in the areas of “biomarker”, “predictive model”, and “data mining”, highlighting their potential to shape future research directions.

Conclusions
Over two decades, research on the AI applications in RDs has made remarkable progress and shown promising results in the development. Advancing international transboundary cooperation is essential moving forward. Utilizing AI will play a more crucial role across the spectrum of RDs management, encompassing rapid diagnosis, personalized treatment, drug development, data integration and sharing, and continuous monitoring and care.
Recruitment of USP10 by GCS1 to deubiquitinate GRP78 promotes the progression of colorectal cancer via alleviating endoplasmic reticulum stress
Authors: Chen Yang , Shen Hengyang , Wang Zhenling , Huang Changzhi , Zhang Hongqiang , Shao Yu , Tong Ying , Xu Lei , Lu Yunfei , Fu Zan 
Published: September 2024

Abstract
Background
Long-term accumulation of misfolded proteins leads to endoplasmic reticulum (ER) stress in colorectal cancer (CRC). However, the precise pathways controlling the decision between survival and apoptosis in CRC are unclear. Therefore, in this study, we investigated the function and molecular mechanism of glucosidase I (GCS1) in regulating ER stress in CRC.

Methods
A public database was used to confirm the expression level of GCS1 in CRC and normal tissues. Clinical samples from our center were used to confirm the mRNA and protein expression levels of GCS1. Cell proliferation, migration, invasion, and apoptosis assays revealed the biological role of GCS1. Immunohistochemical techniques were used to evaluate the expression of key proteins in subcutaneous implanted tumors in nude mice, which provided further evidence for the biological function of GCS1 in promoting cancer in vivo. The results of coimmunoprecipitation-mass spectrometry analysis and immunofluorescence colocalization analysis the interaction between GCS1 and GRP78. In addition, the mechanism of action of USP10, GRP78, and GCS1 at the post- translational level was investigated. Finally, a tissue microarray was used to examine the connection between GCS1 and GRP78 expression and intracellular localization of these proteins using immunohistochemistry and immunofluorescence.

Results
The experimental results revealed that GCS1 was substantially expressed in CRC, with higher expression indicating a worse prognosis. Thus, GCS1 can enhance the proliferation and metastasis while inhibiting the apoptosis of CRC cells both in vivo and in vitro. Mechanistically, GCS1 binds to GRP78, recruits USP10 for deubiquitination of GRP78 to promote its degradation, and decreases ER stress-mediated apoptosis, increasing CRC cell proliferation and metastasis.

Conclusions
In summary, GCS1 stimulates CRC growth and migration and reduces ER stress-mediated apoptosis via USP10-mediated deubiquitination of GRP78. Our findings identify a possible therapeutic target for CRC.
STUB1-mediated K63-linked ubiquitination of UHRF1 promotes the progression of cholangiocarcinoma by maintaining DNA hypermethylation of PLA2G2A
Authors: Chen Junsheng , Wang Da , Wu Guanhua , Xiong Fei , Liu Wenzheng , Wang Qi , Kuai Yiyang , Huang Wenhua , Qi Yongqiang , Wang Bing , Chen Yongjun 
Published: September 2024

Abstract
Background
Cholangiocarcinoma (CCA) is a highly malignant tumor characterized by a lack of effective targeted therapeutic strategies. The protein UHRF1 plays a pivotal role in the preservation of DNA methylation and works synergistically with DNMT1. Posttranscriptional modifications (PTMs), such as ubiquitination, play indispensable roles in facilitating this process. Nevertheless, the specific PTMs that regulate UHRF1 in CCA remain unidentified.

Methods
We confirmed the interaction between STUB1 and UHRF1 through mass spectrometry analysis. Furthermore, we investigated the underlying mechanisms of the STUB1-UHRF1/DNMT1 axis via co-IP experiments, denaturing IP ubiquitination experiments, nuclear‒cytoplasmic separation and immunofluorescence experiments. The downstream PLA2G2A gene, regulated by the STUB1-UHRF1/DNMT1 axis, was identified via RNA-seq. The negative regulatory mechanism of PLA2G2A was explored via bisulfite sequencing PCR (BSP) experiments to assess changes in promoter methylation. The roles of PLA2G2A and STUB1 in the proliferation, invasion, and migration of CCA cells were assessed using the CCK-8 assay, colony formation assay, Transwell assay, wound healing assay and xenograft mouse model. We evaluated the effects of STUB1/UHRF1 on cholangiocarcinoma by utilizing a primary CCA mouse model.

Results
This study revealed that STUB1 interacts with UHRF1, resulting in an increase in the K63-linked ubiquitination of UHRF1. Consequently, this facilitates the nuclear translocation of UHRF1 and enhances its binding affinity with DNMT1. The STUB1-UHRF1/DNMT1 axis led to increased DNA methylation of the PLA2G2A promoter, subsequently repressing its expression. Increased STUB1 expression in CCA was inversely correlated with tumor progression and overall survival. Conversely, PLA2G2A functions as a tumor suppressor in CCA by inhibiting cell proliferation, invasion and migration.

Conclusions
These findings suggest that the STUB1-mediated ubiquitination of UHRF1 plays a pivotal role in tumor progression by epigenetically silencing PLA2G2A, underscoring the potential of STUB1 as both a prognostic biomarker and therapeutic target for CCA.

Graphical Abstract
Endogenous retroviral ERVH48-1 promotes human urine cell reprogramming
Authors: Peng Yuling , Zhu Jieying , Zhang Qi , Zhang Ran , Wang Zhenhua , Ye Zesen , Ma Ning , Qin Dajiang , Pei Duanqing , Li Dongwei 
Published: September 2024

AbstractEndogenous retroviruses (ERVs), once thought to be mere remnants of ancient viral integrations in the mammalian genome, are now recognized for their critical roles in various physiological processes, including embryonic development, innate immunity, and tumorigenesis. Their impact on host organisms is significant driver of evolutionary changes, offering insight into evolutionary mechanisms. In our study, we explored the functionality of ERVs by examining single-cell transcriptomic profiles from human embryonic stem cells and urine cells. This led to the discovery of a unique ERVH48-1 expression pattern between these cell types. Additionally, somatic cell reprogramming efficacy was enhanced when ERVH48-1 was overexpressed in a urine cell-reprogramming system. Induced pluripotent stem cells (iPSCs) generated with ERVH48-1 overexpression recapitulated the traits of those produced by traditional reprogramming approaches, and the resulting iPSCs demonstrated the capability to differentiate into all three germ layers in vitro. Our research elucidated the role of ERVs in somatic cell reprogramming.
Anxiety matters: a pilot lab study into food, weight, and virtual body exposure in anorexia nervosa
Authors: Melles Hanna , Jansen Anita 
Published: September 2024

Abstract
Background
Anxiety is a core characteristic of anorexia nervosa and a potential target of exposure therapy, which requires a profound understanding of the patients’ fears in order to be successful. The knowledge about fears in anorexia nervosa that should be targeted during exposure therapy can be enriched by laboratory research to the precise emotional and behavioral responses of anorexia nervosa patients when they are exposed to disorder relevant fear stimuli.

Methods
In the laboratory, patients with anorexia nervosa (n = 15) and healthy controls (n = 51) were exposed to 1. their own body weight and a 10% higher body weight on the scale, 2. a standardized lab breakfast, and 3. five virtual bodies with different BMIs ranging from extreme underweight to lower healthy weight. The participants emotional (anxiety, disgust, satisfaction, acceptance) and behavioral responses (calorie consumption) were assessed. Patients with anorexia nervosa but not the healthy controls then received an intensive exposure treatment (~ 30 individual exposure sessions) targeting their individual fears, next to standard care. After the exposure treatment, it was investigated whether the patients’ responses to the laboratory tasks changed.

Results
Across all tasks, the patients reported more anxiety than healthy controls. The patients also consumed less calories during the breakfast and accepted the different body weights on the scale less than healthy controls. During the virtual body exposure, the patients’ emotional responses did not differ per avatar but they reacted more negatively towards avatars with healthier weights than did healthy controls. After the exposure treatment, the patients reported less fears and they consumed more calories while their BMIs had increased. They were also more accepting of healthier weights.

Conclusions
Exposure to food-, body- and weight-related stimuli in the laboratory induces emotional reactions in patients with anorexia nervosa that are informative for the identification of exposure therapy treatment targets. In addition, exposure therapy targeting individual fears in patients with anorexia nervosa led to symptom reduction and is a promising intervention for the treatment of anorectic fears, though more research is needed to optimize its efficacy.
18F-FDG PET/CT metrics-based stratification of large B-cell lymphoma receiving CAR-T cell therapy: immunosuppressive tumor microenvironment as a negative prognostic indicator in patients with high tumor burden
Authors: Sheng Ling-Shuang , Shen Rong , Yan Zi-Xun , Wang Chao , Zheng Xin , Zhang Yi-Lun , Yang Hao-Xu , Wu Wen , Xu Peng-Peng , Cheng Shu , Bachy Emmanuel , Sesques Pierre , Jacquet-Francillon Nicolas , Jiang Xu-Feng , Zhao Wei-Li , Wang Li 
Published: September 2024

AbstractChimeric antigen receptor T (CAR-T) cell therapy has greatly improved the prognosis of relapsed and refractory patients with large B-cell lymphoma (LBCL). Early identification and intervention of patients who may respond poorly to CAR-T cell therapy will help to improve the efficacy. Ninety patients from a Chinese cohort who received CAR-T cell therapy and underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scans at the screening stage (median time to infusion 53.5 days, range 27–176 days), 1 month and 3 months after CAR-T cell infusion were analyzed, with RNA-sequencing conducted on 47 patients at the screening stage. Patients with maximum diameter of the largest lesion (Dmax) < 6 cm (N = 60) at screening stage showed significantly higher 3-month complete response rate (85.0% vs. 33.3%, P < 0.001), progression-free survival (HR 0.17; 95% CI 0.08–0.35, P < 0.001) and overall survival (HR 0.18; 95% CI 0.08–0.40, P < 0.001) than those with Dmax ≥ 6 cm (N = 30). Besides, at the screening stage, Dmax combined with extranodal involvement was more efficient in distinguishing patient outcomes. The best cut-off values for total metabolic tumor volume (tMTV) and total lesion glycolysis (tTLG) at the screening stage were 50cm3 and 500 g, respectively. A prediction model combining maximum standardized uptake value (SUVmax) at 1 month after CAR-T cell therapy (M1) and tTLG clearance rate was established to predict early progression for partial response/stable disease patients evaluated at M1 after CAR-T cell therapy and validated in Lyon cohort. Relevant association of the distance separating the two farthest lesions, standardized by body surface area to the severity of neurotoxicity (AUC = 0.74; P = 0.034; 95% CI, 0.578–0.899) after CAR-T cell therapy was found in patients received axicabtagene ciloleucel. In patients with Dmax ≥ 6 cm, RNA-sequencing analysis conducted at the screening stage showed enrichment of immunosuppressive-related biological processes, as well as increased M2 macrophages, cancer-associated fibroblasts, myeloid-derived suppressor cells, and intermediate exhausted T cells. Collectively, immunosuppressive tumor microenvironment may serve as a negative prognostic indicator in patients with high tumor burden who respond poorly to CAR-T cell therapy.
Sequence analysis and process mining perspectives to goal setting: What distinguishes business students with high and low self-efficacy beliefs?
Authors: Heikkinen Sami , Cristea Tudor , Saqr Mohammed , Malmberg Jonna , Kleingeld Ad , Snijders Chris , Matzat Uwe , Tedre Matti 
Published: September 2024

AbstractThis study investigates the relationship between students' self-efficacy beliefs, goal-setting, and learning tactics in an online business course. Using sequence analysis and process mining techniques, we analyzed log data from 209 students to identify distinct learning tactics and their association with self-efficacy beliefs, inferred from initial goal-setting and final grades. Four learning tactics were identified, with significant differences observed between students with high and low self-efficacy beliefs. High self-efficacy students demonstrated more varied and adaptive tactics, including greater use of quizzes and project-focused activities. In contrast, low self-efficacy students and those who didn't set goals showed less engagement and fewer monitoring activities. The project-focused tactic had the strongest correlation with final grades and goal achievement. Goal-setting at the course's start was linked to more effective learning behaviors and better outcomes. The study reveals how students' online learning behavior changes based on initial goal-setting and subsequent reflection. These findings contribute to research on self-regulated learning in online environments and offer practical implications for designing online courses and learning analytics interventions. Understanding these differences enables the development of targeted interventions to improve learning tactics and self-efficacy beliefs among students, ultimately enhancing their ability to achieve learning goals in online educational settings.
Volcanic activity around Taipei, Taiwan: new data and perspectives on the Tatun Volcano Group
Authors: Chang Su-Chin , Chu Mei-Fei , Wang Jui-Pin , Lai Yu-Ming , Song Sheng-Rong , Hemming Sidney R. , Ng Samuel Wai-Pan , Chow Timothy Dylan 
Published: September 2024

AbstractThe Tatun Volcano Group (TVG) is located at the northern end of Taiwan, ~ 15 km from the center of Taipei, a metropolitan area of over seven million inhabitants. A volcanic eruption by the TVG of any type or scale could cause catastrophic human and economic impacts. This paper summarizes previous geochemical, geophysical, and geochronological reports and highlights why the widely accepted age model does not comport with the latest observations. This study also reports novel40Ar/39Ar ages for two andesite samples and one basalt sample from the TVG. A sample collected from Chihsingshan yields a robust40Ar/39Ar age of 0.081 ± 0.005 Ma. This provides the first direct evidence of TVG volcanic activity after 0.1 Ma. Two samples yield 0.28 ± 0.02 Ma for Tatunshan and 0.159 ± 0.017 Ma for Honglushan. The younger ages refute previously proposed age models for the TVG. Along with new drone photos and LiDAR images, the age data help resolve eruptive history and advance understanding of volcanic hazards and hazard mitigation in Taiwan and surrounding areas.
Patient engagement as a collaborative process in a large Dutch COVID-19 vaccination study (RECOVAC) – insight into the contribution of patient engagement and learnings for the future
Authors: Vervoort J. P. M. , Konijn W. S. , Jansen D. E. M. C. , Boersma C. , de Zeeuw J. , Ho-dac – Pannekeet M. M. , Gansevoort R. T. , Messchendorp A. L. , Sanders J. S. F. , de Wildt-Liesveld R. 
Published: September 2024

Abstract
Background
The need for patient engagement in health research has been increasingly acknowledged and accepted in recent years. However, implementation is still limited due to lack of evidence on its value and lack of guidance on how to implement patient engagement. This study aims to provide insight into the contribution of patient engagement in the RECOVAC project, which studied COVID-19 vaccination in kidney patients, and formulate concrete practice-based action perspectives for patient engagement.

Methods
We used a qualitative participatory mixed methods approach, based on the Patient Engagement Monitoring and Evaluation (PEME) framework. Patient engagement and data collection were based on the Reflexive Monitoring in Action (RMA) approach. Data collection included participant observations, open ended questionnaires and interactive reflection sessions. Qualitative analysis was done via a thematic approach.

Results
We have described the process of patient engagement systematically, provided insight in its value and found that there is a need for clear aims, expectations and preparations from the start of the engagement process. We have shown that reflection throughout the process is of utmost importance and the same applies to clear communication between researchers and patient representatives. By being part of the consortium patient representatives had direct access to information, straight from the source, on for example the vaccination schedule and medication availability and had indirect influence on decisions made by the National Institute for Public Health and the Environment (RIVM) on preventive measures and treatment against COVID-19. Having experienced patient representatives is important, otherwise training needs to be provided. We also found that patient engagement had impact on conduct and outcomes of research activities itself and may have impact on future research and patient engagement activities in general.

Conclusion
Patient engagement has changed the course of the project. Concrete practice-based action perspectives have been formulated, which are already being implemented by the Dutch Kidney Patients Association (NVN). Studying patient engagement in a high pace project with high public interest has resulted in lessons learned and will help prepare and implement patient involvement in future research projects.

Clinical trial registration
The RECOVAC studies in which the patient engagement took place are registered at clinicialtrial.gov (NCT04741386 registration date 2021-02-04, NCT04841785 registration date 2021-03-22 and NCT05030974 registration date 2021-08-20).
A mixed methods study of suicide protective factors in college students
Authors: Cecchin Hareli Fernanda Garcia , da Costa Hellen Emily Rodrigues , Pacheco Gabriela Ramos , de Valencia Gabriel Barcellos , Murta Sheila Giardini 
Published: September 2024

Abstract
Introduction
Mental health professionals, teachers, families, and public administrators are concerned about suicide rates among young people, particularly in the university context. For every ten college students worldwide, three attempt suicide in their lifetime, and two experience suicidal ideation. Reducing these rates requires interventions that recognize the problem in terms of risk factors and protective factors.

Objective
The general aim of the study was to map the protective factors for suicide among college students, as perceived by them, mental health professionals, and coordinators of undergraduate courses in a public university in the North of Brazil.

Methods
The study followed an exploratory, mixed-method design. Data were collected through interviews and the application of a questionnaire with 54 participants, including college students (n = 20), mental health professionals (n = 22), and course coordinators (n = 12). Data were analyzed using Content Analysis and simple descriptive statistics.

Results
The findings show that the protective factors for suicide most cited among the three groups were social support, strengthening of internal resources, institutional support, and finding meaning about the change to enter the university. Although the three audiences did not converge, the protective factors also frequently reported were psychological treatment, leisure activities, religious engagement, medical treatment, civic engagement, employability, opportunities for social ascension offered by the university, and quality family relationships.

Conclusion
It is suggested that these protective factors are considered when formulating policies to promote mental health and suicide prevention in the university environment.
Carbon dioxide-enhanced angiography for detection of colonic diverticular bleeding and clinical outcomes
Authors: Kitamura Ryoichi , Maruhashi Takaaki , Woodhams Reiko , Suzuki Koyo , Kurihara Yutaro , Fujii Kaoru , Asari Yasushi 
Published: September 2024

Abstract
Purpose
To determine the ability of CO2-enhanced angiography to detect active diverticular bleeding that is not detected by iodinated contrast medium (ICM)-enhanced angiography and its impact on clinical outcomes when used to confirm embolization, particularly the risks of rebleeding and ischemic complications.

Materials and methods
We retrospectively identified a cohort of patients with colonic diverticular bleeding who underwent catheter angiography between August 2008 and May 2023 at our institution. We divided them according to whether they underwent CO2 angiography following a negative ICM angiography study or to confirm hemostasis post-embolization (the CO2 angiography group) or ICM angiography alone in the absence of active bleeding or for confirmation of hemostasis post-embolization (the ICM angiography group). The ability to detect active colonic diverticular bleeding and clinical outcomes were compared between the two groups.

Results
There were 31 patients in the ICM angiography group and 29 in the CO2 angiography group. The rate of detection of active bleeding by CO2 angiography that was not identified by ICM angiography was 48%. The rebleeding rate was 23% in the ICM angiography group and 6.9% in the CO2 angiography group. Among the patients who underwent TAE, the ischemic complications rate was 7.1% in the ICM angiography group and 4.5% in the CO2 angiography group.

Conclusions
CO2 angiography may detect active diverticular bleeding that is not detectable by ICM angiography and appears to be associated with a lower rebleeding rate.

Level of evidence
IV.

Graphical Abstract