bluuebunny/crossref_metadata_2025_split huggingface dataset:
A machine learning approach towards assessing consistency and reproducibility: an application to graft survival across three kidney transplantation eras
Authors: Achilonu Okechinyere , Obaido George , Ogbuokiri Blessing , Aruleba Kehinde , Musenge Eustasius , Fabian June 
Published: September 2024

BackgroundIn South Africa, between 1966 and 2014, there were three kidney transplant eras defined by evolving access to certain immunosuppressive therapies defined as Pre-CYA (before availability of cyclosporine), CYA (when cyclosporine became available), and New-Gen (availability of tacrolimus and mycophenolic acid). As such, factors influencing kidney graft failure may vary across these eras. Therefore, evaluating the consistency and reproducibility of models developed to study these variations using machine learning (ML) algorithms could enhance our understanding of post-transplant graft survival dynamics across these three eras.MethodsThis study explored the effectiveness of nine ML algorithms in predicting 10-year graft survival across the three eras. We developed and internally validated these algorithms using data spanning the specified eras. The predictive performance of these algorithms was assessed using the area under the curve (AUC) of the receiver operating characteristics curve (ROC), supported by other evaluation metrics. We employed local interpretable model-agnostic explanations to provide detailed interpretations of individual model predictions and used permutation importance to assess global feature importance across each era.ResultsOverall, the proportion of graft failure decreased from 41.5% in the Pre-CYA era to 15.1% in the New-Gen era. Our best-performing model across the three eras demonstrated high predictive accuracy. Notably, the ensemble models, particularly the Extra Trees model, emerged as standout performers, consistently achieving high AUC scores of 0.95, 0.95, and 0.97 across the eras. This indicates that the models achieved high consistency and reproducibility in predicting graft survival outcomes. Among the features evaluated, recipient age and donor age were the only features consistently influencing graft failure throughout these eras, while features such as glomerular filtration rate and recipient ethnicity showed high importance in specific eras, resulting in relatively poor historical transportability of the best model.ConclusionsOur study emphasises the significance of analysing post-kidney transplant outcomes and identifying era-specific factors mitigating graft failure. The proposed framework can serve as a foundation for future research and assist physicians in identifying patients at risk of graft failure.
Field strength prediction of 220 kV cable oil terminal defects based on multivariate nonlinear regression model
Authors: Ren Zhigang , Guo Wei , Ji Hongquan , Geng Junwei , Cai Jing , Men Yekun , Liu Bo 
Published: September 2024

During the installation of a cable oil terminal, it is easy to leave scratches on the main insulation owing to uneven forces when removing the semi-conductive layer. Scratch defects cause field intensity distortion, which leads to partial discharge and insulation failure. This study attempts to establish a simulation model of a 220 kV cable terminal to determine the effect of the length, depth, and position of the scratch on the maximum field strength at the defect. The simulation and experiment demonstrate that the maximum field strength at the defect increases with greater length and decreases as the depth increases. Therefore, a prediction method for the terminal defect field strength based on a multivariate nonlinear regression model was proposed in this study. When the defect is located at 20 mm from the root of the stress cone, the maximum field strength is 14.5 MV/m when the length and depth are 2 mm and 1 mm, respectively. The maximum field strength at the defect was predicted based on the length, depth, and position of the scratch defect to evaluate the severity of the defect.
Safety assessment of anti-B cell maturation antigen chimeric antigen receptor T cell therapy: a real-world study based on the FDA adverse event reporting system database
Authors: Liu Wei , Lin Shuzhi , Zhu Xiaoying , Yin Lin , Liu Qian , Lei Shuang , Feng Bianling 
Published: September 2024

BackgroundOn April 18, 2024, the U.S. Food and Drug Administration officially required updating of the “boxed warning” for T cell malignancies for all chimeric antigen receptor T cell (CAR-T) therapies. Given the clinical significance of these therapies, a rigorous safety assessment is paramount. However, comprehensive real-world safety studies have been lacking for the newly marketed CAR-T products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), which target B cell maturation antigen, especially regarding the risk of secondary malignancies. Therefore, we aimed to thoroughly analyze the adverse events (AEs) information in the FDA Adverse Event Reporting System (FAERS) database to comprehensively understand the safety risks of ide-cel and cilta-cel.MethodsWe extracted AE reports related to ide-cel and cilta-cel from the FAERS database (https://fis.fda.gov/extensions/FPD-QDE-FAERS/FPD-QDE-FAERS.html.) from January 1, 2019 to December 31, 2023. Disproportionality analysis and Bayesian analysis were used to identify risk signals across subgroups and specific cases (including for death and secondary malignancies). Weibull distribution analysis was employed to determine the time to AE onset.ResultsA total of 695 AE reports for ide-cel and 848 for cilta-cel were included in the FAERS database. This analysis identified 81 positive signals for ide-cel and 74 for cilta-cel. Notably, comparisons with the drug labels revealed “unexpected signals,” including febrile bone marrow aplasia (reporting odds ratio=69.10; confidence interval 39.12–122.03) and plasma cell myeloma (12.45; 8.18–18.95) for ide-cel, and increased serum ferritin (24.98; 8.0–77.58) and large intestine perforation (18.57; 5.98–57.69) for cilta-cel. Both drugs showed a higher AE incidence among male recipients and patients aged ≥65 years, although female recipients faced a greater risk. Most AEs occurred at the early stage of administration. However, secondary malignancies were detected for both drugs, primarily occurring one-year post-administration.ConclusionThis study provides a foundation for understanding the safety profile of CAR-T cell therapy, particularly in relation to the emergence of secondary malignancies. Such insights are helpful for clinical decision-making and the safe and effective utilization of these therapeutic agents.
Case report: Bridging radiation therapy before chimeric antigen receptor T-cell therapy induces sustained remission in patients with relapsed/refractory double-expressor diffuse large B-cell lymphoma with localized compressive symptoms
Authors: Yang Liying , Wu Mengdi , Yang Hao , Sun Xiaorong , Xing Lijie , Liu Dan , Xing Ligang , Yu Jinming 
Published: September 2024

BackgroundHigh-risk double-expressor diffuse large B-cell lymphoma has an inferior prognosis following standard first-line therapy. After failure of second-line therapy, treatment options are limited if accompanied by localized compressive symptoms. Chimeric Antigen Receptor T cell (CAR-T) therapy preceded by bridging radiotherapy may be an effective emerging therapy.Case presentationWe report a 66-year-old female patient diagnosed with stage IV double-expressor diffuse large B-cell lymphoma. The patient achieved progressive disease after two cycles of rituximab, cyclophosphamide, liposomal doxorubicin, vincristine, and prednisone and continued to develop cervical lymph node recurrence after second-line therapy. The patient was infused with CAR-T cells after receiving focal bridging radiotherapy and remained in complete response more than 9 months after treatment. In addition, the patients did not experience serious adverse reactions related to radiotherapy as well as CAR-T cell therapy.ConclusionsIn this article, we describe a patient with double-expressor diffuse large B-cell lymphoma with localized compression symptoms after second-line treatment failure who benefited from CAR-T combined with focal bridging radiotherapy.
Differential immunological profiles in seronegative versus seropositive rheumatoid arthritis: Th17/Treg dysregulation and IL-4
Authors: Li Baochen , Su Rui , Guo Qiaoling , Su Ronghui , Gao Chong , Li Xiaofeng , Wang Caihong 
Published: September 2024

BackgroundRheumatoid arthritis (RA) is an autoimmune disease with various subtypes. Among these, seronegative rheumatoid arthritis (SnRA), distinguished by its distinctive seronegative antibody phenotype, presents clinical diagnosis and treatment challenges. This study aims to juxtapose the immunological features of SnRA with seropositive rheumatoid arthritis (SpRA) to investigate potential mechanisms contributing to differences in antibody production.MethodsThis study included 120 patients diagnosed with RA and 78 patients diagnosed with psoriatic arthritis (PsA), comprising 41 cases of SnRA and 79 cases of SpRA. Clinical, serological, and immune data were collected from all participants to systematically identify and confirm the most pivotal immunological distinctions between SnRA and SpRA.Results(1) SpRA demonstrates more pronounced T-helper 17 cells (Th17)/Regulatory T cells (Treg) dysregulation, vital immunological differences from SnRA. (2) SpRA exhibits higher inflammatory cytokine levels than SnRA and PsA. (3) Lymphocyte subset ratios and cytokine overall distribution in SnRA close to PsA. (4) Interleukin-4 (IL-4) emerges as the central immunological disparity marker between SnRA and SpRA.ConclusionTh17/Treg imbalance is one of the vital immunological disparities between SnRA and SpRA. Interestingly, PsA and SnRA display similar peripheral blood immunological profiles, providing immunological evidence for these two diseases’ clinical and pathological similarities. Furthermore, IL-4 emerges as the central immunological disparity marker between SnRA and SpRA, suggesting its potential role as a triggering mechanism for differential antibody production.
Chemotherapy combined with lenvatinib and PD-1 may be a potential better alternative option for advanced unresectable intrahepatic cholangiocarcinoma: a retrospective real-world study
Authors: Dong Zhitao , Sui Chengjun , Lu Jiongjiong , Guo Junwu , Duan Kecai , Wang Kui , Geng Li , Dai Binghua , Yang Jiamei 
Published: September 2024

BackgroundCurrently, the prognosis of advanced intrahepatic cholangiocarcinoma (ICC) is poor, and the current treatment methods are not effective.ObjectiveThe aim of this study was to evaluate the anticancer efficacy of chemotherapy combined with PD-1 inhibitors and tyrosine kinase inhibitors (TKIs) in patients with ICC.MethodsWe retrospectively screened patients with advanced intrahepatic cholangiocarcinoma (ICC) who received chemotherapy combined with lenvatinib and PD-1. We evaluated overall survival (OS), progression-free survival (PFS), the objective response rate (ORR), the disease control rate (DCR), the tumor shrinkage rate, and safety.ResultsWe enrolled 95 patients with ICC and divided them into three groups with a median follow-up duration of 15.1 months. The chemotherapy group (chemo-regimen group), chemotherapy combined with immune checkpoint inhibitors (dual-regimen group), and chemotherapy combined with lenvatinib (triple-regimen group) had median OS times of 13.1 months, 20.8 months, and 39.6 months, respectively. Notably, the triple-regimen group had a significantly longer OS than did the chemo-regimen and dual-regimen groups. The chemo-regimen group, dual-regimen group, and triple-regimen group reported median PFS durations of 4.8 months, 11.9 months, and 23.4 months, respectively. Both combination groups exhibited significantly longer PFS than the chemotherapy-only group (P&lt;0.05). The ORRs of the chemo-regimen, dual-regimen, and triple-regimen groups were 18.2%, 55.5%, and 54.7%, respectively. The DCRs were 72.7%, 90%, and 96.2%, respectively, indicating significantly better outcomes in the combination therapy groups.ConclusionThe combination of chemotherapy with PD-1 inhibitors and lenvatinib demonstrates considerable efficacy and tolerability as a treatment strategy for patients with advanced ICC.
Sequencing technology in sarcopenia: current research progress and future trends
Authors: Yang Yuxia , Meng Xiangji , Dai Xiaomei , Zhang Jian , Dai Jihang , Wang Jingcheng , Fei Wenyong 
Published: September 2024

BackgroundMuscle is an important tissue of the human body. Muscle atrophy is common in people of all ages, which will lead to human weakness and decline of motor function, which is one of the important causes of disability. The common methods of genomics research are transcriptome, proteomics and metabolomics, which are important means to explore the molecular pathology of diseases. In recent years, combinatorial research has been carried out on a large scale in the field of muscle atrophy. However, no author in this field has carried out bibliometrics and visual analysis.MethodsIn this study, articles related to the histological study of muscular dystrophy since 2000 were searched from the Web of Science core database (WoSCC). We will retrieve the results through CiteSpace, VosViewer and R for data statistics and visual analysis.ResultsIn this study, a total of 141 publications were collected, and the number of publications increased year by year. These 141 articles came from 1031 co-authors from 361 institutions in 31 countries and were published in 92 journals. A total of 6286 articles from 1383 journals were cited. Authors from American institutions have published the most articles and have been cited the most, and authors from other countries have also made considerable contributions.ConclusionThis is the first bibliometric and visual analysis of published research in the field of muscular dystrophy through systematic data retrieval and combined with a variety of bibliometric analysis tools. Through these data, we summarize the previous studies of scholars, and provide prospects for future research in the field.
De novo and recurrent post-transplant membranous nephropathy cases show similar rates of concurrent antibody-mediated rejection
Authors: Khorsandi Nikka , Han Hwarang Stephen , Rajalingam Raja , Shoji Jun , Urisman Anatoly 
Published: September 2024

BackgroundMembranous nephropathy (MN) can develop post-kidney transplant and is classified as a recurrent disease in patients with a history of MN in the native kidneys or as de novo disease in patients without such history. The mechanism of recurrent MN is thought to be like that of primary MN, but the mechanism of de novo MN is not well delineated. An association between de novo MN and antibody-mediated rejection (AMR) has been suggested.MethodsA search of the pathology database from our medical center identified 11 cases of recurrent and 15 cases of de novo MN, in which clinical and histologic findings were compared. No significant differences were identified in the demographic characteristics, serum creatinine and proteinuria trends, or rates of allograft failure between the recurrent and de novo MN groups.ResultsRates of concurrent AMR were high in both groups (36% and 40%, respectively) but not statistically different from each other. PLA2R immunofluorescence (IF) positivity was seen in 64% of recurrent MN cases compared to 33% of de novo MN cases, suggesting a higher incidence of PLA2R-positive de novo MN than previously reported. No significant histologic differences were identified in the initial biopsies from the two groups, except mean IgG intensity by IF was higher in the recurrent group, suggesting a higher load of immune complex deposits at diagnosis in this group.ConclusionThe findings do not provide support for a specific association between AMR and de novo MN, but whether there is a possible link between both forms of post-transplant MN and AMR remains an unanswered question.
Examining the overlap between tinnitus and depression questionnaires—protocol for an ICF based content analysis
Authors: Fuchten Denise , Smit Adriana L. , Stegeman Inge 
Published: September 2024

IntroductionTinnitus is a common phenomenon with an estimated prevalence of 14.4% in the adult population. The experienced severity of tinnitus varies significantly among this population. Psychological factors have been identified as major contributors to this perceived severity, and numerous studies have demonstrated a correlation between symptoms of depression and tinnitus severity. However, the assessment of tinnitus severity and depressive symptoms often relies on self-report questionnaires, which show content overlap. This can pose challenges in distinguishing both conditions and interpreting their relationship. To address these challenges, the proposed study aims to examine the overlap between tinnitus and depressive symptom questionnaires by analyzing their content based on the International Classification of Functioning, Disability and Health (ICF) framework.Methods and analysisSix validated, multi-item, self-report questionnaires measuring perceived tinnitus severity (THI, TQ, mTQ, THQ, TRQ, TFI) and seven validated, multi-item, self-report, depressive symptom questionnaires (BDI-II, HADS-D, SDS, PHQ-9, CES-D, SCL-90-R depression subscale, DASS-42 depression subscale) will be included in the content analysis. The content of all items of these questionnaires will be linked to ICF categories and item overlap between the tinnitus and depressive symptom questionnaires will be analyzed.DiscussionBy exploring the overlap between depression and tinnitus questionnaires, this study seeks to gain a better understanding of the relationship between tinnitus and depression, by distinguishing between shared content and independent constructs of symptom scores and shedding light on the factors influencing their measured severity.Ethics and disseminationEthical approval is not required for this study, due to the characteristics of the study design. Findings will be disseminated through peer-reviewed open access publication and scientific conferences.
The different effects of four adenosine receptors in liver fibrosis
Authors: Yang Lan , Gao Zhao-wei , Wang Xi , Wu Xia-nan , Li Si-min , Dong Ke , Zhu Xiao-ming 
Published: September 2024

BackgroundThe adenosine–adenosine receptor pathway plays important roles in the immune system and inflammation. Four adenosine receptors (i.e., A1R, A2AR, A2BR, and A3R) have been identified. However, the roles of these receptors were different in the disease progress and even play opposite roles in the same disease. This study aims to investigate the roles of A1R/A2AR/A2BR/A3R activation in liver fibrosis.MethodsIntraperitoneal injection of CCl4 into C57BL/6 mice was used to induce liver fibrosis in the models. Adenosine receptor agonists CCPA, CGS21680, BAY 60-6583, and namodenoson were used for A1R/A2AR/A2BR/A3R activation, respectively. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were used to evaluate the liver function. Hematoxylin and eosin (H&amp;E) staining was used to investigate the pathological damage. Masson staining and Sirius Red staining were performed to evaluate the degree of collagen deposition. CCK8 and scratch assays were used to investigate the proliferation and migration ability of hepatic stellate cells (HSCs).ResultsBy using liver fibrosis mouse models, we observed that the A1R and A2AR agonists aggravated liver fibrosis, characterized by increasing ALT and AST levels, more serious liver pathological damage, and collagen deposition. However, the A2BR and A3R agonists alleviated liver fibrosis. Moreover, the A1R and A2AR agonist treatment promotes the proliferation and migration of HSC line LX2, while A2BR and A3R agonist treatment inhibited LX2 proliferation and migration. Consistently, A1R and A2AR agonist treatment elevated the expression of α-SMA and Col1α1 in LX2, whereas A2BR and A3R agonist treatment inhibited the expression of α-SMA and Col1α1 in LX2 cells. Additionally, 5′-N-ethyl-carboxamidoadenosine (NECA), a metabolically stable adenosine analog, alleviated liver fibrosis and inhibited LX2 cell activity, proliferation, and migration.ConclusionThis study demonstrated the different roles of A1R/A2AR/A2BR/A3R during liver fibrosis development via regulating the HSC activity and proliferation.
Effect of ketone monoester supplementation on elite operators’ mountaineering training
Authors: Miyatsu Toshiya , McAdam Jeremy , Coleman Kody , Chappe Ed , Tuggle Steven C. , McClure Tyler , Bamman Marcas M. 
Published: September 2024

IntroductionSpecial Operations Forces (SOF) often conduct operations in physiologically stressful environments such as severe heat, cold, or hypoxia, which can induce decreases in a variety of cognitive abilities. Given the promising empirical demonstration of the efficacy of exogenous ketone monoester (KME) supplementation in attenuating cognitive performance decrease during hypoxia at rest in a laboratory setting, we conducted a real-world, field experiment examining KME’s efficacy during high-altitude mountaineering, an austere environment in which US SOF have conducted increasing numbers of operations over the past two decades.MethodsSpecifically, 34 students and cadre at the US Army 10th Special Forces Group Special Operations Advanced Mountaineering School (SOAMS) participated in a randomized, double-blind, placebo (PLA)–controlled crossover trial (KME vs. PLA) over 2 days of tactical mountain operations training. The participants ascended from 7,500 ft in altitude (basecamp) to 12,460 ft on 1 day and 13,627 ft the other day (in randomized order), while performing various training activities inducing high physical and cognitive loads over 8–12 h, and consumed six doses of KME or PLA 2–3 h apart throughout each training day.Results and DiscussionWhile KME increased blood ketone levels and decreased glucose levels, there were no clear indications that the elevated ketone level enhanced physical or cognitive performance. KME also produced a greater incidence of heartburn, nausea, and vomiting. In these elite operators, high-altitude mountaineering had a limited impact on cognitive performance, and KME supplementation did not demonstrate any benefit.