bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and biomarker analyses of hepatic arterial infusion chemotherapy plus lenvatinib and PD-1 inhibitor for patients with advanced intrahepatic cholangiocarcinoma
Authors: Huang YeXing , Du ZeFeng , Kan Anna , He MinKe , Li HuiFang , Lai ZhiCheng , Wen DongSheng , Huang LiChang , Li QiJiong , Xu Li , Shi Ming 
Published: February 2024

BackgroundIntrahepatic cholangiocarcinoma (iCCA) is a highly aggressive cancer with a dismal prognosis and few effective therapeutic approaches. This study aimed to investigate the efficacy, safety, and predictive biomarkers of hepatic arterial infusion chemotherapy (FOLFOX-HAIC) in combination with lenvatinib and PD-1 inhibitor for patients with advanced iCCA.MethodsLocally advanced or metastatic iCCA patients receiving the triple combination therapy of lenvatinib, PD-1 inhibitor, and FOLFOX-HAIC were included in this retrospective study. Primary endpoint was the progression-free survival, evaluated using the RECIST criterion. The secondary endpoints included overall survival, objective response rate, and safety. Whole exome and RNA sequencing of tumor biopsy tissues were performed for biomarker exploration.ResultsBetween May, 2019 and December 2022, a total of 46 patients were included in this study. The primary endpoint showed a median progression-free survival of 9.40 months (95% CI: 5.28-13.52), with a 6-month progression-free survival rate of 76.1%. The median overall survival was 16.77 months (95% CI, 14.20-19.33), with an objective response rate of 47.8% and disease control rate of 91.3% per RECIST. In addition, 4.3% and 8.7% of patients achieved complete response of all lesions and intrahepatic target lesions per mRECIST, respectively. The most common treatment-related adverse events were neutropenia, thrombocytopenia, elevated aspartate aminotransferase and alanine aminotransferase level. Furthermore, integrated analysis of genetic, transcriptomic, and immunohistochemistry data revealed that pre-existing immunity (high expression level of immune-related signatures and intra-tumoral CD8+ T cell density) in baseline tumor tissues was associated with superior clinical benefits. However, the evaluation of tumor mutation burden did not show potential predictive value in this triple combination.ConclusionFOLFOX-HAIC in combination with lenvatinib and PD-1 inhibitor demonstrated a promising antitumor activity with manageable safety profiles in patients with advanced iCCA. Moreover, our study also revealed new perspectives on potential biomarkers for clinical efficacy.
Global research trends on innate lymphoid cells in the brain, gut and lung field: a bibliometric and visualized analysis
Authors: Huang Jianliang , Deng Kun , Liu Ying , Xia Mingkai , Lei Mingsheng , Wu Minghua 
Published: February 2024

BackgroundILCs play important roles in the brain, gut, and lungs. Researchers are attempting to establish a research framework on the brain-gut-lung axis using ILCs. However, no one has yet conducted a bibliometric analysis to summarize the findings. In this study, we utilized bibliometrics to analyze the emerging trends and focal areas of ILCs in the brain, intestine, and lung. We aim to provide references for future research on the brain-gut-lung axis.MethodsTo conduct a comprehensive bibliometric analysis on ILCs in the fields of brain, intestine, and lung, we utilized software such as HistCite, VOSviewer, and CiteSpace. Our analysis focused on various aspects, including the number of publications, countries, authors, journals, co-cited documents, and keywords. This approach allowed us to gain valuable insights into the research landscape surrounding ILCs in these specific fields.ResultsA total of 8411 articles or reviews on ILCs in the fields of brain, intestine, and lung were included. The number of published articles has shown a consistent upward trend since 2003. A total of 45279 authors from 99 countries have contributed to these articles. The United States has the highest number of publications (n=3044) and the most cited articles (TGCS=210776). The top three published authors in this field are David Artis, Marco Colonna and Andrew NJ McKenzie. The journal Immunity is the most authoritative choice for researchers. The main research focuses in this field include NK cell, ILC2, tumor immunity, multiple sclerosis, inflammatory bowel disease, airway inflammation, RORγT, and immunotherapy. In recent years, cancer and tumor microenvironment have emerged as hot keywords, particularly immunotherapy, PD-1 related directions, indicating a potential shift in research focus.ConclusionEuropean and American countries have been pivotal in conducting research on ILCs, while China has produced a significant number of publications, its impact is still limited. Tumors are likely to emerge as the next focal points in this field. The connection and regulation between the brain and the lung are not yet fully understood, and further investigation is necessary to explore the role of ILCs in the brain-lung axis.
Fc receptors are key discriminatory markers of granulocytes subsets in people living with HIV-1
Authors: Marsile-Medun Soledad , Souchard Manon , Abba Moussa Daouda , Reynaud Élisa , Tuaillon Edouard , Naranjo-Gomez Mar , Pelegrin Mireia 
Published: February 2024

IntroductionGranulocytes are innate immune cells that play a key role in pathogen elimination. Recent studies revealed the diversity of granulocytes in terms of phenotype and function. In particular, a subset of granulocytes identified as low-density granulocytes (LDG) has been described in physiological conditions and with increased frequencies in several pathological contexts. However, the properties of LDG are still controversial as they vary according to the pathophysiological environment. Here we investigated the heterogeneity of granulocyte populations and the potential differences in phenotype and immunomodulatory capacity between LDG and normal density granulocytes (NDG) in people living with HIV-1 (PLWH).MethodsTo this end, we developed an optimized method to purify LDG and NDG from a single blood sample, and performed in-depth, comparative phenotypic characterization of both granulocyte subtypes. We also assessed the impact of purification steps on the expression of cell surface markers on LDG by immunophenotyping them at different stages of isolation.ResultsWe identified 9 cell surface markers (CD16, CD32, CD89, CD62L, CD177, CD31, CD10, CXCR4 and CD172α) differentially expressed between LDG and NDG. Noteworthy, markers that distinguish the two subsets include receptors for the Fc part of IgG (CD16, CD32) and IgA (CD89). Importantly, we also highlighted that the purification procedure affects the expression of several cell surface markers (i.e.CD63, CD66b, …) which must be taken into account when characterizing LDG. Our work sheds new light on the properties of LDG in PLWH and provides an extensive characterization of this granulocyte subset in which Fc receptors are key discriminatory markers.
The experience of good mentoring focused on overcoming turnover intention among millennial nurses
Authors: Jung Seo-Yeon , Kim Jung-Hee 
Published: February 2024

IntroductionMillennials are emerging as a prominent demographic in the nursing workforce. It is necessary to create an environment that harmonizes the advantages of each generation in a nursing workforce in which various generations coexist. As the importance of mentoring programs for millennial nurses grows, it is believed that the effectiveness of mentoring to support millennial nurses can be enhanced by identifying the attributes of good mentors as perceived by nurses. This study aimed to explore the attributes of good mentors according to millennial nurses in the nursing workforce with a focus on overcoming turnover intention problems.MethodsFour focus group interviews were conducted to collect data, which were subsequently analyzed using Braun and Clarke’s thematic analysis method. A descriptive qualitative design involving 22 millennial nurses employed at a tertiary hospital, Hospital A, in Seoul, Republic of Korea was utilized.Results and discussionFour themes emerged from the analysis: the concept of a significant others, the presence of a driving force to endure, the importance of a guide to a harmonious life, and the value of a partner for growth. The participants themselves identified these themes. To prevent turnover intention among millennial nurses, mentors should employ diverse strategies, and institutional supports are crucial. Furthermore, since it is unrealistic to expect all ideal mentor characteristics to be present in one person, mentor development education is also necessary. This information is valuable for designing mentor development programs and for establishing a solid framework for effective mentoring programs.
Risk factors for progression of pulmonary fibrosis: a single-centered, retrospective study
Authors: Fan Jia-Jia , Gu Jin-Min , Xiao Si-Yao , Jia Ming-Yue , Han Gui-Ling 
Published: February 2024

ObjectiveThis study aimed to identify clinical characteristics associated with the prevalence of progressive pulmonary fibrosis (PPF) in interstitial lung disease (ILD) and to develop a prognostic nomogram model for clinical use.MethodsIn this single-centered, retrospective study, we enrolled ILD patients with relatively comprehensive clinical data and assessed the incidence of PPF within a year using collected demographics, laboratory data, high-resolution computed tomography (HRCT), and pulmonary function test (PFT) results. We used a training cohort of ILD patients to identify early predictors of PPF and then validated them in an internal validation cohort and subsets of ILD patients using a multivariable logistic regression analysis. A prognostic nomogram was formulated based on these predictors, and the accuracy and efficiency were evaluated using the area under the receiver operating characteristic curve (AUC), calibration plot, and decision curve analysis (DCA).ResultsAmong the enrolled patients, 120 (39.09%) cases had connective tissue disease-associated interstitial lung disease (CTD-ILD), 115 (37.46%) had non-idiopathic pulmonary fibrosis idiopathic interstitial pneumonia (non-IPF IIP), and 35 (11.4%) had hypersensitivity pneumonitis (HP). Overall, 118 (38.4%) cases experienced pulmonary fibrosis progression. We found that baseline DLco% pred (OR 0.92; 95% CI, 8.93–0.95) was a protective factor for ILD progression, whereas combined pneumonia (OR 4.57; 95% CI, 1.24–18.43), modified Medical Research Council dyspnea score (mMRC) (OR 4.9; 95% CI, 2.8–9.5), and high-resolution computed tomography (HRCT) score (OR 1.22; 95% CI, 1.07–1.42) were independent risk factors for PPF. The AUC of the proposed nomogram in the development cohort was 0.96 (95% CI, 0.94, 0.98), and the calibration plot showed good agreement between the predicted and observed incidence of PPF (Hosmer–Lemeshow test: P = 0.86).ConclusionILD patients with combined pneumonia, low baseline DLco% pred, high mMRC marks, and high HRCT scores were at higher risk of progression. This nomogram demonstrated good discrimination and calibration, indicating its potential utility for clinical practice.
The systemic immune-inflammation index is significantly associated with the severity of silicosis: a 9-year retrospective study in Beijing
Authors: Kang Han-Yu-Jie , Cao Si-Yu , Shao Shuai , Liang Li-Rong , Tong Zhao-Hui 
Published: February 2024

BackgroundSilicosis shows an increasing trend with the development of new industries. However, the potential biomarkers for predicting the disease severity are lacking. A novel inflammatory marker, the systemic immune-inflammation Index (SII), has not been studied in silicosis.MethodsIn this retrospective study, we used data from a big database platform of a tertiary general hospital in Beijing, which was established based on the electronic medical records of the hospital. The clinical data of adult patients diagnosed with silicosis at the Department of Occupational Medicine and Toxicology from 2013 to 2022 were collected. The data extracted from the database were in de-identified form. Only patients with a first diagnosis of silicosis and without conditions that might affect the parameters of routine blood tests were included in the analysis. Analyses were performed to assess the relationship between SII and the advanced stage of silicosis.ResultsA total of 246 participants were included in the study. Most of the patients were exposed to silica particles during excavation and digging (n = 149, 60.6%). SII level was significantly higher in patients with advanced stages of silicosis. A multivariate logistic regression analysis revealed that a higher SII level was associated with the advanced stage of silicosis [odds ratio (OR) = 1.002; 95% confidence interval (CI): 1.000–1.003, p &lt; 0.001] after adjusting for all covariates. The best cutoff value of SII was 444.1. The results of the subgroup analysis also showed a significant correlation between SII level over 444.1 and the advanced stage of silicosis in groups stratified by gender, history of smoking, and duration of silica exposure. Moreover, our results showed a significant but weak negative correlation between the level of SII and some lung function parameters in silicosis.ConclusionHigher SII is associated with the advanced stage of silicosis and impaired lung function. More long-term, large-scale studies are needed to confirm these findings.
No evidence for a causal link between Helicobacter pylori infection and Irritable bowel syndrome: a Mendelian randomization study
Authors: Wang Chenchen , Zhang Jing , Han Fengli , Liu Dong , Han Yuying 
Published: February 2024

BackgroundAlthough clinical studies have revealed a potential link between Helicobacter pylori (H. pylori) infection and irritable bowel syndrome (IBS), the causal relationship between them remains unknown. The objective of this study was to investigate whether H. pylori infection is causally associated with IBS.MethodA two-sample Mendelian randomization (MR) analysis using the inverse variance weighted (IVW), weighted mode, weighted median and MR-Egger methods was performed. We used the publicly available summary statistics data sets of genome-wide association studies (GWAS) for H. pylori infection in individuals of European descent (case = 1,058, control = 3,625) as the exposure and a GWAS for non-cancer illness code self-reported: IBS (case = 10,939, control = 451,994) as the outcome.ResultsWe selected 10 single nucleotide polymorphisms at genome-wide significance from GWASs on H. pylori infection as the instrumental variables. The IVW, weighted mode, weighted median and MR-Egger methods all provided consistent evidence that suggests a lack of causal association between H. pylori and IBS. MR-Egger regression revealed that directional pleiotropy was unlikely to be biasing the result (intercept = −1e-04; P = 0.831). Cochran’s Q-test and the funnel plot indicated no evidence of heterogeneity and asymmetry, indicating no directional pleiotropy.ConclusionThe results of MR analysis support that H. pylori infection may not be causally associated with an increased risk of IBS.
Computational pathology-based weakly supervised prediction model for MGMT promoter methylation status in glioblastoma
Authors: He Yongqi , Duan Ling , Dong Gehong , Chen Feng , Li Wenbin 
Published: February 2024

IntroductionThe methylation status of oxygen 6-methylguanine-DNA methyltransferase (MGMT) is closely related to the treatment and prognosis of glioblastoma. However, there are currently some challenges in detecting the methylation status of MGMT promoters. The hematoxylin and eosin (H&amp;E)-stained histopathological slides have always been the gold standard for tumor diagnosis.MethodsIn this study, based on the TCGA database and H&amp;E-stained Whole slide images (WSI) of Beijing Tiantan Hospital, we constructed a weakly supervised prediction model of MGMT promoter methylation status in glioblastoma by using two Transformer structure models.ResultsThe accuracy scores of this model in the TCGA dataset and our independent dataset were 0.79 (AUC = 0.86) and 0.76 (AUC = 0.83), respectively.ConclusionThe model demonstrates effective prediction of MGMT promoter methylation status in glioblastoma and exhibits some degree of generalization capability. At the same time, our study also shows that adding Patches automatic screening module to the computational pathology research framework of glioma can significantly improve the model effect.
Differential diagnosis of frontotemporal dementia subtypes with explainable deep learning on structural MRI
Authors: Ma Da , Stocks Jane , Rosen Howard , Kantarci Kejal , Lockhart Samuel N. , Bateman James R. , Craft Suzanne , Gurcan Metin N. , Popuri Karteek , Beg Mirza Faisal , Wang Lei ,   on behalf of the ALLFTD consortium
Published: February 2024

BackgroundFrontotemporal dementia (FTD) represents a collection of neurobehavioral and neurocognitive syndromes that are associated with a significant degree of clinical, pathological, and genetic heterogeneity. Such heterogeneity hinders the identification of effective biomarkers, preventing effective targeted recruitment of participants in clinical trials for developing potential interventions and treatments. In the present study, we aim to automatically differentiate patients with three clinical phenotypes of FTD, behavioral-variant FTD (bvFTD), semantic variant PPA (svPPA), and nonfluent variant PPA (nfvPPA), based on their structural MRI by training a deep neural network (DNN).MethodsData from 277 FTD patients (173 bvFTD, 63 nfvPPA, and 41 svPPA) recruited from two multi-site neuroimaging datasets: the Frontotemporal Lobar Degeneration Neuroimaging Initiative and the ARTFL-LEFFTDS Longitudinal Frontotemporal Lobar Degeneration databases. Raw T1-weighted MRI data were preprocessed and parcellated into patch-based ROIs, with cortical thickness and volume features extracted and harmonized to control the confounding effects of sex, age, total intracranial volume, cohort, and scanner difference. A multi-type parallel feature embedding framework was trained to classify three FTD subtypes with a weighted cross-entropy loss function used to account for unbalanced sample sizes. Feature visualization was achieved through post-hoc analysis using an integrated gradient approach.ResultsThe proposed differential diagnosis framework achieved a mean balanced accuracy of 0.80 for bvFTD, 0.82 for nfvPPA, 0.89 for svPPA, and an overall balanced accuracy of 0.84. Feature importance maps showed more localized differential patterns among different FTD subtypes compared to groupwise statistical mapping.ConclusionIn this study, we demonstrated the efficiency and effectiveness of using explainable deep-learning-based parallel feature embedding and visualization framework on MRI-derived multi-type structural patterns to differentiate three clinically defined subphenotypes of FTD: bvFTD, nfvPPA, and svPPA, which could help with the identification of at-risk populations for early and precise diagnosis for intervention planning.
The effects of flux on the radiation-induced embrittlement of reactor pressure vessel steels: review of current understanding and application to high fluences
Authors: Ortner Susan , Styman Paul , Long Elliot 
Published: February 2024

It is necessary to quantify the effects of flux on reactor pressure vessel steel embrittlement under neutron irradiation, if surveillance or high-flux test reactor data is used to predict vessel embrittlement occurring at lower fluxes. This is particularly important when considering embrittlement occurring during extended (60–80 years) operation for which there is no direct experience. Dedicated investigations are time-consuming and expensive even when only small flux-fluence ranges are investigated, so collating data from multiple campaigns is necessary to provide sufficient information to cover the wide range of fluxes required for vessel assessment in the long term. This paper collates and reviews such data. The review finds that flux dependences probably differ in sign and strength in different regimes (low flux and fluence, intermediate flux at low and high fluence, high flux at low and high fluence) with the regime limits affected by composition and temperature. The current understanding of diffusion processes and microstructural development are invaluable in interpreting the trends and limits. Many contradictory data sets were found, however, and not all contradictions could be dismissed as resulting from poor quality data. Suggestions are made for investigations to clarify the uncertainties. One wide-ranging model of flux effects, based on an extensive data set, is used to compare high-fluence data from different sources, to assess whether embrittlement rates accelerate after a high, threshold fluence. The model helps to identify experiments which investigated comparable flux-fluence-temperature regimes. The comparable data are split evenly between data sets supporting acceleration after a particular fluence and data sets contradicting it. The model identifies regimes in which further campaigns would clarify the causes of these contrasting observations.
CT-based radiomics for predicting Ki-67 expression in lung cancer: a systematic review and meta-analysis
Authors: Luo Xinmin , Zheng Renying , Zhang Jiao , He Juan , Luo Wei , Jiang Zhi , Li Qiang 
Published: February 2024

BackgroundRadiomics, an emerging field, presents a promising avenue for the accurate prediction of biomarkers in different solid cancers. Lung cancer remains a significant global health challenge, contributing substantially to cancer-related mortality. Accurate assessment of Ki-67, a marker reflecting cellular proliferation, is crucial for evaluating tumor aggressiveness and treatment responsiveness, particularly in non-small cell lung cancer (NSCLC).MethodsA systematic review and meta-analysis conducted following the preferred reporting items for systematic review and meta-analysis of diagnostic test accuracy studies (PRISMA-DTA) guidelines. Two authors independently conducted a literature search until September 23, 2023, in PubMed, Embase, and Web of Science. The focus was on identifying radiomics studies that predict Ki-67 expression in lung cancer. We evaluated quality using both Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) and the Radiomics Quality Score (RQS) tools. For statistical analysis in the meta-analysis, we used STATA 14.2 to assess sensitivity, specificity, heterogeneity, and diagnostic values.ResultsTen retrospective studies were pooled in the meta-analysis. The findings demonstrated that the use of computed tomography (CT) scan-based radiomics for predicting Ki-67 expression in lung cancer exhibited encouraging diagnostic performance. Pooled sensitivity, specificity, and area under the curve (AUC) in training cohorts were 0.78, 0.81, and 0.85, respectively. In validation cohorts, these values were 0.78, 0.70, and 0.81. Quality assessment using QUADAS-2 and RQS indicated generally acceptable study quality. Heterogeneity in training cohorts, attributed to factors like contrast-enhanced CT scans and specific Ki-67 thresholds, was observed. Notably, publication bias was detected in the training cohort, indicating that positive results are more likely to be published than non-significant or negative results. Thus, journals are encouraged to publish negative results as well.ConclusionIn summary, CT-based radiomics exhibit promise in predicting Ki-67 expression in lung cancer. While the results suggest potential clinical utility, additional research efforts should concentrate on enhancing diagnostic accuracy. This could pave the way for the integration of radiomics methods as a less invasive alternative to current procedures like biopsy and surgery in the assessment of Ki-67 expression.