bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrating CT-based radiomic model with clinical features improves long-term prognostication in high-risk prostate cancer
Authors: Ching Jerry C. F. , Lam Saikit , Lam Cody C. H. , Lui Angie O. Y. , Kwong Joanne C. K. , Lo Anson Y. H. , Chan Jason W. H. , Cai Jing , Leung W. S. , Lee Shara W. Y. 
Published: April 2023

ObjectiveHigh-risk prostate cancer (PCa) is often treated by prostate-only radiotherapy (PORT) owing to its favourable toxicity profile compared to whole-pelvic radiotherapy. Unfortunately, more than 50% patients still developed disease progression following PORT. Conventional clinical factors may be unable to identify at-risk subgroups in the era of precision medicine. In this study, we aimed to investigate the prognostic value of pre-treatment planning computed tomography (pCT)-based radiomic features and clinical attributes to predict 5-year progression-free survival (PFS) in high-risk PCa patients following PORT.Materials and methodsA total of 176 biopsy-confirmed PCa patients who were treated at the Hong Kong Princess Margaret Hospital were retrospectively screened for eligibility. Clinical data and pCT of one hundred eligible high-risk PCa patients were analysed. Radiomic features were extracted from the gross-tumour-volume (GTV) with and without applying Laplacian-of-Gaussian (LoG) filter. The entire patient cohort was temporally stratified into a training and an independent validation cohort in a ratio of 3:1. Radiomics (R), clinical (C) and radiomic-clinical (RC) combined models were developed by Ridge regression through 5-fold cross-validation with 100 iterations on the training cohort. A model score was calculated for each model based on the included features. Model classification performance on 5-year PFS was evaluated in the independent validation cohort by average area-under-curve (AUC) of receiver-operating-characteristics (ROC) curve and precision-recall curve (PRC). Delong’s test was used for model comparison.ResultsThe RC combined model which contains 6 predictive features (tumour flatness, root-mean-square on fine LoG-filtered image, prostate-specific antigen serum concentration, Gleason score, Roach score and GTV volume) was the best-performing model (AUC = 0.797, 95%CI = 0.768-0.826), which significantly outperformed the R-model (AUC = 0.795, 95%CI = 0.774-0.816) and C-model (AUC = 0.625, 95%CI = 0.585-0.665) in the independent validation cohort. Besides, only the RC model score significantly classified patients in both cohorts into progression and progression-free groups regarding their 5-year PFS (p&lt; 0.05).ConclusionCombining pCT-based radiomic and clinical attributes provided superior prognostication value regarding 5-year PFS in high-risk PCa patients following PORT. A large multi-centre study will potentially aid clinicians in implementing personalised treatment for this vulnerable subgroup in the future.
Identification of a prognostic signature and ENTR1 as a prognostic biomarker for colorectal mucinous adenocarcinoma
Authors: Huang An , Shi Jingyi , Sun Zhuang , Yang Yong , Gao Zhaoya , Gu Jin 
Published: April 2023

BackgroundMucinous adenocarcinoma (MAC) is a unique clinicopathological colorectal cancer (CRC) type that has been recognized as a separate entity from non-mucinous adenocarcinoma (NMAC), with distinct clinical, pathologic, and molecular characteristics. We aimed to construct prognostic signatures and identifying candidate biomarkers for patients with MAC.MethodsDifferential expression analysis, weighted correlation network analysis (WGCNA), and least absolute shrinkage and selection operator (LASSO)-Cox regression model were used to identify hub genes and construct a prognostic signature based on RNA sequencing data from TCGA datasets. The Kaplan-Meier survival curve, gene set enrichment analysis (GSEA), cell stemness, and immune infiltration were analyzed. Biomarker expression in MAC and corresponding normal tissues from patients operated in 2020 was validated using immunohistochemistry.ResultsWe constructed a prognostic signature based on ten hub genes. Patients in the high-risk group had significantly worse overall survival (OS) than patients in the low-risk group (p &lt; 0.0001). We also found that ENTR1 was closely associated with OS (p = 0.016). ENTR1 expression was significantly positively correlated with cell stemness of MAC (p &lt; 0.0001) and CD8+ T cell infiltration (p = 0.01), whereas it was negatively associated with stromal scores (p = 0.03). Finally, the higher expression of ENTR1 in MAC tissues than in normal tissues was validated.ConclusionWe established the first MAC prognostic signature, and determined that ENTR1 could serve as a prognostic marker for MAC.
Systematic review of the perioperative immunotherapy in patients with non-small cell lung cancer: evidence mapping and synthesis
Authors: Ni Yunfeng , Lei Jie , Huang Wan , Wang Jian , Guo Haihua , Lv Feng , Kang Shuhong , Lan Ke , Jiang Tao 
Published: April 2023

ObjectivesThis study aimed to use evidence mapping to provide an overview of immune checkpoint inhibitors (ICIs) as perioperative treatments for non-small cell lung cancer (NSCLC) and to identify areas of this field where future research is most urgently needed.MethodsMultiple databases (PubMed, EMBASE, Cochrane Library, and Web of Science) were searched to identify clinical trials published up to November 2021 that examined the effect of perioperative ICIs for perioperative treatment of NSCLC. Study design, sample size, patient characteristics, therapeutic regimens, clinical stages, short-term and long-term therapeutic outcomes, surgery associated parameters, and therapeutic safety were examined.ResultsWe included 66 trials (3564 patients) and used evidence mapping to characterize the available data. For surgery associated outcomes, sixty-two studies (2480 patients) provided complete information regarding the use of surgery after neoadjuvant immunotherapy and data on R0 resection were available in 42 studies (1680 patients); for short-term clinical outcomes, 57 studies (1842 patients) evaluated pathologic complete response (pCR) after neoadjuvant immunotherapy and most of included studies achieved pCR in the range of 30 to 40%; for long-term clinical outcomes, 15 studies (1932 patients) reported DFS, with a median range of 17.9-53.6 months; and only a few studies reported the safety profiles of perioperative immunotherapies.ConclusionOur evidence mapping systematically summarized the results of all clinical trials and studies that examined ICIs as perioperative treatments for NSCLC. The results indicated more studies that evaluate long-term patient outcomes are needed to provide a stronger foundation for the use of these treatments.
Construction of an interferon regulatory factors-related risk model for predicting prognosis, immune microenvironment and immunotherapy in clear cell renal cell carcinoma
Authors: Pan Hao , Lu Wei , Zhang Mengyuan , Liu Chengxiao 
Published: April 2023

BackgroundInterferon regulatory factors (IRFs) played complex and essential roles in progression, prognosis, and immune microenvironment in clear cell renal cell carcinoma (ccRCC). The purpose of this study was to construct a novel IRFs-related risk model to predict prognosis, tumor microenvironment (TME) and immunotherapy response in ccRCC.MethodsMulti-omics analysis of IRFs in ccRCC was performed based on bulk RNA sequencing and single cell RNA sequencing data. According to the expression profiles of IRFs, the ccRCC samples were clustered by non-negative matrix factorization (NMF) algorithm. Then, least absolute shrinkage and selection operator (LASSO) and Cox regression analyses were applied to construct a risk model to predict prognosis, immune cells infiltration, immunotherapy response and targeted drug sensitivity in ccRCC. Furthermore, a nomogram comprising the risk model and clinical characteristics was established.ResultsTwo molecular subtypes with different prognosis, clinical characteristics and infiltration levels of immune cells were identified in ccRCC. The IRFs-related risk model was developed as an independent prognostic indicator in the TCGA-KIRC cohort and validated in the E-MTAB-1980 cohort. The overall survival of patients in the low-risk group was better than that in the high-risk group. The risk model was superior to clinical characteristics and the ClearCode34 model in predicting the prognosis. In addition, a nomogram was developed to improve the clinical utility of the risk model. Moreover, the high-risk group had higher infiltration levels of CD8+ T cell, macrophages, T follicular helper cells and T helper (Th1) cells and activity score of type I IFN response but lower infiltration levels of mast cells and activity score of type II IFN response. Cancer immunity cycle showed that the immune activity score of most steps was remarkably higher in the high-risk group. TIDE scores indicated that patients in the low-risk group were more likely responsive to immunotherapy. Patients in different risk groups showed diverse drug sensitivity to axitinib, sorafenib, gefitinib, erlotinib, dasatinib and rapamycin.ConclusionsIn brief, a robust and effective risk model was developed to predict prognosis, TME characteristics and responses to immunotherapy and targeted drugs in ccRCC, which might provide new insights into personalized and precise therapeutic strategies.
ER predicts poor prognosis in male lung squamous cell cancer of stage IIIA-N2 disease after sequential adjuvant chemoradiotherapy
Authors: Yang Xue , Wang Lili , Jin Xiangfeng , Xu Rongjian , Yu Zhuang , Li Hongmei , Lu Haijun , An Ning 
Published: April 2023

IntroductionThe efficacy of postoperative radiotherapy (PORT) is still unclear in non-small cell lung cancer (NSCLC) patients with pIIIA-N2 disease. Estrogen receptor (ER) was proven significantly associated with poor clinical outcome of male lung squamous cell cancer (LUSC) after R0 resection in our previous study.MethodsA total of 124 male pIIIA-N2 LUSC patients who completed four cycles of adjuvant chemotherapy and PORT after complete resection were eligible for enrollment in this study from October 2016 to December 2021. ER expression was evaluated using immunohistochemistry assay.ResultsThe median follow-up was 29.7 months. Among 124 patients, 46 (37.1%) were ER positive (stained tumor cells≥1%), and the rest 78 (62.9%) were ER negative. Eleven clinical factors considered in this study were well balanced between ER+ and ER- groups. ER expression significantly predicted a poor prognosis in disease-free survival (DFS, HR=2.507; 95% CI: 1.629-3.857; log-rank p=1.60×10-5). The 3-year DFS rates were 37.8% with ER- vs. 5.7% with ER+, with median DFS 25.9 vs. 12.6 months, respectively. The significant prognostic advantage in ER- patients was also observed in overall survival (OS), local recurrence free survival (LRFS), and distant metastasis free survival (DMFS). The 3-year OS rates were 59.7% with ER- vs. 48.2% with ER+ (HR, 1.859; 95% CI: 1.132-3.053; log-rank p=0.013), the 3-year LRFS rates were 44.1% vs. 15.3% (HR=2.616; 95% CI: 1.685-4.061; log-rank p=8.80×10-6), and the 3-year DMFS rates were 45.3% vs. 31.8% (HR=1.628; 95% CI: 1.019-2.601; log-rank p=0.039). Cox regression analyses indicated that ER status was the only significant factor for DFS (p=2.940×10-5), OS (p=0.014), LRFS (p=1.825×10-5) and DMFS (p=0.041) among other 11 clinical factors.ConclusionsPORT might be more beneficial for ER negative LUSCs in male, and the examination of ER status might be helpful in identifying patients suitable for PORT.
Identification of lncRNAs involved in response to ionizing radiation in fibroblasts of long-term survivors of childhood cancer and cancer-free controls
Authors: Grandt Caine Lucas , Brackmann Lara Kim , Poplawski Alicia , Schwarz Heike , Marini Federico , Hankeln Thomas , Galetzka Danuta , Zahnreich Sebastian , Mirsch Johanna , Spix Claudia , Blettner Maria , Schmidberger Heinz , Marron Manuela 
Published: April 2023

IntroductionLong non-coding ribonucleic acids (lncRNAs) are involved in the cellular damage response following exposure to ionizing radiation as applied in radiotherapy. However, the role of lncRNAs in radiation response concerning intrinsic susceptibility to late effects of radiation exposure has not been examined in general or in long-term survivors of childhood cancer with and without potentially radiotherapy-related second primary cancers, in particular.MethodsPrimary skin fibroblasts (n=52 each) of long-term childhood cancer survivors with a first primary cancer only (N1), at least one second primary neoplasm (N2+), as well as tumor-free controls (N0) from the KiKme case-control study were matched by sex, age, and additionally by year of diagnosis and entity of the first primary cancer. Fibroblasts were exposed to 0.05 and 2 Gray (Gy) X-rays. Differentially expressed lncRNAs were identified with and without interaction terms for donor group and dose. Weighted co-expression networks of lncRNA and mRNA were constructed using WGCNA. Resulting gene sets (modules) were correlated to the radiation doses and analyzed for biological function.ResultsAfter irradiation with 0.05Gy, few lncRNAs were differentially expressed (N0: AC004801.4; N1: PCCA-DT, AF129075.3, LINC00691, AL158206.1; N2+: LINC02315). In reaction to 2 Gy, the number of differentially expressed lncRNAs was higher (N0: 152, N1: 169, N2+: 146). After 2 Gy, AL109976.1 and AL158206.1 were prominently upregulated in all donor groups. The co-expression analysis identified two modules containing lncRNAs that were associated with 2 Gy (module1: 102 mRNAs and 4 lncRNAs: AL158206.1, AL109976.1, AC092171.5, TYMSOS, associated with p53-mediated reaction to DNA damage; module2: 390 mRNAs, 7 lncRNAs: AC004943.2, AC012073.1, AC026401.3, AC092718.4, MIR31HG, STXBP5-AS1, TMPO-AS1, associated with cell cycle regulation).DiscussionFor the first time, we identified the lncRNAs AL158206.1 and AL109976.1 as involved in the radiation response in primary fibroblasts by differential expression analysis. The co-expression analysis revealed a role of these lncRNAs in the DNA damage response and cell cycle regulation post-IR. These transcripts may be targets in cancer therapy against radiosensitivity, as well as provide grounds for the identification of at-risk patients for immediate adverse reactions in healthy tissues. With this work we deliver a broad basis and new leads for the examination of lncRNAs in the radiation response.
An anoikis-related gene signature predicts prognosis and reveals immune infiltration in hepatocellular carcinoma
Authors: Chen Yang , Lin Qiao-xin , Xu Yi-ting , Qian Fang-jing , Lin Chen-jing , Zhao Wen-ya , Huang Jing-ren , Tian Ling , Gu Dian-na 
Published: April 2023

BackgroundHepatocellular carcinoma (HCC) is a global health burden with poor prognosis. Anoikis, a novel programmed cell death, has a close interaction with metastasis and progression of cancer. In this study, we aimed to construct a novel bioinformatics model for evaluating the prognosis of HCC based on anoikis-related gene signatures as well as exploring the potential mechanisms.Materials and methodsWe downloaded the RNA expression profiles and clinical data of liver hepatocellular carcinoma from TCGA database, ICGC database and GEO database. DEG analysis was performed using TCGA and verified in the GEO database. The anoikis-related risk score was developed via univariate Cox regression, LASSO Cox regression and multivariate Cox regression, which was then used to categorize patients into high- and low-risk groups. Then GO and KEGG enrichment analyses were performed to investigate the function between the two groups. CIBERSORT was used for determining the fractions of 22 immune cell types, while the ssGSEA analyses was used to estimate the differential immune cell infiltrations and related pathways. The “pRRophetic” R package was applied to predict the sensitivity of administering chemotherapeutic and targeted drugs.ResultsA total of 49 anoikis-related DEGs in HCC were detected and 3 genes (EZH2, KIF18A and NQO1) were selected out to build a prognostic model. Furthermore, GO and KEGG functional enrichment analyses indicated that the difference in overall survival between risk groups was closely related to cell cycle pathway. Notably, further analyses found the frequency of tumor mutations, immune infiltration level and expression of immune checkpoints were significantly different between the two risk groups, and the results of the immunotherapy cohort showed that patients in the high-risk group have a better immune response. Additionally, the high-risk group was found to have higher sensitivity to 5-fluorouracil, doxorubicin and gemcitabine.ConclusionThe novel signature of 3 anoikis-related genes (EZH2, KIF18A and NQO1) can predict the prognosis of patients with HCC, and provide a revealing insight into personalized treatments in HCC.
Bibliometric analysis of ferroptosis: a comprehensive evaluation of its contribution to cancer immunity and immunotherapy
Authors: Wang Zhen , Zhang Hui , Wang Li , Ma Zhen , Cui Yu’ang , Fu Haitian , Yu Chunjing 
Published: April 2023

BackgroundIn the past 5 years, ferroptosis-associated cancer immunity has been attracted significant research interest.ObjectiveThis study was performed to identify and analyze the global output trend for ferroptosis in cancer immunity.MethodsRelevant studies were retrieved from the Web of Science Core Collection on Feb 10th, 2023. The VOSviewer and Histcite softwares were utilized to perform the visual bibliometric and deep mining analyses.ResultsA total of 694 studies (530 articles (76.4%) and 164 (23.6%) review articles) were retrieved from the Web of Science Core Collection for visualization analyses. The top 3 key keywords were ferroptosis, prognosis and immunotherapy. The top 30 local citation score (LCS) authors were all collaborators of Zou Weiping. Deep mining of 51 nanoparticle-related articles showed that BIOMATERIALS was the most popular journal. The primary goal of gene signatures related to ferroptosis and cancer immunity was to establish prognostic predictions.ConclusionThere has been a significant increase in ferroptosis-associated immune publications in the recent 3 years. The key research hotspots include mechanisms, prediction and therapeutic outcomes. The most influential article was from the Zou Weiping’s group, which proposed that system xc-mediated ferroptosis is induced by CD8(+) T cell-secreted IFNγ after PD-L1 blockage for immunotherapy. The frontier of research in the field of ferroptosis-associated immune is the study on nanoparticle and gene signature The limitation of this bibliometric study is that publications on this topic are few.
Immunosuppressant drugs and quality-of-life outcomes in kidney transplant recipients: An international cohort study (EU-TRAIN)
Authors: Girardin François R. , Nicolet Anna , Bestard Oriol , Lefaucheur Carmen , Budde Klemens , Halleck Fabian , Brouard Sophie , Giral Magali , Gourraud Pierre-Antoine , Horcholle Béatrice , Villard Jean , Marti Joachim , Loupy Alexandre 
Published: April 2023

Introduction: Patient-Reported Outcomes (PRO) integrate a wide range of holistic dimensions that arenot captured within clinical outcomes. Particularly, from induction treatment to maintenance therapy, patient quality-of-life (QoL) of kidney transplant recipients have been sparsely investigated in international settings.Methods: In a prospective, multi-centric cohort study, including nine transplant centers in four countries, we explored the QoL during the year following transplantation using validated elicitation instruments (EQ-5D-3L index with VAS) in a population of kidney transplant patients receiving immunosuppressive therapies. Calcineurin inhibitors (tacrolimus and ciclosporin), IMPD inhibitor (mycophenolate mofetil), and mTOR inhibitors (everolimus and sirolimus) were the standard-of-care (SOC) medications, together with tapering glucocorticoid therapy. We used EQ-5D and VAS data as QoL measures alongside descriptive statistics at inclusion, per country and hospital center. We computed the proportions of patients with different immunosuppressive therapy patterns, and using bivariate and multivariate analyses, assessed the variations of EQ-5D and VAS between baseline (i.e., inclusion Month 0) and follow up visits (Month 12).Results: Among 542 kidney transplant patients included and followed from November 2018 to June 2021, 491 filled at least one QoL questionnaire at least at baseline (Month 0). The majority of patients in all countries received tacrolimus and mycophenolate mofetil, ranging from 90.0% in Switzerland and Spain to 95.8% in Germany. At M12, a significant proportion of patients switched immunosuppressive drugs, with proportion varying from 20% in Germany to 40% in Spain and Switzerland. At visit M12, patients who kept SOC therapy had higher EQ-5D (by 8 percentage points, p &lt; 0.05) and VAS (by 4 percentage points, p &lt; 0.1) scores than switchers. VAS scores were generally lower than EQ-5D (mean 0.68 [0.5–0.8] vs. 0.85 [0.8–1]).Discussion: Although overall a positive trend in QoL was observed, the formal analyses did not show any significant improvements in EQ-5D scores or VAS. Only when the effect of a therapy use was separated from the effect of switching, the VAS score was significantly worse for switchers during the follow up period, irrespective of the therapy type. If adjusted for patient characteristics and medical history (e.g., gender, BMI, eGRF, history of diabetes), VAS and EQ-5D delivered sound PRO measures for QoL assessments during the year following renal transplantation.
Suvorexant, an FDA-approved dual orexin receptor antagonist, reduces oxycodone self-administration and conditioned reinstatement in male and female rats
Authors: Illenberger Jessica M. , Flores-Ramirez Francisco J. , Matzeu Alessandra , Mason Barbara J. , Martin-Fardon Rémi 
Published: April 2023

Background: The Department of Health and Human Services reports that prescription pain reliever (e.g., oxycodone) misuse was initiated by 4,400 Americans each day in 2019. Amid the opioid crisis, effective strategies to prevent and treat prescription opioid use disorder (OUD) are pressing. In preclinical models, the orexin system is recruited by drugs of abuse, and blockade of orexin receptors (OX receptors) prevents drug-seeking behavior. The present study sought to determine whether repurposing suvorexant (SUV), a dual OX receptor antagonist marketed for the treatment of insomnia, can treat two features of prescription OUD: exaggerated consumption and relapse.Methods: Male and female Wistar rats were trained to self-administer oxycodone (0.15 mg/kg, i. v., 8 h/day) in the presence of a contextual/discriminative stimulus (SD) and the ability of SUV (0–20 mg/kg, p. o.) to decrease oxycodone self-administration was tested. After self-administration testing, the rats underwent extinction training, after which we tested the ability of SUV (0 and 20 mg/kg, p. o.) to prevent reinstatement of oxycodone seeking elicited by the SD.Results: The rats acquired oxycodone self-administration and intake was correlated with the signs of physical opioid withdrawal. Additionally, females self-administered approximately twice as much oxycodone as males. Although SUV had no overall effect on oxycodone self-administration, scrutiny of the 8-h time-course revealed that 20 mg/kg SUV decreased oxycodone self-administration during the first hour in males and females. The oxycodone SD elicited strong reinstatement of oxycodone-seeking behavior that was significantly more robust in females. Suvorexant blocked oxycodone seeking in males and reduced it in females.Conclusions: These results support the targeting of OX receptors for the treatment for prescription OUD and repurposing SUV as pharmacotherapy for OUD.