bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel lipid metabolism-related lncRNA signature predictive of clinical prognosis in cervical cancer
Authors: Lu Yanzhen , He Xiujun , Fang Xia , Chai Ningxia , Xu Fangfang 
Published: October 2022

Background: Cervical cancer (CC) is a serious threat to women populations worldwide. Lipid metabolism is believed to have modulating functions in cancer. Long non-coding RNAs (lncRNAs) are potential biomarkers for the different tumor prognosis. Our work aims at investigating the prognostic value of lipid metabolism-related lncRNAs in CC.Methods: LncRNA expression profiling was conducted in 291 patients from The Cancer Genome Atlas (TCGA). Patient samples were randomly assigned to the training or testing set in a 3:2 ratio. A novel lipid metabolism-related five-lncRNA signature with prognostic value for CC was built through the univariate Cox regression, least absolute contraction and selection operator (LASSO) regression and multivariate Cox regression analyses, and was further evaluated by the Kaplan-Meier methods. Relevant analyses were also applied to identify the independent clinicopathological factors. GO and KEGG analyses were conducted to investigate the biological functions and molecular pathways. Immune infiltration analysis was included to probe the relationship between lncRNA signature and cancer cell microenvironment.Results: The novel lipid metabolism-related five-lncRNA signature was confirmed to be predictive of overall survival (OS) in CC patients. Risk score, cancer stage, pregnancy, and BMI were validated as independent factors with prognostic value. GO and KEGG indicated that lipid metabolism participated in several tumor associated functions and pathways. Moreover, our results suggested that the five-lncRNA expression has potential link with tumor immune microenvironment.Conclusion: In conclusion, we built an innovative prognostic risk signature based upon lipid metabolism-related lncRNAs. The five-lncRNA signature may be beneficial to provide novel potential therapeutic targets and improve personalized treatment strategies for CC patients in future clinical treatments.
Identification of genes modified by N6-methyladenosine in patients with colorectal cancer recurrence
Authors: Zhu Qianru , Huang Xingxing , Yu Shuxian , Shou Lan , Zhang Ruonan , Xie Han , Liang Zimao , Sun Xueni , Feng Jiao , Duan Ting , Zhang Mingming , Xiang Yu , Sui Xinbing , Jin Weiwei , Yu Lili , Wu Qibiao 
Published: October 2022

Background: Recent studies demonstrate that N6-methyladenosine (m6A) methylation plays a crucial role in colorectal cancer (CRC). Therefore, we conducted a comprehensive analysis to assess the m6A modification patterns and identify m6A-modified genes in patients with CRC recurrence.Methods: The m6A modification patterns were comprehensively evaluated by the NMF algorithm based on the levels of 27 m6A regulators, and tumor microenvironment (TME) cell-infiltrating characteristics of these modification patterns were systematically assessed by ssGSEA and CIBERSORT algorithms. The principal component analysis algorithm based on the m6A scoring scheme was used to explore the m6A modification patterns of individual tumors with immune responses. The weighted correlation network analysis and univariable and multivariable Cox regression analyses were applied to identify m6A-modified gene signatures. The single-cell expression dataset of CRC samples was used to explore the tumor microenvironment affected by these signatures.Results: Three distinct m6A modification patterns with significant recurrence-free survival (RFS) were identified in 804 CRC patients. The TME characterization revealed that the m6A modification pattern with longer RFS exhibited robust immune responses. CRC patients were divided into high- and low-score subgroups according to the m6A score individually, which was obtained from the m6A-related signature genes. The patients with low m6A scores had both longer RFS and overall survival (OS) with altered immune cell infiltration. Notably, m6A-modified genes showed significant differences related to the prognosis of CRC patients in the meta-GEO cohort and TCGA cohort. Single-cell expression indicated that ALVRL1 was centrally distributed in endothelial tip cells and stromal cells.Conclusion: The m6A modification plays an indispensable role in the formation of TME diversity and complexity. Importantly, the signatures (TOP2A, LRRC58, HAUS6, SMC4, ACVRL1, and KPNB1) were identified as m6A-modified genes associated with CRC recurrence, thereby serving as a promising predictive biomarker or therapeutic target for patients with CRC recurrence.
Angioimmunoblastic T-cell lymphoma with predominant CD8+ tumor-infiltrating T-cells is a distinct immune pattern with an immunosuppressive microenvironment
Authors: Chen Zihang , Zhu Qiqi , Deng Xueqin , Yao Wenqing , Zhang Wenyan , Liu Weiping , Tang Yuan , Zhao Sha 
Published: October 2022

BackgroundAngioimmunoblastic T-cell lymphoma (AITL) has a rich tumor microenvironment (TME) that typically harbors plenty of CD4+tumor infiltrating lymphocytes, (TIL)-T-cells (so called common AITL). Nonetheless, AITL with large numbers of CD8+TIL-Ts that outnumber CD4+cells have been observed (CD8-predominant AITL). However, detailed comparison of CD8-predominant AITL and common AITL are still lacking.MethodsWe compared clinicopathological features, TIL subsets, TME T cell receptor-β (TRB), and immunoglobulin heavy chain (IGH) repertoires, and gene expression profiles in six CD8-predominant and 12 common AITLs using case-control matching (2014 to 2019).ResultsComparing with common AITLs, CD8-predominant AITLs showed more frequent edema (P = 0.011), effusion (P = 0.026), high elevated plasma EBV-DNA (P = 0.008), and shorter survival (P = 0.034). Moreover, they had more pronounced eosinophil increase (P = 0.004) and a higher Ki67 index (P = 0.041). Flow cytometry revealed an inverted CD4/CD8 ratio in TIL-Ts and lower TIL-B proportions (P = 0.041). TRB repertoire metrics deteriorated, including lower productive clones (P = 0.014) and higher clonality score (P = 0.019). The IGH repertoire was also narrowed, showing a higher proportion of the top 10 clones (P = 0.002) and lower entropy (P = 0.027). Gene expression analysis showed significant enrichment for upregulated negative regulation of immune system processes and downregulated T-cell activation and immune cell differentiation.ConclusionOur findings demonstrated that CD8-predominant AITL is a distinct immune pattern of AITL characterized by anti-tumor immunity impairment and an immunosuppressive microenvironment. These characteristics can interpret its severe clinical manifestations and poor outcomes.
Role of cross-diagonal reinforcements in lieu of seismic confining stirrups in the performance enhancement of square RC columns carrying axial load subjected to close-range explosive loading
Authors: Anas S. M. , Alam Mehtab , Isleem Haytham F. , Najm Hadee Mohammed , Sabri Sabri Mohanad Muayad 
Published: October 2022

Exposure of building infrastructures to accidental or intentional blasts is an extreme load condition that may cause irreparable damage leading to the collapse of buildings. Columns being principal elements are the most important for the stability and safety of the buildings under accidental explosions and subversive blast events and therefore attract the attention of structural engineers and researchers. Some recent examples are the Beirut seaport explosion (August 2020), the explosion at an ammunition warehouse in Ryazan City of Russia (October 2020), the gas explosion in China’s Hubei Province (June 2021), a blast at a chemical factory on the outskirts of Bangkok (July 2021), and the explosion on a container ship docked at Dubai’s Jebel Ali Port (July 2021). In the crises like ongoing conflict between Russia and Ukraine, the enhanced response of the principal components of a structure may save the life of the building users by limiting severe damage to the structure. In this study, three experimentally tested 3000-mm-long normal strength concrete columns, 300mm x 300mm, provided with (i) conventional reinforcement, (ii) seismic reinforcements over top and bottom confining regions (600 mm), and (iii) seismic reinforcement over confining and mid-height regions, carrying an axial working load of 950 kN available in the literature, are modeled in the ABAQUS 2020 code and are subjected to 82 kg TNT close-range explosive load at a scaled distance 1.0 m/kg1/3using the software’s explicit module. In addition to this, one column with seismic reinforcement over its entire length has been considered and modeled. The concrete damage plasticity model is explored for nonlinear elastic and inelastic behaviors, degradation of stiffness, and loading rate effect on concrete. Following the validation of the numerical models, the seismic reinforcements of the columns have been replaced by the cross-diagonal reinforcements between the conventional stirrups with the same axial load. Blast performance of the columns with the seismic reinforcements and with replaced diagonal reinforcements is critically examined and discussed. The results show that the application of cross-diagonal reinforcements as a replacement for the seismic reinforcements enhances the blast resistance of the reinforced concrete column significantly by reducing the damage and displacement.
18 kDa translocator protein positron emission tomography facilitates early and robust tumor detection in the immunocompetent SB28 glioblastoma mouse model
Authors: Bartos Laura M. , Kirchleitner Sabrina V. , Blobner Jens , Wind Karin , Kunze Lea H. , Holzgreve Adrien , Gold Lukas , Zatcepin Artem , Kolabas Zeynep Ilgin , Ulukaya Selin , Weidner Lorraine , Quach Stefanie , Messerer Denise , Bartenstein Peter , Tonn Joerg C. , Riemenschneider Markus J. , Ziegler Sibylle , von Baumgarten Louisa , Albert Nathalie L. , Brendel Matthias 
Published: October 2022

IntroductionThe 18 kDa translocator protein (TSPO) receives growing interest as a biomarker in glioblastoma. Mouse models can serve as an important tool for the investigation of biomarkers in glioblastoma, but several glioblastoma models indicated only low TSPO-PET signals in contrast to high TSPO-PET signals of human glioblastoma. Thus, we aimed to investigate TSPO-PET imaging in the syngeneic immunocompetent SB28 mouse model, which is thought to closely represent the tumor microenvironment (TME) of human glioblastoma.MethodsDynamic TSPO-PET/CT imaging was performed for 60 min after injection of 13.6 ± 4.2 MBq [18F]GE-180. Contrast enhanced CT (ceCT) was acquired prior to PET and served for assessment of tumor volumes and attenuation correction. SB28 and sham mice were imaged at an early (week-1; n = 6 SB28, n = 6 sham) and a late time-point (week-3; n = 8 SB28, n = 9 sham) after inoculation. Standard of truth ex vivo tumor volumes were obtained for SB28 mice at the late time-point. Tracer kinetics were analyzed for the lesion site and the carotid arteries to establish an image derived input function (IDIF). TSPO-PET and ceCT lesion volumes were compared with ex vivo volumes by calculation of root-mean-square-errors (RMSE). Volumes of distribution (VTmax/mean) in the lesion were calculated using carotid IDIF and standardized uptake values (SUVmax/mean) were obtained for a 40–60 min time frame.ResultsHigher uptake rate constants (K1) were observed for week-1 SB28 tumor lesions when compared to week-3 SB28 tumor lesions. Highest agreement between TSPO-PET lesion volumes and ex vivo tumor volumes was achieved with a 50% maximum threshold (RMSE-VT: 39.7%; RMSE-SUV: 34.4%), similar to the agreement of ceCT tumor volumes (RMSE: 30.1%). Lesions of SB28 mice had higher PET signal when compared to sham mice at week-1 (VTmax 6.6 ± 2.9 vs. 3.9 ± 0.8, p = 0.035; SUVmax 2.3 ± 0.5 vs. 1.2 ± 0.1, p &lt; 0.001) and PET signals remained at a similar level at week-3 (VTmax 5.0 ± 1.6 vs. 2.7 ± 0.8, p = 0.029; SUVmax 1.9 ± 0.5 vs. 1.2 ± 0.2, p = 0.0012). VTmax correlated with SUVmax (R2 = 0.532, p &lt; 0.001).ConclusionTSPO-PET imaging of immunocompetent SB28 mice facilitates early detection of tumor signals over sham lesions. SB28 tumors mirror high TSPO-PET signals of human glioblastoma and could serve as a valuable translational model to study TSPO as an imaging biomarker.
Effective prediction of potential ferroptosis critical genes in clinical colorectal cancer
Authors: Huang Hongliang , Dai Yuexiang , Duan Yingying , Yuan Zhongwen , Li Yanxuan , Zhang Maomao , Zhu Wenting , Yu Hang , Zhong Wenfei , Feng Senling 
Published: October 2022

BackgroundColon cancer is common worldwide, with high morbidity and poor prognosis. Ferroptosis is a novel form of cell death driven by the accumulation of iron-dependent lipid peroxides, which differs from other programmed cell death mechanisms. Programmed cell death is a cancer hallmark, and ferroptosis is known to participate in various cancers, including colon cancer. Novel ferroptosis markers and targeted colon cancer therapies are urgently needed. To this end, we performed a preliminary exploration of ferroptosis-related genes in colon cancer to enable new treatment strategies.MethodsFerroptosis-related genes in colon cancer were obtained by data mining and screening for differentially expressed genes (DEGs) using bioinformatics analysis tools. We normalized the data across four independent datasets and a ferroptosis-specific database. Identified genes were validated by immunohistochemical analysis of pathological and healthy clinical samples.ResultsWe identified DEGs in colon cancer that are involved in ferroptosis. Among these, five core genes were found: ELAVL1, GPX2, EPAS1, SLC7A5, and HMGB1. Bioinformatics analyses revealed that the expression of all five genes, except for EPAS1, was higher in tumor tissues than in healthy tissues.ConclusionsThe preliminary exploration of the five core genes revealed that they are differentially expressed in colon cancer, playing an essential role in ferroptosis. This study provides a foundation for subsequent research on ferroptosis in colon cancer.
Late health effects and changes in lifestyle factors after cancer in childhood with and without subsequent second primary cancers – the KiKme case-control study
Authors: Brackmann Lara Kim , Foraita Ronja , Schwarz Heike , Galetzka Danuta , Zahnreich Sebastian , Hankeln Thomas , Löbrich Markus , Poplawski Alicia , Grabow Desiree , Blettner Maria , Schmidberger Heinz , Marron Manuela 
Published: October 2022

BackgroundImproved treatments for childhood cancer result in a growing number of long-term childhood cancer survivors (CCS). The diagnosis and the prevalence of comorbidities may, however, influence their lifestyle later in life. Nonetheless, little is known about differences in late effects between CCS of a first primary neoplasm (FPN) in childhood and subsequent second primary neoplasms (SPN) and their impact on lifestyle. Therefore, we aim to investigate associations between the occurrence of FPN or SPN and various diseases and lifestyle in the later life of CCS.MethodsCCS of SPN (n=101) or FPN (n=340) and cancer-free controls (n=150) were matched by age and sex, and CCS additionally by year and entity of FPN. All participants completed a self-administered questionnaire on anthropometric and socio-economic factors, medical history, health status, and lifestyle. Mean time between FPN diagnosis and interview was 27.3 years for SPN and 26.2 years for FPN CCS. To confirm results from others and to generate new hypotheses on late effects of childhood cancer as well as CCS´ lifestyles, generalized linear mixed models were applied.ResultsCCS were found to suffer more likely from diseases compared to cancer-free controls. In detail, associations with cancer status were observed for hypercholesterinemia and thyroid diseases. Moreover, CCS were more likely to take regular medication compared to controls. A similar association was observed for CCS of SPN compared to CCS of FPN. In contrast to controls, CCS rarely exercise more than 5 hours per week, consumed fewer soft and alcoholic drinks, and were less likely to be current, former, or passive smokers. Additionally, they were less likely overweight or obese. All other exploratory analyses performed on cardiovascular, chronic lung, inflammatory bone, allergic, and infectious diseases, as well as on a calculated health-score revealed no association with tumor status.ConclusionCCS were more affected by pathologic conditions and may consequently take more medication, particularly among CCS of SPN. The observed higher disease burden is likely related to the received cancer therapy. To reduce the burden of long-term adverse health effects in CCS, improving cancer therapies should therefore be in focus of research in this area.
Perioperative and short-term outcomes of laparoscopic liver resection for recurrent hepatocellular carcinoma: A retrospective study comparing open hepatectomy
Authors: Bao Dandan , Hu Yiren , Zhang Chenghao , Jin Yibang , Wang Pengwei , Lin Yinfeng , Wang Wei , Shan Yunfeng 
Published: October 2022

BackgroundTo compare the perioperative and short-term outcomes of laparoscopic liver resection (LLR) and open liver resection (OLR) in recurrent hepatocellular carcinoma (rHCC) based on propensity score matching (PSM) to investigate therapeutic safety, efficacy, and value for clinical application.MethodsForty-nine patients with rHCC who underwent surgery at Wenzhou People’s Hospital between January 2017 and March 2022 were retrospectively analyzed and classified into LLR (n=30) and OLR (n=22) cases based on the surgical method. Thirty-eight patients were screened using PSM for data analysis to compare basic clinical characteristics, perioperative outcomes, and postoperative recurrence in both groups.ResultsBefore PSM, the tumour diameter was larger, tumor staging (BCLC staging system), intraoperative blood loss, units of blood transfused, constituent ratio of liver cirrhosis, incidence of MVI and intravascular tumour thrombus and postoperative complication were higher, and duration of hospital stay was significantly longer in the OLR group compared to those in the LLR group (p &lt; 0.05). After PSM, there were no significant differences regarding tumour diameter, MVI incidence, blood transfusion amount or postoperative complication rate in the LLR and OLR groups. The tumor staging, incidence of vascular cancer thrombus, intraoperative blood loss and postoperative duration of hospitalisation were significantly higher in the OLR group than in the LLR group (p&lt;0.05). The difference in recurrence-free survival (RFS) between the two groups was not statistically significant (p = 0.383).ConclusionLLR for recurrent hepatocellular carcinoma can reduce intraoperative blood loss and postoperative complication rate, shorten the duration of hospitalisation, and is superior to OLR regarding perioperative and short-term efficacy, demonstrating good safety and feasibility.
An individualized medication model of sodium valproate for patients with bipolar disorder based on machine learning and deep learning techniques
Authors: Zheng Ping , Yu Ze , Mo Liqian , Zhang Yuqing , Lyu Chunming , Yu Yongsheng , Zhang Jinyuan , Hao Xin , Wei Hai , Gao Fei , Li Yilei 
Published: October 2022

Valproic acid/sodium valproate (VPA) is a widely used anticonvulsant drug for maintenance treatment of bipolar disorders. In order to balance the efficacy and adverse events of VPA treatment, an individualized dose regimen is necessary. This study aimed to establish an individualized medication model of VPA for patients with bipolar disorder based on machine learning and deep learning techniques. The sequential forward selection (SFS) algorithm was applied for selecting a feature subset, and random forest was used for interpolating missing values. Then, we compared nine models using XGBoost, LightGBM, CatBoost, random forest, GBDT, SVM, logistic regression, ANN, and TabNet, and CatBoost was chosen to establish the individualized medication model with the best performance (accuracy = 0.85, AUC = 0.91, sensitivity = 0.85, and specificity = 0.83). Three important variables that correlated with VPA daily dose included VPA TDM value, antipsychotics, and indirect bilirubin. SHapley Additive exPlanations was applied to visually interpret their impacts on VPA daily dose. Last, the confusion matrix presented that predicting a daily dose of 0.5 g VPA had a precision of 55.56% and recall rate of 83.33%, and predicting a daily dose of 1 g VPA had a precision of 95.83% and a recall rate of 85.19%. In conclusion, the individualized medication model of VPA for patients with bipolar disorder based on CatBoost had a good prediction ability, which provides guidance for clinicians to propose the optimal medication regimen.
An analysis of the essential medicines policy in primary care: Findings from MedMinas project
Authors: Luz Tatiana Chama Borges , Tavares Noemia Urruth Leão , Marques Isabela Cristina , de Castro Ana Karine Sarvel , Cota Betania Barros 
Published: October 2022

Background: Essential Medicines Policy (EMP) has been adopted in Brazil to improve the provision and use of pharmaceuticals. This mixed methods study aims to bring evidence of the EMP implemented in municipalities in the context of primary care in Minas Gerais (20,997,560 inhabitants), Southeast Brazil.Methods: We analysed the core output of the EMP, i.e., the municipal essential medicines lists (MEML) and the effects of the policy on the procurement and availability of medicines. Data sources included a sample of 1,019 individuals (patients, health managers and health professionals), 995 prescriptions, 2,365 dispensed medicines and policy documents from 26 municipalities. Data were collected between April and October 2019. Document analysis and thematic content analysis were performed, and four availability indexes were estimated.Results: The findings suggest an overall lack of standardised and methodologically sound procedures to elaborate the MEML. Funding and public purchasing processes were found to be the major obstacles to medicine procurement. Only 63% of medicines were available at public community pharmacies and just 46.2% of patients had full access to their pharmaceutical treatment.Conclusion: This study reveals weaknesses in the implementation of EMP and a clear disconnection between medicines selection, procurement, and availability, the three core elements of the supply system. These findings contribute to informing future policy improvement actions to strengthen this system. Other countries aiming to advance towards universal health coverage may learn from the challenges that primary care in Brazil still needs to address.