bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Verification of Glutamatergic Synapse-Associated Prognosis Signature for Lower-Grade Gliomas
Authors: Ye Liguo , Xu Yang , Hu Ping , Wang Long , Yang Ji’an , Yuan Fan’en , Wang Yixuan , Zhang Chunyu , Tian Daofeng , Chen Qianxue 
Published: October 2021

Background: Lower-grade glioma (LGG) is the most common histology identified in gliomas, a heterogeneous tumor that may develop into high-grade malignant glioma that seriously shortens patient survival time. Recent studies reported that glutamatergic synapses might play an essential role in the progress of gliomas. However, the role of glutamatergic synapse-related biomarkers in LGG has not been systemically researched yet.Methods: The mRNA expression data of glioma and normal brain tissue were obtained from The Cancer Genome Atlas database and Genotype-Tissue Expression, respectively, and the Chinese Glioma Genome Atlas database was used as a validation set. Difference analysis was performed to evaluate the expression pattern of glutamatergic synapse-related genes (GSRGs) in LGG. The least absolute shrinkage and selection operator (LASSO) Cox regression was applied to construct the glutamatergic synapse-related risk signature (GSRS), and the risk score of each LGG sample was calculated based on the coefficients and expression value of selected GSRGs. Univariate and multivariate Cox regression analyses were used to investigate the prognostic value of risk score. Immunity profile and single-sample gene set enrichment analysis (ssGSEA) were performed to explore the association between risk score and the characters of tumor microenvironment in LGG. Gene set variation analysis (GSVA) was performed to investigate the potential pathways related to GSRS. The HPA database and real-time PCR were used to identify the expression of hub genes identified in GSRS.Results: A total of 22 genes of 39 GSRGs were found differentially expressed among normal and LGG samples. Through the LASSO algorithm, 14-genes GSRS constructed were associated with the prognosis and clinicopathological features of patients with LGG. Furthermore, the risk score level was significantly positively correlated with the infiltrating level of immunosuppressive cells, including M2 macrophages and regulatory T cells. GSVA identified a series of cancer-related pathways related to GSRS, such as P13K-AKT and P53 pathways. Moreover, ATAD1, NLGN2, OXTR, and TNR, hub genes identified in GSRS, were considered as potential prognostic biomarkers in LGG.Conclusion: A 14-genes GSRS was constructed and verified in this study. We provided a novel insight into the role of GSRS in LGG through a series of bioinformatics methods.
Association Between the Nutritional Risk and the Survival Rate in Newly Diagnosed GIST Patients
Authors: Ding Ping'an , Guo Honghai , Yang Peigang , Sun Chenyu , Tian Yuan , Liu Yang , Li Yong , Zhao Qun 
Published: October 2021

Background: Currently, the incidence of gastrointestinal stromal tumors (GIST) is increasing rapidly worldwide. Malnutrition may increase the risk of perioperative complications and affect the prognosis of patients. However, previous studies on the nutritional status of GIST patients and its impact on prognosis are limited. Therefore, this study aims to explore the incidence of malnutrition in newly diagnosed GIST patients, the proportion of participants in need of nutritional intervention, and the relationship between nutritional status and overall survival (OS).Methods: We retrospectively analyzed the clinical data of GIST patients treated in our hospital from January 2014 to January 2018. Nutritional Risk Screening 2002 (NRS2002) and Patient-Generated Subjective Global Assessment (PG-SGA) were used to assess the nutritional status of all patients. This study was to investigate the clinical significance of PG-SGA by analyzing the relationship between PG-SGA score and OS.Results: A total of 1,268 newly diagnosed GIST patients were included in this study, of which 77.76% were at risk of malnutrition (NRS2002 score ≥ 3), and the incidence of malnutrition was 10.09% (PG-SGA score ≥ 4). Meanwhile, we found 2.29% of the patients required urgent nutritional support (PG-SGA score ≥ 9). Multivariate analysis showed that age (p = 0.013), BMI (p = 0.001), weight loss (p = 0.001), anemia (p = 0.005), pre-albumin (p = 0.010), albumin (p = 0.002), tumor location (p = 0.001), tumor size (p = 0.002), and NIH classification (p = 0.001) were risk factors for nutritional status. The prognosis was significantly in GIST patients with different PG-SGA score at admission (p &lt; 0.05).Conclusion: This study suggested that malnutrition is common in newly diagnosed GIST patients, and the higher the PG-SGA score, the worse the clinical outcome.
Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor
Authors: Yuan Xiaodong , Huang Lei , Luo Wenwu , Zhao Yufei , Nashan Björn , Yu Fazhi , Liu Yun 
Published: October 2021

BackgroundThymic epithelial tumors (TETs) are rare tumors originating from the thymic epithelial cells. SOX9, a member of the family of SOX (SRY-related high-mobility group box) genes, has been considered as an oncogene and therapeutic target in various cancers. However, its role in TETs remains uncertain.MethodsUsing the immunohistochemistry method, the expression of SOX9 was analyzed in TETs tissues, including 34 thymoma (8 cases with type A, 6 with type AB, 6 with type B1, 9 with type B2, and 5 with type B3 thymomas) and 20 thymic cancer tissues and the clinicopathologic and prognostic significances were evaluated. Further bioinformatics analysis of gene expression profiles of thymomas with high and low SOX9 expressions and the corresponding survival analyses were based on the thymoma cases identified in The Cancer Genome Atlas (TCGA) database, with the median expression level of SOX9 selected as cutoff.ResultsImmunohistochemistry staining showed that SOX9 was highly expressed in the nuclei of the epithelial cells of the Hassall’s corpuscles and of the TET tumor cells. SOX9 expression was significantly associated with histological type and high expression indicated unfavorable clinical outcomes of thymomas. Bioinformatics analysis revealed that genes positively associated with SOX9 expression were mapped in proteoglycans in cancer, cell adhesion molecules, and molecules involved in extracellular matrix-receptor interaction and the TGF-β signaling pathway, and that genes negatively associated with SOX9 expression were mapped in molecules involved in primary immunodeficiency, the T cell receptor signaling pathway, Th17 cell differentiation, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. In addition, SOX9 expression was positively associated with POU2F3 and TRPM5 expressions, the master regulators of tuft cells, suggesting that high SOX9 expression might be associated with the tuft cell phenotype of thymomas. Moreover, high SOX9 expression was associated with immune dysregulation of thymoma, and M2 macrophage significantly dominated in the high SOX9 expression group.ConclusionSOX9 may serve as a diagnostic and prognostic marker for TETs. Notably, high SOX9 expression in TETs may indicate a tuft cell phenotype and an immune suppressive microenvironment of thymomas.
Recombinant Human Thrombopoietin Accelerates the Recovery of Platelet in Patients With Lower-Risk Myelodysplastic Syndrome: A Proof-of-Concept Study
Authors: Yang Yuan , Tang Zengwei , Ji Jiang , Yang Chen , Chen Miao , Han Bing 
Published: October 2021

AimThe effect of recombinant human thrombopoietin (rhTPO) is largely unknown in lower-risk myelodysplastic syndrome (LR-MDS). This study aimed at investigating the safety and efficacy of rhTPO in patients with LR-MDS.MethodsLR-MDS patients receiving stanozolol (2 mg, t.i.d.) and supportive care alone (non-rhTPO) or additional rhTPO were enrolled in this study prospectively. rhTPO was given at 15,000 U (q.d.) for 7 days/month for at least 3 months. Patients stopped rhTPO if the platelet count was higher than 50 × 109/L or had no effects after 3 months of treatment. The overall response (OR), complete response (CR), platelet response, side effects, clone evolution, and clinical outcome were evaluated.ResultThirty-five patients were enrolled: 20 (57.1%) patients in the rhTPO group and 15 (42.9%) patients in the non-rhTPO group. The demographic and baseline characteristics were balanced between the two groups. Platelet response was higher at 1 and 2 months as compared with that in the non-rhTPO group (p = 0.006 and p = 0.001, respectively). Meanwhile, the rhTPO group had a shorter time to achieve a platelet transfusion-free state compared with the non-rhTPO group (p = 0.034). Hematologic response was higher at 1 and 2 months compared with that in the non-rhTPO group (p = 0.006 and p = 0.001, respectively). There was no significant difference in the overall response or complete response at 1, 2, 3, 6, and 12 months between the two groups. One patient in the rhTPO group evolved into higher-risk MDS at 9 months. No significant difference in disease progression, infection, gastrointestinal disorders, or drug-related liver/renal injuries was found between the two groups (p &gt; 0.05).ConclusionAdding short-term rhTPO can accelerate the early platelet response and decrease platelet transfusion, with no obvious side effects.Clinical Trial Registrationhttps://clinicaltrials.gov/ct2/show/NCT04324060?cond=NCT04324060&amp;draw=2, identifier NCT04324060
Efficacy and Safety of PARP Inhibitors in Advanced or Metastatic Triple-Negative Breast Cancer: A Systematic Review and Meta-Analysis
Authors: Liu Xu , Wu Kan , Zheng Dan , Luo Chuanxu , Fan Yu , Zhong Xiaorong , Zheng Hong 
Published: October 2021

PurposePoly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in metastatic triple-negative breast cancers (TNBCs). We therefore performed a systematic review and meta-analysis to evaluate the efficacy and safety of this drug in patients with advanced or metastatic TNBC.MethodsA systematic literature search of PubMed, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials for synonyms of “PARP inhibitors” and “breast cancer” was carried out. All published phase II/III clinical studies of PARP inhibitors in patients with advanced/metastatic TNBC were screened. Data were extracted independently by two authors and analyzed using Review Manager software version 5.3. End points include overall response rate (ORR), progression-free survival (PFS), and adverse events.ResultsTen clinical trials were identified, with a total of 1,495 patients included. Pooled analyses showed that PARP inhibitors could provide a significant improvement of ORR [risk ratio (RR) = 2.00; 95% confidence interval (CI), 1.14–3.50; p = 0.02) and PFS [hazard ratio (HR) = 0.68; 95%Cl, 0.59–0.77; p &lt; 0.0001) compared to chemotherapy in the whole population. In subgroup analysis, patients with BRCA mutation had a higher objective response to PARP inhibitor, with an RR of 2.85 (95%CI, 1.34–6.06; p = 0.007) compared to BRCA wild-type patients. However, no significant difference in ORR was observed between the homologous recombination deficiency (HRD) positive and non-HRD subgroups (RR = 1.82; 95%CI, 0.81–4.08; p = 0.14). Hematological toxicity is a common adverse event of PARP inhibitors.ConclusionsPARP inhibitors are effective options for the treatment of patients with advanced or metastatic TNBC. Compared with patients without germline BRCA mutation, patients with germline BRCA mutation could benefit more from PARP inhibitors. In clinical setting, hematological toxicity associated with PARP inhibitors should be monitored regularly.
Glucose Metabolism Reprogramming of Primary Tumor and the Liver Is Associated With Disease-Free Survival in Patients With Early NSCLC
Authors: Tan Hongpei , Ma Mengtian , Huang Jing , Zhu Wenhao , Hu Shuo , Zheng Kai , Rong Pengfei 
Published: October 2021

PurposeTumor promote disease progression by reprogramming their metabolism and that of distal organs, so it is of great clinical significance to study the changes in glucose metabolism at different tumor stages and their effect on glucose metabolism in other organs.MethodsA retrospective single-centre study was conducted on 253 NSCLC (non-small cell lung cancer) patients with negative lymph nodes and no distant metastasis. According to the AJCC criteria, the patients were divided into different groups based on tumor size: stage IA, less than 3 cm (group 1, n = 121); stage IB, greater than 3-4 cm (group 2, n = 64); stage IIA, greater than 4-5 cm (group 3, n = 36); and stage IIB, greater than 5-7 cm (group 4, n = 32). All of the patients underwent baseline 18F-FDG PET/CT scans, and the primary lesion SUVmax (maximum standardized uptake value), liver SUVmean (mean standardized uptake value), spleen SUVmean, TLR (Tumor-to-liver SUV ratio) and TSR (Tumor-to-spleen SUV ratio) were included in the study, combined with clinical examination indicators to evaluate DFS (disease free survival).ResultsIn NSCLC patients, with the increase in the maximum diameter of the tumor, the SUVmax of the primary lesion gradually increased, and the SUVmean of the liver gradually decreased. The primary lesion SUVmax, liver SUVmean, TLR and TSR were related to disease recurrence or death. The best predictive parameters were different when the tumor size differed. SUVmax had the highest efficiency when the tumor size was less than 4 cm (AUC:0.707 (95% CI, 0.430-0.984) tumor size &lt; 3 cm), (AUC:0.726 (95% CI, 0.539-0.912) tumor size 3-4 cm), liver SUVmean had the highest efficiency when the tumor size was 4-5 cm (AUC:0.712 (95% CI, 0.535-0.889)), and TLR had the highest efficiency when the tumor size was 5-7 cm [AUC:0.925 (95%CI, 0.820-1.000)].ConclusionsIn patients with early NSCLC, glucose metabolism reprogramming occurs in the primary lesion and liver. With the increase in tumor size, different metabolic parameters should be selected to evaluate the prognosis of patients.
Portal Venous Circulating Tumor Cells Undergoing Epithelial-Mesenchymal Transition Exhibit Distinct Clinical Significance in Pancreatic Ductal Adenocarcinoma
Authors: Pan Yujin , Li Deyu , Yang Jiuhui , Wang Ning , Xiao Erwei , Tao Lianyuan , Ding Xiangming , Sun Peichun , Li Dongxiao 
Published: October 2021

BackgroundMuch importance is attached to the clinical application value of circulating tumor cells (CTCs), meanwhile tumor-proximal CTCs detection has interested researchers for its unique advantage. This research mainly discusses the correlation of portal venous (PoV) CTCs counts in different epithelial-mesenchymal transition status with clinicopathologic parameters and postoperative prognosis in resectable pancreatic ductal adenocarcinoma patients (PDAC).MethodsPDAC patients (n=60) who received radical resection were enrolled in this research. PoV samples from all patients and peripheral venous (PV) samples from 32 patients among them were collected to verify spatial heterogeneity of CTCs distribution, and explore their correlation with clinicopathologic parameters and clinical prognosis.ResultsCTCs detectable rate and each phenotype count of PoV were higher than those of PV. Patients with recurrence had higher PV and PoV epithelial CTCs (E-CTCs) counts than recurrence-free patients (P&lt;0.05). Some unfavourable clinicopathologic parameters were closely related to higher PoV CTCs counts. Multivariate regression analysis demonstrated that PoV mesenchymal CTC (M-CTC)s≥1/5 ml was an independent risk factor for metastasis free survival (MFS) (P=0.003) and overall survival (OS) (P=0.043).ConclusionsOur research demonstrated that portal venous was a preferable vessel for CTC test, and patients with PoV M-CTC≥1/5 ml had shorter MFS and OS time in resectable PDAC patients. PoV CTC phenotype detection has the potential to be a reliable and accurate tool to identify resectable PDAC patients with high tendency of postoperative metastasis for better stratified management.
Dosimetric Comparison of Upfront Boosting With Stereotactic Radiosurgery Versus Intraoperative Radiotherapy for Glioblastoma
Authors: Sarria Gustavo R. , Smalec Zuzanna , Muedder Thomas , Holz Jasmin A. , Scafa Davide , Koch David , Garbe Stephan , Schneider Matthias , Hamed Motaz , Vatter Hartmut , Herrlinger Ulrich , Giordano Frank A. , Schmeel Leonard Christopher 
Published: October 2021

PurposeTo simulate and analyze the dosimetric differences of intraoperative radiotherapy (IORT) or pre-operative single-fraction stereotactic radiosurgery (SRS) in addition to post-operative external beam radiotherapy (EBRT) in Glioblastoma (GB).MethodsImaging series of previously treated patients with adjuvant radiochemotherapy were analyzed. For SRS target definition, pre-operative MRIs were co-registered to planning CT scans and a pre-operative T1-weighted gross target volume (GTV) plus a 2-mm planning target volume (PTV) were created. For IORT, a modified (m)GTV was expanded from the pre-operative volume, in order to mimic a round cavity as during IORT. Dose prescription was 20 Gy, homogeneously planned for SRS and calculated at the surface for IORT, to cover 99% and 90% of the volumes, respectively. For tumors &gt; 2cm in maximum diameter, a 15 Gy dose was prescribed. Plan assessment was performed after calculating the 2-Gy equivalent doses (EQD2) for both boost modalities and including them into the EBRT plan. Main points of interest encompass differences in target coverage, brain volume receiving 12 Gy or more (V12), and doses to various organs-at-risk (OARs).ResultsSeventeen pre-delivered treatment plans were included in the study. The mean GTV was 21.72 cm3 (SD ± 19.36) and mGTV 29.64 cm3 (SD ± 25.64). The mean EBRT and SRS PTV were 254.09 (SD ± 80.0) and 36.20 cm3 (SD ± 31.48), respectively. Eight SRS plans were calculated to 15 Gy according to larger tumor sizes, while all IORT plans to 20 Gy. The mean EBRT D95 was 97.13% (SD ± 3.48) the SRS D99 99.91% (SD ± 0.35) and IORT D90 83.59% (SD ± 3.55). Accounting for only-boost approaches, the brain V12 was 49.68 cm3 (SD ± 26.70) and 16.94 cm3 (SD ± 13.33) (p&lt;0.001) for SRS and IORT, respectively. After adding EBRT results respectively to SRS and IORT doses, significant lower doses were found in the latter for mean Dmax of chiasma (p=0.01), left optic nerve (p=0.023), right (p=0.008) and left retina (p&lt;0.001). No significant differences were obtained for brainstem and cochleae.ConclusionDose escalation for Glioblastoma using IORT results in lower OAR exposure as conventional SRS.
Sevoflurane Increases Hippocampal Theta Oscillations and Impairs Memory Via TASK-3 Channels
Authors: Han Linlin , Zhao Shuai , Xu Feng , Wang Yafeng , Zhou Ruihui , Huang Shiqian , Ding Yuanyuan , Deng Daling , Mao Weike , Chen Xiangdong 
Published: October 2021

Sevoflurane can induce memory impairment during clinical anesthesia; however, the underlying mechanisms are largely unknown. TASK-3 channels are one of the potential targets of sevoflurane. Accumulating evidence supports a negative role of intracranial theta rhythms (4–12 Hz) in memory formation. Here, we investigated whether TASK-3 channels contribute to sevoflurane-induced memory impairment by regulating hippocampal theta rhythms. In this study, the memory performance of mice was tested by contextual fear conditioning and inhibitory avoidance experiments. The hippocampal local field potentials (LFPs) were recorded from chronically implanted electrodes located in CA3 region. The results showed that sevoflurane concentration-dependently impaired the memory function of mice, as evidenced by the decreased time mice spent on freezing and reduced latencies for mice to enter the shock compartment. Our electrophysiological results revealed that sevoflurane also enhanced the spectral power of hippocampal LFPs (1–30 Hz), particularly in memory-related theta rhythms (4–12 Hz). These effects were mitigated by viral-mediated knockdown of TASK-3 channels in the hippocampal CA3 region. The knockdown of hippocampal TASK-3 channels significantly reduced the enhancing effect of sevoflurane on hippocampal theta rhythms and alleviated sevoflurane-induced memory impairment. Our data indicate that sevoflurane can increase hippocampal theta oscillations and impair memory function via TASK-3 channels.
Quercetin Attenuates Cardiac Hypertrophy by Inhibiting Mitochondrial Dysfunction Through SIRT3/PARP-1 Pathway
Authors: Chen Wen-Jing , Cheng Yan , Li Wen , Dong Xiao-Kang , Wei Jian-liang , Yang Chuan-Hua , Jiang Yue-Hua 
Published: October 2021

Cardiac hypertrophy is an important characteristic in the development of hypertensive heart disease. Mitochondrial dysfunction plays an important role in the pathology of cardiac hypertrophy. Recent studies have shown that sirtuin 3 (SIRT3)/poly (ADP-ribose) polymerase-1 (PARP-1) pathway modulation inhibits cardiac hypertrophy. Quercetin, a natural flavonol agent, has been reported to attenuate cardiac hypertrophy. However, the molecular mechanism is not completely elucidated. In this study, we aimed to explore the mechanism underlying the protective effect of quercetin on cardiac hypertrophy. Spontaneously hypertensive rats (SHRs) were treated with quercetin (20 mg/kg/d) for 8 weeks to evaluate the effects of quercetin on blood pressure and cardiac hypertrophy. Additionally, the mitochondrial protective effect of quercetin was assessed in H9c2 cells treated with Ang II. SHRs displayed aggravated cardiac hypertrophy and fibrosis, which were attenuated by quercetin treatment. Quercetin also improved cardiac function, reduced mitochondrial superoxide and protected mitochondrial structure in vivo. In vitro, Ang II increased the mRNA level of hypertrophic markers including atrial natriuretic factor (ANF) and β-myosin heavy chain (β-MHC), whereas quercetin ameliorated this hypertrophic response. Moreover, quercetin prevented mitochondrial function against Ang II induction. Importantly, mitochondrial protection and PARP-1 inhibition by quercetin were partly abolished after SIRT3 knockdown. Our results suggested that quercetin protected mitochondrial function by modulating SIRT3/PARP-1 pathway, contributing to the inhibition of cardiac hypertrophy.
Traditional Herbal Medicine for Insomnia in Patients With Cancer: A Systematic Review and Meta-Analysis
Authors: Yoon Jee-Hyun , Kim Eun Hye , Park Su Bin , Lee Jee Young , Yoon Seong Woo 
Published: October 2021

Background: Insomnia is one of the most prevalent cancer-related symptoms and has a severe impact on the quality of life. This study aimed to evaluate the efficacy and safety of traditional herbal medicine (THM) for improving sleep quality in patients with cancer.Methods: Randomized controlled trials (RCTs) evaluating orally administered THM in a cancer population with insomnia were searched using nine electronic databases up to November 30, 2020. The outcome measurements were sleep quality measured by validated questionnaire such as the Pittsburgh Sleep Quality Index (PSQI), total effective rate, and adverse effects. The included studies were appraised using the Cochrane risk of bias tool and meta-analyzed. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) method.Results: Fourteen RCTs were included in the systematic review, and 10 RCTs were analyzed quantitatively. Compared to hypnotics, THM showed a significant improvement in sleep quality by reducing the PSQI score [mean difference (MD) -2.25, 95% confidence interval (CI) −3.46 to −1.05, I2 = 84%] and increasing the total effective rate [risk ratio (RR) 1.26, 95% CI 1.07 to 1.48, I2 = 70%] with low quality of evidence. Compared to placebo, THM also reduced the PSQI score significantly (MD −2.56, 95% CI −3.81 to −1.31, I2 = 91%) with moderate quality of evidence. The most frequently used herbs were Ziziphus jujuba Mill. No serious adverse events were observed.Conclusion: This review suggests that THM may be an effective therapeutic option for insomnia in patients with cancer. However, considering the limited methodological qualities and inconsistent results of the included trials, further rigorous RCTs are required.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero], PROSPERO 2021 [CRD42021265070]