bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic value of lymph node micrometastasis in esophageal cancer: A systematic review and meta-analysis
Authors: Yang Jing , Liu Qianqian , Bai Yuping , Zhao Haitong , He Tingting , Zhao Ziru , Huang Min , Jiang Mengyuan , Zhang Rui , Zhang Min 
Published: January 2023

ObjectiveWhether lymph node micrometastasis (LNM) increases the risk in esophageal cancer patients remains controversial. We conducted a systematic review and meta-analysis to explore the prognosis value of LNM in esophageal cancer patients.MethodsTwo reviewers independently searched electronic databases, including PubMed, Embase, and the Cochrane Library, for eligible citations until February 2022. We calculated pooled estimates of the hazards ratio with a random-effects model. The certainty of evidence was determined by the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) method. A sensitivity analysis was performed to assess the stability. Publication bias was assessed using funnel plots and Egger’s test. We also performed subgroup analysis to explore the source of heterogeneity.ResultsA total of 16 studies, with 1,652 patients, were included. The overall survival (OS) was significantly increased with LNM negativity compared with LNM positivity (HR 1.95; 95% CI, 1.53–2.49; P &lt; 0.001; I2 = 0.0%, P = 0.930; certainty of evidence: low). Relapse-free survival (RFS) was significantly increased with LNM negativity compared with LNM positivity (HR 3.39; 95% CI, 1.87–6.16; P &lt; 0.001; I2 = 50.18%, P = 0.060; certainty of evidence: moderate). No significant difference was observed in recurrence between the two groups (certainty of evidence: low). Sensitivity analysis revealed a stable trend. In addition, the funnel plot and Egger’s test did not show significant publication bias.ConclusionLNM positivity worsens the prognosis in esophageal cancer, and the evidence for RFS is moderate. Future relevant high-quality studies are warranted to validate our results further and provide a reference for guidelines.Systematic review registrationhttps://www.crd.york.ac.uk/prospero, identifier (CRD42022321768).
Treatment dependent impact of plasma-derived exosomes from head and neck cancer patients on the epithelial-to-mesenchymal transition
Authors: Hofmann Linda , Waizenegger Marie , Röth Ralph , Schmitteckert Stefanie , Engelhardt Daphne , Schuler Patrick J. , Laban Simon , Hoffmann Thomas K. , Brunner Cornelia , Theodoraki Marie-Nicole 
Published: January 2023

BackgroundEpithelial to mesenchymal transition (EMT) is a key process in carcinogenesis of head and neck squamous cell carcinoma (HNSCC), contributing to tumor invasiveness, distant metastasis, and recurrence. Exosomes are known mediators and regulators of EMT. Here, we analyze the impact of exosomes that were primed by conventional therapy on EMT modulation.MethodsPlasmas of n = 22 HNSCC patients were collected before and after standard of care surgery and adjuvant or primary (chemo)radiotherapy. Exosomes were isolated by size exclusion chromatography. Upon co-incubation of exosomes with HNSCC cells, the cellular EMT profile was analyzed by flow cytometry and RT-qPCR. Wound healing assays were performed to evaluate migratory potential of exosome-treated cells.ResultsReduction of total exosome protein after therapy and in vitro exosome induced EMT profiles were dependent on the type of treatment. Exosomal TFG-β and miRNA cargo were partly responsible for observed exosome induced EMT changes. Exosomes from recurrent patients induced higher tumor cell migration after therapy than exosomes from disease-free patients.ConclusionsHNSCC patients’ exosomes from timepoints before and after therapy were able to confer therapy induced EMT modulation in vitro and have the potential to monitor the EMT process. Exosome induced changes in migratory potential emerged as discriminants of therapy outcome.
A pan-cancer landscape of IGF2BPs and their association with prognosis, stemness and tumor immune microenvironment
Authors: Shao Wei , Zhao Hui , Zhang Shoudu , Ding Qian , Guo Yugang , Hou Kaiqi , Kan Yunchao , Deng Fan , Xu Qian 
Published: January 2023

BackgroundThe human insulin-like growth factor 2 mRNA binding proteins 1–3 (IGF2BP1–3, also called IMP1–3) play essential roles in mRNA regulation, including its splicing, translocation, stability, and translation. However, knowledge regarding the involvement of IGF2BPs in tumor immunity and stemness across cancer types is still lacking.MethodsIn this study, we comprehensively analyzed pan-cancer multi-omic data to determine the correlation of IGF2BPs mRNA and protein expression with various cancer parameters such as mutation frequency, prognostic value, the tumor microenvironment (TME), checkpoint blockade, tumor immune infiltration, stemness and drug sensitivity. Validation of the expression of IGF2BPs in cancer samples and glioma cells were performed by quantitative real-time (qRT)-PCR, and immunofluorescence staining. Investigation of the functional role of IGF2BP3 in glioma stem cells(GSCs) were performed by sphere formation, cytotoxicity, transwell, and wound healing assays.ResultsWe found that IGF2BP1 and 3 are either absent or expressed at very low levels in most normal tissues. However, IGF2BP1-3 can be re-expressed in a broad range of cancer types and diverse cancer cell lines, where their expression often correlates with poor prognosis. Immunofluorescence staining and qRT-PCR analyses also showed that the expression of IGF2BP2 and IGF2BP3 were higher in cancer tissues than that in adjacent normal tissues. Moreover, IGF2BPs are associated with TME and stemness in human pan-cancer. Remarkably, IGF2BP3 participated in the maintenance and self-renewal of glioma stem cell (GSCs). Knockdown of IGF2BP3 attenuated GSC and glioma cell proliferation, invasion, and migration.ConclusionsOur systematic pan-cancer study confirmed the identification of IGF2BPs as therapeutic targets and highlighted the need to study their association with stemness, and the TME, which contribute to the cancer drug-discovery research. Especially, preliminary studies demonstrate the IGF2BP3 as a potential negative regulator of glioma tumorigenesis by modulating stemness.
Endoplasmic reticulum stress related IncRNA signature predicts the prognosis and immune response evaluation of uterine corpus endometrial carcinoma
Authors: Chen Jun , Shen Licong , Yang Yongwen 
Published: January 2023

BackgroundEndoplasmic reticulum (ER) stress is closely related to the occurrence, development and treatment of tumors. Recent studies suggest ER stress as a therapeutic strategy of choice for cancer. However, ER stress-related long non-coding RNA (lncRNA) predictive value in endometrial carcinoma (UCEC) remains to be further evaluated. The purpose of this study was to establish relies on the signature of ER stress-related lncRNA forecast to predict the prognosis of patients with UCEC.MethodsWe downloaded the RNA expression profile dataset and matched clinical data from the Cancer Genome Atlas (TCGA) database, and applied univariate and multivariate Cox regression analysis to build predictive signature. Kaplan-meier method was used to evaluate overall survival (OS) and disease-free survival (DFS). Gene set enrichment analysis (GSEA) was used to study the functional characteristics. Single sample Gene set enrichment analysis (ssGSEA) was used to analyze the relationship between immune status and predicted signature. Correlations between the potential usefulness of treatment for UCEC patients and predictive signature were also analyzed.ResultsWe established a signature composed of eight ER stress-related lncRNAs (MIR34AHG, AC073842.2, PINK1AS, AC024909.2, MIR31HG, AC007422.2, AC061992.1, AC003102.1). The signature of ER stress-related lncRNA provided better diagnostic value compared with age and tumor grade, and the area under the receiver operating curve was 0.788. The overall and disease-free survival probability of patients in the high-risk group is lower than that in the low-risk group. GSEA indicated that the pathways were mainly enriched for cancer, immunity and reproduction related pathways. ss-GSEA shows that prediction signature and activation of dendritic cells, immature dendritic cells, T helper cells and immune status of the Treg are significantly related. High-risk groups may against PD - 1/L1 immunotherapy and JNK inhibitors VIII, Z.LLNle.CHO, DMOG and JNK. 9 l more sensitive.ConclusionThe ER stress signature can independently predict the prognosis of UCEC patients, and provide guidance for conventional chemotherapy and immunotherapy of UCEC patients.
Closure strategy for endoscopic pituitary surgery: Experience from 3015 patients
Authors: Baussart Bertrand , Venier Alice , Jouinot Anne , Reuter Gilles , Gaillard Stephan 
Published: January 2023

IntroductionEffective strategies are required to ensure optimal management of the crucial closure step in endoscopic pituitary surgery. Many surgical techniques have been reported but no significant consensus has been defined.MethodsBetween January 2006 and March 2022, 3015 adult patients with pituitary adenomas were operated on by a single expert neurosurgical team, using a mononostril endoscopic endonasal approach. Based of preoperative risk factors of and operative findings, a detailed closure strategy was used. Body mass index &gt;40, sellar floor lysis, number of surgeries&gt;2, large skull base destruction, prior radiotherapy were considered as preoperative risk factors for closure failure. All patients treated with an expanded endonasal approach were excluded.ResultsPatients were mostly women (F/M ratio: 1.4) with a median age of 50 (range: 18 –89). Intraoperative CSF leak requiring specific surgical management was observed in 319/3015 (10.6%) of patients. If intraoperative leak occurred, patients with predictive risk factors were managed using a Foley balloon catheter in case of sellar floor lysis or BMI&gt;40 and a multilayer repair strategy with a vascularized nasoseptal flap in other cases. Postoperative CSF leak occurred in 29/3015 (1%) of patients, while meningitis occurred in 24/3015 (0.8%) of patients. In patients with intraoperative leak, closure management failed in 11/319 (3.4%) of cases.ConclusionBased on our significant 16-year experience, our surgical management is reliable and easy to follow. With a planned and stepwise strategy, the closure step can be optimized and tailored to each patient with a very low failure rate.
Quantitative analysis of superb microvascular imaging for monitoring tumor response to chemoradiotherapy in locally advanced cervical cancer
Authors: Zhu Yi , Tang Yixin , Zhang Guonan , Zhang Jie , Li Yanjie , Jiang Zhuolin 
Published: January 2023

ObjectivesAs an ultrasound (US) image processing method, superb microvascular imaging (SMI) extracts and visualizes flow signals from vessels through advanced clutter suppression technology. We investigated the feasibility of SMI in monitoring treatment response in patients with locally advanced cervical cancer (LACC) undergoing chemoradiotherapy (CRT).MethodsForty-nine patients underwent CRT and received SMI examination at 3 time points: before therapy (baseline), 3 weeks during, and 1 month after CRT. The maximum tumor diameter (Dmax), vascularity index (VI), and their percentage changes (ΔDmax and ΔVI) were calculated. ΔDmax was compared with MRI results as the reference standard.ResultsBased on the MRI findings, 44 were classified as complete response (CR) group and 5 as partial response (PR) group. The Dmax and ΔDmax showed decrease in CR and PR groups at 3 weeks during CRT (P&lt; 0.05), but no significant difference between the two groups (P &gt; 0.05). Compared to the baseline, significant decrease in VI and ΔVI were observed at during and after treatment in the two groups (P&lt; 0.05). Moreover, there were significant differences in VI and ΔVI at 3 weeks during CRT between the CR and PR groups (P&lt; 0.05). ΔVI at 3 weeks during CRT showed a better predictive performance for responder prognosis than VI (AUC = 0.964, AUC = 0.950, respectively, P = 0.001), with a cut-off value of 41.6% yielding 100% sensitivity and 86.4% specificity.ConclusionsThe SMI parameters (VI and ΔVI) have potential for monitoring treatment response in LACC.
MRI-based multiregional radiomics for predicting lymph nodes status and prognosis in patients with resectable rectal cancer
Authors: Li Hang , Chen Xiao-li , Liu Huan , Lu Tao , Li Zhen-lin 
Published: January 2023

PurposeTo establish and evaluate multiregional T2-weighted imaging (T2WI)-based clinical-radiomics model for predicting lymph node metastasis (LNM) and prognosis in patients with resectable rectal cancer.MethodsA total of 346 patients with pathologically confirmed rectal cancer from two hospitals between January 2019 and December 2021 were prospectively enrolled. Intra- and peritumoral features were extracted separately, and least absolute shrinkage and selection operator regression was applied for feature selection. Radiomics signatures were built using the selected features from different regions. The clinical-radiomic nomogram was developed by combining the intratumoral and peritumoral radiomics signatures score (radscore) and the most predictive clinical parameters. The diagnostic performances of the nomogram and clinical model were evaluated using the area under the receiver operating characteristic curve (AUC). The prognostic model for 3-year recurrence-free survival (RFS) was constructed using univariate and multivariate Cox analysis.ResultsThe intratumoral radscore (radscore 1) included four features, the peritumoral radscore (radscore 2) included five features, and the combined intratumoral and peritumoural radscore (radscore 3) included ten features. The AUCs for radscore 3 were higher than that of radscore 1 in training cohort (0.77 vs. 0.71, P=0.182) and internal validation cohort (0.76 vs. 0.64, P=0.041). The AUCs for radscore 3 were higher than that of radscore 2 in training cohort (0.77 vs. 0.74, P=0.215) and internal validation cohort (0.76 vs. 0.68, P=0.083). A clinical-radiomic nomogram showed a higher AUC compared with the clinical model in training cohort (0.84 vs. 0.67, P&lt;0.001) and internal validation cohort (0.78 vs. 0.64, P=0.038) but not in external validation (0.72 vs. 0.76, P=0.164). Multivariate Cox analysis showed MRI-reported extramural vascular invasion (EMVI) (HR=1.099, 95%CI: 0.462-2.616; P=0.031) and clinical-radiomic nomogram-based LNM (HR=2.232, 95%CI:1.238-7.439; P=0.017) were independent risk factors for assessing 3-year RFS. Combined clinical-radiomic nomogram based LNM and MRI-reported EMVI showed good performance in training cohort (AUC=0.748), internal validation cohort (AUC=0.706) and external validation (AUC=0.688) for predicting 3-year RFS.ConclusionA clinical-radiomics nomogram exhibits good performance for predicting preoperative LNM. Combined clinical-radiomic nomogram based LNM and MRI-reported EMVI showed clinical potential for assessing 3-year RFS.
The role of radiotherapy in HER2+ early-stage breast cancer patients after breast-conserving surgery
Authors: Yang Huanzuo , Qiu Mengxue , Feng Yu , Wen Nan , Zhou Jiao , Qin Xiangquan , Li Juan , Liu Xinran , Wang Xiaodong , Du Zhenggui 
Published: January 2023

BackgroundDue to radioresistance, some HER2+ patients may gain limited benefit from radiotherapy (RT) after breast-conserving surgery (BCS). This study aimed to develop an individualized nomogram to identify early-stage HER2+ patients who could omit RT after BCS.MethodsThe data of HER2+ patients with T0-2N0M0 breast cancer after BCS between 2010 and 2015 were extracted from Surveillance, Epidemiology, and End Results (SEER). Based on the independent prognostic factors determined by the Cox analysis in patients without RT after propensity score matching (PSM), the nomogram and risk stratification model were constructed, and then the prognosis of patients with and without RT was compared in each stratified group.ResultsA total of 10799 early-stage HER2+ patients after BCS were included. Baseline characteristics were similar between groups after PSM. Multivariate Cox analysis indicated that RT could improve overall survival (OS) (HR: 0.45, P&lt;0.001) and breast cancer-specific survival (BCSS) (HR: 0.53, P&lt;0.001). Age, marital status, tumor location, tumor size, and chemotherapy were identified by multivariate Cox analysis in patients without RT and were incorporated into a well-validated nomogram. The risk stratification model based on the nomogram indicated that RT was associated with improved OS (HR 0.40, P&lt; 0.001) and BCSS (HR 0.39, P&lt; 0.001) in the high-risk group but not in the low-risk group [OS: HR 1.04, P = 0.94; BCSS: HR 1.06, P = 0.93].ConclusionRT could significantly improve the OS and BCSS of HER2+ early-stage breast cancer patients after BCS on the whole. For high-risk patients, RT is an essential component of cancer therapy. However, the omission of radiotherapy may be considered for low-risk HER2+ early-stage patients. Further validation and improvement of the nomogram by prospective study or randomized controlled trials are warranted.
Echinacoside exerts antidepressant-like effects through enhancing BDNF-CREB pathway and inhibiting neuroinflammation via regulating microglia M1/M2 polarization and JAK1/STAT3 pathway
Authors: Lu Renrui , Zhang Li , Wang Huihui , Li Meng , Feng Weisheng , Zheng Xiaoke 
Published: January 2023

The present study was performed to investigate the antidepressant effect of echinacoside (ECH) using chronic unpredictable mild stress (CUMS) induced depression mice and lipopolysaccharide (LPS)-stimulated N9 microglial cells. CUMS treatment was performed on C57BL/6 mice for 28 days, followed by gavaging with different doses of echinacoside (15 and 60 mg/kg) for 21 consecutive days. Sucrose preference test (SPT), open field test (OFT), tail suspension test (TST), and forced swimming test (FST) were measured to assess the effects of echinacoside on CUMS-Induced Depressive-Like Behaviors. After that, the pathological changes of hippocampus were determined by Hematoxylin and eosin (HE) staining and Nissl staining; the neurotransmitters, pro-inflammatory cytokines and indoleamine 2,3-dioxygenase (IDO) levels, and the hypothalamic–pituitary–adrenal (HPA) axis activity were determined by enzyme linked immunosorbent assay (ELISA); Iba 1were evaluated by Immunofluorescence assay; Key protein expression levels of CREB/BDNF signal pathway were measured by western blotting. Subsequently, N9 cells were stimulated with 1 μg/ml LPS to induce N9 microglia activation, and were treated with 5–20 μM of echinacoside for 24 h. After that, the levels of NO, interleukin (IL)-1β, IL-6, tumor necrosis factor alpha (TNF-α), IL-4, IL-10, and transforming growth factor beta (TGF-β) in N9 cell culture supernatants were measured by enzyme-linked immunosorbent assay (ELISA) kits; morphology and Iba 1 expression level were observed by high-content screening assay; the M1 markers of CD11b, CD86 and M2 markers of CD206 were analyzed by imaging flow cytometry. Results show that treatment with echinacoside reversed CUMS-increased immobility time in OFT, TST, FST and reversed CUMS-reduced sucrose preference in SPT. In addition, echinacoside reduced the levels of pro-inflammatory cytokines and Iba 1. Moreover, echinacoside significantly increased p-CREB/CREB ratio and BDNF level in hippocampus. Furthermore, echinacoside reduced the secretion of inflammatory factors and inhibited microglia M1 polarization in N9 cells. In conclusion, echinacoside may be beneficial for the treatment of depression diseases through regulating the microglia balance by inhibiting the polarization of microglia to M1 phenotype, and improving hippocampal neurogenesis by the CREB-BDNF signaling pathway.
Electronic transport and thermoelectric properties of phosphorene nanodisk under an electric field
Authors: Bazrafshan M. Amir , Khoeini Farhad 
Published: January 2023

The Seebeck coefficient is an important quantity in determining the thermoelectric efficiency of a material. Phosphorene is a two-dimensional material with a puckered structure, which makes its properties anisotropic. In this work, a phosphorene nanodisk (PDisk) with a radius of 3.1 nm connected to two zigzag phosphorene nanoribbons is studied, numerically, by the tight-binding and non-equilibrium Green’s function (NEGF) methods in the presence of transverse and perpendicular electric fields. Our results show that the change in structure from a zigzag ribbon to a disk form creates an energy gap in the structure, such that for a typical nanodisk with a radius of 3.1 nm, the size of the energy gap is 3.88 eV. Besides, with this change, the maximum Seebeck coefficient increases from 1.54 to 2.03 mV/K. Furthermore, we can control the electron transmission and Seebeck coefficients with the help of the electric fields. The numerical results show that with the increase of the electric field, the transmission coefficient decreases and the Seebeck coefficient changes. The effect of a perpendicular electric field on the Seebeck coefficient is weaker than a transverse electric field. For an applied transverse electric field of 0.3 V/nm, the maximum Seebeck coefficient enhances to 2.09 mV/K.
Weak magnetic fields modulate superoxide to control planarian regeneration
Authors: Kinsey Luke J. , Van Huizen Alanna V. , Beane Wendy S. 
Published: January 2023

Reactive oxygen species (ROS) signaling regulates cell behaviors and tissue growth in development, regeneration, and cancer. Commonly, ROS are modulated pharmacologically, which while effective comes with potential complications such as off-target effects and lack of drug tolerance. Thus, additional non-invasive therapeutic methods are necessary. Recent advances have highlighted the use of weak magnetic fields (WMFs, &lt;1 mT) as one promising approach. We previously showed that 200 μT WMFs inhibit ROS formation and block planarian regeneration. However, WMF research in different model systems at various field strengths have produced a range of results that do not fit common dose response curves, making it unclear if WMF effects are predictable. Here, we test hypotheses based on spin state theory and the radical pair mechanism, which outlines how magnetic fields can alter the formation of radical pairs by changing electron spin states. This mechanism suggests that across a broad range of field strengths (0–900 μT) some WMF exposures should be able to inhibit while others promote ROS formation in a binary fashion. Our data reveal that WMFs can be used for directed manipulation of stem cell proliferation, differentiation, and tissue growth in predictable ways for both loss and gain of function during regenerative growth. Furthermore, we examine two of the most common ROS signaling effectors, hydrogen peroxide and superoxide, to begin the identification and elucidation of the specific molecular targets by which WMFs affect tissue growth. Together, our data reveal that the cellular effects of WMF exposure are highly dependent on ROS, and we identify superoxide as a specific ROS being modulated. Altogether, these data highlight the possibilities of using WMF exposures to control ROS signaling in vivo and represent an exciting new area of research.