bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aberrant Intraregional Brain Activity and Functional Connectivity in Patients With Diarrhea-Predominant Irritable Bowel Syndrome
Authors: Chen Xiao-Fei , Guo Yun , Lu Xing-Qi , Qi Le , Xu Kuang-Hui , Chen Yong , Li Guo-Xiong , Ding Jian-Ping , Li Jie 
Published: September 2021

Background and PurposeThe appearance and aggravation of diarrhea-predominant irritable bowel syndrome (IBS-D) have proven to be closely related to psychosocial factors. We aimed to measure altered spontaneous brain activity and functional connectivity (FC) in patients with IBS-D using resting-state functional magnetic resonance imaging (RS-fMRI) and to analyze the relationship between these parameters and emotional symptoms.MethodsThirty-six adult IBS-D patients and thirty-six demographic-matched healthy controls (HCs) underwent RS-fMRI scans. After processing RS-fMRI data, the values of the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) of the two groups were compared. The abnormal regions were selected as the regions of interest to compare whole-brain seed-based FC between the groups. The relationships between RS-fMRI data and mood and gastrointestinal symptoms were analyzed using correlation and mediation analyses.ResultsCompared with HCs, IBS-D patients showed increased ALFF in the right cerebellum posterior lobe, the right lingual gyrus/calcarine, the right postcentral gyrus, the right superior frontal gyrus (SFG), and middle frontal gyrus (MFG), with decreased ALFF in the right inferior parietal lobule, the right striatum, the right anterior cingulated cortex, the right insula, the right hippocampus, the right thalamus, the right midbrain, and the left precuneus. IBS-D patients showed increased ReHo in the bilateral lingual gyrus/calcarine, the bilateral SFG, the right MFG, and the right postcentral gyrus, with decreased ReHo in the orbital part of the left inferior frontal gyrus and the right supplementary motor area. Patients showed enhanced FC between the left precuneus and the bilateral orbitofrontal cortex (OFC). There was a positive correlation between increased ALFF values in the right midbrain and anxiety-depression symptoms in IBS-D patients, and the mediating effect of gastrointestinal symptoms indirectly caused this correlation.ConclusionIBS-D patients had dysregulated spontaneous activity and FC in regions related to pain regulation and emotional arousal involved in prefrontal–limbic–midbrain circuit and somatosensory processing. The development of mood disorders in IBS-D patients may be partly related to the dysfunction of components in the dopamine pathway (especially the midbrain, OFC) due to visceral pain.
Acute Corticotropin-Releasing Factor Receptor Type 2 Agonism Results in Sustained Symptom Improvement in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome
Authors: Pereira Gerard , Gillies Hunter , Chanda Sanjay , Corbett Michael , Vernon Suzanne D. , Milani Tina , Bateman Lucinda 
Published: September 2021

BackgroundMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex multi-symptom disease with widespread evidence of disrupted systems. The authors hypothesize that it is caused by the upregulation of the corticotropin-releasing factor receptor type 2 (CRFR2) in the raphé nuclei and limbic system, which impairs the ability to maintain homeostasis. The authors propose utilizing agonist-mediated receptor endocytosis to downregulate CRFR2.Materials and MethodsThis open-label trial tested the safety, tolerability and efficacy of an acute dose of CT38s (a short-lived, CRFR2-selective agonist, with no known off-target activity) in 14 ME/CFS patients. CT38s was subcutaneously-infused at one of four dose-levels (i.e., infusion rates of 0.01, 0.03, 0.06, and 0.20 μg/kg/h), for a maximum of 10.5 h. Effect was measured as the pre-/post-treatment change in the mean 28-day total daily symptom score (TDSS), which aggregated 13 individual patient-reported symptoms.ResultsME/CFS patients were significantly more sensitive to the transient hemodynamic effects of CRFR2 stimulation than healthy subjects in a prior trial, supporting the hypothesized CRFR2 upregulation. Adverse events were generally mild, resolved without intervention, and difficult to distinguish from ME/CFS symptoms, supporting a CRFR2 role in the disease. The acute dose of CT38s was associated with an improvement in mean TDSS that was sustained (over at least 28 days post-treatment) and correlated with both total exposure and pre-treatment symptom severity. At an infusion rate of 0.03 μg/kg/h, mean TDSS improved by −7.5 ± 1.9 (or −25.7%, p = 0.009), with all monitored symptoms improving.ConclusionThe trial supports the hypothesis that CRFR2 is upregulated in ME/CFS, and that acute CRFR2 agonism may be a viable treatment approach warranting further study.Clinical Trial RegistrationClinicalTrials.gov, identifier NCT03613129.
A Comparative Study of Two In Vivo PET Verification Methods in Clinical Cases
Authors: Zhang Junyu , Lu Yan , Sheng Yinxiangzi , Wang Weiwei , Hong Zhengshan , Sun Yun , Zhou Rong , Cheng Jingyi 
Published: September 2021

PurposePositron emission tomography (PET) range verification is an important method that can help improve the confidence in proton therapy for clinical applications. Two kinds of verification methods are implemented and compared based on clinical cases in this study.MethodThe study is conducted on 14 breast cancer patients following proton irradiation treatment. Verification is done by calculating the depth error between the numerically predicted values with the measured PET image along the beam direction. Point-based and segment-based methods are applied and compared. The verification results are presented as depth error means and standard deviations in a region of interest (ROI).ResultsThe mean value of the depth error of all 14 cases is within the range of [−3, 3] mm for both point-based and segment-based methods, and only one case result calculated by the point-based method is slightly beyond −3 mm. When comparing the mean depth error from the two methods, the paired t-test result shows that the p-value is 0.541, and the standard deviation of the segment-based method is smaller than that of the point-based method.ConclusionIn breast cancer case verification application, point-based and segment-based methods show no significant difference in the mean value of results. Both methods can quantify the accuracy of proton radiotherapy to the millimeter level.
Appropriate PD-L1 Cutoff Value for Gastric Cancer Immunotherapy: A Systematic Review and Meta-Analysis
Authors: Xie Tong , Zhang Zhening , Zhang Xiaotian , Qi Changsong , Shen Lin , Peng Zhi 
Published: September 2021

BackgroundImmunotherapy dramatically changed the treatment landscape of gastric cancer in recent years. PD-L1 expression was proposed as a biomarker; however, the treatment strategy according to PD-L1 is still uncertain. Here, we aimed to find the appropriate cutoff value of PD-L1 expression for gastric cancer immunotherapy.MethodsWe did a systematic electronic research of prospective clinical trials of gastric cancer immunotherapy across databases. Studies that provided subgroup analysis results stratified by PD-L1 expression were included. Objective response rate (ORR), disease control rate (DCR), hazard ratio (HR), and 95% confidential interval (CI) of progression-free survival (PFS) and overall survival (OS) at different PD-L1 cutoff values were extracted.ResultsTwelve studies and 6,488 patients in total were finally included for pooled analysis. ORR in allover, PD-L1-negative, combined positive score (CPS) ≥1, CPS ≥5, and CPS ≥10 population was 10%, 3%, 13%, 20%, and 23%, respectively. Immune checkpoint inhibitor (ICI) monotherapy failed to show survival advantage in allover and PD-L1-negative patients. Single-agent ICI therapy prolonged OS (HR = 0.84, 95% CI: 0.74–0.96) but not PFS (HR = 1.38, 95% CI: 0.91–2.09) in PD-L1 CPS ≥1 patients. For combined immunotherapy, ORR in allover, PD-L1-negative, CPS ≥1, CPS ≥5, and CPS ≥10 population was 64%, 57%, 48%, 60%, and 58%, respectively. Allover population could gain survival benefit from combined immunotherapy based on the results from Checkmate-649. OS (HR = 0.81, 95% CI: 0.71–0.92) and PFS (HR = 0.77, 95% CI: 0.69–0.86) were significantly prolonged in PD-L1 CPS ≥1 patients receiving combined immunotherapy.ConclusionEfficacy and survival advantages improved with PD-L1 CPS. CPS ≥1 was the cutoff value for ICI monotherapy to gain survival benefit. Combined immunotherapy prolonged PFS and OS in allover population but needs further study to confirm it.
Development and Validation of a Novel Model for Predicting Prognosis of Non-PCR Patients After Neoadjuvant Therapy for Breast Cancer
Authors: Yu Yongqiang , Wu Si , Xing Hui , Han Mengxue , Li Jinze , Liu Yueping 
Published: September 2021

PurposePathologic complete response (pCR) after neoadjuvant therapy is an important indicator of long-term prognosis and the primary endpoint of many neoadjuvant studies. For breast cancer patients who do not achieve pCR, prognostic indicators related to prognosis are particularly important. This study is constructing a prediction model with more accurate and reliable prediction results by combining multiple clinicopathological factors, so as to provide a more accurate decision-making basis for subsequent clinical treatment.Patients and MethodsIn this study, 1,009 cases of invasive breast cancer and surgically resected after neoadjuvant therapy from 2010 to 2017. All indicators in this trial were interpreted in a double-blind manner by two pathologists with at least 10 years of experience, including histological grading, Tils, ER, PR, HER2, and Ki67. The prediction model used R language to calculate the calibration degree and ROC curve of the prediction model in the training set and validation set.ResultsThrough univariate survival analysis, the results showed histological grade (P=0.037), clinical stage (P&lt;0.001), HER2 (P=0.044), RCB class (P&lt;0.001), Tils (P&lt;0.001), lymph node status (P =0.049), MP grade (P=0.013) are related to OS in non-PCR patients after neoadjuvant. Data were analyzed by substituting in a multivariate analysis, and the results were that clinical stage, HER2, RCB grading, and Tils grading were correlated with OS in non-PCR patients after neoadjuvant therapy for breast cancer. Among all cases in the training set, the prediction model predicted that the 3-year survival AUC value was 0.95 and 5-year survival AUC value was 0.79, and the RCB classification of 3-year survival and 5-year survival were 0.70 and 0.67, respectively, which proved that the prediction model could predict the OS of non-PCR patients after neoadjuvant therapy for breast cancer more accurately than the RCB classification, and showed the same results in HR, HER2+, and TN classifications. It also showed the same results in validation set.ConclusionThese data indicate that the predicted values of the prediction model developed in this study match the actual survival rates without underestimating the mortality risk and have a relatively accurate prediction effect.
A Radiomics Model for Predicting Early Recurrence in Grade II Gliomas Based on Preoperative Multiparametric Magnetic Resonance Imaging
Authors: Wang Zhen-hua , Xiao Xin-Lan , Zhang Zhao-Tao , He Keng , Hu Feng 
Published: September 2021

ObjectiveThis study aimed to develop a radiomics model to predict early recurrence (&lt;1 year) in grade II glioma after the first resection.MethodsThe pathological, clinical, and magnetic resonance imaging (MRI) data of patients diagnosed with grade II glioma who underwent surgery and had a recurrence between 2017 and 2020 in our hospital were retrospectively analyzed. After a rigorous selection, 64 patients were eligible and enrolled in the study. Twenty-two cases had a pathologically confirmed recurrent glioma. The cases were randomly assigned using a ratio of 7:3 to either the training set or validation set. T1-weighted image (T1WI), T2-weighted image (T2WI), and contrast-enhanced T1-weighted image (T1CE) were acquired. The minimum-redundancy-maximum-relevancy (mRMR) method alone or in combination with univariate logistic analysis were used to identify the most optimal predictive feature from the three image sequences. Multivariate logistic regression analysis was then used to develop a predictive model using the screened features. The performance of each model in both training and validation datasets was assessed using a receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).ResultsA total of 396 radiomics features were initially extracted from each image sequence. After running the mRMR and univariate logistic analysis, nine predictive features were identified and used to build the multiparametric radiomics model. The model had a higher AUC when compared with the univariate models in both training and validation data sets with an AUC of 0.966 (95% confidence interval: 0.949–0.99) and 0.930 (95% confidence interval: 0.905–0.973), respectively. The calibration curves indicated a good agreement between the predictable and the actual probability of developing recurrence. The DCA demonstrated that the predictive value of the model improved when combining the three MRI sequences.ConclusionOur multiparametric radiomics model could be used as an efficient and accurate tool for predicting the recurrence of grade II glioma.
Two-Trait Predictor of Venous Invasion on Contrast-Enhanced CT as a Preoperative Predictor of Outcomes for Early-Stage Hepatocellular Carcinoma After Hepatectomy
Authors: Li Xinming , Zhang Xuchang , Li Zhipeng , Xie Chuanmiao , Qin Shuping , Yan Meng , Ke Qiying , Jin Xuan , Lin Ting , Zhou Muyao , Liang Wen , Qi Zhendong , Geng Zhijun , Quan Xianyue 
Published: September 2021

ObjectivesThis study aimed to assess the effectiveness of the two-trait predictor of venous invasion (TTPVI) on contrast-enhanced computed tomography (CECT) for the preoperative prediction of clinical outcomes in patients with early-stage hepatocellular carcinoma (HCC) after hepatectomy.MethodsThis retrospective study included 280 patients with surgically resected HCC who underwent preoperative CECT between 2012 and 2013. CT imaging features of HCC were assessed, and univariate and multivariate Cox regression analyses were used to evaluate the CT features associated with disease-free survival (DFS) and overall survival (OS). Subgroup analyses were used to summarized the hazard ratios (HRs) between patients in whom TTPVI was present and those in whom TTPVI was absent using a forest plot.ResultsCapsule appearance [HR, 0.504; 95% confidence interval (CI), 0.341–0.745; p &lt; 0.001], TTPVI (HR, 1.842; 95% CI, 1.319–2.572; p &lt; 0.001) and high level of alanine aminotransferase (HR, 1.620; 95% CI, 1.180–2.225, p = 0.003) were independent risk factors for DFS, and TTPVI (HR, 2.509; 95% CI, 1.518–4.147; p &lt; 0.001), high level of alpha-fetoprotein (HR, 1.722; 95% CI, 1.067–2.788; p = 0.026), and gamma-glutamyl transpeptidase (HR, 1.787; 95% CI, 1.134–2.814; p = 0.026) were independent risk factors for OS. A forest plot revealed that the TTPVI present group had lower DFS and OS rates in most subgroups. Patients in whom TTPVI was present in stages I and II had a lower DFS and OS than those in whom TTPVI was absent. Moreover, there were significant differences in DFS (p &lt; 0.001) and OS (p &lt; 0.001) between patients classified as Barcelona Clinic Liver Cancer stage A in whom TTPVI was absent and in whom TTPVI was present.ConclusionsTTPVI may be used as a preoperative biomarker for predicting postoperative outcomes for patients with early-stage HCC.
RETRACTED: MiR-1236-3p Inhibits the Proliferation, Invasion, and Migration of Colon Cancer Cells and Hinders Epithelial-Mesenchymal Transition by Targeting DCLK3
Authors: Zhao Yibin , Zhou Hongyi , Shen Jie , Yang Shaohui , Deng Ke , Li Qi , Cui Wei 
Published: September 2021

BackgroundDysregulated microRNAs (miRNAs) are common in human cancer and are involved in the proliferation, promotion, and metastasis of tumor cells. Therefore, this study aimed to evaluate the expression and biological function of miR-1236-3p in colon cancer.MethodsThis study screened the miRNA in normal and colon cancer tissues through array analysis. In addition, quantitative Reverse Transcription–Polymerase Chain Reaction (qRT-PCR) analysis was performed to validate the expression of miR-1236-3p in normal and tumor tissues from colon cancer patients and cancer cell lines. Online predicting algorithms and luciferase reporter assays were also employed to confirm Doublecortin Like Kinase 3 (DCLK3) was the target for miR-1236-3p. Moreover, the impact of miR-1236-3p on the progression of colon cancer was evaluated in vitro and in vivo. Western blotting and qRT-PCR were also performed to investigate the interactions between miR-1236-3p and DCLK3.ResultsMiR-1236-3p was significantly downregulated in colon cancer tissues and its expression was associated with the TNM stage and metastasis of colon. In addition, the in vitro and in vivo experiments showed that miR-1236-3p significantly promoted cancer cell apoptosis and inhibited the proliferation, invasion, and migration of cancer cells. The results also showed that miR-1236-3p hindered Epithelial–mesenchymal Transition (EMT) by targeting DCLK3. Moreover, the expression of DCLK3 mediated the effects of miR-1236-3p on the progression of cancer.ConclusionsMiR-1236-3p functions as a tumor suppressor in colon cancer by targeting DCLK3 and is therefore a promising therapeutic target for colon cancer.
Prognostic Value of NLRP3 Inflammasome and TLR4 Expression in Breast Cancer Patients
Authors: Saponaro Concetta , Scarpi Emanuela , Sonnessa Margherita , Cioffi Antonella , Buccino Francesca , Giotta Francesco , Pastena Maria Irene , Zito Francesco Alfredo , Mangia Anita 
Published: September 2021

Inflammasome complexes play a pivotal role in different cancer types. NOD-like receptor protein 3 (NLRP3) inflammasome is one of the most well-studied inflammasomes. Activation of the NLRP3 inflammasome induces abnormal secretion of soluble cytokines, generating advantageous inflammatory surroundings that support tumor growth. The expression levels of the NLRP3, PYCARD and TLR4 were determined by immunohistochemistry in a cohort of primary invasive breast carcinomas (BCs). We observed different NLRP3 and PYCARD expressions in non-tumor vs tumor areas (p&lt;0.0001). All the proteins were associated to more aggressive clinicopathological characteristics (tumor size, grade, tumor proliferative activity etc.). Univariate analyses were carried out and related Kaplan-Meier curves plotted for NLRP3, PYCARD and TLR4 expression. Patients with higher NLRP3 and TLR4 expression had worse 5-year disease-free survival (DFS) compared to patients with lower NLRP3 and TLR4 expression (p =0.021 and p = 0.009, respectively). In multivariate analysis, TLR4 was confirmed as independent prognostic factors for DFS (HR = 2.03, 95% CI 1.16–3.57, p = 0.014), and high NLRP3 expression showed a slight association with DFS (HR = 1.75, 95% CI 0.98–3.15, p = 0.06). In conclusion, we showed TLR4 expression as independent prognostic factors and we highlighted for the first time that high expression of NLRP3 is linked to a poor prognosis in BC patients. These results suggest that NLRP3 and TLR4 could be two new good prognostic factor for BC patients.
Efficacy of Omentum-Preserving Gastrectomy for Patients With Gastric Cancer: A Systematic Review and Meta-Analysis
Authors: Li Zonglin , Song Min , Zhou Yejiang , Jiang Huaiwu , Xu Linxia , Hu Zhengchuan , Liu Yi , Jiang Yifan , Li Xin 
Published: September 2021

BackgroundComplete omentectomy is considered to be essential in the radical gastrectomy for gastric cancer (GC), but its clinical benefit remains unclear. This study aims to evaluate the efficacy of omentum-preserving gastrectomy (OPG) for patients with GC.MethodsStudies comparing the surgical and oncological outcomes of OPG and gastrectomy with complete omentectomy (GCO) for GC up to March 2021 were systematically searched from PubMed, Web of Science, Embase, and Cochrane Library. A pooled analysis was performed for the available data regarding the baseline features, surgical and oncological outcomes. The RevMan 5.3 software was used to perform the statistical analysis. Quality evaluation and publication bias were also conducted.ResultsNine studies with a total of 3335 patients (1372 in the OPG group and 1963 in the GCO group) undergoing gastrectomy were included. In the pooled analysis, the baseline data in two groups were all comparable (p &gt; 0.05). However, the OPG group was associated with shorter operative time (MD = −18.67, 95% CI = −31.42 to −5.91, P = 0.004) and less intraoperative blood loss (MD = −38.09, 95% CI = −53.78 to −22.41, P &lt; 0.00001) than the GCO group. However, the number of dissected lymph nodes (MD = 2.16, 95% CI = −0.61 to 4.93, P = 0.13), postoperative complications (OR = 0.92, 95% CI = 0.74 to 1.15, p = 0.47), overall recurrence rate (OR = 0.83, 95% CI = 0.66 to 1.06, p = 0.14), peritoneal recurrence rate (OR = 0.91, 95% CI = 0.65 to 1.29, p = 0.60), 3-year relapse-free survival (RFS) rate (OR = 1.40, 95% CI = 0.86 to 2.27, p = 0.18), and 5-year RFS rate (OR = 1.21, 95% CI = 0.95 to 1.55, p = 0.12) of the two groups were comparable.ConclusionsOPG might be an oncologically safe procedure with better surgical outcomes for patients with GC than GCO. However, high-quality randomized controlled trials are needed to confirm this benefit.
Comparison of Sutureless Versus Suture Partial Nephrectomy for Clinical T1 Renal Cell Carcinoma: A Meta-Analysis of Retrospective Studies
Authors: Zhang Wenjun , Che Bangwei , Xu Shenghan , Mu Yi , He Jun , Tang Kaifa 
Published: September 2021

BackgroundPartial nephrectomy (PN) is the recommended treatment for T1 renal cell carcinoma (RCC). Compared with suture PN, sutureless PN reduces the difficulty and time of operation, but the safety and feasibility have been controversial. This meta-analysis was conducted to compare the function and perioperative outcomes of suture and sutureless PN for T1 RCC.MethodsSystematic literature review was performed up to April 2021 using multiple databases to identify eligible comparative studies. According to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) criteria, identification and selection of the studies were conducted. Meta-analysis was performed for studies comparing suture to sutureless PN for both T1a and T1b RCC. In addition, subgroup analysis was performed on operation time, warm ischemia time, estimated blood loss, and postoperative complications. Sensitivity analysis was used in analysis with high heterogeneity (operation time and estimated blood loss).ResultsEight retrospective studies were included with a total of 1,156 patients; of the 1,156 patients, 499 received sutureless PN and 707 received suture PN. The results showed that sutureless PN had shorter operative time (I2 = 0%, P &lt; 0.001), warm ischemia time (I2 = 97.5%, P &lt; 0.001), and lower clamping rate (I2 = 85.8%, P = 0.003), but estimated blood loss (I2 = 76.6%, P = 0.064) had no difference. In the comparison of perioperative outcomes, there was no significant difference in postoperative complications (I2 = 0%, P = 0.999), positive surgical margins (I2 = 0%, P = 0.356), postoperative estimated glomerular filtration rat (eGFR) (I2 = 0%, P = 0.656), and tumor recurrence (I2 = 0%, P = 0.531).ConclusionsIn T1a RCC with low RENAL score, sutureless PN is a feasible choice, whereas it should not be overestimated in T1b RCC.