bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted Functional Connectivity Within and Between Resting-State Networks in the Subacute Stage of Post-stroke Aphasia
Authors: Zhang Chao , Xia Yingying , Feng Tao , Yu Ke , Zhang Haiyan , Sami Muhammad Umair , Xiang Jie , Xu Kai 
Published: December 2021

Background: Post-stroke aphasia (PSA) results from brain network disorders caused by focal stroke lesions. However, it still remains largely unclear whether the impairment is present in intra- and internetwork functional connectivity (FC) within each resting-state network (RSN) and between RSNs in the subacute stage of PSA.Objectives: This study aimed to investigate the resting-state FC within and between RSNs in patients with PSA and observe the relationships between FC alterations and Western Aphasia Battery (WAB) measures.Methods: A total of 20 individuals with subacute PSA and 20 healthy controls (HCs) were recruited for functional MRI (fMRI) scanning, and only patients with PSA underwent WAB assessment. Independent component analysis was carried out to identify RSNs. Two-sample t-tests were used to calculate intra- and internetwork FC differences between patients with PSA and HCs. The results were corrected for multiple comparisons using the false discovery rate (FDR correction, p &lt; 0.05). Partial correlation analysis was performed to observe the relationship between FC and WAB scores with age, gender, mean framewise displacement, and lesion volume as covariates (p &lt; 0.05).Results: Compared to HCs, patients with PSA showed a significant increase in intranetwork FC in the salience network (SN). For internetwork FC analysis, patients showed a significantly increased coupling between left frontoparietal network (lFPN) and SN and decreased coupling between lFPN and right frontoparietal network (rFPN) as well as between lFPN and posterior default mode network (pDMN) (FDR correction, p &lt; 0.05). Finally, a significant positive correlation was found between the intergroup difference of FC (lFPN-rFPN) and auditory-verbal comprehension (p &lt; 0.05).Conclusion: Altered FC was revealed within and between multiple RSNs in patients with PSA at the subacute stage. Reduced FC between lFPN and rFPN was the key element participating in language destruction. These findings proved that PSA is a brain network disorder caused by focal lesions; besides, it may improve our understanding of the pathophysiological mechanisms of patients with PSA at the subacute stage.
Comparison Between Clinicopathological Characteristics, BRAF V600E and TERT Promoter Mutation of Familial Non-Medullary Thyroid Carcinomas, and Sporadic Case
Authors: Yang Tian , Huang Longsheng , Chen Chang , Luo Han , Jiang Yong 
Published: December 2021

BackgroundIt has been debated whether familial non-medullary thyroid carcinoma (FNMTC) is more aggressive and has a worse prognosis than sporadic non-medullary thyroid carcinoma (SNMTC). Our aim was to compare the invasiveness and prognosis of FNMTC and SNMTC by their biological behavior and molecular changes.Method and MaterialOur group mainly compared 106 patients with FNMTC whom have complete clinicopathological data during 2011–2019 in West China Hospital, Sichuan University, and 212 randomly selected cases with SNMTC were included to compare their biological behavior, recurrence and mortality, and molecular expression of BRAF V600E and TERT promoter. At the same time, FNMTC cases were divided into four subgroups, namely, two affected members group, three or more affected members, parent/offspring group, and sibling group, and they were compared with SNMTC separately to analyze the difference in their invasiveness and prognosis.ResultsWe found that the mean tumor size of FNMTC (0.96 ± 0.53cm) was smaller than that of SNMTC (1.15 ± 0.72 cm) (p = 0.020), while no significant difference in the incidence of other clinicopathological factors, including bilateral growth, capsular invasion, with thyroid nodular goiter or not, multifocality, lymph node metastasis, extrathyroidal extension, iodine 131 treatments, T stage, and American Joint Committee on Cancer (AJCC) stage, was observed between FNMTC and SNMTC (p &gt; 0.05), between each FNMTC subgroup (p &gt; 0.05), and between each FNMTC subgroup and SNMTC (p &gt; 0.05). There was no significant difference in recurrence, mortality, and BRAF V600E and TERT promoter mutation between FNMTC and SNMTC, among which 50/60 (83.33%) of FNMTC patients had BRAF V600E mutation and 1/32 (3.13%) had TERT promoter mutation, while the mutation rates of SNMTC were 93/108 (86.11%) and 3/64 (4.69%) (p &gt; 0.05).ConclusionThere was no significant difference in invasiveness and prognosis between FNMTC and SNMTC by biological behavior, patient survival, and molecular level comparison.
Efficacy and Safety of Lenalidomide Monotherapy for Relapsed/Refractory Diffuse Large B Cell Lymphoma: Systematic Review and Meta-Analysis
Authors: Li Jia , Zhou Jianpeng , Guo Wei , Wang Xingtong , Zhao Yangzhi , Bai Ou 
Published: December 2021

IntroductionSeveral maintenance therapies are available for treatment of patients with relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). The objective of this review was to assess the efficacy and safety of lenalidomide monotherapy in these patients.MethodsMEDLINE, EMBASE, and the Cochrane Library databases were searched for publications up to April 7, 2021. Original studies that had information on lenalidomide monotherapy for DLBCL patients with R/R status were included. Meta-analyses of response rates, adverse events (AEs), overall survival (OS), and progression-free survival (PFS) were performed. The pooled event rates were calculated using a double arcsine transformation to stabilize the variances of the original proportions. Subgroup analysis was used to compare patients with different germinal center B-cell-like (GCB) phenotypes.ResultsWe included 11 publications that examined DLBCL patients with R/R status. These studies were published from 2008 to 2020. The cumulative objective response rate (ORR) for lenalidomide monotherapy was 0.33 (95% CI: 0.26, 0.40), and the ORR was better in patients with the non-GCB phenotype (0.50; 95% CI: 0.26, 0.74) than the GCB phenotype (0.06; 95% CI: 0.03, 0.11). The major serious treatment-related AEs were neutropenia, thrombocytopenia, respiratory disorders, anemia, and diarrhea. The median PFS ranged from 2.6 to 34 months and the median OS ranged from 7.8 to 37 months.ConclusionThis study provides evidence that lenalidomide monotherapy was active and tolerable in DLBCL patients with R/R status. Patients in the non-GCB subgroup had better responsiveness.
Case Report: Dacomitinib Overcomes Osimertinib Resistance in NSCLC Patient Harboring L718Q Mutation: A Case Report
Authors: Shen Qian , Qu Jingjing , Chen Zhen , Zhou Jianying 
Published: December 2021

BackgroundAdvanced non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations has been successfully treated with tyrosine kinase inhibitors (TKIs). However, resistance to osimertinib, a third-generation TKI, can be difficult to overcome in this small subset of patients and is attributed to secondary resistant mutations. Here, we report a case of acquired EGFR L858R/L718Q mutation with advanced NSCLC that resistant to osimertinib, which was successfully overcome using dacomitinib.Case PresentationA 64-year-old non-smoker woman was diagnosed with stage IV non-small cell lung adenocarcinoma with EGFR L858R mutation and brain metastasis in November 2018. Treatment with gefitinib and gamma knife radiosurgery was started as the first-line treatment. After 7 months, she experienced disease progression with increased primary lung lesions and switched to osimertinib based on an acquired EGFR T790M mutation. After another 4 months, the disease progressed, and she was switched to chemotherapy. During chemotherapy, brain MRI showed an increasing number of parietal lobe metastases. Hence, gamma knife radiosurgery was performed again. After 12 months, the disease progression resumed, and an EGFR L718Q mutation was found on biopsy. The patient was then challenged with dacomitinib, and the disease was partially responsive and under control for 6 months.ConclusionCurrently, there are no established guidelines for overcoming osimertinib resistance caused by the L718Q mutation. The acquired EGFR L718Q mutation in subsequent resistance to osimertinib could be overcome using dacomitinib, indicating a promising treatment option in the clinic.
Combination of C-Reactive Protein and Neutrophil-to-Lymphocyte Ratio as a Novel Prognostic Index in Patients With Bladder Cancer After Radical Cystectomy
Authors: Wang Yidi , Wang Keyi , Ni Jinliang , Zhang Houliang , Yin Lei , Zhang Yifan , Shi Huajuan , Zhang Tao , Zhou Naichun , Mao Weipu , Peng Bo 
Published: December 2021

BackgroundInflammation is widely considered an important hallmark of cancer and associated with poor postoperative survival. The objective of this study is to assess the significance of preoperative C-NLR, a new inflammation-based index that includes preoperative C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR), on therapeutic outcomes for bladder cancer (BC) patients after radical cystectomy (RC).Materials and MethodsBC patients who underwent RC between 2010 and 2019 were retrospectively analyzed from our medical center. The predictive effect of CRP, NLR, and C-NLR on the survival of BC patients were analyzed by the receiver operating characteristic (ROC) curves. The relationship between C-NLR and postoperative survival was investigated by Cox regression. The corresponding nomograms were built based on the Cox regression results of overall survival (OS) and disease-free survival (DFS), which were further validated by ROC curves, decision curve analysis (DCA) curves, and calibration curves.ResultsOf the 199 eligible patients, 83 (41.70%) were classified as high C-NLR group and the remaining 116 (58.30%) were classified as low C-NLR group. ROC analysis showed that C-NLR had the largest area under curve (AUC) compared to CRP and NLR. Multivariate analysis revealed that T-stage and C-NLR [high C-NLR vs. low C-NLR, hazard ratio (HR) = 2.478, 95% confidence interval (CI), 1.538–3.993, p &lt; 0.001] were independent predictors of OS, whereas T-stage, M-stage, and C-NLR (high C-NLR vs. low C-NLR, HR = 2.817, 95% CI, 1.667–4.762, p &lt; 0.001) were independent predictors of DFS. ROC and DCA analysis demonstrated better accuracy and discrimination of 3- and 5-year OS and DFS with C-NLR-based nomogram compared to TNM stage. The calibration curve reconfirmed the accurate predicting performance of nomograms.ConclusionC-NLR is a reliable predictor of long-term prognosis of BC patients after RC and will contribute to the optimization of individual therapy for BC patients.
PKM2 Is the Target of a Multi-Herb-Combined Decoction During the Inhibition of Gastric Cancer Progression
Authors: Sun Qingmin , Yuan Mengyun , Wang Hongxing , Zhang Xingxing , Zhang Ruijuan , Wang Haidan , Chen Xu , Zhu Min , Liu Shenlin , Wu Jian 
Published: December 2021

Gastric cancer is the third leading cause of cancer death worldwide. Traditional Chinese medicine (TCM) is increasingly extensively applied as a complementary therapy for gastric cancer (GC) in China, which shows unique advantages in preventing gastric cancer metastasis. Previous study indicates modified Jian-pi-yang-zheng (mJPYZ) decoction inhibit the progression of gastric cancer by regulating tumor-associated macrophages (TAM). However, it is unclear whether mJPYZ can affect metabolic reprogramming of gastric cancer cells. Here, we showed that mJPYZ effectively attenuated GC cells proliferation, migration and invasion. Meantime, mJPYZ reduced the aerobic glycolysis level of GC cells in vivo and in vitro by regulating the expression and nuclear translocation of PKM2. Overexpression of PKM2 that could reverse the inhibitory effect of mJPYZ, migration and epithelial to mesenchymal transition (EMT). Our results showed PKM2/HIF-1α signaling was the key metabolic regulator of mJPYZ in GC cells. In summary, our present study suggested that abnormal PKM2 is required for maintaining the malignant phenotype of GC cells. The TCM decoction mJPYZ inhibited GC cells growth and EMT by reducing of glycolysis in PKM2 dependent manner. This evidence expanded our understanding of the anti-tumor mechanism of mJPYZ and further indicated mJPYZ a potential anti-tumor agent for GC patients.Chemical Compounds Studied in this ArticleRutin (PubChem CID: 5280805); Lobetyolin (PubChem CID: 53486204); Calycosin-7-glucoside (PubChem CID: 71571502); Formononetin (PubChem CID: 5280378); Calycosin (PubChem CID: 5280448); Ononin (PubChem CID: 442813); P-Coumaric Acid (PubChem CID: 637542).
Impact of Cell-of-Origin on Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Uniform R-CHOP Protocol: A Single-Center Retrospective Analysis From North India
Authors: Gogia Ajay , Nair Sukesh , Arora Shalabh , Kumar Lalit , Sharma Atul , Gupta Ritu , Biswas Ahitagni , Mallick Saumyaranjan 
Published: December 2021

IntroductionThere is a scarcity of data from India on the impact of cell of origin (COO) on outcomes of diffuse large B-cell lymphoma (DLBCL). This study was conducted to evaluate the impact of COO on outcomes of DLBCL patients treated with uniform rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) protocol.Materials and MethodsThis retrospective analysis included patients who received uniform RCHOP chemoimmunotherapy during the study period (2014–2020) at the Department of Medical Oncology at All India Institute of Medical Sciences (AIIMS), New Delhi, India. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification.ResultsFour hundred seventeen patients with median age of 48 years (range, 18–76) and a male-female ratio of 2:1 were included in the analysis. B symptoms and bulky disease were seen in 42.9% and 35.5%. Extranodal involvement was seen in 50.8% of cases. ECOG performance status (0-2) was present in 65%, and 51% presented with advanced disease. GCB subtype was seen in 43%, and 47% were ABC type. Low- and intermediate-risk international prognostic index (IPI) score was seen in 76% of cases. The overall response rate to RCHOP was 85.8%, including a complete response rate of 74.8%. After a median follow-up of 30 months, the 3-year event-free survival (EFS) and overall survival (OS) were 80% and 88%, respectively. The presence of B symptoms and poor ECOG performance status (3-4) was associated with inferior CR rate. Low albumin (p &lt; 0.001), age &gt;60 years (p = 0.001), bulky disease (p &lt; 0.001), and extranodal involvement (p = 0.001) were associated with inferior EFS, whereas a high IPI risk score was associated with an inferior OS (p &lt; 0.001). EFS and OS were not significantly different between the GCB and ABC subtypes. Grade III/IV anemia, neutropenia, and thrombocytopenia were seen in 7.6%, 13.6%, and 2.7% of patients, respectively. Febrile neutropenia was seen in 8.9% of patients, and there were four treatment-related deaths.ConclusionsCell of origin for DLBCL has no impact on CR, EFS, and OS if patients are appropriately treated with standard doses and frequency of RCHOP. RCHOP is well tolerated in our patients, and results are comparable with the Western data.
A Comparative Assessment of MR BI-RADS 4 Breast Lesions With Kaiser Score and Apparent Diffusion Coefficient Value
Authors: Meng Lingsong , Zhao Xin , Lu Lin , Xing Qingna , Wang Kaiyu , Guo Yafei , Shang Honglei , Chen Yan , Huang Mengyue , Sun Yongbing , Zhang Xiaoan 
Published: December 2021

ObjectivesTo investigate the diagnostic performance of the Kaiser score and apparent diffusion coefficient (ADC) to differentiate Breast Imaging Reporting and Data System (BI-RADS) Category 4 lesions at dynamic contrast-enhanced (DCE) MRI.MethodsThis was a single-institution retrospective study of patients who underwent breast MRI from March 2020 to June 2021. All image data were acquired with a 3-T MRI system. Kaiser score of each lesion was assigned by an experienced breast radiologist. Kaiser score+ was determined by combining ADC and Kaiser score. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of Kaiser score+, Kaiser score, and ADC. The area under the curve (AUC) values were calculated and compared by using the Delong test. The differences in sensitivity and specificity between different indicators were determined by the McNemar test.ResultsThe study involved 243 women (mean age, 43.1 years; age range, 18–67 years) with 268 MR BI-RADS 4 lesions. Overall diagnostic performance for Kaiser score (AUC, 0.902) was significantly higher than for ADC (AUC, 0.81; p = 0.004). There were no significant differences in AUCs between Kaiser score and Kaiser score+ (p = 0.134). The Kaiser score was superior to ADC in avoiding unnecessary biopsies (p &lt; 0.001). Compared with the Kaiser score alone, the specificity of Kaiser score+ increased by 7.82%, however, at the price of a lower sensitivity.ConclusionFor MR BI-RADS category 4 breast lesions, the Kaiser score was superior to ADC mapping regarding the potential to avoid unnecessary biopsies. However, the combination of both indicators did not significantly contribute to breast cancer diagnosis of this subgroup.
Preoperative CT-Based Radiomics Combined With Nodule Type to Predict the Micropapillary Pattern in Lung Adenocarcinoma of Size 2 cm or Less: A Multicenter Study
Authors: Li Meirong , Ruan Yachao , Feng Zhan , Sun Fangyu , Wang Minhong , Zhang Liang 
Published: December 2021

PurposeTo construct an optimal radiomics model for preoperative prediction micropapillary pattern (MPP) in adenocarcinoma (ADC) of size ≤ 2 cm, nodule type was used for stratification to construct two radiomics models based on high-resolution computed tomography (HRCT) images.Materials and MethodsWe retrospectively analyzed patients with pathologically confirmed ADC of size ≤ 2 cm who presented to three hospitals. Patients presenting to the hospital with the greater number of patients were included in the training set (n = 2386) and those presenting to the other two hospitals were included in the external validation set (n = 119). HRCT images were used for delineation of region of interest of tumor and extraction of radiomics features; dimensionality reduction was performed for the features. Nodule type was used to stratify the data and the random forest method was used to construct two models for preoperative prediction MPP in ADC of size ≤ 2 cm. Model 1 included all nodule types and model 2 included only solid nodules. The receiver operating characteristic curve was used to assess the prediction performance of the two models and independent validation was used to assess its generalizability.ResultsBoth models predicted ADC with MPP preoperatively. The area under the curve (AUC) of prediction performance of models 1 and 2 were 0.91 and 0.78, respectively. The prediction performance of model 2 was lower than that of model 1. The AUCs in the external validation set were 0.81 and 0.72, respectively. The DeLong test showed statistically significant differences between the training and validation sets in model 1 (p = 0.0296) with weak generalizability. There was no statistically significant difference between the training and validation sets in model 2 (p = 0.2865) with some generalizability.ConclusionNodule type is an important factor that affects the performance of radiomics predictor model for MPP with ADC of size ≤ 2 cm. The radiomics prediction model constructed based on solid nodules alone, can be used to evaluate MPP and may contribute to proper surgical planning in patients with ADC of size ≤ 2 cm.
Single-Nucleotide Polymorphisms Promote Dysregulation Activation by Essential Gene Mediated Bio-Molecular Interaction in Breast Cancer
Authors: Wang Xue , Zhao Zihui , Han Xueqing , Zhang Yutong , Zhang Yitong , Li Fenglan , Li Hui 
Published: December 2021

BackgroundBreast cancer (BRCA) is a malignant tumor with a high mortality rate and poor prognosis in patients. However, understanding the molecular mechanism of breast cancer is still a challenge.Materials and MethodsIn this study, we constructed co-expression networks by weighted gene co-expression network analysis (WGCNA). Gene-expression profiles and clinical data were integrated to detect breast cancer survival modules and the leading genes related to prognostic risk. Finally, we introduced machine learning algorithms to build a predictive model aiming to discover potential key biomarkers.ResultsA total of 42 prognostic modules for breast cancer were identified. The nomogram analysis showed that 42 modules had good risk assessment performance. Compared to clinical characteristics, the risk values carried by genes in these modules could be used to classify the high-risk and low-risk groups of patients. Further, we found that 16 genes with significant differential expressions and obvious bridging effects might be considered biological markers related to breast cancer. Single-nucleotide polymorphisms on the CYP24A1 transcript induced RNA structural heterogeneity, which affects the molecular regulation of BRCA. In addition, we found for the first time that ABHD11-AS1 was significantly highly expressed in breast cancer.ConclusionWe integrated clinical prognosis information, RNA sequencing data, and drug targets to construct a breast cancer–related risk module. Through bridging effect measurement and machine learning modeling, we evaluated the risk values of the genes in the modules and identified potential biomarkers for breast cancer. The protocol provides new insight into deciphering the molecular mechanism and theoretical basis of BRCA.
The Impact of Tumor Mutation Burden on the Effect of Frontline Trastuzumab Plus Chemotherapy in Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric Cancers
Authors: Kim Hye Ryeon , Ahn Soomin , Jo Hyunji , Kim Hongsik , Hong Joohyun , Lee Jeeyun , Lim Ho-Yeong , Kang Won Ki , Kim Seung Tae 
Published: December 2021

BackgroundTrastuzumab is a HER2-trargeted humanized monoclonal antibody that has been studied as a first-line treatment for patients with HER2-positive advanced gastric cancer (AGC). The effect of anti-HER2 therapy according to tumor mutational burden (TMB) in HER2-positive AGC remains unclear.MethodsWe performed next-generation sequencing (NGS), including TMB analysis, in 31 HER2-positive AGC patients with trastuzumab plus chemotherapy as first-line therapy for recurrent (n=8) or metastatic (n=23) tumors. The TruSight Oncology 500 Assay from Illumina (San Diego, CA, USA) was used to evaluate TMB.ResultsAmong 31 patients, 30 had tumors with immunohistochemistry (IHC) 3+, and one was IHC 2+ and silver in situ hybridization (SISH) positive. The median age was 57.0 years old (range, 35-76), and the majority had tumors with low TMB (87.1%, n=27/31). Only four (12.9%) had tumors with high TMB. Of these four, three achieved complete response (CR) or partial response (PR) to treatment, and the remaining patient was not evaluable for tumor response. Objective response rate (ORR) to trastuzumab plus chemotherapy showed a favorable trend in patients with high TMB (75.0%, n=3/4) compared to patients with low TMB (59.3%, n=16/27) (P=0.546). The median progression-free survival (PFS) was not reached in the TMB-high group but was 8.0 months (95% CI, 7.6-8.5) in the TMB-low group (P=0.019)ConclusionThe status of TMB could be a novel biomarker in predicting the efficacy of trastuzumab plus chemotherapy in HER2-positive AGCs.