bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Adding Immune Checkpoint Inhibitors to Neoadjuvant Chemotherapy Against Triple-Negative Breast Cancer: A Meta-Analysis of Randomized Controlled Trials
Authors: Li Yunhai , Xing Lei , Li Fan , Liu Hong , Gan Lu , Yang Dejuan , Wang Mengxue , Yin Xuedong , Li Hongyuan , Ren Guosheng 
Published: December 2021

BackgroundImmune checkpoint inhibitors (ICIs) have shown promising anti-tumor activity in multiple malignances including breast cancer. However, the responses can vary. This meta-analysis was conducted to evaluate the efficacy and safety profile of adding ICIs to neoadjuvant chemotherapy against triple-negative breast cancer (TNBC) and assess correlation of PD-L1 tumor status with responses.MethodsEligible studies were retrieved from the PubMed, Embase, and Web of Science databases. Randomized controlled trials (RCTs) that investigated ICI-containing versus ICI-free neoadjuvant therapy were included in this study. Meta-analyses were performed using Review Manager Version 5.2 software.ResultsThis study included four RCTs containing 1795 patients with early TNBC. Compared with ICI-free neoadjuvant therapy, ICI-containing neoadjuvant therapy significantly increased the pathological complete response (pCR) rates in TNBC (odds ratio [OR] = 2.14, 95% confidence interval [CI]: 1.37–3.35, P &lt; 0.001). In subgroup analysis, the addition of ICI to neoadjuvant chemotherapy was significantly associated with increased pCR rate in both PD-L1-positive TNBC (OR = 1.79, 95% CI: 1.33–2.41, P &lt; 0.001) and PD-L1-negative TNBC (OR = 1.84, 95% CI: 1.14–2.99, P = 0.01). Patients with TNBC receiving ICI-containing neoadjuvant therapy had a better event-free survival (hazard ratio = 0.66, 95% CI: 0.48–0.89, P = 0.007) than those who receiving ICI-free neoadjuvant therapy. A significantly higher risk of adverse events including adrenal insufficiency, increased aspartate aminotransferase, dry skin, hepatitis, hyperthyroidism, hypothyroidism, infusion related reaction, pyrexia, and stomatitis was associated with ICI-containing neoadjuvant therapy.ConclusionICI-containing neoadjuvant therapy significantly increased the pCR rate in TNBC patients, independently of PD-L1 status. The addition of ICI to neoadjuvant chemotherapy may be considered an option for TNBC patients.
Microscopic Extrathyroidal Extension Results in Increased Rate of Tumor Recurrence and Is an Independent Predictor of Patient’s Outcome in Middle Eastern Papillary Thyroid Carcinoma
Authors: Parvathareddy Sandeep Kumar , Siraj Abdul K. , Qadri Zeeshan , DeVera Felisa , Siddiqui Khawar , Al-Sobhi Saif S. , Al-Dayel Fouad , Al-Kuraya Khawla S. 
Published: December 2021

BackgroundPapillary Thyroid Cancer (PTC) is the most common endocrine malignancy, with recurrence rate as high as 30%. A great deal of controversy surrounds the significance of microscopic extrathyroidal extension (m-ETE) as a prognostic factor. The most recent edition (8th) of American Joint Committee on Cancer (AJCC) staging system has removed m-ETE from the definition of pT3, which suggests that m-ETE may lack prognostic impact in PTC patients. Moreover, data about m-ETE prevalence and clinical impact on Middle Eastern PTC remains unknown. We therefore investigate the prevalence of m-ETE and its clinico-pathological correlation and prognostic impact in Middle Eastern PTC. We also compared the AJCC 7th and 8th staging systems and their prognostic performance.MethodsPTCs from 1430 consecutive adult (&gt; 18 years) patients from single tertiary care hospital were included in this study. A retrospective analysis of PTC patients’ survival and recurrence were compared between AJCC 8th and AJCC 7th staging systems using Proportion of Variation Explained (PVE) and Harrell’s C-index.ResultsMedian follow up of the study cohort was 9.3 years. 31.2% (446/1430) of patients had m-ETE. In the overall cohort, m-ETE was associated with multiple adverse features such as older age (p &lt; 0.0001), male sex (p = 0.0245), tall cell variant (p &lt; 0.0001), bilateral tumors (p &lt; 0.0001), multifocality (p &lt; 0.0001), lymphovascular invasion (p &lt; 0.0001), lymph node metastasis (p &lt; 0.0001), distant metastasis (p = 0.0166), tumor recurrence (p &lt; 0.0001), radioactive iodine refractoriness (p &lt; 0.0001), BRAF mutation (p &lt; 0.0001) and reduced recurrence-free survival (RFS; HR = 1.75; 95% CI = 1.30 – 2.35; p &lt; 0.0001) irrespective of tumor size. Of the 611 patients with T3 disease based on AJCC 7th edition, 359 (58.8%) were down-staged in AJCC 8th edition classification. Overall, the prognostic performance of AJCC 8th edition was inferior to AJCC 7th on the basis of lower PVE (3.04% vs. 3.73%) and lower C-index (0.40 vs. 0.48).ConclusionsIn Middle Eastern PTC, m-ETE is significantly associated with compromised survival and acts as an independent predictor of RFS. Given these findings, m-ETE should be included in the thyroid cancer treatment guidelines.
Using Ultrasound-Based Multilayer Perceptron to Differentiate Early Breast Mucinous Cancer and its Subtypes From Fibroadenoma
Authors: Liang Ting , Shen Junhui , Zhang Shumei , Cong Shuzhen , Liu Juanjuan , Pei Shufang , Shang Shiyao , Huang Chunwang 
Published: December 2021

ObjectivesMucinous breast cancer (MBC), particularly pure MBC (pMBC), often tend to be confused with fibroadenoma (FA) due to their similar images and firm masses, so some MBC cases are misdiagnosed to be FA, which may cause poor prognosis. We analyzed the ultrasonic features and aimed to identify the ability of multilayer perceptron (MLP) to classify early MBC and its subtypes and FA.Materials and MethodsThe study consisted of 193 patients diagnosed with pMBC, mMBC, or FA. The area under curve (AUC) was calculated to assess the effectiveness of age and 10 ultrasound features in differentiating MBC from FA. We used the pairwise comparison to examine the differences among MBC subtypes (pure and mixed types) and FA. We utilized the MLP to differentiate MBC and its subtypes from FA.ResultsThe nine features with AUCs over 0.5 were as follows: age, echo pattern, shape, orientation, margin, echo rim, vascularity distribution, vascularity grade, and tumor size. In subtype analysis, the significant differences were obtained in 10 variables (p-value range, 0.000–0.037) among pMBC, mMBC, and FA, except posterior feature. Through MLP, the AUCs of predicting MBC and FA were both 0.919; the AUCs of predicting pMBC, mMBC, and FA were 0.875, 0.767, and 0.927, respectively.ConclusionOur study found that the MLP models based on ultrasonic characteristics and age can well distinguish MBC and its subtypes from FA. It may provide a critical insight into MBC preoperative clinical management.
Development and Validation of a Predictive Model to Evaluate the Risk of Bone Metastasis in Kidney Cancer
Authors: Dong Shengtao , Yang Hua , Tang Zhi-Ri , Ke Yuqi , Wang Haosheng , Li Wenle , Tian Kang 
Published: December 2021

BackgroundBone is a common target of metastasis in kidney cancer, and accurately predicting the risk of bone metastases (BMs) facilitates risk stratification and precision medicine in kidney cancer.MethodsPatients diagnosed with kidney cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database to comprise the training group from 2010 to 2017, and the validation group was drawn from our academic medical center. Univariate and multivariate logistic regression analyses explored the statistical relationships between the included variables and BM. Statistically significant risk factors were applied to develop a nomogram. Calibration plots, receiver operating characteristic (ROC) curves, probability density functions (PDF), and clinical utility curves (CUC) were used to verify the predictive performance. Kaplan-Meier (KM) curves demonstrated survival differences between two subgroups of kidney cancer with and without BMs. A convenient web calculator was provided for users via “shiny” package.ResultsA total of 43,503 patients were recruited in this study, of which 42,650 were training group cases and 853 validation group cases. The variables included in the nomogram were sex, pathological grade, T-stage, N-stage, sequence number, brain metastases, liver metastasis, pulmonary metastasis, histological type, primary site, and laterality. The calibration plots confirmed good agreement between the prediction model and the actual results. The area under the curve (AUC) values in the training and validation groups were 0.952 (95% CI, 0.950–0.954) and 0.836 (95% CI, 0.809–0.860), respectively. Based on CUC, we recommend a threshold probability of 5% to guide the diagnosis of BMs.ConclusionsThe comprehensive predictive tool consisting of nomogram and web calculator contributes to risk stratification which helped clinicians identify high-risk cases and provide personalized treatment options.
Familial Breast Cancer: Disease Related Gene Mutations and Screening Strategies for Chinese Population
Authors: Shen Lu , Zhang Shizhen , Wang Kaiyue , Wang Xiaochen 
Published: December 2021

BackgroundAbout 5%–10% of the breast cancer cases have a hereditary background, and this subset is referred to as familial breast cancer (FBC). In this review, we summarize the susceptibility genes and genetic syndromes associated with FBC and discuss the FBC screening and high-risk patient consulting strategies for the Chinese population.MethodsWe searched the PubMed database for articles published between January 2000 and August 2021. Finally, 380 pieces of literature addressing the genes and genetic syndromes related to FBC were included and reviewed.ResultsWe identified 16 FBC-related genes and divided them into three types (high-, medium-, and low-penetrance) of genes according to their relative risk ratios. In addition, six genetic syndromes were found to be associated with FBC. We then summarized the currently available screening strategies for FBC and discussed those available for high-risk Chinese populations.ConclusionMultiple gene mutations and genetic disorders are closely related to FBC. The National Comprehensive Cancer Network (NCCN) guidelines recommend corresponding screening strategies for these genetic diseases. However, such guidelines for the Chinese population are still lacking. For screening high-risk groups in the Chinese population, genetic testing is recommended after genetic counseling.
The Impact of Preoperative and Postoperative Malnutrition on Outcomes for Ampullary Carcinoma After Pancreaticoduodenectomy
Authors: Jin Jikuan , Xiong Guangbing , Wang Xiaoxiang , Peng Feng , Zhu Feng , Wang Min , Qin Renyi 
Published: December 2021

PurposeThe aim of this study was to investigate the effect of preoperative and postoperative malnutrition on postoperative short- and long-term outcomes for ampullary carcinoma after pancreatoduodenectomy (PD).MethodsData were collected retrospectively from 511 patients with ampullary carcinoma who underwent PD between June 2012 and June 2019. Nutritional status before and at 3, 6, and 12 months after operation was assessed by the scored Patient-Generated Subjective Global Assessment (PG-SGA). The patients were classified into well-nourished, moderately malnourished, and severely malnourished group according to the PG-SGA score. Propensity score matching (PSM) was performed to adjust baseline characteristics between preoperative group A (well-nourished and moderately malnourished group) and group B (severely malnourished group). After PSM, clinicopathological variables and postoperative complications were compared between the two groups. Univariate and multivariate Cox analysis was also conducted to investigate the prognostic factors of overall survival of patients with ampullary carcinoma who underwent PD.ResultsPreoperatively, 122 (23.9%) patients were classified into well-nourished group, 189 (37.0%) into moderately malnourished group, and 200 (39.1%) into severely malnourished group. After PSM analysis, the incidence of overall postoperative complications was higher in group B than that in group A (50.5% vs. 32.5%, p &lt; 0.001). Multivariate Cox proportional hazards regression model showed that severe malnutrition (PG-SGA score &gt;9 scores) before operation [hazard ratio (HR) = 1.508; 95% CI, 1.103–2.061; p = 0.01] and at 6 months (HR = 4.148; 95% CI, 2.523–6.820; p &lt; 0.001) and 12 months (HR = 5.272; 95% CI, 3.630–7.656; p &lt; 0.001) after operation was an independent prognostic factor of patients who underwent PD for ampullary carcinoma.ConclusionsSevere malnutrition before and at 6 and 12 months after operation significantly affects the long-term survival of patients with ampullary carcinoma who underwent PD. Additionally, the preoperative malnutrition was closely related to postoperative complications.
Efficacy of Intraoperative Hypertonic Glucose Solution Administration on Persistent Air Leak After Extended Pleurectomy/Decortication for Malignant Pleural Mesothelioma: A Retrospective Case–Control Study
Authors: Testori Alberto , Perroni Gianluca , Alloisio Marco , Voulaz Emanuele , Giudici Veronica Maria , Cariboni Umberto , Bottoni Edoardo 
Published: December 2021

BackgroundPersistent air leak is a common complication occurring from 6% to 23% of cases after extended pleurectomy/decortication for malignant pleural mesothelioma. Treatment options for this complication after major lung resection are well documented in literature; nevertheless, lines of evidence in extended pleurectomy/decortication for malignant pleural mesothelioma are absent. The aim of the study is to evaluate the efficacy of intraoperative administration of 50% hypertonic glucose solution in reducing duration of air leak following extended pleurectomy/decortication for malignant pleural mesothelioma.Materials and MethodsIn this retrospective case–control study, we analyzed our electronic health record and selected those patients with a histological diagnosis of malignant pleural mesothelioma who underwent extended pleurectomy/decortication in the period 2013–2021. From 2018, we introduced a lavage with 500 ml of glucose solution at 50% concentration into the chest cavity at the end of the surgical procedure. Patients operated before 2018 were used as the control group. Postoperative glycemia was measured, and patients were followed after hospital discharge until the air leak resolved and the chest tube was removed. Statistical analysis was performed using R software.ResultsA total of 71 patients met our criteria. Treatment and control groups were similar for age, sex, smoking status, number of comorbidities, tumor histotype, and side of disease. Use of hypertonic glucose solution resulted in shorter chest tube maintenance after hospital discharge (p = 0.0028). A statistically significant difference (p = 0.02) was also found in postoperative glycemia between the treatment (103 g/dl ± 8.9) and control group (98.8 g/dl ± 8.6). Days of hospitalization and chest tube maintenance during hospitalization did not significantly differ between the groups.InterpretationIntraoperative administration of 50% hypertonic glucose solution reduced the duration of air leak after hospital discharge. An increase in postoperative glycemia was found in the treatment group, but with no clinical effect. Hypertonic glucose solution is an effective and safe method to manage persistent air leak after extended pleurectomy/decortication for malignant pleural mesothelioma.
Detection and Segmentation of Pelvic Bones Metastases in MRI Images for Patients With Prostate Cancer Based on Deep Learning
Authors: Liu Xiang , Han Chao , Cui Yingpu , Xie Tingting , Zhang Xiaodong , Wang Xiaoying 
Published: December 2021

ObjectiveTo establish and evaluate the 3D U-Net model for automated segmentation and detection of pelvic bone metastases in patients with prostate cancer (PCa) using diffusion-weighted imaging (DWI) and T1 weighted imaging (T1WI) images.MethodsThe model consisted of two 3D U-Net algorithms. A total of 859 patients with clinically suspected or confirmed PCa between January 2017 and December 2020 were enrolled for the first 3D U-Net development of pelvic bony structure segmentation. Then, 334 PCa patients were selected for the model development of bone metastases segmentation. Additionally, 63 patients from January to May 2021 were recruited for the external evaluation of the network. The network was developed using DWI and T1WI images as input. Dice similarity coefficient (DSC), volumetric similarity (VS), and Hausdorff distance (HD) were used to evaluate the segmentation performance. Sensitivity, specificity, and area under the curve (AUC) were used to evaluate the detection performance at the patient level; recall, precision, and F1-score were assessed at the lesion level.ResultsThe pelvic bony structures segmentation on DWI and T1WI images had mean DSC and VS values above 0.85, and the HD values were &lt;15 mm. In the testing set, the AUC of the metastases detection at the patient level were 0.85 and 0.80 on DWI and T1WI images. At the lesion level, the F1-score achieved 87.6% and 87.8% concerning metastases detection on DWI and T1WI images, respectively. In the external dataset, the AUC of the model for M-staging was 0.94 and 0.89 on DWI and T1WI images.ConclusionThe deep learning-based 3D U-Net network yields accurate detection and segmentation of pelvic bone metastases for PCa patients on DWI and T1WI images, which lays a foundation for the whole-body skeletal metastases assessment.
Long Noncoding RNA SNHG1 Regulates LMNB2 Expression by Sponging miR-326 and Promotes Cancer Growth in Hepatocellular Carcinoma
Authors: Mu Wentao , Guo Lingyu , Liu Yang , Yang Hui , Ning Shanglei , Lv Guoyue 
Published: December 2021

ObjectiveThe purpose of the study is to explore the potential competing endogenous RNA (ceRNA) network and investigate the molecular mechanism of long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) in hepatocellular carcinoma (HCC) development.MethodsBy analyzing the data of HCC in The Cancer Genome Atlas (TCGA) database, we included differentially expressed lncRNA and microRNA (miRNA) profiles and constructed ceRNA networks related to the prognosis of HCC patients. qRT-PCR, Western blotting, 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), transwell assay, and the nude mouse model were employed to test the effects of SNHG1 and LMNB2 on tumor proliferation and growth in vitro and in vivo.ResultsIn the study, we identified 115 messenger RNAs (mRNAs), 12 lncRNAs, and 37 miRNAs by intersecting differentially expressed genes (DEGs) in TCGA and StarBase databases. Then, SNHG1–miR-326–LMNB2 pathway came into notice after further survival analysis and hub gene screening. Our results showed that SNHG1 expression was upregulated significantly in HCC tissues and cell lines. Downregulation of both LMNB2, the target of miR-326 in HCC, and SNHG1 inhibited tumor proliferation and growth in vitro and in vivo. Furthermore, SNHG1 could regulate LMNB2 expression through binding to miR-326 in HCC cell lines.ConclusionSNHG1 is a promising prognostic factor in HCC, and the SNHG1–miR-326–LMNB2 axis may be a potential therapeutic target for HCC.
Unplanned Surgery After Transcatheter Closure of Ventricular Septal Defect in Children: Causes and Risk Factors
Authors: Yang Penghui , Wu Zhijun , Liu Zhiyuan , Zhang Jing , Zhou Hao , Ji Xiaojuan , Yi Qijian , Li Mi 
Published: December 2021

Objectives: To evaluate the causes and risk factors of unplanned surgery after transcatheter closure of ventricular septal defect (VSD) in children.Methods: A total of 773 patients with VSD who had the devices transcatheter released between January 2013 and December 2018 in our institution were retrospectively reviewed. Univariate and multivariate analyses were used to identify the risk factors for unplanned surgery.Results: Twenty four patients (3.1%) underwent unplanned surgery after transcatheter closure of VSD. The most common cause for unplanned surgery was new-onset or worsening aortic regurgitation (14/24; 58.3%), followed by occluder migration (4/24; 16.7%), complete atrioventricular block (2/24; 8.3%), severe hemolysis (2/24; 8.3%), residual shunt (1/24; 4.2%), and occluder edge near the tricuspid valve chordae (1/24; 4.2%). Logistic regression analysis revealed that primary aortic valve prolapse (OR: 5.507, 95%CI: 1.673–18.123, P = 0.005); intracristal VSD (OR: 8.731, 95%CI: 2.274–33.527, P = 0.002); eccentric occluder (OR: 4.191, 95%CI: 1.233–14.246, P = 0.022); larger occluder size (OR: 1.645, 95%CI: 1.331–2.033, P &lt; 0.001); and pulmonary artery systolic pressure ≥45 mmHg (OR: 4.003, 95%CI: 1.073–14.941, P = 0.039) were risk factors for unplanned surgery.Conclusions: New-onset or worsening aortic regurgitation was the primary cause for unplanned surgery after transcatheter closure of VSD in children. Primary aortic valve prolapse, intracristal VSD, eccentric occluder, larger occluder size, pulmonary artery systolic pressure ≥45 mmHg could increase the risk of unplanned surgery.
Quantitative Determination and Toxicity Evaluation of Aristolochic Acid Analogues in Asarum heterotropoides F. Schmidt (Xixin) and Traditional Chinese Patent Medicines
Authors: Liu Suyan , Xian Zhong , Zhao Yong , Wang Lianmei , Tian Jingzhuo , Pan Chen , Han Jiayin , Zhang Yushi , Li Chunying , Yi Yan , Liu Chenyue , Wang Dunfang , Meng Jing , Qin Shasha , Wang Fang , Liang Aihua 
Published: December 2021

Asarum (Xixin), which contains analogues of aristolochic acid (AA), is the only species of the genus Aristolochia included in the Chinese Pharmacopoeia 2020. However, the contents and nephrotoxic effects of AA analogs in Asarum (Xixin) and its formulations have not been clarified. An automatic, effective solid phase extraction process and UPLC-MS/MS method were established for the pretreatment and quantitative detection of AA analogues in commercially available traditional Chinese patent medicines. The cytotoxicity and DNA damage induced by five analogues of AA were evaluated by CCK8 using human kidney cells (HK-2) and comet assays. HPLC was used to detect the analogues of AA in Asarum heterotropoides F. Schmidt (Xixin). The results showed that the contents of AA I, AA II, and AA IIIa were below the detection limit, while AA IVa and AL I presented relatively high contents of Asarum heterotropoides F. Schmidt (Xixin), within the range of 66.50–121.03 μg/g and 19.73–43.75 μg/g, respectively. The levels of AA analogues were in the nanogram-per-gram level in the main traditional Chinese patent medicines. AA I and AL I exhibited relatively high cytotoxicity at 48 h in CCK8 assays, while AA II, AA IIIa, and AA IVa showed weak cytotoxicity even at 800–1,000 μM. AA I induced significant pathological alterations and direct DNA damage at 40 mg/kg and 20 mg/kg, respectively. No distinct nephrotoxicity or hepatotoxicity was observed in mice treated with AA II, AA IIIa, AA IVa, or AL I at 40 mg/kg in this study. Consumption of Asarum heterotropoides F. Schmidt (Xixin) with controlled doses and periods is relatively safe as the contents of AA analogues in Asarum heterotropoides F. Schmidt (Xixin) and its formulations were far below those causing acute toxicity in this study. But, the long-term toxicity of Asarum heterotropoides F. Schmidt (Xixin) still needs further study.