bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Role and Mechanism of ATM-Mediated Autophagy in the Transition From Hyper-Radiosensitivity to Induced Radioresistance in Lung Cancer Under Low-Dose Radiation
Authors: Wang Qiong , Chen Yangyang , Chang Haiyan , Hu Ting , Wang Jue , Xie Yuxiu , Cheng Jing 
Published: May 2021

Objective: This study aimed to investigate the effect of ataxia telangiectasia mutated (ATM)–mediated autophagy on the radiosensitivity of lung cancer cells under low-dose radiation and to further investigate the role of ATM and its specific mechanism in the transition from hyper-radiosensitivity (HRS) to induced radioresistance (IRR).Methods: The changes in the HRS/IRR phenomenon in A549 and H460 cells were verified by colony formation assay. Changes to ATM phosphorylation and cell autophagy in A549 and H460 cells under different low doses of radiation were examined by western blot, polymerase chain reaction (PCR), and electron microscopy. ATM expression was knocked down by short interfering RNA (siRNA) transfection, and ATM-regulated molecules related to autophagy pathways were screened by transcriptome sequencing analysis. The detection results were verified by PCR and western blot. The differential metabolites were screened by transcriptome sequencing and verified by colony formation assay and western blot. The nude mouse xenograft model was used to verify the results of the cell experiments.Results: (1) A549 cells with high expression of ATM showed positive HRS/IRR, whereas H460 cells with low expression of ATM showed negative HRS/IRR. After the expression of ATM decreased, the HRS phenomenon in A549 cells increased, and the radiosensitivity of H460 cells also increased. This phenomenon was associated with the increase in the autophagy-related molecules phosphorylated c-Jun N-terminal kinase (p-JNK) and autophagy/Beclin 1 regulator 1 (AMBRA1). (2) DL-Norvaline, a product of carbon metabolism in cells, inhibited autophagy in A549 cells under low-dose radiation. DL-Norvaline increased the expression levels of ATM, JNK, and AMBRA1 in A549 cells. (3) Mouse experiments confirmed the regulatory role of ATM in autophagy and metabolism and its function in HRS/IRR.Conclusion: ATM may influence autophagy through p-JNK and AMBRA1 to participate in the regulation of the HRS/IRR phenomenon. Autophagy interacts with the cellular carbon metabolite DL-Norvaline to participate in regulating the low-dose radiosensitivity of cells.
Integrated Whole-Exome and Transcriptome Sequencing of Sporadic Parathyroid Adenoma
Authors: Hu Ya , Zhang Xiang , Wang Ou , Cui Ming , Li Xiaobin , Wang Mengyi , Hua Surong , Liao Quan 
Published: May 2021

PurposeHyperparathyroidism is the third most common endocrine disease. Parathyroid adenoma (PA) accounts for approximately 85% of cases of primary hyperparathyroidism, but the molecular mechanism is not fully understood. Herein, we aimed to investigate the genetic and transcriptomic profiles of sporadic PA.MethodsWhole-exome sequencing (WES) and transcriptome sequencing (RNA-seq) of 41 patients with PA and RNA-seq of 5 normal parathyroid tissues were performed. Gene mutations and characterized expression changes were identified. To elucidate the molecular mechanism underlying PA, unsupervised consensus clustering of RNA-seq data was performed. The correlations between the sequencing data and clinicopathological features of these patients were analyzed.ResultsPreviously reported PA driver gene mutations, such as MEN1 (9/41), mTOR (4/41), ZFX (3/41), CASR (3/41), EZH2 (2/41) and FAT1 (2/41), were also identified in our cohort. Furthermore, somatic mutation of EZH1, which had not been reported in PA, was found in 4 samples. RNA-seq showed that the expression levels of 84 genes were upregulated and 646 were downregulated in PA samples compared with normal samples. Unsupervised clustering analysis of RNA-seq data clustered these patients into 10 subgroups related to mutation or abnormal expression of a group of potential pathogenic genes.ConclusionMEN1, EZH2, CASR, EZH1, ZFX, mTOR and FAT1 mutations in PA were revealed. According to the RNA-seq data clustering analysis, cyclin D1, β-catenin, VDR, CASR and GCM2 may be important factors contributing to the PA gene expression profile.
Association of Dynamic Changes in Peripheral Blood Indexes With Response to PD-1 Inhibitor-Based Combination Therapy and Survival Among Patients With Advanced Non-Small Cell Lung Cancer
Authors: Chen Yuzhong , Wen Shaodi , Xia Jingwei , Du Xiaoyue , Wu Yuan , Pan Banzhou , Zhu Wei , Shen Bo 
Published: May 2021

BackgroundPD-1 inhibitors have been routinely used in the treatment of advanced non-small cell lung cancer (NSCLC), and have demonstrated to significantly improve survivorship when combining with other conventional therapies, such as chemotherapy and anti-angiogenesis therapy. PD-L1 is the most commonly used biomarker to select benefiting groups, while not all patients with high PD-L1 expression benefit from immunotherapy. Therefore, identifying other prognostic and predictive biomarkers, including peripheral blood indexes, is essential.MethodsWe retrospectively collected medical records and hematological data of 151 patients with advanced NSCLC treated with PD-1 inhibitor-based combination therapy in our hospital. The peripheral blood indexes of interest were NLR, PLR, PAR, Hb, LDH, CEA, and NSE. The association between peripheral blood indexes and treatment responses or survival outcomes was examined by multivariable logistic regression and Cox regression, respectively.ResultsThe decreased CEA at week 6 (OR = 4.209, 95%CI: 1.287-13.758) or 12 (OR = 7.267, 95%CI: 1.508-35.006) post-treatment was related to a higher disease control rate. The decrease or NLR at week 6 (OR = 3.081, 95%CI: 1.464-6.483) or 12 (OR = 3.304, 95%CI: 1.560-7.001) post-treatment, or CEA at week 12 post-treatment (OR = 2.469, 95%CI: 1.134-5.375), was associated with a higher objective response rate. Patients whose NLR (HR = 0.610, 95%CI: 0.411-0.907) or CEA (HR = 0.477, 95%CI: 0.320-0.710) decreased at week 6 post-treatment tended to have longer progression-free survival, and similar results were found in those with decreased NLR (HR = 0.587, 95%CI: 0.388-0.886) or CEA (HR = 0.406, 95%CI: 0.270-0.609) at week 12 post-treatment. Patients whose CEA (HR = 0.543, 95%CI: 0.339-0.871) or NSE (HR = 0.619, 95%CI: 0.386-0.994) decreased after 6 weeks post-treatment appeared to have longer overall survival, and the same was found for those whoseCEA (HR = 0.620, 95%CI: 0.390-0.986) or NSE (HR = 0.578, 95%CI: 0.353-0.947) was decreased at 12 weeks after treatment.ConclusionPost-treatment NLR, CEA and NSE changes are suggestive indicators for the prognosis of NSCLC patients after immunotherapy.
Effects of Titanium Corrosion Products on In Vivo Biological Response: A Basis for the Understanding of Osseointegration Failures Mechanisms
Authors: Biguetti Claudia Cristina , Cavalla Franco , Fonseca Angélica Cristina , Tabanez Andre Petenucci , Siddiqui Danyal A. , Wheelis Sutton E. , Taga Rumio , Fakhouri Walid D. , Silva Renato Menezes , Rodrigues Danieli C. , Garlet Gustavo Pompermaier 
Published: May 2021

Corrosion resistance is a key feature of titanium biocompatibility. However, Ti surfaces exposed to critical environments (such as, chronic infection and inflammation) can undergo corrosion processes in vivo, leading to an unfavorable biological response and clinical failure, which remains poorly explored. In this study, we characterized an experimental model to replicate the surface features of Ti corrosion process observed within in vivo failures, and the cellular, tissue and molecular events associated with corroded Ti surface implantation into subcutaneous and bone tissue of C57Bl/6 mice. Prior to in vivo implantation, commercially pure Ti Commercially pure titanium and Ti–6Al–4V alloy (Ti64) specimens were exposed to electrochemical polarization in 30% citric acid, while being polarized at 9 V against a saturated calomel electrode for 20 min. The electrochemical attack induced accelerated corrosion on both Ti-based specimens, producing structural and chemical changes on the surface, comparable to changes observed in failed implants. Then, microscopy and molecular parameters for healing and inflammation were investigated following control and corroded Ti implantation in subcutaneous (cpTi disks) and oral osseointegration (Ti64 screws) models at 3, 7, 14 and 21 days. The host response was comparatively evaluated between control and corroded Ti groups by microCT (bone), histology (H&amp;E, histomorphometry, immunostaining and picrosirius red), and real-time PCR array for inflammatory and healings markers. Corroded cpTi disks and Ti64 screws induced a strong foreign body response (FBR) from 3 to 21 days-post implantation, with unremitting chronic inflammatory reaction lasting up to 21 days in both subcutaneous and osseointegration models. In the subcutaneous model, FBR was accompanied by increased amount of blood vessels and their molecular markers, as well as increased TRAP+ foreign body giant cell count. In the osseointegration model, failures were identified by an osteolytic reaction/bone loss detected by microCT and histological analyses. The corroded devices were associated with a dominant M1-type response, while controls showed transient inflammation, an M2-type response, and suitable healing and osseointegration. In conclusion, corrosion of Ti-based biomaterials induced exacerbated inflammatory response in both connective tissue and bone, linked to the upregulation of fibrosis, pro-inflammatory and osteoclastic markers and resulted in unfavorable healing and osseointegration outcomes.
Risk Factors and Prediction Model for Non-curative Resection of Early Gastric Cancer With Endoscopic Resection and the Evaluation
Authors: Ma Xiaoqian , Zhang Qian , Zhu Shengtao , Zhang Shutian , Sun Xiujing 
Published: May 2021

Background and Study Aim: EGC, also known as Early Gastric Cancer is known to lack the lymph node metastasis and confined along the mucosa, which is treated through an endoscopic resection procedure that includes ESD (Endoscopic Submucosal dissection) and EMR (Endoscopic Mucosal Resection). However, some cases underwent residual disease, recurrence, or additional gastrectomy because of non-curative resection. The following research aims to delineate the threat factors causing the non-curative resection as well as develop a predictive model.Patient and Methods: Effort was taken to collect all the records about the health history of pathologically diagnosed EGC who experienced endoscopic treatment in the Department of Endoscopy, the Capital Medical University, and Beijing Friendship Hospital from January 2012 to January 2020. Patients were grouped into two categories primarily; a curative resection group and finally a non-curative resection group based on the outcomes of the postoperative pathological and immunohistochemical examination results. The statistical methods used included single factor analysis, a multivariate logistic regression analysis and a chi-square test. A nomogram for the prediction of non-curative resection was constructed, which included information on age, gender, resection method, postoperative pathology, tumor size, ulcer, treatment, and infiltration depth. Receiver operating characteristic (ROC) curve analysis and calibration were performed to present the predictive accuracy of the nomogram.Results: Of 443 patients with 478 lesions who had undergone ESD or EMR for EGCs, 127 were identified as being treated non-curative resection. Older patients (&gt;60 years), a large tumor size (&gt;30 mm), submucosal lesion, piecemeal resection, EMR for treatment and undifferentiated tumor histology were associated with non-curative resection group. Our risk nomogram showed good discriminated performance in internal validation (bootstrap-corrected area under the receiver-operating characteristic curve, 0.881; P &lt; 0.001).Conclusions: A validated prediction model was developed to identify people who were subject to undergoing a non-curative resection for ESD. The predictive model that we formulated is essential in providing reliable information to guide the decision-making process on the treatment for EGC before undertaking an endoscopic resection.
Deep Brain Stimulation in KMT2B-Related Dystonia: Case Report and Review of the Literature With Special Emphasis on Dysarthria and Speech
Authors: Abel Maria , Pfister Robert , Hussein Iman , Alsalloum Fahd , Onyinzo Christina , Kappl Simon , Zech Michael , Demmel Walter , Staudt Martin , Kudernatsch Manfred , Berweck Steffen 
Published: May 2021

Objective: KMT2B-related dystonia is a progressive childhood-onset movement disorder, evolving from lower-limb focal dystonia into generalized dystonia. With increasing age, children frequently show prominent laryngeal or facial dystonia manifesting in dysarthria. Bilateral deep brain stimulation of the globus pallidus internus (GPi-DBS) is reported to be an efficient therapeutic option. Especially improvement of dystonia and regaining of independent mobility is commonly described, but detailed information about the impact of GPi-DBS on dysarthria and speech is scarce.Methods: We report the 16-months outcome after bilateral GPi-DBS in an 8-year-old child with KMT2B-related dystonia caused by a de-novo c.3043C&gt;T (p.Arg1015*) non-sense variant with special emphasis on dysarthria and speech. We compare the outcome of our patient with 59 patients identified through a PubMed literature search.Results: A remarkable improvement of voice, articulation, respiration and prosodic characteristics was seen 16 months after GPi-DBS. The patients' speech intelligibility improved. His speech became much more comprehensible not only for his parents, but also for others. Furthermore, his vocabulary and the possibility to express his feelings and wants expanded considerably.Conclusion: A positive outcome of GPi-DBS on speech and dysarthria is rarely described in the literature. This might be due to disease progression, non-effectiveness of DBS or due to inadvertent spreading of the electrical current to the corticobulbar tract causing stimulation induced dysarthria. This highlights the importance of optimal lead placement, the possibility of horizontal steering of the electrical field by applying directional stimulation with segmented leads as well as the use of the lowest possible effective stimulation intensity.
Health-Risk Behaviors and Dietary Patterns Among Jordanian College Students: A Pilot Study
Authors: Alkhalidy Hana , Orabi Aliaa , Alzboun Tamara , Alnaser Khadeejah , Al-Shami Islam , Al-Bayyari Nahla 
Published: May 2021

Background/Aims:Health promotion and the incorporation of health-protective behaviors in people's lifestyles have a great role in enhancing individuals' overall health and well-being. College students are at increased risk of developing unhealthy dietary and lifestyle behaviors. A cross-sectional pilot study was conducted to assess the health-risk behaviors among undergraduate college students at Jordan University of Science and Technology.Methods:The final sample included 136 students, with a mean age of 21.1 ± 2.37 years, mostly females (69%). A self-reported questionnaire was used for data collection about dietary and lifestyle behaviors among college students. The questionnaire consisted of four parts: sociodemographic characteristics, body weight classifications, lifestyle behaviors, and dietary patterns and intake, and eating behaviors.Results:Most of the students did not meet the daily recommendations for fruit (76%) and vegetable (82%) intake. Males were significantly consuming fast food more frequently (p= 0.019), and smoked cigarettes (p&lt; 0.001) or hookah (p= 0.015) more frequently than did females. Further, the majority met the recommendations for physical activity (81%), but exceeded recommendations for sedentary behavior. Females were more likely to have normal weight or be underweight (OR = 4.865), to have a fear of weight gain (OR = 3.387), and to have the recommended sleeping hours (OR = 7.685) than were males.Conclusion:The results indicate the health-risk behaviors and the gender-related differences among college students.
Evaluation of Cell Surface Vimentin Positive Circulating Tumor Cells as a Diagnostic Biomarker for Lung Cancer
Authors: Xie Xiaohong , Wang Liqiang , Wang Xinni , Fan Wan-Hung , Qin Yinyin , Lin Xinqing , Xie Zhanhong , Liu Ming , Ouyang Ming , Li Shiyue , Zhou Chengzhi 
Published: May 2021

BackgroundCirculating tumor cells (CTCs) represent a collection of heterogeneous cells. Studies have shown epithelial CTCs and folate receptor (FR) positive CTCs could be used as diagnostic biomarkers for lung cancer (LC). This study aimed to determine whether cell surface vimentin (CSV) positive CTCs could be used as a biomarker for LC as well.Methods78 treatment-naïve non-small-cell lung cancer (NSCLC) patients, 21 patients with benign lung diseases (BLD) and 9 healthy donors (HD) were enrolled in this study. CTC detection was performed using CytoSorter® mesenchymal CTC kit (CSV). The correlation between CSV positive CTCs (CSV-CTCs) and LC patients’ clinicopathological characteristics would be evaluated, and diagnostic performances of CSV-CTCs and serum tumor markers for LC would be compared.ResultsCTC detection rates (average CTC count: range) in LC patients, patients with BLD and HD were 83.33% (2.47: 0-8), 47.62% (0.5: 0-3) and 0% (0: 0), respectively. CSV-CTCs could be used to differentiate LC patients from the patients with BLD and HD (P &lt; 0.0001). CSV-CTCs were correlated with cancer stage, lymph node involvement and distant metastasis (P = 0.0062, 0.0014 and 0.0021, respectively). With a CTC cut-off value of 2, CSV-CTCs would have a sensitivity and specificity of 0.67 and 0.87, respectively, for diagnosing LC. CSV-CTC positive rates showed statistical differences among HD, BLD patients and LC patients at different cancer stages (P &lt; 0.0001). Furthermore, CSV-CTC positive rates were positively correlated with tumor size, lymph node involvement and distant metastasis (P = 0.0163, 0.0196 and 0.03, respectively). CSV-CTCs had a better diagnostic performance than serum tumor makers, such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), cancer antigen 125 (CA125) and CA153.ConclusionWhen CTC cut-off is set to 2 CTCs per 7.5 mL of blood, CSV-CTCs can be considered as an acceptable biomarker for diagnosing LC with a sensitivity and specificity of 0.67 and 0.87, respectively.
Case Report: Spontaneous Intramural Hematoma of the Colon Secondary to Low Molecular Weight Heparin Therapy
Authors: Zhu Ye , Wang Chao , Xu Chao , Liu Jia 
Published: May 2021

Background: Hematoma of the colon is a rare hemorrhagic complication that affects patients accepting low molecular weight heparin (LMWH) therapy. Only scarce cases of colon hematoma have been reported, usually in children or patients accepting warfarin therapy.Case summary: A 76-year-old Chinese man was diagnosed with atrial fibrillation and heart failure, with cardiac function NYHA grade III on March 21, 2018. This patient was given LMWH for anticoagulation therapy and developed a colon hematoma on the third day of hospitalization. Abdominal computed tomography (CT) showed the thickening of areas of the colon up to 110 mm × 78 mm in thickness, which was a symptom of colon hematoma. The patient underwent conservative treatment successfully. On March 27, the patient’s abdominal pain was alleviated, and a CT scan showed that the intestinal hematoma was absorbed.Conclusions: The most frequent minor bleeding events of LMWH anticoagulation are hemorrhage and subcutaneous hematoma. This case demonstrated that bowel hematoma despite its low incidence should be considered as an ADR of LMWH therapy, especially among patients who present with gastrointestinal symptoms.
Neuroprotective and Angiogenesis Effects of Levetiracetam Following Ischemic Stroke in Rats
Authors: Yao Xiang , Yang Wenping , Ren Zhendong , Zhang Haoran , Shi Dafa , Li Yanfei , Yu Ziyang , Guo Qiu , Yang Guangwei , Gu Yingjiang , Zhao Hairong , Ren Ke 
Published: May 2021

Objective: The present study explored whether levetiracetam (LEV) could protect against experimental brain ischemia and enhance angiogenesis in rats, and investigated the potential mechanisms in vivo and in vitro.Methods: The middle cerebral artery was occluded for 60 min to induce middle cerebral artery occlusion (MCAO). The Morris water maze was used to measure cognitive ability. The rotation test was used to assess locomotor function. T2-weighted MRI was used to assess infarct volume. The neuronal cells in the cortex area were stained with cresyl purple. The anti-inflammatory effects of LEV on microglia were observed by immunohistochemistry. Enzyme-linked immunosorbent assays (ELISA) were used to measure the production of pro-inflammatory cytokines. Western blotting was used to detect the levels of heat shock protein 70 (HSP70), vascular endothelial growth factor (VEGF), and hypoxia-inducible factor-1α (HIF-1α) in extracts from the ischemic cortex. Flow cytometry was used to observe the effect of LEV on neuronal cell apoptosis.Results: LEV treatment significantly increased the density of the surviving neurons in the cerebral cortex and reduced the infarct size (17.8 ± 3.3% vs. 12.9 ± 1.4%, p &lt; 0.01) after MCAO. Concurrently, the time required to reach the platform for LEV-treated rats was shorter than that in the saline group on day 11 after MCAO (p &lt; 0.01). LEV treatment prolonged the rotarod retention time on day 14 after MCAO (84.5 ± 6.7 s vs. 59.1 ± 6.2 s on day 14 compared with the saline-treated groups, p &lt; 0.01). It also suppressed the activation of microglia and inhibited TNF-α and Il-1β in the ischemic brain (135.6 ± 5.2 pg/ml vs. 255.3 ± 12.5 pg/ml, 18.5 ± 1.3 pg/ml vs. 38.9 ± 2.3 pg/ml on day 14 compared with the saline-treated groups, p &lt; 0.01). LEV treatment resulted in a significant increase in HIF-1α, VEGF, and HSP70 levels in extracts from the ischemic cerebral cortex. At the same time, LEV reduced neuronal cell cytotoxicity and apoptosis induced by an ischemic stroke (p &lt; 0.01).Conclusion: LEV treatment promoted angiogenesis and functional recovery after cerebral ischemia in rats. These effects seem to be mediated through anti-inflammatory and antiapoptotic activities, as well as inducing the expression of HSP70, VEGF, and HIF-1α.