bluuebunny/crossref_metadata_2025_split huggingface dataset:
Co-expression of Mesothelin and CA125/MUC16 Is a Prognostic Factor for Breast Cancer
Authors: Einama Takahiro , Yamagishi Yoji , Takihata Yasuhiro , Suzuki Takafumi , Yamasaki Tamio , Hirose Yuichi , Kobayashi Kazuki , Yonamine Naoto , Fujinuma Ibuki , Tsunenari Takazumi , Koga Makiko , Ishibashi Yusuke , Nagata Ken , Shiraishi Takehiro , Nakazawa Akiko , Iwasaki Toshimitsu , Shinto Eiji , Kato Kimi , Sato Kimiya , Ueno Hideki , Kishi Yoji , Tsuda Hitoshi 
Published: June 2021

Abstract
Background: The expression of mesothelin correlates with a poor prognosis in patients with breast cancer. Since mesothelin plays a role in cancer metastasis in association with CA125, we herein examined the clinicopathological significance and prognostic implications of the co-expression of mesothelin and CA125 in breast cancer. Methods: The expression of mesothelin and CA125 was immunohistochemically examined in tissue samples collected from 478 breast cancer patients. The expression of these two molecules in more than 1% of tumor cells was defined as positive. The relationships between the co-expression of mesothelin and CA125, clinicopathological parameters, and clinical outcomes were analyzed by the chi-squared test and Cox’s univariate and multivariate proportional hazard model analyses. Results: Among 478 patients, mesothelin and CA125 were co-expressed in 48 (10%), mesothelin only in 75 (16%), CA125 only in 217 (45%), and neither in 234 (49%). A strong correlation was observed between the expression of mesothelin and CA125 (P =0.0004). The co-expression of mesothelin and CA125 correlated with unfavorable patient relapse-free survival (RFS) (P = 0.0001) and was identified as an independent predictor of RFS by Cox’s multivariate analysis. Conclusion: This is the first study to demonstrate the prognostic significance of the co-expression of mesothelin and CA125 in breast cancer. The co-expression of these two molecules may play a significant role in the acquisition of aggressive clinical behavior.
A Hybrid CNN- GLCM Classifier for Detection and Grade Classification of Brain Tumor
Authors: gurunathan Akila , Krishnan Batri 
Published: June 2021

Abstract
Early identification and diagnosis of brain tumor using a supervised approach plays an essential role in the field of medicine. In this paper, an automated computer-aided method using deep learning architecture named CNN Deep net is proposed for the detection, classification and diagnosis of meningioma brain tumor. This proposed method includes preprocessing, classification, and segmentation of the primary occurring brain tumor in adults. The proposed CNN Deep Net architecture extracts the features internally from enhanced image and classifies them into normal and abnormal tumor images. The segmentation of tumor region is performed by the global thresholding with area morphological function method. This proposed method of fully automated classification and segmentation of brain tumor preserves the spatial invariance and inheritance. Furthermore, based on its feature attributes the proposed CNN Deep net classifier, classifies the detected tumor image belongs either to (low grade)benign or (high grade)malignant. This proposed CNN Deep net classification methodology approach with grading system is evaluated both quantitatively and qualitatively. The quantitative measures such as sensitivity, specificity, accuracy, Dice similarity coefficient, precision, F-score of the proposed classification and segmentation methodology states a better segmentation accuracy and classification rate of 99.4% and 99.5% with respect to ground truth images.
Chemotherapy Choice in Neoadjuvant Dual Her2 Blockade; is it Really Necessary to add Anthracycline?
Authors: ozveren ahmet , Erdogan Atike Pinar , Ekinci Ferhat , Kirdok Kutay , Almuradova Elvina , Karabulut Bulent 
Published: June 2021

Abstract
1. BackgroundAddition of trastuzumab and pertuzumab to neoadjuvant chemotherapy in human epidermal growth factor receptor 2(HER-2) positive patients is the current clinical standard today. In studies on neoadjuvant chemotherapy, the primary endpoint is pathological complete response (pCR). More real-life data are needed to answer whether the presence of anthracycline in the chemotherapy regimen enhances complete response with neoadjuvant dual HER-2 blockade, and whether cardiotoxicity increases with dual HER-2 blockade after anthracycline.2. Methods52 patients with HER-2 positive breast cancer who received neoadjuvant chemotherapy were retrospectively evaluated. Three centers participated in the study (İzmir Kent Hospital, Manisa Celal Bayar University, Ege University). The effects of chemotherapy regimen and several other factors such as age, stage, menopause status, lymph node positivity, hormone receptor positivity on pCR were evaluated. Also presence of cardiotoxicity was evaluated.3. ResultsThe mean age of diagnosis was 46 ± 9 (range: 26-67), and 50% (26) of the patients were postmenopausal. The pCR rate was 71.2% (37) in the entire study group. In terms of pCR, there was no significant difference between those who use an anthracycline containing and non-anthracycline containing regimens (71.4% vs 70%, p=1.000), those with negative and positive hormone receptors (64.7% vs 74.3%, p=0.525), those with Ki67 levels of %20 or less and those over 20% (60% vs 73.8%, p=0.447), premenopausal and postmenopausal ones (76.9% vs 65.4%, p=0.054). 4. ConclusionsAs a result of the data we obtained, it was concluded that adding anthracycline regimen to dual HER-2 blockade in the neoadjuvant period did not bring additional benefits in terms of pCR. Additional studies are needed on whether the use of anthracycline-containing regimen contributes additionally in patients who will use the neoadjuvant pertuzumab-trastuzumab combination.
N-Acetylcysteine Attenuates Monocrotophos-induced Toxicity by Mitigating Oxidative Stress and Structural Changes in Rat Liver
Authors: Singh Jagjeet , Phogat Annu , Prakash Chandra , Kumar Vijay , Malik Vinay 
Published: June 2021

Abstract
The present study evaluated the effect of N-acetylcysteine (NAC) against sub chronic monocrotophos (MCP) exposure induced oxidative stress in rat liver. Albino wistar rats were divided into control, NAC treated, MCP and MCP treated groups. An oral dose of MCP (0.9 mg/kg b.wt) and NAC (200 mg/kg b.wt) was administered for 28 days. We observed high oxidative stress generation on MCP exposure in liver tissue as evident by significant increase in lipid peroxidation, protein oxidation and decreased glutathione content followed by altered activities of superoxide dismutase, catalase and acetylcholinesterase. Sub chronic MCP exposure caused an array of cellular and structural alternations in lipids and proteins of liver tissue as depicted by the FTIR, histopathological and electron microscopic analysis. N-acetylcysteine attenuated the loss of glutathione and prevented lipid peroxidation and protein oxidation. Pre-treatment of NAC also restored histological and ultra space structural alternations. So NAC protects oxidative stress and tissue damage induced by sub chronic MCP exposure in rat liver; suggesting the therapeutic and antioxidant potential of NAC.
Accelerated Hypofractionated Radiotherapy With Simultaneous Integrated Boost With Volumetric Modulated Arc Technique in Patients With Breast Cancer: a Phase 2 Study.
Authors: Yadav Budhi Singh , Gupta Shipra , Dahiya Divya , Gupta Ankita , Oinam Arun 
Published: June 2021

Abstract
PurposeTo assess feasibility of accelerated hypofractionated radiotherapy with simultaneous integrated boost (SIB) with volumetric modulated arc technique (VMAT) in patients with breast cancer.Methods Total 27 patients after breast conserving surgery (BCS) were included in this study. Patients were planned on 4-dimensional computerized tomogram (4D-CT) and contouring was done using RTOG guidelines. Dose delivered was 34 Gy/10#/2wk to the breast and 40 Gy/10#/2wk to the tumor bed as SIB with VMAT technique. The primary endpoint was grade 2 acute skin toxicity. Doses to the organs at risk were calculated. Toxicities and cosmesis were assessed using RTOG LENT-SOMA and HARVARD/NSABP/RTOG grading scales, respectively. Disease-free survival (DFS) and overall survival (OS) was calculated with Kaplan Meier curves.ResultsMean age of the patients was 42 years. Left and right breast cancer was seen in 17 (63%) and 10 (37%) patients, respectively. Ipsilateral lung mean V16 and contralateral lung V5 was 16.01% and 3.73%, respectively. Mean heart dose from the left and right breast was 7.25Gy and 4.37Gy, respectively. Mean dose to the contralateral breast, oesophagus and spinal cord was 2.64Gy, 3.69Gy and 3.15Gy, respectively. Thyroid V25 mean was 19.69%.Grade 1 and 2 acute skin toxicity was observed in 9 (33%) and 5 (18.5%) patients, respectively. Grade 2 hyperpigmentation, edema and induration were observed in 1 (3.7%), 2 (7.4%) and 4(14.8%) patients, respectively. Mild breast pain and arm/shoulder discomfort were reported by 1 (3.4%) patient each. Median follow-up was 48 months (range 12-58 months). At 4 years breast induration, edema and fibrosis each were observed in 1(3.7%) patient. Cosmesis was excellent and good in 21 (78%) and 6 (22%) patients, respectively. Local recurrence and distant metastases occurred 1(3.7%) and 2(7.4%) patients, respectively. DFS and OS at 3-years was 88% and 92%, respectively.ConclusionWith this RT schedule acute and late toxicity rates were acceptable with no adverse cosmesis. Local control, DFS and OS were good.
Sex differences in a cohort of COVID-19 Italian patients hospitalized during the first and second pandemic waves.
Authors: Quaresima Virginia , Scarpazza Cristina , Sottini Alessandra , Fiorini Chiara , Signorini Simona , Delmonte Ottavia Maria , Signorini Liana , Quiros-Roldan Eugenia , Imberti Luisa 
Published: June 2021

Abstract
Background: Coronavirus Disease 2019 (COVID-19) severity seems to be influenced by genetic background, sex, age, and presence of specific comorbidities. So far, little attention has been paid to sex-specific variations of demographic, clinical and laboratory features of COVID-19 patients referred to the same hospital in the two consecutive pandemic waves.Methods: Demographic, clinical and laboratory data were collected in 1,000 COVID-19 patients (367 females and 633 males), 500 hospitalized in the first wave and 500 in the second one, at the ASST Spedali Civili of Brescia from March to December 2020. Statistical analyses have been employed to compare data obtained in females and males, taking into account their age, and during the first and second COVID-19 waves. Results: The mean age at the time of hospitalization was similar in females and males but was significantly higher for both in the second wave; the time elapsed from symptoms onset to hospital admission did not differ between sexes in the two waves and no correlation was observed between delayed hospital admission and length of hospitalization. The number of multi-symptomatic males was higher than that of females and patients with a higher number of comorbidities were more frequently admitted to intensive care unit (ICU) and more frequently died. Older males remained in ICU longer than females and showed a longer disease duration, mainly the first wave. The highest levels of white blood cells, neutrophils, C-reactive protein and fibrinogen were significantly higher in males and in the first, and along with higher levels of D-dimer, ferritin, lactate dehydrogenase and procalcitonin which were preferentially documented in patients requiring ICU or died. While the ICU death rate was higher in males, the overall death rate did not differ between the sexes; however, the deceased women were older.Conclusions: These data indicate that once patients were hospitalized, the risk of dying was similar between females and males. Therefore, future studies should aim at understanding the reasons why, for a given number of SARS-CoV-2 infection, less females develop the disease requiring hospitalization.
Role of APOA1 in the Resistance to Platinum-Based Chemotherapy in Squamous Cervical Cancer
Authors: He Yue , Han Su-Bin , Liu Yang , Zhang Jing-Jing , Wu Yu-Mei 
Published: June 2021

Abstract
Introduction: To investigate the mechanism by which apolipoprotein A1 (APOA1) enhances the resistance of cervical squamous carcinoma to platinum-based chemotherapy.Methods: Two cervical squamous carcinoma cell lines (SiHa and Caski) overexpressing APOA1 (OE) were constructed, treated with carboplatin (CBP), and compared to normal control (NC) cells.Results: In both cell lines, the clone-forming ability of CBP-treated cells was lower than that of untreated cells, and the clone formation rate of OE cells was lower than that of NC cells (p < 0.05), indicating that APOA1 overexpression enhanced chemoresistance. A screen for APOA1 downstream proteins affecting platinum-based chemoresistance using TMT revealed 64 differentially expressed proteins, which were subjected to GO annotation, KEGG enrichment, subcellular localization, structural domain annotation and enrichment, clustering, and interaction network analyses. Twenty-nine differentially expressed proteins matching cancer-relavent association terms were screened and parallel response monitoring identified 21 as possibly involved in the mechanism of platinum-based chemoresistance.Conclusions: Our analysis suggested that the mechanism may involve numerous regulatory pathways, including promoting tumor growth via the P38 MAPK signaling pathway through STAT1, promoting tumor progression via the PI3K signaling pathway through CD81 and C3, and promoting resistance to platinum-based chemotherapy resistance through TOP2A.
Elucidating Multiple Negative Differential Resistance and Rectification Ratio Through L-Aspartic Acid at Nanometre Scale Using Symmetrical Metal Electrodes
Authors: Sikri Gaurav , Sawhney Ravinder Singh 
Published: June 2021

Abstract
Protein-based electronics is one of the growing areas of bio-nanoelectronics, where novel electronic devices possessing distinctive properties, are being fabricated using specific proteins. Furthermore, if the bio-molecule is analysed amidst different electrodes, intriguing properties are elucidated. This research article investigates the electron transport properties of L-aspartic acid (i.e., L-amino acid) bound to symmetrical electrodes of gold, silver, copper, platinum and palladium employing NEGF-DFT approach using self-consistent function. The theoretical work function of different electrodes is calculated using local density approximation and generalized gradient approximation approach. The calculated work function correlates well with the hole tunnelling barrier and conductance of the molecular device, which further authenticate the coupling strength between molecule and electrode. Molecule under consideration also exhibits the multiple negative differential resistance and rectification ratio with all the different electrodes, due to its asymmetrical structure. The molecular device using platinum electrodes exhibits the highest peak to valley ratio of 1.38 and rectification ratio of 3.20, at finite bias. The switching characteristics of different molecular device are justified with detailed transmission spectra and MPSH. These results indicate that L-aspartic acid and similar biomolecule can be vital to the growth of Proteotronics.
Neohesperidin Protects Hypertension-induced Endothelial Injury by Intervening Oxidative Stress
Authors: Zhang Jingsi , Hui Yuanshu , Liu Fengyi , Yang Qian , Lu Yi , Chang Yeting , Liu Qinlong , Ding Yanchun 
Published: June 2021

Abstract
Background: Currently, vascular endothelial damage caused by hypertension is one of the major health challenges facing countries around the world. Neohesperidin has been shown to play an important role in tumorigenesis and tumorigenesis, cardiac hypertrophy and remodeling, and oxidative stress. However, whether Nehesperidin plays an important role in endothelial injury induced by hypertension has not been clarified.Results: In this study, Angiotensin II was used to induce hypertension in mice. Blood pressure and vasoconstrictor function were measured, vascular thickness and fibrosis were detected by H&E and Masson tricolor staining, vascular inflammation was detected by immunofluorescence, oxidative stress was detected by DHE staining, and markers such as fibrosis, hypertrophy and oxidative stress were detected by qPCR. At the same time, we observed the effect of Nehesperidin on Ang II-induced HUVECs. The results showed that neohesperidin can significantly inhibit Ang II-induced hypertension, vascular thickness, fibrosis, oxidative stress and inflammation in vivo and in vitro. Conclusions: The results suggested that Nehesperidin could act as an antioxidant to significantly inhibit Ang II-induced hypertension and endothelial injury in HUVECs in mice by inhibiting oxidative stress response.
NAT10 as a Potential Prognostic Biomarker and Therapeutic Target for HNSCC
Authors: Tao Wenjie , Tian Guocai , Xu Shengming , Li Jiayi , Zhang Zhiyuan , Li Jiang 
Published: June 2021

Abstract
Background. Increasing evidence has demonstrated the critical roles of mRNA modification regulators on multiple types of cancers. However, it is still poorly known about the prognostic and therapeutic value of mRNA modification regulators in HNSCC.Methods. The gene expression profile of 36 mRNA modification regulators and their corresponding clinical data were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Stepwise regression in R with both directions was used to construct a model for the prognosis of HNSCC. Univariate Cox regression survival analysis was performed to find the most significant risk gene. Gene set enrichment analysis (GSEA) was applied to identify the cancer-associated pathways with NAT10. Immunohistochemistry (IHC) staining was performed to evaluate the expression of NAT10 in formalin fixed paraffin-embedded (FFPE) samples of HNSCC. Univariate and multivariate Cox regression survival analysis performed to identify the independent risk factors associated with the OS of patients with HNSCC. HNSCC cell lines (Cal-27, FaDu, and Detroit-562) were transfected with short interfering RNA (siRNA) targeting NAT10 or treated with Remodelin, a small-molecule inhibitor of NAT10. Knockdown efficiency of siRNA was assessed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting. In addition, CCK-8 assay, scratch assay and transwell assay were used to examine the proliferation, migration, and invasion abilities of the three HNSCC cell lines after NAT10 was inhibited genetically and pharmaceutically. Cell cycle and cell apoptosis assays were performed by flow cytometry. Finally, the therapeutic value of Remodelin in HNSCC was evaluated via a patient-derived xenograft (PDX) model. The statistical analysis was performed with SPSS 23.0.Results. A risk prediction model containing ten mRNA modification regulators was constructed and showed prognostic value in HNSCC. NAT10 was further identified as a key risk gene and independent prognostic factor in TCGA HNSCC dataset. The GSEA analysis suggested that high NAT10 expression was associated with MYC, E2F, G2M checkpoint, mTORC1, DNA repair and oxidative phosphorylation pathways. NAT10 protein expression was significantly up-regulated in tumour cells compared to normal epithelial cells in FFPE samples and increased NAT10 protein expression was correlated with poor overall survival of 267 HNSCC patients. Genetic depletion of NAT10 using siRNA or chemical inhibition of NAT10 using Remodelin resulted in reduced cell proliferation, migration and invasion abilities in Cal-27, FaDu and Detroit-562 cells. Knockdown of NAT10 using siRNA significantly increased cell cycle arrest in S/G2-phase. Remodelin significantly inhibited tumour growth and tumour cell proliferation in the PDX model of HNSCC.Conclusions. NAT10 could be a potential prognostic marker and a therapeutic target for HNSCC.
Contrast-enhanced Mammographic Features of In-situ and Invasive Ductal Carcinoma Manifesting Microcalcifications Only: Feasibility for Predicting Underestimation
Authors: Cheung Yun-chung , Chen Kueian , Yu Chi-Chang , Ueng Shir-Hwa , Lee Chia-Wei , Chen Shin-Cheh 
Published: June 2021

Abstract
Background:The contrast-enhanced mammographic features of ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) manifesting microcalcifications only on mammograms were evaluated to determine whether they could predict DCIS underestimation.Methods:We reviewed the records of patients who underwent mammography-guided breast biopsy with vacuum-assisted core needle biopsy to enrol patients meeting the following inclusion criteria: (1) mammographic microcalcifications only; (2) contrast-enhanced spectral mammography within 2 weeks before biopsy; (3) mammography-guided biopsy-proven cancer (including DCIS and IDC); and (4) subsequent surgical treatment in our hospital. The presence or absence, size, morphology and texture of enhancement on contrast-enhanced spectral mammography were compared to determine any significant differences.Results:A total of 49 patients (27 DCIS, 22 IDC) were enrolled. Forty patients (81.6%) showed enhancement, including 18 (45%) DCIS and 22 (55%) IDC patients. All 9 unenhanced cancers were DCIS. DCIS showed 72.22% nonmass enhancement and 83.33% pure ground glass enhancement. IDC showed more mass (72.2% to 27.8%) and solid enhancements (83.33% to 16.67%). The cancer and texture of enhancement were significantly different, with moderate diagnostic performance for the former (p value <0.01, AUC= 0.66, sensitivity= 93%, specificity= 39%) and the latter (p value <0.01, AUC= 0.74, sensitivity= 0.65, specificity= 83%). DCIS showed a significant difference in enhanced texture compared with upgraded IDC and IDC (p=0.0226 and 0.0018, respectively).Conclusions:CESM-enhanced features can feasibly predict DCIS underestimation. Biopsy-proven DCIS without associated enhancement has a low DCIS upgrade rate.Nonmass and pure ground glass enhancements were closely related to DCIS, and cases showing mass and unpurified solid enhancements should be suspected as IDC.
HOXB9 Promotes Laryngeal Squamous Cell Carcinoma Progression by Upregulating MMP12
Authors: Sun Chuanhui , Wang Peng , Chen Yujiang , Li Qiuying , Deng Hua , Han Changsong , Sun Yanan 
Published: June 2021

Abstract

Background：The HOX family transcription factor HOXB9 is a crucial element in the progression of various cancers. In the previous study conducted by the investigators, a drastically higher HOXB9 expression was reported in laryngeal squamous cell cancer (LSCC), when compared to adjacent normal laryngeal squamous tissues. Furthermore, a high level of HOXB9 was closely correlated with histological grade and overall survival in LSCC patients. However, the underlying molecular mechanisms have not been fully elucidated.Results: The present study explored the molecular mechanisms of HOXB9 in LSCC progression. Furthermore, the in vitro and in vivo studies revealed that the gene knockout of HOXB9 using the CRISPR/CAS9 system inhibited cell proliferation, migration and invasion, and promoted cell apoptosis. Mechanistic studies in LSCC cell lines and human LSCC specimens demonstrated that HOXB9 promotes LSCC progression by directly upregulating the MMP12 expression at the level of its transcription.Conclusions: Collectively, the present study is the first to demonstrate the role of HOXB9 in the regulation of LSCC progression by enhancing the upregulation of MMP12.