bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-20a mediates the cytotoxicity of natural killer cells in endometriosis via ERG/HLX/STAT4/perforin axis
Authors: Chen Li-Juan , Hu Bin , Han Zhi-Qiang , Ni Jian , Zhou Yong-Ming , Chen Xue-Xing , Zhou Hao
Published: November 2019

Background: Intriguingly, microRNA-20a (miR-20a) has been recently witnessed to be involved in the pathogenesis of endometriosis (EMS) but the molecular mechanism controlled by miR-20a is to be undefined. The present study is designed to probe into how miR-20a acts to regulate the cytotoxicity of natural killer (NK) cells. Methods: Most of all, consistent with the clinical determination in EMS patients, miR-20a was determined to be down-regulated in NK cells isolated from nude mice. miR-20a could specifically bind to ERG and negatively regulates its expression in NK cells. Additionally, shRNA-mediated silencing of ERG decreased the expression of HLX. HLX up-regulated STAT4 by inducing proteasome degradation and inhibited NK cell cytotoxicity. Results: Of great importance, forced expression of miR-20a consequently induced NK cell cytotoxicity in vitro by increasing perforin expression via enhancement of STAT4 that was caused by impairing the binding of ERG to HLX enhancer. The in vivo experiments further confirmed the promoting role of miR-20a in the cytotoxicity of NK cells isolated from EMS nude mice and subsequent protective role of miR-20a against EMS-induced endometrial injury. Conclusion: The aforementioned data suggest that miR-20a potentiates the cytotoxicity of NK via up-regulating perforin mediated by ERG/HLX/STAT4, highlighting potential novel mechanisms associated with EMS progression.
Preoperative predictive factor analysis of ovarian malignant involvement in premenopausal patients with clinical stage I endometrioid endometrial carcinoma
Authors: Chen Qin , Feng Yan , Wang Wenwen , Lv Weiguo , Li Baohua
Published: November 2019

Background Earlier literature suggests that ovarian preservation in young premenopausal clinical stage I endometrioid endometrial carcinoma patients does not negatively impact prognosis and is a more suitable choice for management of the disease. The main purpose of this study was to clarify the incidence of ovarian malignant involvement in premenopausal clinical stage I endometrioid endometrial carcinoma and further identify potential preoperative predictive factors of ovarian malignant involvement.Methods Premenopausal patients (≤50 years) with clinical stage I endometrioid endometrial carcinoma subjected to total hysterectomy and bilateral salpingo-oophorectomy with or without pelvic and/or para-aortic lymph node dissection at Women’s Hospital, Zhejiang University School of Medicine between 2002 and 2016 were enrolled for study. Patients were excluded in cases of gross extra pelvic disease on examination or imaging and family history of colon or gastrointestinal carcinoma. The included patient population was examined for incidence of ovarian malignant involvement and potential preoperative clinical predictive factors.Results A total of 511 premenopausal (age≤50 years) patients diagnosed with clinical stage I endometrioid endometrial carcinoma were included for the study. Ovarian malignant involvements were detected in 23 of the patients (4.5%). Kaplan-Meier analysis showed poorer prognoses of patients with ovarian malignant involvement than those without ovarian involvement. Univariate logistic analysis revealed significant association of preoperative imaging of myometrial invasion depth and serum CA125 with prediction of ovarian malignant involvement in patients. Multivariate logistic analysis further validated preoperative imaging of myometrial invasion depth and serum CA125 as independent risk predictors of postoperative ovarian malignant involvement. Receiver operating characteristic (ROC) curves were individually generated for preoperative myometrial invasion depth and serum CA125 as well as a combination of the two factors. The area under the curve (AUC) was 0.772 (95% confidence interval [CI], 0.661–0.884) for combined preoperative myometrial invasion depth and serum CA125.Conclusions The incidence of ovarian malignant involvement in premenopausal patients with clinical stage I endometrioid endometrial carcinoma was relatively minimal. Preoperative imaging of myometrial invasion depth and serum CA125 were independent risk predictors of ovarian malignant involvement. These findings may facilitate preoperative counseling of patients and informed clinical decision-making on ovarian preservation in these patients.
The Clinical Characteristics and Prognosis of Chinese Patients With Primary Light-Chain Amyloidosis: A Retrospective Multicenter Analysis
Authors: He Donghua , Guan Fangshu , Hu Minli , Zheng Gaofeng , Hong Pan , Wang Gang , He Jingsong , Han Xiaoyan , Wu Wenjun , Zhao Yi , Yang Yang , Cai Zhen
Published: November 2019

Objective To retrospectively identify the critical characteristics and prognostic factors of primary light-chain amyloidosis. Patients and Methods: Data were collected and compared from 91 patients who were diagnosed with primary light-chain amyloidosis at four hospitals between January 2010 and November 2018. We analyzed the clinical characteristics and performed an overall survival (OS) analysis. Results: Patients (median age, 60 years) were diagnosed with organ involvement of the kidney (91.2%), heart (56%), liver (14.3%), soft tissue (18.7%), or gastrointestinal tract (15.4%), and 68.1% of patients had more than two organs involved. Patients were most commonly treated with bortezomib-based regimens (56%), and only one patient had autologous stem cell transplantation (auto-ASCT). The median OS was 36.33 months and was affected by the ECOG score, renal involvement, cardiac involvement, hepatic involvement and negative immunofixation in the serum and urine after treatment. Multivariate analysis indicated that cardiac involvement and negative immunofixation in the serum and urine after treatment were independent prognostic factors for OS. Conclusion: Cardiac involvement and the hematologic response to treatment were independent prognostic factors for OS in primary light-chain amyloidosis patients. The type and number of organs involved is more important than the number of organs involved for the OS.
Albumin to alkaline phosphatase ratio: does it predict survival in grade 1 and grade 2 neuroendocrine tumors?
Authors: Acikgoz Yusuf , Bal Öznur , Doğan Mutlu
Published: November 2019

BACKGROUND: Neuroendocrine tumors (NETs) are very heterogeneous tumors. Although it is classified according to Ki-67 proliferation index and mitotic count, their behavior may greatly vary even in the same group. Therefore, more accurate prognostic markers are required to predict prognosis in patients with well differentiated NETs. This study is aimed to evaluate prognostic value of albumin to alkaline phosphatase ratio (AAPR) in patients with well differentiated neuroendocrine tumors. PATIENTS AND METHODS: A total of 110 patients included in this study. Patients' data were obtained from registration data-base of the hospital and reviewed retrospectively. AAPR was calculated by dividing albumin concentration (g/dl) to alkaline phosphatase level (U/L). Cut off value for AAPR was determined by Receiver Operating Characteristic (ROC) analysis. Survival analysis was performed by Kaplan-Meier method with the Long-rank test. We reported two-sided p value and p<0.05 was considered statistically significant.RESULT: The calculated optimum cut-off value for AAPR was 0.028. Patients were divided into two groups as patients with AAPR ≤0.028 (n:22, 20%) and, with AAPR >0.028 (n:88, 80%). Patients with AAPR >0.028 had statistically longer overall survival (OS) compared with patients with ≤0.028 ( NR vs 96,8 months, p=0.001). Additionally, AAPR has been shown to be an independent prognostic factor for OS in in multivariate analysis (HR=4.942, 95% CI=1.693-14.420, p=0.003).CONCLUSION: Patients with higher AAPR had more favourable prognosis compared to patients with lower AAPR. We demonstrated that AAPR can be of prognostic value in well-differentiated NETs.
Meta-analytic evaluation of the correlation between event-free survival and overall survival in randomized controlled trials of newly diagnosed Ewing sarcoma.
Authors: Tanaka Kazuhiro , Kawano Masanori , Iwasaki Tatsuya , Itonaga Ichiro , Tsumura Hiroshi
Published: November 2019

Background In randomized controlled trials (RCTs) of adjuvant treatment for malignant tumors, event-free survival (EFS) is considered the most acceptable surrogate for overall survival (OS). However, even though EFS has repeatedly been selected as a primary endpoint in RCTs of Ewing sarcoma (ES), the surrogacy of EFS for OS has not been investigated. This study aimed to evaluate the surrogacy of EFS for OS in RCTs of chemotherapy for newly diagnosed ES using a meta-analytic approach. Methods We identified seven RCTs of newly diagnosed ES through a systematic review, and a meta-analysis was performed to evaluate the efficacy and adverse events associated with chemotherapy for previously untreated ES. The correlation between EFS and OS was investigated by weighted linear regression analysis and Spearman rank correlation coefficients (ρ). The strength of the correlation was evaluated using the coefficient of determination (R2). Results A total of 3,612 patients were randomly assigned to 17 treatment arms in the eligible RCTs. The meta-analysis demonstrated that the hazard ratios for OS and EFS showed significantly better results in the experimental treatment groups with increasing toxicities. The correlation between the hazard ratios for EFS and OS was good (R2 = 0.747, ρ = 0.683), and the correlation tended to be more favorable in cases of localized ES (R2 = 0.818, ρ = 0.929). Conclusions Overall, the trial-level correlation between EFS and OS was good for newly diagnosed ES and was very good in cases of localized disease. Given the rare occurrence of ES and difficulty in conducting large-scale RCTs, EFS may be useful as a surrogate endpoint in RCTs of ES. The surrogacy of EFS is worth verifying using individual data.
Prognostic value of Ki-67 and prediction in patients with hypertension and prostate cancer: A Real-World Study of Chinese Group for Prostate Cancer Party
Authors: Cao Zhijun , Xiang Mengqi , Zhang Zhiyu , Zhang Jianglei , Jiang Minjun , Shen Gang , Zhou Yongqiang , Ouyang Jun , Chen Jianjun
Published: November 2019

Purpose Prostate cancer is the second most common malignancy with high mortality among males around the world, especially combine with hypertension. Ki-67 is one of the most reliable markers for growth fraction of neoplastic human cell populations. However, the prognostic value and prediction of Ki-67 in patients with hypertension and prostate cancer remain unclear. Materials and methods We launched a retrospective analysis of 296 patients with hypertension and prostate cancer from May 1, 2012, to Oct 1, 2015. The overall survival was evaluated using Cox regression models and Kaplan-Meier analysis. A nomogram was established. The accuracy of the model was assessed by calibration curve. Results Multivariate analysis showed that the Ki-67 (+) class was associated with an over 5-fold increase in the risk of death (HR 5.83, 95% CI 3.35-10.14, p<0.001) and a 2-fold increase in the risk of progression (HR 2.06, 95% CI 1.37-3.10, p<0.001). Multivariate Lasso regression showed that smoking, heart failure, ACS, Ki-67 expression, serum albumin, prognostic nutritional index, surgery, Gealson score, and stage were positively associated with prognosis in patients with prostate cancer. To quantify the contribution of each covariate to the prognosis, a nomogram of the Cox model was generated and displayed. The nomogram demonstrated excellent accuracy in estimating the risk of death, with a bootstrap-corrected C index of 0.829. There was also a suitable calibration curve for risk estimation.Conclusions Ki-67(+) predicts worsened outcomes of OM. A cross-validated multivariate score, including Ki-67(+), showed excellent concordance and efficacy of predicting prostate cancer.
Candidate methylation sites associated with endocrine therapy resistance in the TCGA ER+/HER2- breast cancer cohort
Authors: Soleimani Maryam , Borgoni Simone , Sofyalı Emre , Verschure Pernette J. , Wiemann Stefan , Moerland Perry , Kampen Antoine H.C. van
Published: November 2019

Background: Estrogen receptor (ER) positive breast cancer is often effectively treated with drugs that inhibit ER signaling, i.e., tamoxifen (TAM) and aromatase inhibitors (AIs). However, about 30% of ER+ breast cancer patients develop resistance to therapy leading to tumour recurrence. Changes in the methylation profile have been implicated as one of the mechanisms through which therapy resistance develops. Therefore, we aimed to identify methylation loci associated with endocrine therapy resistance. Methods: We used genome-wide DNA methylation profiles of primary ER+ tumors from The Cancer Genome Atlas in combination with curated data on survival and treatment to predict development of endocrine resistance. Association of individual DNA methylation markers with survival was assessed using Cox proportional hazards models in a cohort of ER+/HER2- tumours (N=552) and two sub-cohorts corresponding to the endocrine treatment (AIs or TAM) that patients received (N=210 and N=172, respectively). Models were adjusted for clinical variables tumour stage, age, and AI treatment. We also identified signatures of multiple methylation loci associated with survival using Cox proportional hazards models with elastic net regularization. Individual markers and multivariable signatures were compared with DNA methylation profiles generated in a time course experiment using the T47D ER+ breast cancer cell line treated with tamoxifen or deprived from estrogen. Results: We identified 132, 9 and 1 CpGs for which DNA methylation is significantly associated with survival in the ER+/HER2-, TAM and AI cohorts respectively. Corresponding multi-locus signatures consisted of 171, 50 and 160 CpGs and showed a large overlap with the corresponding single-locus signatures. The methylation signatures were associated with survival independently of luminal status. Single-locus signatures for the ER+/HER2- and TAM cohorts were conserved among the loci that were differentially methylated in endocrine-resistant T47D cells. Similarly, multi-locus signatures for the ER+/HER2- and AI cohorts were conserved in endocrine-resistant T47D cells. Conclusions: We identified individual and multivariable DNA methylation markers associated with therapy resistance independently of luminal status. Our results suggest that these markers identified from primary tumours and prior to any endocrine treatment are associated with development of endocrine resistance.
Enhanced antitumor efficacy on colon cancer using EGF functionalized PLGA nanoparticles loaded with 5-Fluorouracil and perﬂuorocarbon
Authors: Wu Pingping , Zhou Qing , Zhu Huayun , Zhuang Yan , Bao Jun
Published: November 2019

Recurrence and metastasis are the shortcomings of the clinical treatment of colon cancer. Finding an efficacy strategy for the treatment of colon cancer is important. In recent years, PLGA has been shown to have potential as a broad therapeutic drug delivery system. this study aimed to design a dual-loaded nanoparticles drug delivery system to overcome the limitations of chemotherapeutic drugs in colon cancer therapy. We developed epidermal growth factor (EGF) functionalized poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) co-loaded with 5-fluorouracil (5Fu) and perﬂuorocarbon (PFC) (EGF-PLGA@5Fu/PFC) for target therapy of colon cancer. EGF-PLGA@5Fu /PFC NPs were estimated to have an average size of 200 nm with a 5Fu-loading efficiency of 7.29%. In vitro release profile exhibited a pH-responsive release. CCK-8, Hoechst33342 staining and flow cytometry assays were performed to investigate the functions of EGF-PLGA@5Fu/PFC NPs in SW620 cells. Targeted EGF-PLGA@5Fu/PFC NPs also exhibited higher cellular uptake than non-targeted NPs in colon cancer cells. EGF-PLGA@5Fu/PFC NPs were found to have the best efficiency on cell viability suppression and apoptosis induction in SW620 cells. In xenograft mice, EGF-PLGA@5Fu/PFC NPs had the best suppressive effects on tumor growth compared with 5Fu, PLGA@5Fu and PLGA@5Fu/PFC NPs. The results of histopathological analysis further indicated that EGF-targeted NPs were the most efficient on tumor growth inhibition. Mechanically, the data demonstrated the improved therapeutic outcomes were owing to the fact that PFC could relieve tumor hypoxia via transporting oxygen to the tumor. We creatively constructed a biocompatible nanodrug delivery system and functionalized nanoparticles may provide new potential for selective delivery of chemotherapy drugs to cancers.
Immunohistochemical Expression of Vitamin D Receptor and Forkhead Box P3 in Classic Hodgkin Lymphoma: Correlation with Clinical and Pathologic Findings
Authors: Gupta Gaurav , Agrawal Tanupriya , Pilichowska Monika
Published: November 2019

Expression of forkhead box P3 (FOXP3), a key regulator of T-cell function, in the tumor immune microenvironment is related to survival in classic Hodgkin lymphoma (CHL). Vitamin D receptor (VDR), a transcription factor, agonists have been shown to induce FOXP3 expression in T-cells and enhance recruitment of these cells to the inflammatory sites. VDR expression is CHL is described. However, there is no data on expression of VDR in context of quantity of FOXP3 expressing cells in CHL. We examined and correlated immunohistochemical expression of VDR and FOXP3 with clinical and pathology findings in 29 cases of CHL. VDR was expressed in Hodgkin Reed-Sternberg (HRS) cells and background lymphocytes and FOXP3 was expressed in background lymphocytes. 82% of CHL cases, regardless of the subtype, expressed VDR and in majority of the cases, VDR expression was directly proportional to the quantity of FOXP3 expressing lymphocytes in the tumor microenvironment. In cases with higher clinical stage (III/IV), only 28.5% of cases diffusely expressed VDR and FOXP3 compared to 71.4% showing focal positivity. Whereas in cases with lower clinical stages (I/II), the expression pattern of VDR and FOXP3 was almost similar (41.6% diffuse versus 33.3% focal). Interestingly, focal VDR and FOXP3 expression pattern was significantly higher among males. Mixed cellularity cases showed predilection for focal VDR and FOXP3 expression (80% cases); whereas nodular sclerosis subtype had focal and diffuse VDR and FOXP3 expression patterns in similar proportion. Cases with diffuse VDR and FOXP3 expression were less likely to have bone marrow involvement. Epstein Barr virus- encoded small RNA (EBER) positive cases were predominantly focally positive (80%) for VDR and FOXP3. In summary, quantity of FOXP3 positive T-cells in CHL microenvironment seems to correlate with VDR expression. Clinical stage show a trend of inverse correlation with expression of VDR and quantity of FOXP3 positive T-cells. These findings suggest that VDR could be a possible prognostic and therapeutic target in CHL.
Comparison of the touch-screen and traditional versions of the Corsi block-tapping test in patients with psychosis and healthy controls.
Authors: Siddi Sara , Preti Antonio , Lara Elvira , Brébion Gildas , Vila Regina , Iglesias Maria , Cuevas-Esteban Jorge , López-Carrilero Regina , Butjosa Anna , Haro Josep Maria
Published: November 2019

Working memory (WM) refers to the capacity system for temporary storage and processing of information, which is known to depend on the integrity of the prefrontal cortex. Impairment in working memory is a core cognitive deficit among individuals with psychotic disorders. The Corsi block-tapping test is a widely used instrument to assess visuospatial working memory. The traditional version is composed of 9 square blocks positioned on a physical board. In recent years, the number of digital instruments has increased significantly; several advantages might derive from the use of a digital version of the Corsi test.
This study aimed to compare the digital and traditional versions of the Corsi test in 45 patients with psychotic disorders and 45 healthy controls. Both groups completed a neuropsychological assessment involving attention and working memory divided into two conditions. Results were consistent between the traditional and digital versions of the Corsi test. Overall, patients performed worse relative to the healthy comparison group. The traditional Corsi test was positively related to intelligence and verbal working memory, probably due to a more significant effort to execute the test. The digital version is able to discriminate between patients with psychosis and healthy controls. It would be of use in determining who is at risk of developing a psychotic disorder, and in those already with psychosis, it might provide a prognostic marker for future functional outcome. Further, it is easy to administer while ensuring a standard procedure.
Characterization of the interactions between Codanin-1 and C15Orf41, two proteins implicated in Congenital dyserythropoietic anemia type I disease
Authors: Swickley Grace , Bloch Yehoshua , Malka Lidor , Meiri Adi , Noy-Lotan Sharon , Yanai Amiel , Tamary Hannah , Motro Benny
Published: November 2019

Background Congenital dyserythropoietic anemia type I (CDA I), is an autosomal recessive disease with macrocytic anemia in which erythroid precursors in the bone marrow exhibit pathognomonic abnormalities including spongy heterochromatin and chromatin bridges. We have shown previously that the gene mutated in CDA I encodes Codanin-1, a ubiquitously expressed and evolutionarily conserved large protein. Recently, an additional etiologic factor for CDA I was reported, C15Orf41, a predicted nuclease. Mutations in both CDAN1 and C15Orf41 genes results in very similar erythroid phenotype. However, the possible relationships between these two etiologic factors is not clear. the sequence of Codanin-1 protein does not resemble any known protein.Results We demonstrate here that Codanin-1 and C15Orf41 bind to each other, and that Codanin-1 stabilizes C15Orf41. C15Orf41 protein is mainly nuclear and Codanin-1 overexpression shifts it to the cytoplasm. Phylogenetic analyses demonstrated that even though Codanin-1 is an essential protein in mammals, it was lost from several diverse and unrelated animal taxa. Interestingly, C15Orf41 was eliminated in the exact same animal taxa. This is an extreme case of the Phylogenetic Profiling phenomenon, which strongly suggests common pathways for these two proteins. Lastly, as the 3D structure is more conserved through evolution than the protein sequence, we have used the Phyre2 alignment program to find structurally homologous proteins. We found that Codanin-1 is highly similar to CNOT1, a conserved protein which serves as a scaffold for proteins involved in mRNA stability and transcriptional control. Conclusions The physical interaction and the stabilization of C15Orf41 by Codanin-1, combined with the phylogenetic co-existence and co-loss of these two proteins during evolution, suggest that the major function of the presumptive scaffold protein, Codanin-1, is to regulate C15Orf41 activities. The similarity between Codanin-1 and CNOT1 suggest that Codanin-1 is involved in RNA metabolism and activity, and opens up a new avenue for the study of the molecular pathways affected in CDAI.
The DNA hypermethylation phenotype of colorectal cancer liver metastases resembles that of the primary colorectal cancers.
Authors: Orjuela Stephany , Menigatti Mirco , Schraml Peter , Kambakamba Patryk , Robinson Mark D. , Marra Giancarlo
Published: November 2019

Background: Identifying molecular differences between primary and metastatic colorectal cancers—now possible with the aid of omics technologies—can improve our understanding of the biological mechanisms of cancer progression and facilitate the discovery of novel treatments for late-stage cancer. We compared the DNA methylomes of primary colorectal cancers (CRCs) and CRC metastases to the liver. Laser microdissection was used to obtain epithelial tissue (10 to 25 x 106 µm2) from sections of fresh-frozen samples of primary CRCs (n=6), CRC liver metastases (n=12), and normal colon mucosa (n=3). DNA extracted from tissues was enriched for methylated sequences with a methylCpG binding domain (MBD) polypeptide-based protocol and subjected to deep sequencing. The performance of this protocol was compared with that of targeted enrichment for bisulfite sequencing used in a previous study of ours.
Results: MBD enrichment captured a total of 322,551 genomic regions (249.5 Mb of the genome) that included over seven million CpG sites. A few of these regions were differentially methylated at an expected false discovery rate (FDR) of 5% in neoplastic tissues (primaries: 0.67%, i.e., 2155 regions containing 279,441 CpG sites; liver metastases: 1%, i.e., 3223 regions containing 312,723 CpG sites) as compared with normal mucosa samples. Most of the differentially methylated regions (DMRs; 94% in primaries; 70% in metastases) were hypermethylated, and almost 80% of these (1882 of 2396) were present in both lesion types. At 5% FDR, no DMRs were detected in liver metastases vs. primary CRC. However, short regions of low-magnitude hypomethylation were frequent in metastases but rare in primaries. Hypermethylated DMRs were far more abundant in sequences classified as intragenic, gene-regulatory, or CpG shelves-shores-island segments, whereas hypomethylated DMRs were equally represented in extragenic (mainly, open-sea) and intragenic (mainly, gene bodies) sequences of the genome. Compared with targeted enrichment, MBD capture provided a better picture of the extension of CRC-associated DNA hypermethylation but was less powerful for identifying hypomethylation.
Conclusions: Our findings demonstrate that the hypermethylation phenotype in CRC liver metastases remains similar to that of the primary tumor, whereas CRC-associated DNA hypomethylation probably undergoes further progression after the cancer cells have migrated to the liver.
Prognostic value of C-reactive protein/albumin ratio in renal cell carcinoma: a systematic review and meta-analysis
Authors: song hualin , xiang Peng , liu Zhifu , hu shuai , Jin Jie
Published: November 2019

Background: There are a mass of studies declared the prognostic significance of C-reactive protein/albumin ratio (CRP/Alb) in renal cell carcinoma (RCC). Nevertheless, these works are controversial. In our study, we investigate the expression of CRP/Alb in RCC and its role in prognosis and clinicopathological features.
Methods: The PubMed, Embase and Cochrane databases were searched systematically for correlative articles published before August 1, 2019. Hazard ratios (HRs) and 95% confidence intervals (CIs) were determined according to eligible studies. And we use fixed and random effects models to calculate on the basis of heterogeneity.
Results: Six relevant studies were identified in this study, 1959 participants included in total. Our results showed that CRP/Alb was related to poor overall survival (HR=1.86, 95% CI: 1.56-2.21). In addition, CRP/Alb was also associated with tumor stage (OR=3.29, 95% CI: 1.66-6.50), lymph node involvement (OR=3.76, 95% CI: 2.57-5.51), metastasis (OR=5.69, 95% CI: 2.40-13.51), Fuhrman nuclear grade (OR=4.21, 95% CI: 3.14-5.64), pTNM (OR=4.34, 95% CI: 1.94-9.70) and tumor size (WMD=2.26, 95% CI: 1.86–2.67). However, CRP/Alb was not associated with necrosis.
Conclusion: Our study illustrates that the higher CRP/Alb expression was correlated with poorer prognosis and more advanced clinicopathological features in RCC patients. High CRP/Alb expression may act as a valuable predictive biomarker for poor prognosis in RCC patients.
Molecular Characterization of Prostate Cancer in Middle Eastern Population Highlights Differences with Western Populations with Prognostic Implication
Authors: Abdelsalam Ramy A. , Khalifeh Ibrahim , Box Alan , Kalantarian Maria , Ghosh Sunita , Abou-Ouf Hatem , Lotfi Tamara , Shahait Mohammed , Palanisamy Nallasivam , Bismar Tarek A.
Published: November 2019

Background To investigate the incidence and prognostication of ERG, PTEN and SPINK1 protein expressions in prostate cancer cohort of Middle Eastern descent in comparison to published data from Western populationMethods Immunohistochemistry for ERG, PTEN and SPINK1 was performed in cohort of localized PCa (n=340). Data correlated to pathological and clinical outcomes and compared to Western populations.Results ERG expression and PTEN loss noted in 123/288 (42.7%) and 91/297 (30.6%) of patients, respectively. SPINK1 expression assessed in subset of cases, noted in 6/150 (4%) of patients. Only ERG expression was associated with grade groups, being more common in lower grade groups (1-3 vs 4-5; p=0.04). In contrast to Western population, PTEN loss foci were more likely to be ERG negative, observed in 81% of tumor foci and patients with PTEN neg/ERG pos were more likely to exhibit biochemical recurrence (OR 2.831; 95% CI: 1.10-726, p=0.03). This association remained significant in multivariate analysis (OR 2.68; 95% CI: 0.98-7.33, p=0.05), after adjusting for GG, path stage and surgical margin.Conclusion This study documents significant differences in key molecular events in PCa in Middle Eastern population compared to Western populations that could explain differences in PCa incidence, progression and prognostication. ERG, PTEN and SPINK1 genomic alteration occur less frequently and the enrichment of ERG for PTEN loss is not observed. Additionally, patients with combined PTEN loss/ERG positive are at highest rate for BCR vs North American Caucasian population where PTEN loss alone seems to be associated with the worst clinical outcome. The data presented here further support differences in clonal evolution between Middle Eastern and Western population in relation to PCa and add further insight to understanding PCa molecular pathways.
Value of digital mammography in predicting lymphovascular invasion of breast cancer
Authors: Liu Zhuangsheng , Li Ruqiong , Liang Keming , Chen Junhao , Chen Xiangmeng , Li Xiaoping , Li Ronggang , Zhang Xin , Yi Lilei , Long Wansheng
Published: November 2019

Background: To use digital mammography, a more popular imaging tool, for predicting lymphovascular invasion(LVI) in breast cancer patients preoperatively.
Methods: 122 cases of invasive ductal carcinoma diagnosed between May 2017 and September 2018 were collected, which were divided into positive group (n=42) and negative group (n=80) according to the presence or absence of LVI.
Results: The differences of these variables(childbearing history, miscarriage history, other breast diseases history, nipple discharge, breast cancer marker CA153, age, ER, PR, HER-2, E-CAD, P53, Ki-67) between LVI positive group and the LVI negative group were not statistically significant, except that of Ki-67 (P=0.012). For the image features of digital mammography, the differences of interstitial edema (P=0.013) and skin thickening (P=0.000) between LVI positive group and negative groups were statistically significant. The differences of other imaging patterns, that is, fibroglandular tissue density, size , solitary/multiple, mass shape, mass margin , subcutaneous fat, axillary adenopathy and so on, between the two groups were not statistically significant. Multiple factor analysis shows that, there are three independent risk factors for predicting LVI occurrence: interstitial edema (OR = 12.610, 95% confidence interval CI: 1.061, 149.922, P=0.045), subcutaneous fat (OR=0.081, 95% confidence interval CI: 0.012, 0.645, P =0.017) and skin thickening (OR=9.041, 95% confidence interval CI: 2.553, 32.022, P=0.001).
Conclusion: Interstitial edema, blurring of subcutaneous fat layer, and skin thickening were independent risk factors for predicting LVI occurrence. When applying these three imaging patterns together, the specificity of LVI prediction was as high as 98.8%.
Propagation of Sweetgale, Rhodora, and Catberry by Stem Cuttings
Authors: Peterson Bryan J. , Melcher Gregory J.R. , Scott Ailish K. , Tkacs Rebecca A. , Chase Andrew J.
Published: November 2019

Sweetgale (Myrica gale), rhodora (Rhododendron canadense), and catberry (Ilex mucronata) are shrubs of eastern North America that may have potential for broader use in horticultural landscapes. Because information on their vegetative propagation is scarce, we conducted experiments over 2 years to evaluate the effects of cutting collection date, wounding, substrate composition, and the concentration of applied potassium salt of indole-3-butyric acid (K-IBA) on rooting of each species. In 2015, we collected cuttings of each species on three dates to obtain both softwood and semihardwood cuttings. Cuttings were unwounded or wounded with a razor blade, and treated by dipping into water containing K-IBA at concentrations ranging from 0 to 15,000 mg·L−1, after which they were inserted into a substrate of 3:1 perlite:peat (by volume) and placed under intermittent mist. In 2016, semihardwood cuttings of each species were all wounded, treated with K-IBA from 0 to 15,000 mg·L−1, and inserted into substrates of 100%, 75%, or 50% perlite, with the remaining volume occupied by peat. In both years, the greatest percentage of sweetgale cuttings rooted when no K-IBA was applied. K-IBA application also reduced root ratings, root dry weights, and root lengths of sweetgale. For rhodora and catberry, maximal responses for all measures of rooting occurred when 5000 to 15,000 mg·L−1 K-IBA was applied. We recommend that growers use no exogenous auxin to propagate sweetgale, and 5000 to 10,000 mg·L−1 K-IBA to propagate rhodora and catberry. Cuttings of all three species can be collected from softwood or semihardwood shoots. Finally, sweetgale can be rooted in perlite alone, whereas rhodora and catberry required the addition of peatmoss for satisfactory root development.
A Comparison of Machine Learning Algorithms in Manufacturing Production Process
Authors: Rosalina Rosalina
Published: November 2019

This research aims to improve the productivity and reliability of incoming orders in the manufacturing process. The unclassified data attributes of the incoming order can affect the order plan which will impact to the low productivity and reliability in the manufacturing process. In order to overcome the problem, machine learning algorithms are implemented to analyze the data and expected to help the manufacturing process in deciding the incoming order arrangement process. Four machine learning algorithms are implemented (Decision Tree, Nave Bayes, Support Vector Machine, and Neural Network). These machine learning algorithms are compared by their algorithm performance to the manufacturing process problem. The result of the research shows that machine learning algorithms can improve the productivity and reliability rate in production area up to 41.09% compared to the previous rate without any dataset arrangement before. The accuracy of this prediction test achieves 97%.
Sonochemistry in Transition Metal Catalyzed Cross-coupling Reactions: Recent Developments
Authors: Ujwaldev Sankuviruthiyil M. , Rohit K. R. , Radhika Sankaran , Anilkumar Gopinathan
Published: November 2019

:

Transition metal catalyzed cross-coupling reactions have always been very important
in synthetic organic chemistry due to their versatility in forming all sorts of carbon-carbon
and carbon-hetero atom bonds. Incorporation of ultrasound assistance to these protocols resulted
in milder reaction conditions, faster reaction rates, etc. This review focuses on the contributions
made by ultrasound-assisted protocols towards transition metal catalyzed crosscoupling
reactions.
Hierarchical Extension Based on the Boolean Matrix for LncRNA-Disease Association Prediction
Authors: Tang Lin , Liang Yu , Jin Xin , Liu Lin , Zhou Wei
Published: November 2019

Background:

Accumulating experimental studies demonstrated that long non-coding RNAs (LncRNAs) play crucial roles in the occurrence and development progress of various complex human diseases. Nonetheless, only a small portion of LncRNA–disease associations have been experimentally verified at present. Automatically predicting LncRNA–disease associations based on computational models can save the huge cost of wet-lab experiments.

Methods and Result:

To develop effective computational models to integrate various heterogeneous biological data for the identification of potential disease-LncRNA, we propose a hierarchical extension based on the Boolean matrix for LncRNA-disease association prediction model (HEBLDA). HEBLDA discovers the intrinsic hierarchical correlation based on the property of the Boolean matrix from various relational sources. Then, HEBLDA integrates these hierarchical associated matrices by fusion weights. Finally, HEBLDA uses the hierarchical associated matrix to reconstruct the LncRNA– disease association matrix by hierarchical extending. HEBLDA is able to work for potential diseases or LncRNA without known association data. In 5-fold cross-validation experiments, HEBLDA obtained an area under the receiver operating characteristic curve (AUC) of 0.8913, improving previous classical methods. Besides, case studies show that HEBLDA can accurately predict candidate disease for several LncRNAs.

Conclusion:

Based on its ability to discover the more-richer correlated structure of various data sources, we can anticipate that HEBLDA is a potential method that can obtain more comprehensive association prediction in a broad field.
CDK12 Promotes Breast Cancer Progression and Maintains Stemness by Activating c-myc/β -catenin Signaling
Authors: Peng Fang , Yang Chuansheng , Kong Yanan , Huang Xiaojia , Chen Yanyu , Zhou Yangfan , Xie Xinhua , Liu Peng
Published: November 2019

Background:

CDK12 is a promising therapeutic target in breast cancer with an effective
ability of maintaining cancer cell stemness.

Objective:

We aim to investigate the mechanism of CDK12 in maintaining breast cancer stemness.

Methods:

CDK12 expression level was accessed by using RT-qPCR and IHC. CDK12-altered breast
cancer cell lines MDA-MB-231-shCDK12 and SkBr-3-CDK12 were then established. CCK8, colony
formation assays, and xenograft model were used to value the effect of CDK12 on tumorigenicity.
Transwell assay, mammosphere formation, FACS, and lung metastasis model in vivo were determined.
Western blot further characterized the mechanism of CDK12 in breast cancer stemness
through the c-myc/β-catenin pathway.

Results:

Our results showed a higher level of CDK12 exhibited in breast cancer samples. Tumor
formation, cancer cell mobility, spheroid forming, and the epithelial-mesenchymal transition will be
enhanced in the CDK12high group. In addition, CDK12 was associated with lung metastasis and
maintained breast cancer cell stemness. CDK12high cancer cells presented higher tumorigenicity and
a population of CD44+ subset compared with CDK12low cells. Our study demonstrated c-myc positively
expressed with CDK12. The c-myc/β-catenin signaling was activated by CDK12, which is a
potential mechanism to initiate breast cancer stem cell renewal and may serve as a potential biomarker
of breast cancer prognosis.

Conclusion:

CDK12 overexpression promotes breast cancer tumorigenesis and maintains the
stemness of breast cancer by activating c-myc/β-catenin signaling. Inhibiting CDK12 expression
may become a potential therapy for breast cancer.
Adult Neurogenesis in Epileptogenesis: An Update for Preclinical Finding and Potential Clinical Translation
Authors: Chen Liying , Wang Yi , Chen Zhong
Published: November 2019

Epileptogenesis refers to the process in which a normal brain becomes epileptic, and is characterized by hypersynchronous spontaneous recurrent seizures involving a complex epileptogenic network. Current available pharmacological treatment of epilepsy is generally symptomatic in controlling seizures but is not disease-modifying in epileptogenesis. Cumulative evidence suggests that adult neurogenesis, specifically in the subgranular zone of the hippocampal dentate gyrus, is crucial in epileptogenesis. In this review, we describe the pathological changes that occur in adult neurogenesis in the epileptic brain and how adult neurogenesis is involved in epileptogenesis through different interventions. This is followed by a discussion of some of the molecular signaling pathways involved in regulating adult neurogenesis, which could be potential druggable targets for epileptogenesis. Finally, we provide perspectives on some possible research directions for future studies.
Recent Trends in Nanoelectronic Device Fabrication
Authors: Abbas Mohamed , Algahtani Ali , Kessentini Amir , Loukil Hassen , Parayangat Muneer , Ijyas Thafasal , Salaheldin Bushara , Mohammed Abdul Wase
Published: November 2019

Most current modern devices have micro dimensions. For engineers and manufacturers, it
is now possible to manufacture completely remote devices in a modern way. To determine the critical
points in measuring the dimensions for the manufacturing of devices, which is achieved in practice
and at an appropriate cost, numerous studies have been conducted around the world. Researchers
have attempted to develop a pragmatic approach to interface various nanoscale devices together and
to study their focal points and disadvantages. The objective of this study is to focus on modern trends
in the manufacturing of nanoscale devices. These trends are divided into the following five sections:
development of tribotronic devices, nanodevice fabrication using two-dimensional materials, fabrication
using carbon nanotubes (CNTs), on-chip nanodevice fabrication, and nanodevices based on photonics.
In this study, the views on these trends and how to effectively apply them in the future are
presented. To enhance the structure and features of nanowires inside a scanning tunneling microscope
(STM) scanner, a novel view about the structure of nanowire is presented. These nanowires
demonstrate unique metal properties that enable them to operate in multiple environments with high
efficiency. Using these nanowires inside an STM scanner can improve their ability to withstand high
pressure because their metal properties minimize the chances of breakage.
Effectiveness of Stem Cell Therapy in the Treatment of Ovarian Disorders and Female Infertility: A Systematic Review
Authors: Ahmadian Shahin , Mahdipour Mahdi , Pazhang Mohammad , Sheshpari Sepideh , Mobarak Halimeh , Bedate Alberto Miranda , Rahbarghazi Reza , Nouri Mohammad
Published: November 2019

Background:

Infertility is a major problem worldwide. Various strategies are being used to
develop better treatments for infertility and The most trending strategy is the stem cell therapy. In this
study, the literature on stem cell therapy for ovarian disorders is summarized with analysis of current
developments.

Objective:

Different published studies on stem cell-based therapy for the treatment of various types of
ovarian insufficiency and disorders such as Premature Ovarian Insufficiency (POI) in the affected female
population in animal or human clinical studies are systematically reviewed.

Method:

We monitored five databases, including PubMed, Cochrane, Embase, Scopus, and ProQuest.
A comprehensive online search was done using the criteria targeting the application of stem cells in
animal models for menopause. Two independent reviewers carefully evaluated titles and abstracts of
studies. The stem cell type, source, dosage, route of administration were highlighted in various POI
animals models. Non-relevant and review articles were excluded.

Outcomes:

648 published studies were identified during the initial comprehensive search process from
which 41 were selected according to designed criteria. Based on our analysis, stem cells could accelerate
ovarian tissues rejuvenation, regulate systemic sex-related hormones levels and eventually increase
fertility rate.

Conclusion:

The evidence suggests that stem cell-based therapies could be considered as an alternative
modality to deal with women undergoing POI.
A Comparative Analysis of Bark and Leaf Essential Oil and their Chemical Composition, Antioxidant, Anti-inflammatory, Antimicrobial Activities and Genotoxicity of North East Indian Cinnamomum zeylanicum Blume
Authors: Gogoi Roktim , Sarma Neelav , Loying Rikraj , Pandey Sudin Kumar , Begum Twahira , Lal Mohan
Published: November 2019

Background:

Cinnamomum zeylanicum Blume ( Lauraceae) bark and leaf essential oil
possesses eugenol as the major component. Both the essential oils have the potential antioxidant, anti-
inflammatory, antimicrobial and negligible genotoxicity.

Objective:

A comparative chemical composition and biological evaluation of Cinnamomum zeylanicum
Blume, bark and leaf essential oils, originated from North-East India has been investigated in
the present study.

Methods:

Gas chromatography/mass spectroscopy analysis was used to investigate the chemical
composition of the essential oil samples. DPPH free radical scavenging activity, and reducing power
assay were used for antioxidant activity evaluation. Similarly, egg albumin denaturation assay, protease
inhibitory activities were used for anti-inflammatory activity, while genotoxicity was evaluated
by using Allium cepa assay and antimicrobial activities using disc diffusion and minimum inhibitory
concentration assay.

Results:

The GC/MS results showed that eugenol is the major component of C. zeylanicum bark
(84.48%) and leaf (48.78 %) essential oil. Significant antioxidant activity was observed for both essential
oils in the DPPH free radical scavenging assay (IC50= 103.2 μg/mL, bark; IC50= 234.7
μg/mL, leaf), and reducing power assay (absorbance of 1.802 nm, 0.907 nm in 48 μg/mL for bark
and leaf essential oil respectively). In-vitro anti-inflammatory activity revealed strong potential of
leaf essential oil (protein denaturation assay, IC50= 0.05279 μg/mL; protease inhibitory activity
IC50= 3.607 μg/mL) in comparison to bark essential oil (protein denaturation assay IC50= 0.1491,
protease inhibitory activity IC50= 61.06). Allium cepa root growth test, mitotic index, and chromosomal
aberration test were performed to investigate the genotoxicity of C. zeylanicum bark and leaf
essential oil, which resulted in no toxic nature of both the essential oils. Antimicrobial activity
against eight bacterial and fungal strains revealed good antimicrobial properties with the MIC value
of Staphylococcus aureus at 5 μL/mL (bark), Aspergillus niger at 2.5 μL/mL (bark); Bacillus cereus
at 5 μL/mL (leaf) and Aspergillus niger at 2.5 μL/mL (leaf).

Conclusion:

Collectively, these findings indicated the strong biological potential of both essential
oils, although bark essential possesses better biological activities than the leaf essential oil and could
be used in the food and beverage industries.