bluuebunny/crossref_metadata_2025 huggingface dataset:
Contribution of rs2232365 Polymorphism of FOXP3 Gene in Cervical Cancer Development
Authors: Kldiashvili Ekaterina , Metreveli Tornike
Published: February 2020

Objective Cervical cancer is the second common malignancy in women. This is an immunogenic malignancy, and high-risk human papilloma virus (HPV) subtypes may cause its development. Persistent infection of high-risk HPV subtypes may significantly facilitate the development of cervical intraepithelial neoplasia, which has been confirmed as a major risk factor of cervical cancer. Regulatory T cells (Treg cells) are a group of mature T cells generated in the thymus following the induction of peripheral naïve T cells. They are essential for the inhibition of immune overreaction induced damage, but over-production of Treg cells may block the protective immune response to infection and tumors. FOXP3 (Forkhead box protein P3) is a key transcription factor in regulatory T cells (Tregs), and has important roles in the immunosuppressive functions in Tregs. The role of FOXP3 gene polymorphisms in cancer patients is not determined till now. Results We have investigated the association of rs2232365 (A to G) of FOXP3 gene with cervical cancer. rs2232365A/G polymorphism has been detected in cervical cancer (25 cases, 73.53% of cancer cases, p=0.03) and CIN (36 cases, 64.29% of CIN cases, p=0.02). We assume that rs2232365 polymorphism of the Foxp3 gene may contribute to the cervical cancer development.
Prognostic Value of Sarcopenia in Patients Treated by Radiochemotherapy for Locally Advanced Oesophageal Cancer
Authors: Mallet Romain , Modzelewski Romain , Lequesne Justine , Decazes Pierre , Auvray Hugues , Benyoucef Ahmed , Fiore Frederic Di , Vera Pierre , Dubray Bernard , THUREAU SEBASTIEN
Published: February 2020

Background Sarcopenia is defined by a loss of skeletal muscle mass with or without loss of fat mass. Sarcopenia has been associated to reduced tolerance to treatment and worse prognosis in cancer patients, including patients undergoing surgery for limited oesophageal cancer. Concomitant chemo-radiotherapy is the standard treatment for locally-advanced tumour, not accessible to surgical resection. Using automated delineation of the skeletal muscle, we have investigated the prognostic value of sarcopenia in locally advanced oesophageal cancer patients treated by curative-intent chemo-radiotherapy. Methods The clinical, nutritional, anthropometric, and functional-imaging ( 18 FDG-PET/CT) data were collected in 97 patients treated between 2006 and 2012 in our institution (RTEP3). The skeletal muscle area was automatically delineated on cross-sectional CT images acquired at the 3 rd . lumbar vertebra level and divided by the patient’s squared height (SML3/h 2 ) to obtain the Skeletal Muscle Index (SMI). The primary endpoint was overall survival probability. Results Seventy-six deaths were reported. The median survival time was 27 [95% Confidence Interval 23 – 40] months for the whole population. Univariate analyses (Cox Proportional Hazard Model) showed decreased survival probabilities in patients with reduced SMI, WHO >0, Body Mass Index ≤21, and Nutritional Risk Index ≤97.5. Multivariate analyses showed that reduced SMI (Hazard Ratio 0.948 [0.919 - 0.978] and male sex (2.977 [1.427 - 6.213] were significantly associated to decreased survival. Using Receiver Operating Characteristics curves, the Area Under the Curve (AUC) was 0.73 in males (p=0.0002], the optimal threshold being 51.5 cm 2 /m 2 . In women, the AUC was 0.65 (p=0.19). Conclusion Sarcopenia is a powerful independent prognostic factor, associated with a rise of the overall mortality in patients treated exclusively by radiochemotherapy for a locally advanced oesophageal cancer. L3 CT images are easily gathered from 18 FDG-PET/CT acquisitions
The involvement of MCTP1 in the drug-resistance of esophageal cancer cells
Authors: Kong Lingsuo , Wei Ran , Yang Wan , Chen Lanren , Qian Liting
Published: February 2020

Background: Accumulating studies demonstrated that drug-resistance remains a great obstacle for the effective treatment of cancers. Esophageal cancer (EC) is still one of the most common cancers worldwide, which also suffers from drug-resistance during clinical treatment. Methods: We performed the drug-resistance profiling assays and identified several drug-resistant and drug-sensitive EC cell lines. The following methylation sequencing showed that the MCTP1 gene is hypermethylated in the drug-resistant EC cells. Results: As a result, the expression of MCTP1 is down-regulated in the drug-resistant EC cells. Down-regulation of MCTP1 also affects the cell proliferation and apoptosis of EC cells, as revealed by the cell proliferation and apoptosis assays. Further investigations proposed two signaling pathways that might involve in the MCTP1-mediated drug-resistance of EC cell. Conclusions: All these results suggested that MCTP1 is associated with the drug-resistance of EC cells, which has implications for further design of new biomarker of EC treatment.
Antibiotic resistance associated with air quality and transferred by airborne particulate matter
Authors: Zhou Zhen-Chao , Liu Yang , Lin Ze-Jun , Shuai Xin-Yi , Zhu Lin , Xu Lan , Meng Ling-Xuan , Sun Yu-Jie , Chen Hong
Published: February 2020

Background: Environmental spread of antibiotic resistance has become a public health problem, but the relationship between air quality and antibiotic resistance has not been fully investigated, the effect and mechanism of air pollutants on horizontal genes transfer of antibiotic resistance are rarely mentioned. Results: In the present study, significant correlation ( P < 0.05) between resistance rates of 10 clinical antibiotic-resistant pathogens and number of days when air quality index was below 100 were observed in an extensive survey from 2014 to 2017 in China. In addition, characterization of antibiotic resistance genes (ARGs), mobile genetic elements (MGEs), and bacterial communities in airborne particulate matter (PM), dust, and human airway sputum samples were profiled in a hospital. PM 2.5 and PM 10 were shown to contain ARGs and MGEs high relative abundance and diversity index. Importantly, transferable multi-resistant plasmids were identified from air, e.g., pTAir-3 with 26 MGEs and 10 ARGs, using conjugative mating assays and nanopore sequencing . Furthermore, PM 2.5 and PM 10 significantly enhanced the conjugative transfer frequencies between bacteria, via inducing increased levels of reactive oxygen species and cell membrane permeability; upregulated gene expression levels were confirmed by genome-wide RNA sequencing. Conclusions: These findings provide a new perspective on antibiotic resistance research and have profound implications for antibiotic resistance control in clinics and environments.
G-protein subunit Gai in mitochondria, MrGPA1, affects conidiation, stress resistance, and virulence of entomopathogenic fungus Metarhizium robertsii﻿
Authors: Tong Youmin , Wu Hao , Liu Zhenbang , Wang Zhangxun , huang bo
Published: February 2020

G proteins are critical modulators or transducers in various transmembrane signaling systems. They play key roles in numerous biological processes in fungi, including vegetative growth, development of infection-related structures, asexual sporulation, and virulence. However, their function in entomopathogenic fungi remains unclear. Here, we characterized the roles of MrGPA1, a G-protein subunit Gα i , in conidiation, stress resistance, and virulence in Metarhizium robertsii . MrGPA1 was localized in the mitochondria. MrGpa1 deletion resulted in a significant reduction (47%) in the conidiation capacity, and reduced expression of several key conidiation-related genes, including fluG , flbD , brlA , wetA , phiA , and stuA . Further, MrGpa1 disruption resulted in decreased fungal sensitivity to UV irradiation and thermal stress, as determined based on conidial germination of ∆MrGpa1 and wild-type strains. Chemical stress analysis indicated that MrGpa1 contributes to fungal antioxidant capacity and cell wall integrity, but is not involved in antifungal ability and osmotic stress. Importantly, insect bioassays involving (topical inoculation and injection) of Galleria mellonella larvae revealed decreased virulence of ∆MrGpa1 strain after cuticle infection. This was accompanied by decreased rates of appressorium formation and reduced expression of several cuticle penetration-related genes. These observations suggest that MrGpa1 contributes to the regulation of conidiation, UV irradiation, thermal stress response, antioxidant capacity and cell wall integrity in M. robertsii . This gene is also involved in insect cuticle penetration during infection. These findings raise the possibility of designing powerful strategies for genetic improvement of M. robertsii conidiation capacity and virulence for killing pests.
Prognostic Accuracy of the Eighth Edition of TNM Classification Compared with the Seventh and Sixth Edition for Perihilar Cholangiocarcinoma
Authors: Hau Hans Michael , Meyer Felix , Rademacher Sebastian , Sucher Robert , Seehofer Daniel
Published: February 2020

Background This study was conducted to evaluate and compare the prognostic value and performance of the 6th, 7th, and 8th editions of the American Joint Committee on Cancer (AJCC) staging system when applied to patients undergoing surgery for perihilar cholangiocarcinoma (PHC). Methods Patients undergoing liver resection with curative intention for PHC between 2002 and 2019 were identified from a prospective database. Histopathological parameters and stage of the PHC were assessed according to the 6th, 7th, and 8th editions of the tumor node metastasis (TNM) classification. The prognostic accuracy between staging systems was compared using the area under the receiver operating characteristic curve (AUC) model. Results Data for a total of 95 patients undergoing liver resection for PHC were analyzed. The median overall survival time was 21 months (95% CI 8.1–33.9), and the 3- and 5-year survival rates were 46.1% and 36.2%, respectively. Staging according to the 8th edition versus the 7th edition resulted in reclassification of 25 patients (26.3%). The log-rank p-values for the 7th and 8th edition were highly statistically significant (p ≤ 0.01) compared to the 6th edition (p = 0.035). The AJCC 8th edition staging system had a slightly better discrimination ability, with an AUC of 0.69 (95% CI: 0.52–0.84) compared to 0.61 (95% CI: 0.51–0.73) for the 7th edition. Multivariate survival analysis revealed male gender, age > 65 years, positive resection margins, presence of distant metastases, poorly tumor differentiation, lymph node involvement such as no caudate lobe resection as independent predictors of poor survival (p < 0.05). Conclusion The newly released 8th edition of the AJCC staging system demonstrated a poor to moderate ability to predict prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma; the result was only slightly better than the previous 7th edition. Further refinements are needed to improve the prognostic ability of the AJCC staging system for perihilar cholangiocarcinoma and to identify other prognostic factors that can potentially improve individual patient prognostication.
The role of resistin gene polymorphisms in bladder cancer
Authors: Deng Shi , He Yin sheng , zhao pan , Zhang Peng
Published: February 2020

Background: Published studies have demonstrated that resistin, a recently discovered adipokine, is connected to insulin resistance, type 2 diabetes mellitus, obesity, inflammation, and atherosclerotic vascular disease. A comprehensive study of the adipocytokine family and tumor pathogenesis indicates an intimate relationship between resistin and the incidence, progression, and metastasis of gastric cancer, esophageal cancer, choriocarcinoma, colorectal cancer, pancreatic cancer, and biliary tract cancer. To date, the connection between resistin and bladder cancer has not been thoroughly investigated and remains unclear. Methods: Overall, 322 patients with bladder cancer and 366 normal controls were included in the study. Two SNPs of the resistin gene, rs1862513 (also known as −420 C/G) and rs10401670 (3’UTR C/T) were genotyped across the entire cohort. Next, the association between the two SNPs and the incidence, risk factors, and prognosis of bladder cancer, were analyzed. Results: The frequency of T allele and CT/TT genotype of rs10401670 was significantly lower in bladder cancer patients (P=0.03, OR=0.79 and P = 0.018, OR = 0.68, respectively) compared to normal controls. No differences were found with regards to the rs1862513 genotype frequency and the distribution of allele frequency between the two groups. Stratified analyses showed that the CT heterozygous genotype of rs10401670 was associated with bladder cancer at an earlier age (OR=1.97, 95% CI=1.14–3.40) and the CG heterozygous genotype of rs1862513 was correlated with high incidence of bladder cancer in smokers (OR=1.73, 95 % CI=1.05–2.87). Multiple Cox regression analysis showed that for bladder cancer patients, the presence of a CG heterozygous genotype of rs1862513 was associated with a decrease in the risk of recurrence in MIBC patients (P = 0.04，OR= 0.49). Additionally, the rs1040167 CT/TT genotype (P = 0.03，OR= 2.45), especially the TT homozygous genotype (P = 0.02，OR= 3.00) was associated with high risk of death. These results indicate that the rs1040167 CT/TT and TT homozygous genotype may be a risk factor for overall survival of bladder cancer patients. Conclusions: Our results suggest that resistin genotype serves as a risk factors for the occurrence and prognosis of bladder cancer, and could be be a potential biomarker for this devastating disease.
A multicenter, descriptive epidemiologic survey of the clinical features of spinal metastatic disease in China
Authors: Zhang Hao-ran , Qiao Rui-qi , Yang Xiong-gang , Xu Ming-you , Hu Yong-cheng
Published: February 2020

Background: Spinal metastases have unique epidemiological features and treatment methods. Unfortunately, the relative scarcity of spinal metastases has limited the widespread development of descriptive epidemiological studies, especially in Asian countries. The purpose of this study was to describe the epidemiological characteristics of patients with metastatic spinal tumors in China between 2007 and 2019.Methods: From January 2007 and July 2019, data on patients with spinal metastases were collected from five cancer centers in China, and demographic characteristics, primary tumor types, segments and numbers of vertebral lesions, disease-related scores, and treatment methods were reviewed.Results: A total of 2228 patients with spinal metastases were reviewed in this study, including 1279 male patients and 949 female patients, and the male to female ratio was 1.35: 1. More than half of patients developed metastatic diseases between the ages of 50 years and 69 years (64%). Overall, lung cancer (824 cases, 37%) was the most common primary tumor type and the most common level of spinal involvement was multi-level of metastases (860 cases, 39%). 705 patients (32%) had undergone surgical treatments, 1028 patients (46%) had undergone radiotherapy for metastatic vertebrae, and 855 patients (38%) had received systemic treatments. The age, primary tumor type, number of involved vertebrae, Frankel grade, and spinal instability neoplastic score would affect the surgical decision-making.Conclusions: This study provides insight into the epidemiological characteristics of spinal metastasis and health care service utilization in spinal metastasis patients in China.
Frequency of CDK2 , CCNE1 Copy Number Variation in Acral Melanoma and Implications for CDK Inhibitor in Targeted Therapy
Authors: Wu Xiaowen , Yan Junya , Yu Jiayi , Yu Jinyu , Cheng Zhiyuan , Yin Ting , Guo Qian , Xie Yihong , Kong Yan , Guo Jun
Published: February 2020

Background: Acral melanoma have a high frequency of cell cycle-related gene copy number variation. However, the status and clinical significance of CNVs of CDK 2 and CCNE1 have not been fully elucidated. Methods: A total of 490 acral melanoma samples were examined for CNVs of CDK 2 and CCNE1 using QuantiGenePlex DNA Assay. Correlations of CDK2 and CCNE1 CNVs to clinicopathologic features and prognosis of acral melanoma were evaluated.The sensitivity of cell lines and cell-derived xenograft (CDX) containing CCNE1 CNVs to CDK inhibitor AT7519,Dinaciclib and proteasome inhibitor Bortezomib were also analyzed. Results: Among the 490 samples,140 cases, 139 cases and 39 cases respectively showed CDK2 gain (28.5%), CCNE1 gain (28.3%) and CDK2 gain plus CCNE1 gain (8.0%).The median progression-free survival (PFS) time for acral patients with CCNE1 gain was significantly shorter than that for patients without CCNE1 gain (17.0 versus 27.0 months; P =0.002). Furthermore, CCNE1 gain was an independent prognostic factor for patients receiving chemotherapy. The pan-CDK inhibitor AT7519 could inhibit the cell proliferation, induce apoptosis and cause cell cycle arrest in G2 phase of acral melanoma cells and inhibit the tumor growth of CDX with CCNE1 gain. Dinaciclib and Bortezomib showed CCNE1 copy number independent inhibitory effects on the proliferation of melanoma cells. Conclusions: CDK2 and CCNE1 copy number variations were frequent in acral melanoma and CCNE1 gain may be a useful biomarker to predict the outcome of receiving chemotherapy in patients with acral melanoma. In addition, our study provides a basis for the use of CDK inhibitor in the treatment of acral melanoma. Keywords: acral melanoma, targeted therapy, CDK2 , CCNE1 , copy number variation
Identification of potential biomarkers for CAD using integration with expression and methylation data and validation by case-control study
Authors: Zhang Xiaokang , Xiang Yang , He Dingdong , Liang Bin , Wang Chen , Luo Jing , Zheng Fang
Published: February 2020

Background: DNA methylation plays an essential role in the pathogenesis of coronary artery disease (CAD) through regulating mRNA expressions. This study aimed to identify hub genes as biomarkers functioning in CAD and regulated by DNA methylation. Methods: Gene expression and methylation datasets of peripheral blood leukocytes (PBLs) of CAD were downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified based on differentially methylated CpG sites (DMCs) in intragenic regions. The overlapped genes in DEGs and DMGs were filtered and defined as differentially expressed-methylated genes (DEMGs). Multiple computational approaches were performed to analyze the regulatory networks of DEMGs and recognize hub genes, subsequently. Finally, top hub genes were verified in a case-control study based on their differential expression levels between CAD cases and controls. Results: Totally 535 DEMGs were identified and partitioned into 4 subgroups. TSS200 and 5’UTR were confirmed as high enrichment areas of DMCs. DEMGs mainly enriched in processes of histone H3-K27 methylation, regulation of posttranscription and DNA-directed RNA polymerase activity. Pathway enrichment showed DEMGs participated in VEGF signaling pathway, adipocytokine signaling pathway and PI3K-Akt signaling pathway. Besides, hub genes FN1 (fibronectin 1), PTEN (phosphatase and tensin homolog), POLR3A (RNA polymerase III subunit A) were experimentally proved discordantly expressed in CAD patients when compared with controls. Conclusions: In conclusion, our study demonstrated the probable functional genes of PBLs in CAD, in which FN1, PTEN and POLR3A were confirmed. The underlying mechanism that differential expression-methylation of FN1, PTEN and POLR3A in CAD need further study.
Association of FTO methylation level with incident type 2 diabetes mellitus: a nested case–control study within the Rural Chinese Cohort Study
Authors: Huang Shengbing , Chen Qing , Zhang Dongdong , Cheng Cheng , Guo Chunmei , Li Quanman , Zhou Qionggui , Tian Gang , Qie Ranran , Han Minghui , Wu Xiaoyan , Zhao Yang , Yang Xingjin , Feng Yifei , Li Yang , Qin Pei , Zhao Yang , Zhang YanYan , Wu Yuying , Liu Dechen , Zhang Ming , Hu Dongsheng , Lu Jie
Published: February 2020

Objectives This study aimed to investigate the association of FTO methylation level with type 2 diabetes mellitus (T2DM). Methods We conducted a nested case – control study for DNA methylation of FTO in Chinese pople identified from the Rural Chinese Cohort Study with a 6-year follow-up. Controls were matched to the cases on a 1:1 basis by age, sex, ethnicity, marital status, and residence. Unconditional multivariate logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for association with Tag-single nucleotide polymorphisms (SNPs) and cytosine guanine (CpG) locus. Haploview was used to analyze the association of possible haplotypes with T2DM. Generalized Multifactor Dimensionality Reduction was used to explore the potential interaction. Results We found a significant association for the CpG9 locus located in the promoter region of FTO with T2DM. With CpG9, the risk of T2DM was 1.84 (1.21–2.80) after adjusting for potential confounders. The Tag-SNPs (rs72803657, rs1558902, rs17817449, rs11076023) nor were possible haplotypes associated with T2DM in the strong linkage disequilibrium region. We found no significant interaction between obesity indexes, serum lipid levels and methylation levels. Conclusions Our study identified a CpG locus located in the promoter region of FTO that altered the T2DM risk independent of body mass index, but the variants of FTO were not significantly associated with T2DM. Our study might provide new insights into the pathways of FTO with T2DM and offer new opportunities for risk stratification and prevention of T2DM among rural Chinese population.
Waxy and Soluble Starch SynthaseII-3 Alleles Regulating Rice Resistant Starch Contents from Different Processing Status
Authors: you hui , Xu Liang , Zhang Ouling , Xiang Xunchao
Published: February 2020

BackgroundResistant Starch (RS) is a healthy dietary fiber that has functions of regulating diabetes, hypertension and obesity. Previous studies mainly focused on investigating RS in raw rice or cooked rice separately, which may receive different results. ResultsIn this study, ninety-nine lines from a recombinant inbred line (RIL) were selected to investigate the effects of starch synthesis-related genes on the RS content in different process status. RS content in rice will change by different processing ways. Waxy (Wx) played an important role in controlling RS content and Wxa could elevate RS content, and soluble starch synthaseII-3 (SSII-3) had an impact on RS2. Additionally, interaction of Wx and SSII-3 was responsible for variations of RS content in three sample types and RS2. Wx could affect RS in cooked rice and retrograded rice under the same SSII-3 allele. Moreover, the correlation analysis results indicated that RS was closely relative with many indexes of physicochemical properties. ConclusionsWx and SSII-3 could regulate RS content of rice, but SSII-3 especially affected RS2. The findings herein should provide useful information for molecular breeding of rice RS.
Long-term outcomes following vehicle trauma related acute kidney injury requiring renal replacement therapy: A nationwide population study
Authors: Chan Chieh-Kai , Prowle John R , Wu Vin-Cent
Published: February 2020

Background Acute kidney injury (AKI) is a frequent complication of traumatic injury; however, long-term outcomes such as mortality and end-stage kidney disease (ESKD) have been rarely reported in this important patient population. We compared the long-term outcome of traumatic and non-traumatic AKI requiring renal replacement therapy (AKI-RRT). Methods This nationwide cohort study used data from the Taiwan National Health Insurance Research Database. Vehicle-trauma patients developing AKI-RRT during hospitalization were identified, and matching non-traumatic AKI-RRT patients were identified between 2000 and 2010. The incidences of end-stage kidney disease (ESKD), 30-day, and long-term mortality were evaluated, and clinical and demographic associations with these outcomes were identified using Cox proportional hazards regression models. Results 546 traumatic AKI-RRT patients, median age 47.6 years (interquartile range: 29.0-64.3) and 76.4% male, were identified. Compared to non-traumatic AKI-RRT, traumatic AKI-RRT patients had longer length of stay in hospital [median (IQR):15 (5-34) days vs 6 (3-11) days; p < 0.001). After propensity matching with non-traumatic AKI-RRT cases with similar demographic and clinical characteristics. Traumatic AKI-RRT patients had lower rates of long-term mortality (adjusted hazard ratio (HR), 0.488; 95% CI, 0.405-0.588; p < 0.001), but similar rates of ESKD (HR, 1.075; 95% CI, 0.767–1.509; p = 0.674) and short-term risk of death (HR, 1.165; 95% CI, 0.920-1.476; p = 0.205) as non-traumatic AKI-RRT patients. Conclusions Despite severe injuries, traumatic AKI-RRT patients had better long-term survival than non-traumatic AKI-RRT patients, but a similar risk of ESKD. Our results provide a better understanding of long-term outcomes after traumatic AKI-RRT.
Loss of GLS2 function is essential for obtaining oncogenic functions and promotes the progression of clear cell renal cell carcinoma.
Authors: sun dantong , Tian Lu , Zhao Han , Yan Weihua , Wei Xiaojuan , Wo Yang , hou helei
Published: February 2020

Background The incidence of RCC has drastically increased in recent years. The large intratumor heterogeneity of RCC, especially ccRCC, usually leads to treatment failure. In addition, single biomarkers have a limited ability to predict prognosis. Therefore, we performed this study to select variables and provided a simple but efficient way to predict prognosis. Method Three studies from the GEO database were involved in the selection of DEGs. A total of 840 RCC patients and 524 ccRCC patients from the TCGA database were involved in the prognostic analyses. Nomograms based on the Cox regression model were used to select variables to predict the prognosis, and GSEA was used to demonstrate the potential pathways altered by gene expression. Result Our study suggested that DEGs existed between metastatic and primary tumor tissues. Loss of GLS2 function was related to poor prognosis in RCC and ccRCC. These results revealed that GLS2 expression combined with basic characteristics, including age and TNM stage, could efficiently predict prognosis. GLS2 serves as a tumor suppressor in ccRCC, and loss of GLS2 function endows cells with oncogenic functions and is related to advanced disease. According to the GSEA results, loss of GLS2 function may alter the cell cycle by activating the E2F pathway. Conclusion GLS2 is a tumor suppressor in RCC. Loss of GLS2 function in ccRCC predicts a poor prognosis via the E2F pathway. Nomograms based on DEGs and clinical features provide doctors with a simple but efficient way to predict prognosis. Further studies are needed to verify the pathway in our study.
Ovarian metastasis from non-gynecologic primary sites: a retrospective analysis of 177 cases and 13-year experience
Authors: Zhang Jingjing , Cao Dong-Yan , Yang Jia-Xin , Shen Keng
Published: February 2020

BackgroundMetastasis to the ovary is not rare. Generally, the most common non-gynecologic primary site of Ovarian metastasis is gastrointestinal tract. Differential diagnosis between primary malignant ovarian tumor and metastatic ovarian tumor is important, otherwise appropriate treatment cannot be determined. Furthermore, optimal treatment strategy for ovarian metastasis from non-gynecologic primary sites still are needed to explore. This study described the clinicopathologic characteristics of ovarian metastasis from non-gynecologic primary sites and identified the significance of surgical treatment for these patients. Methods One hundred and seventy-seven patients with ovarian metastasis from non-gynecologic primary sites admitted in Peking Union Medical College Hospital between May 2005 and May 2018 were retrospectively evaluated. Results The mean age was 48 years (range 18 - 83). Approximately 60% of patients were premenopausal women. The mostly two common non-gynecologic primary sites of ovarian metastasis were colorectum (68 cases) and stomach (61 cases). Besides the most common symptoms of abdominal distension (39.0%), abdominal pain (37.9%), ascites (27.7%), there were 18.1% of patients presenting with abnormal uterine bleeding. A half of patients who tested serum CA-125 preoperatively had an elevated CA-125 within the range of 35U/ml to 200U/ml. More than 70% of synchronous ovarian metastasis were misdiagnosed as primary ovarian cancer preoperatively. Of patients, 56.5% achieved optimal cytoreductive surgery (the diameter of largest residual lesion < 2 cm). The overall 5-year survival rate and median survival time were 10% and 20 months, respectively. The primary sites, optimal cytoreductive surgery, differentiation of tumor, and postoperative adjuvant treatment were prognostic indicators. Conclusions Colorectum and stomach are the most common non-gynecologic primary sites of ovarian metastasis. Synchronous ovarian metastasis is easy to be misdiagnosed as primary ovarian cancer. Optimal cytoreductive surgery and postoperative adjuvant treatment can be done to confer survival benefit in selected patients.
Effect of Yangyin Shuxin Decoction on Exercise Capacity in Patients with Heart Failure with Normal Ejection Fraction: Rationale and Design of a Randomized Controlled Trial
Authors: Zhao Zhiqiang , Wang Xianliang , Wang Shuai , Zhou Ruijuan , Su Quan , Liu Yu , Li Qing , Lin Shanshan , Liu Hua , Mao Jingyuan
Published: February 2020

Background The incidence of heart failure with normal ejection fraction (HFNEF) is increasing yearly, accounting for approximately half of all heart failure cases. Even after standardized treatment, the patient's prognosis is not good. Therefore, it is necessary to explore new treatment methods for HFNEF. Yangyin Shuxin Decoction, a traditional Chinese medicine prescription from our clinical experience in the treatment of HFNEF, has a potential cardioprotective effect. Preliminary clinical trials have shown that this prescription can improve the quality of life of HFNEF. This prompted us to use more objective indicators to further evaluate whether Yangyin Shuxin Decoction can improve the exercise capacity in HENEF patients. Methods This is a single-center parallel randomized controlled trial. The 64 patients who met the inclusion criteria were from the Cardiovascular Clinic. They will be randomly assigned to the treatment group (Yangying Shuxin Decoction combined with standard treatment) or the control group (standard treatment) according to the ratio of 1:1. The course of treatment will be 2 weeks. Both groups were interviewed at the following time points: of at enrollment (V1), and week 2 (V2), week 4 (V3), week 8 (V4), and week 12 (V5) after enrollment. The primary indicator is the peak oxygen consumption(Peak VO2) of the cardiopulmonary exercise test (CPET). Secondary indicators include CPET indicators such as anaerobic threshold oxygen consumption, carbon dioxide ventilation equivalent slope, echocardiographic indicators such as the ratio of mitral peak velocity of early filling to early diastolic mitral annular velocity(E/e′), left atrial volume index (LAVI), left ventricular mass index (LVMI), the peak velocity of tricuspid regurgitation (TR), B-type natriuretic peptide (BNP), New York Heart Association (NYHA) cardiac function grading, and so on. These indicators will be used to evaluate the effect of Yangyin Shuxin Decoction on exercise capacity in patients with HFNEF. Discussion At present, it is unclear whether the exercise capacity can be maintained after long-term use of Yangyin Shuxin Decoction. In this study, we will evaluate whether Yangyin Shuxin Decoction can improve the exercise capacity and quality of life of patients with HFNEF. This will provide an objective basis for the therapeutic effect of traditional Chinese medicine on HFNEF.
Protein delivery in intermittent and continuous enteral nutrition with a protein-rich formula in critically ill patients - A protocol for the prospective randomised controlled proof-of-concept Protein Bolus Nutrition (Pro BoNo) study
Authors: Reinhold Simona , Yeginsoy Désirée , Hollinger Alexa , Todorov Atanas , Tintignac Lionel , Sinnreich Michael , Kiss Caroline , Gebhard Caroline Eva , Kovács Balázs , Gysi Bianca , Imwinkelried Lara , Siegemund Martin
Published: February 2020

Background Critically ill patients rapidly develop muscle wasting resulting in sarcopenia, long-term disability and higher mortality. Bolus nutrition (30-60 min period), while having a similar incidence of aspiration as continuous feeding, seems to provide metabolic benefits through increased muscle protein synthesis due to higher leucine peaks. To date, clinical evidence on achievement of nutritional goals and influence of bolus nutrition on skeletal muscle metabolism in ICU patients is lacking. The aim of the Pro BoNo study ( Pro tein Bo lus N utriti o n) is to compare intermittent and continuous enteral feeding with a specific high-protein formula. We hypothesise that target quantity of protein is reached earlier (within 36 hours) by an intermittent feeding protocol with a favourable influence on muscle protein synthesis. Methods Pro BoNo is a prospective randomised controlled study aiming to compare the impact of intermittent and continuous enteral feeding on preventing muscle wasting in 60 critically ill patients recruited during the first 48 hours after ICU admission. The primary outcome measure is the time until the daily protein target (≥1.5 g protein/kg bodyweight/24h) is achieved. Secondary outcome measures include tolerance of enteral feeding and trajectory of glucose, urea and IGF-1. Ultrasound and muscle biopsy of the quadriceps will be performed. Discussion The Basel Pro BoNo study aims to collect innovative data on the effect of intermittent enteral feeding of critically ill patients on muscle wasting.
Effect of Gum Arabic (Acacia Senegal )on C-reactive protein level among Sickle Cell Anemia patients
Authors: Kaddam Lamis AbdelGadir , Kaddam Anas Suliman
Published: February 2020

Objectives: Inflammation is ongoing process among sickle cell anemia even during steady state. C reactive protein (CRP) is cardinal marker that utilized widely as inflammatory indicator. Gum Arabic (GA) is gummy exudates from Acacia Senegal tree. Fermentation by colonic bacteria increases serum butyrate concentrations, so considered as prebiotic agent. Gum Arabic (GA) has anti-inflammatory activity through butyrate. Earlier we proved that regular intake of GA increased fetal hemoglobin and anti-oxidant capacity most likely through raised level of butyrate, which would ameliorate symptoms of sickle cell anemia. Best of our knowledge this is the first study conducted to investigate GA intake on inflammatory markers among sickle patients.Results : This was a retrospective study conducted on stored samples from trial of Gum Arabic and sickle cell anemia. Quantitative CRP was measured by Mindray BS 200 before and after Gum Arabic consumption for 12 weeks. Daily intake of GA significantly decreased C reactive protein level (P.V=001) (95% CI, 0.943 -3.098). No correlation between CRP and age, fetal hemoglobin, hemolysis markers and white blood cells. Our findings revealed novel effect of GA as anti-inflammatory agent can be consumed as natural dietary supplement to modulate disease severity and downregulate inflammatory process.Trial registration: ClinicalTrials.gov Identifier: NCT02467257. Registered 3rd June 2015
Improved recording of work relatedness during patient consultations in occupational primary health care: A cluster randomized controlled trial using routine data
Authors: Atkins Salla , Reho Tiia , Talola Nina , Sumanen Markku , Viljamaa Mervi , Uitti Jukka
Published: February 2020

Background: Prolonging working careers is a key policy goal in ageing populations in Europe, but reaching this goal is complex. Occupational health services are in the best position to contribute towards prolonging working careers, through preventing illnesses that cause work disability and early pensions. However, impacting on the trajectory between illness and work disability requires continuity of care and follow-up, enabled through identifying at-risk clients. We aimed to determine whether a combined educational and electronic reminder system could improve the recording and follow-up of primary care visits made by patients at risk of work disability in occupational health care, and whether the system could impact on sickness absence rates.
Methods: This study is a pragmatic cluster randomized controlled trial using medical record data. Twenty two Pihlajalinna Työterveys units were randomized into an intervention group consisting of education and electronic reminders and a group receiving usual care through minimization methods. Client consultation data were extracted from routine Pihlajalinna Työterveys patient registers 2015 to 2017. In addition, process indicators were collected from the electronic system. Data were cleaned and analysed intention-to-treat using ANCOVA.
Results: There was no significant difference between intervention and control units in terms of sickness absences of different duration. Process indicators suggested that there was a change in physicians’ practice of recording clients’ risk of work disability and work relatedness of visits following the educational intervention.
Conclusion: Education with an electronic reminder can change physicians’ practice, but long-term follow-up is needed to determine whether this impacts on patients’ sickness absences.
Trial registration: ISRCTN45728263

Keywords: Occupational health; Randomized controlled trials; sickness absence; work-related illnesses
Variation within Poa Germplasm for Salinity Tolerance
Authors: Robins Joseph G. , Bushman B. Shaun , Waldron Blair L. , Johnson Paul G.
Published: February 2020

As competition for water resources in areas of western North America intensify as a result of increasing human populations, the sustainability of turfgrass irrigation with limited water resources is questionable. A potential part of the solution is the use of recycled wastewater for landscape irrigation. However, as a result of high levels of salt, successful irrigation with recycled wastewater will likely need to be coupled with selection for increased salinity tolerance in turfgrass species. Additionally, salinity-tolerant turfgrass will allow production on soils with inherently high salt levels. The study described here characterized the relative salinity tolerance of 93 accessions of Poa germplasm from the USDA National Plant Germplasm System (NPGS). Control cultivars of tall fescue [Lolium arundinaceum (Schreb.) S.J. Darbyshire], perennial ryegrass (Lolium perenne L.), and kentucky bluegrass (Poa pratensis L.) were also evaluated for comparison. Kentucky bluegrass accessions exhibited a wide range of LD50 (salinity dosage necessary to kill 50% of plants) values from 811 ECdays (PI 369296 from Russia) to 1922 ECdays (PI 371768 from the United States). Five kentucky bluegrass accessions exhibited salinity tolerance equal to or better than that of the tall fescue (LD50 = 1815 ECdays) and perennial ryegrass (LD50 = 1754 ECdays) checks. Thus, there is sufficient variation within this species to develop bluegrass with substantially higher salinity tolerance.
Outcrossing between ‘Bacon’ Pollinizers and Adjacent ‘Hass’ Avocado Trees and the Description of Two New Lethal Mutants
Authors: Schnell Raymond J. , Tondo Cecile L. , Brown J. Steven , Kuhn David N. , Ayala-Silva Tomás , Borrone James W. , Davenport Thomas L.
Published: February 2020

Avocado (Persea americana Mill.) has an unusual flowering mechanism, diurnally synchronous protogynous dichogamy, that promotes crosspollination among avocado genotypes. In commercial groves, which usually contain pollinizer rows adjacent to the more desirable commercial cultivars, the rate of outcrossing has been measured with variable results. Using microsatellite markers, we estimated outcrossing in a commercial California ‘Hass’ avocado orchard with adjacent ‘Bacon’ pollinizers. Seedlings grown from mature harvested fruit of both cultivars were genotyped with five fully informative microsatellite markers and their parentage determined. Among the 919 seedlings of ‘Hass’, 688 (75%) were hybrids with ‘Bacon’; the remaining 231 (25%) seedlings were selfs of ‘Hass’. Among the 850 seedlings of ‘Bacon’, 382 (45%) were hybrids with ‘Hass’ and the remaining 468 (55%) seedlings were selfs of ‘Bacon’. The high outcrossing rate observed in the ‘Hass’ seedlings was expected, because adjacent rows of opposite flowering types (A versus B) are expected to outcross. However, the high selfing rate in ‘Bacon’ was unexpected. A previous study in Florida using the cultivars ‘Simmonds’ and ‘Tonnage’ demonstrated differences in outcrossing rates between complementary flowering type cultivars. In both Florida and California, the A type parents (‘Hass’ and ‘Simmonds’) had similar outcrossing rates (≈75%); however, the B type parents (‘Bacon’ and ‘Tonnage”) had highly skewed outcrossing rates of 45% and 96%, respectively. Two new avocado lethal mutants were discovered among the selfed seedlings of ‘Hass’ and ‘Bacon’. These were labeled “spindly” and “gnarly” and are similar in phenotype to mutants described in Arabidopsis and other crop species.
Honeybee-mediated Controlled Pollinations in Cornus florida and C. kousa Intra- and Interspecific Crosses
Authors: Wadl Phillip A. , Skinner John A. , Dunlap John R. , Reed Sandra M. , Rinehart Timothy A. , Pantalone Vincent R. , Trigiano Robert N.
Published: February 2020

Flowering (Cornus florida L.) and kousa (C. kousa Hance) dogwoods are ornamental trees valued for their four-season appeal, but also for their importance to retail and wholesale nurseries. The popularity of kousa dogwood has increased in recent years as a result of its resistance to dogwood anthracnose and powdery mildew as compared with flowering dogwood, which is typically susceptible to those diseases. This range of resistance allows the development of intra- and interspecific cultivars with multiple disease resistance or a combination of disease resistance and specific ornamental traits. Breeding requires controlled crosses that are usually done manually, which is a labor-intensive process. Cornus florida and C. kousa have generally been found to be self-incompatible allowing for the breeding process to be made more efficient by not having to emasculate flowers. We have capitalized on the natural ability of honeybees and the self-incompatible nature of dogwood to perform self- and crosspollinations of flowering and kousa dogwood. Self-pollinations were conducted in 2006 and 2007 with C. florida ‘Appalachian Spring’ and ‘Cherokee Brave’ and with C. kousa ‘Blue Shadow’ and Galilean®. The flowering dogwood self-pollinations resulted in no seed production, whereas the kousa dogwood self-pollinations resulted in low seed production, indicating self-incompatibility. Intra- and interspecific crosses of flowering and kousa dogwood cultivars and breeding lines were conducted in 2006 to 2008. Honeybees were effective in facilitating seed production for all intraspecific crosses conducted. Seedling phenotypes of putative intra- and interspecific hybrids are similar and practically indistinguishable, so dogwood-specific simple sequence repeats were used to verify a sample of the putative hybrids. The results demonstrated that honeybees were effective in performing controlled pollinations and that honeybee-mediated pollinations provide an alternative to time-consuming hand pollinations for flowering and kousa dogwood.
Utilization of the S-locus as a Genetic Marker in Cherry to Differentiate Among Different Pollen Donors
Authors: Sebolt Audrey M. , Iezzoni Amy F.
Published: February 2020

Fruit set in sweet (Prunus avium L.) and sour cherry (P. cerasus L.) is frequently less than adequate for profitable production despite the availability of compatible pollen and abundant flowers. When fruit set consistently falls below acceptable levels, growers may attempt to increase fruit set by increasing the availability of compatible pollen. We describe the use of the self-incompatibility locus (S-locus) as a genetic marker to quantify the relative contributions of competing pollen sources in achieving fruit set in ‘Balaton™’ sour cherry. Pollen race experiments were conducted to determine if nonself-pollen provided in a pollen mixture was more competitive than self-pollen in achieving fruit set in ‘Balaton™’. We further investigated what pollen set the ‘Balaton™’ crop in two commercial ‘Balaton™’ orchards where multiple potential pollinators were planted in adjacent orchards. S-allele genotyping using DNA extracted from the seed was done to discriminate among the competing pollen sources. The results suggest that in certain environmental conditions, nonself-pollen may be more competitive in achieving fruit set in ‘Balaton™’ than self-pollen. These examples illustrate how seed genotyping can be used to further our understanding of the competitive abilities of different pollen sources in both controlled experiments and production orchards.
Genetic Characterization of Hazelnut (Corylus avellana L.) Cultivars from Turkey Using Molecular Markers
Authors: Kafkas Salih , Doğan Yıldız , Sabır Ali , Turan Ali , Seker Hasbi
Published: February 2020

Genetic relationships among 18 Turkish hazelnut (Corylus avellana L.) cultivars were investigated using randomly amplified polymorphic DNA (RAPD), intersimple sequence repeat (ISSR), and amplified fragment length polymorphism (AFLP) markers. Twenty-five RAPD primers, 25 ISSR primers, and eight AFLP primer pairs generated a total of 434 polymorphic marker loci. The three marker systems were able to differentiate the cultivars. Genetic similarity index values ranged from a high of 0.96 for ‘Kan’ and ‘UzunMusa’ to a low of 0.73 for ‘Yassi Badem’ and ‘Kalinkara’. The genetic relationships were presented as an unweighted pair group method with arithmetic average (UPGMA) dendrogram and a three-dimensional principal coordinate analysis (PCoA) plot. The UPGMA dendrogram showed two main clusters, while PCoA analysis showed three groups. Cultivar-specific markers were produced by all marker systems for 10 cultivars. This study demonstrates the usefulness of molecular markers for identification of hazelnut cultivars.