bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum Erythropoietin Concentration And Its Correlation With Stage Of Diabetic Retinopathy
Authors: Davidović Sofija , Nikola Babić , Sandra Jovanović , Sava Barišić , Desanka Grković , Aleksandar Miljković
Published: November 2019

Erythropoietin (EPO) is one of the systemic angiogenic factors, and its role in ocular angiogenesis and in diabetic retinopathy (DR) is not yet fully understood. The latest research data reveal a possible correlation of higher erythropoietin concentrations in the blood and in the eye with the development of more advanced stages of DR. The main aim of this work was to examine the possible influence of serum concentrations of erythropoietin on the development of diabetic retinopathy in patients with diabetes mellitus type 2.Methods The research involved 90 patients examined at the University Eye Clinic of the Clinical Center of Vojvodina, Novi Sad, Serbia. The first group comprised 60 patients with diabetes mellitus lasting for ten years or more, with diabetic retinopathy. The second, control group consisted of 30 healthy individuals. In the first group of 60 patients with diabetes, 30 of them had non-proliferative diabetic retinopathy (NPDR), and 30 had proliferative diabetic retinopathy (PDR). Laboratory EPO serum levels were determined, and they were correlated to the stage of DR. Concentration of EPO was assessed by ELISA method.Results The highest average concentration of EPO in serum (9.95 mIU/ml) was determined in the group of people with diabetes with PDR. The lowest average concentration of EPO in the serum (6.90 mIU/ml) was found in the control group. The average concentration of EPO in serum in the group of patients with diabetes with NPDR was 7.00 mIU/ml. The EPO concentration in serum was elevated in the group of PDR, and it was directly proportional to the level of the clinical stadium of PDR, being significantly higher in the moderate and severe subgroup of PDR comparing to the control healthy subjects, NPDR and mild PDR (p=0.007).Conclusions Significantly elevated serum concentration of EPO in the advanced stages of DR, and positive correlation between EPO serum concentration and clinical stages of PDR, suggest that erythropoietin represents an important growth factor from blood, which plays a significant role in retinal ischemia and angiogenesis in diabetic retinopathy, especially in the proliferative stage of this disease.
Serum-to-urine renalase ratio and its differences between healthy adults and chronic kidney disease patients
Authors: Serwin Natalia Maria , Wiśniewska Magda , Cecerska-Heryć Elżbieta , Safranow Krzysztof , Skwirczyńska Edyta , Dołęgowska Barbara
Published: November 2019

Background: Renalase is a flavoprotein that plays a protective role in chronic kidney disease and cardiovascular diseases. The secretion and way of action of this protein are still discussed. The aim of our study was to estimate the balance between serum and urine renalase in healthy individuals and chronic kidney disease (CKD) patients, using two parameters: fractional excretion (FE) and serum-to-urine renalase ratio (StURR).
Methods: Our study involved 28 healthy volunteers and 62 patients with CKD in stages I to IV. The concentration of renalase in serum and urine was measured using an enzyme-linked immunosorbent assay (ELISA) kit (EIAab, Wuhan, China). We analyzed associations between renalase levels in urine and serum, and other parameters: sex, age, GFR, presence of hypertension, diabetes, and proteinuria, and determined the serum-to-urine renalase ratio and fractional excretion of renalase.
Results: Renalase and serum-to-urine ratio were significantly higher in CKD patients in comparison with the control group. Fractional excretion was lower in CKD patients but this difference did not reach the statistical significance (p=0.092). Multivariate analysis performed in the CKD group showed, that from mentioned parameters, serum renalase was the only significant independent factor strongly positively associated with urinary renalase concentration.
Conclusions: The serum-to-urine ratio is significantly and about 6.5-fold higher in CKD patients, and the fractional excretion of renalase is 3-fold, but not significantly lower in CKD patients. Renalase levels in both serum and urine are not related to glomerular filtration rate and not associated with blood pressure.
Metabolic alterations provide insights into Stylosanthes roots responding to phosphorus deficiency
Authors: Luo Jiajia , Liu Yunxi , Zhang Huikai , Wang Jinpeng , Chen Zhijian , Luo Lijuan , Liu Guodao , Liu Pandao
Published: November 2019

Background: Phosphorus (P) deficiency is one of the major constraints limiting plant growth, especially in acid soils. Stylosanthes (stylo) is a pioneer tropical legume with excellent adaptability to low P stress, but its underlying mechanisms remain largely unknown.
Results: In this study, the physiological, molecular and metabolic changes in stylo responding to phosphate (Pi) starvation were investigated. Under low P condition, the root growth in stylo was significantly enhanced, which was accompanied with up-regulation of expansin genes participating in cell wall loosening. Metabolic profiling analysis showed that a total of 256 metabolites with differential accumulation were identified in stylo roots responding to P deficiency, which mainly include flavonoids, sugars, nucleotides, amino acids, phenylpropanoids and phenylamides. P deficiency led to significant reduction in the accumulation of phosphorylated metabolites (e.g., P-containing sugars, nucleotides and cholines), suggesting that internal P utilization was enhanced in stylo roots. However, flavonoid metabolites, such as kaempferol, daidzein and their glycoside derivatives, were significantly increased in P-deficient stylo roots. Furthermore, the transcripts of various genes involved in flavonoids synthesis were found to be up-regulated by Pi starvation in stylo roots. In addition, the abundance of phenolic acids and phenylamides was significantly increased in stylo roots during P deficiency. The enhanced accumulation of the metabolites in stylo roots, such as flavonoids, phenolic acids and phenylamides, might facilitate P solubilization and cooperate with beneficial microorganisms in rhizosphere, and thus contributing to P acquisition and utilization in stylo.
Conclusions: These results suggest that stylo plants cope with P deficiency by modulating root morphology, scavenging internal Pi from phosphorylated metabolites and enhancing accumulation of flavonoids, phenolic acids and phenylamides. This study provides valuable insights into the complex responses and adaptive mechanisms of stylo to P deficiency.
Population Genetic Structure and Habitat Connectivity for Jaguar (Panthera onca) Conservation in Central Belize.
Authors: Menchaca Angelica , Rossi Natalia , Froidevaux Jeremy , Dias-freedman Isabela , Caragiulo Anthony , Wultsch Claudia , Harmsen Bart , Foster Rebecca , Torre Antonio de la , Medellin Rodrigo , Rabinowitz Salisa , Amato George
Published: November 2019

Background Connectivity among jaguar (Panthera onca) populations will ensure natural gene flow and the long-term survival of the species throughout its range. Jaguar conservation efforts have focused primarily on connecting suitable habitat in a broad-scale. Accelerated habitat reduction, human-wildlife conflict, limited funding, and the complexity of jaguar behaviour have proven challenging to maintain connectivity between populations effectively. Here, we used non-invasive genetic sampling and individual-based conservation genetic analyses to assess genetic diversity and levels of genetic connectivity between individuals in the Cockscomb Basin Wildlife Sanctuary and the Maya Forest Corridor. We used expert knowledge and scientific literature to develop models of landscape permeability based on circuit theory with fine-scale landscape features as ecosystem types, distance to human settlements and roads to predict the most probable jaguar movement across central Belize. Results We used 12 highly polymorphic microsatellite loci to identify 50 individual jaguars. We detected high levels of genetic diversity across loci (HE= 0.61, HO= 0.55, and NA=9.33). Using Bayesian clustering and multivariate models to assess gene flow and genetic structure, we identified one single group of jaguars (K = 1). We identified critical areas for jaguar movement that fall outside the boundaries of current protected areas in central Belize. We detected two main areas of high landscape permeability in a stretch of approximately 18 km between Sittee River Forest Reserve and Manatee Forest Reserve that may increase functional connectivity and facilitate jaguar dispersal from and to Cockscomb Basin Wildlife Sanctuary. Our analysis provides important insights on fine-scale genetic and landscape connectivity of jaguars in central Belize, an area of conservation concern. Conclusions The results of our study demonstrate high levels of relatively recent gene flow for jaguars between two study sites in central Belize. Our landscape analysis detected corridors of expected jaguar movement between the Cockscomb Basin Wildlife Sanctuary and the Maya Forest Corridor. We highlight the importance of maintaining already established corridors and consolidating new areas that further promote jaguar movement across suitable habitat beyond the boundaries of currently protected areas. Continued conservation efforts within identified corridors will further maintain and increase genetic connectivity in central Belize.
Absorbable suture can be effectively and safely used to close the mesenteric defect in a Gastric bypass Sprague-Dawley Rat Model
Authors: Yao Libin , Dolo Ponnie Robertlee , Shao Yong , Li Chao , Widjaja Jason , Hong Jian , Zhu Xiaocheng
Published: November 2019

Background: To observe if closing the mesenteric defect with absorbable sutures creates a safe adhesion compared to non-absorbable suture after Roux-en-Y gastric bypass. Methods: Rats were randomly assigned to 5 experimental groups according to the different suture materials used in closing the mesenteric defects (Peterson’s space) after Roux-en-Y gastric bypass. Group A (control group), Group B (non-absorbable suture, Prolene suture), Group C (biological glue), Group D (non-absorbable suture, polyester suture) and Group E (absorbable suture). All rats were followed up for 8 weeks postoperatively and underwent laparotomy to observe the degree of adhesion and closure of the mesenteric defect. Results: No significant difference was found in the decrease in food intake and body weight among all groups. No internal hernia (IH) occurred in any group. The mesenteric defects of Group A remained completely visible without any closure or adhesion. Multiple gaps were found between the Prolene suture and the mesentery along the suture line in Group B. The mesenteric defects of Group C were complete closed with multiple adhesions of the small intestine and the greater omentum. The mesenteric defects in both Group D and Group E closed completely. The average adhesion scores in Group A and Group B were 0 and 0.33±0.52 respectively. The average adhesion score in group C (3.83±0.41) was higher than the other groups (p ＜ 0.05). The average adhesion scores in Group D and E were similar (3.17±0.41 and 3.00±0.00 respectively). Conclusion: Absorbable suture created a safe adhesion score between the mesentery which was not inferior to non-absorbable sutures.
Prevalence of intestinal parasitic infection and associated factors among pregnant women attending antenatal care at public health facilities in Lalo Kile district, Oromia, Western Ethiopia
Authors: Yesuf Dejene Abraham , Abdissa Lensa Tesfaye , Gerbi Emiru Adeba , Tola Edosa Kifle
Published: November 2019

Objective: This study aimed to assess the prevalence of intestinal parasitic infection and associated factors among pregnant women attending antenatal care at public health facilities in Lalo Kile district, Oromia, Western Ethiopia. Results: Out of the 315 respondents, the mean age was 24.7 ± 2.54 years ranging between 15-44 years. The majority of the respondents were Oromo in ethnicity (90.2%) and protestant in religion (83.2%) and almost all (99%) of the study participants were married. Two hundred twenty-six (72%) of pregnant women were attended at least primary school and two hundred forty-six (78.1%) of the respondents were from farmer households. About half of the households (51.7%) had a monthly income of greater than 35 USD. The overall prevalence of intestinal parasitic infection was 138(43.8%) with the predominance of hookworm (33.7%) followed by Ascaris lumbricoides (7.3%). Being a farmer [AOR, 95% CI 7.3 (1.46, 37.00), P = 0.03], walking barefooted [AOR, 95% CI 6.13 (1.98, 19.00), P = 0.002] and absence of proper handwashing after latrine [AOR, 95% CI 5.36 (1.78, 16.00), P = 0.003] were significantly associated with occurrence of the intestinal parasitic infection. Keywords: Prevalence, Intestinal parasitic infection, pregnant women, Lalo Kile district
NaCl-responsive ROS scavenging and energy supply in alkaligrass callus revealed from proteomic analysis
Authors: Zhang Yongxue , Zhang Yue , Yu Juanjuan , Zhang Heng , Wang Liyue , Wang Sining , Guo Siyi , Miao Yuchen , Chen Sixue , Li Ying , Dai Shaojun
Published: November 2019

Background: Salinity has obvious effects on plant growth and crop productivity. The salinity-responsive mechanisms have been well-studied in differentiated organs (e.g., leaves, roots and stems), but not in unorganized cells such as callus. High-throughput quantitative proteomics approaches have been used to investigate callus development, somatic embryogenesis, organogenesis, and stress response in numbers of plant species. However, they have not been applied to callus from monocotyledonous halophyte alkaligrass (Puccinellia tenuifora). Results: The alkaligrass callus growth, viability and membrane integrity were perturbed by 50 mM and 150 mM NaCl treatments. Callus cells accumulated the proline, soluble sugar and glycine betaine for the maintenance of osmotic homeostasis. Importantly, the activities of ROS scavenging enzymes (e.g., SOD, APX, POD, GPX, MDHAR and GR) and antioxidants (e.g., ASA, DHA and GSH) were induced by salinity. The abundance patterns of 55 salt-responsive proteins indicate that salt signal transduction, cytoskeleton, ROS scavenging, energy supply, gene expression, protein synthesis and processing, as well as other basic metabolic processes were altered in callus to cope with the stress. Conclusions: The undifferentiated callus exhibited unique salinity-responsive mechanisms for ROS scavenging and energy supply. Activation of the POD pathway and AsA-GSH cycle was universal in callus and differentiated organs, but salinity-induced SOD pathway and salinity-reduced CAT pathway in callus were different from those in leaves and roots. To cope with salinity, callus mainly relied on glycolysis, but not the TCA cycle, for energy supply.
Gene mutations related to cell adhesion found in lymph node metastasis from papillary thyroid carcinoma by whole exome sequencing
Authors: Xu Peipei , Ye Ziheng , Zeng Su , Zhang Fan , Xia Xiaotian , Li Lianxi , Guo Minggao
Published: November 2019

Background: Lymph node metastasis is the most common metastasis associated with papillary thyroid carcinoma (PTC). There are few data on gene mutations associated with lymph node metastasis from PTC. At present, the mechanism underlying lymph node metastasis of PTC is still poorly understood.Methods: Whole exome sequencing (WES) was performed for PTC of 10 primary tumor tissues and 10 lymph node metastasis tissues (non-match) for gene mutations. Gene ontology (GO) analysis was used to study biological functions and processes related to lymph node metastasis. Sanger sequencing was used to verify these genes in the lymph node metastasis group.Results: A total of 2772 gene mutations were identified in the primary tumor group. A total of 3033 gene mutations were enriched in the lymph node metastasis group. There were 50 gene mutations that were found to be present at higher frequency in the lymph node metastasis group than in the primary tumor group. Among 50 gene mutations, nonsynonymous mutations of 5 genes (LPP, MSLN, MAEA, VCAN, and MUC16) involved in cell adhesion were present. Three nonsynonymous mutations were also found in RP1L1, QSER1, and TLR4. These high-frequency genetic mutations that showed significant enrichment were targeted sequencing and validated by Sanger sequencing.Conclusion: Thyroid cancer and corresponding metastatic lymph nodes contain a large number of SNPs and 50 SNP genes associated with lymph node metastasis. Genes related to cell adhesion (LPP, MSLN, MAEA, VCAN, and MUC16) may play an important role in the process of lymph node metastasis. The contribution of BRAF in lymph node metastasis may not be high.
Opportunistic Infections and Associated Factors among HIV/AIDS Patients taking Ante-Retroviral Therapy at Selected Hospitals in Sidama Zone, Southern Ethiopia: A facility-based cross-sectional study
Authors: Wachamo Demelash , Bonja Fisseha
Published: November 2019

Background Opportunistic infections are late complications of HIV infection is the depletion of the immune system. It is a major public health problem and high morbidity AIDS patients die of AIDS-related infections in developing countries like Ethiopia. Identification of opportunistic infections (OIs) is important to develop a specific intervention. Therefore, this study aimed to assess the burden and associated factors of opportunistic infections.Method A facility-based cross-sectional study was conducted on 420 randomly selected HIV/AIDS patients taking anti-retroviral therapy. Data was collected from selected hospitals in Sidama Zone based on population proportion to size. Data was collected by a pre-tested questionnaire and a pre-tested checklist from the medical records of patients. Data entry and analyzed for descriptive and logistic regression models by SPSS v.23. The result declared as statistically significant at p < 0.05.Result The magnitude of opportunistic infections was 39.6%. Major identified OIs was oral candidacies 23.2%, recurrent bacterial pneumonia 21.5%, Herpes zoster 6.3%, and Pulmonary Tuberculosis 6.0%.The magnitude of opportunistic associated with; older age [AOR=2.69, 95% CI: 1.33-5.43], No formal education [AOR=3.12, 95% CI: 1.06-9.25], Low monthly income [AOR=2.27, 95%CI:1.35-3.83], initial CD4 count less than 200 cells/mm3 [AOR=1.91, 95% CI:1.05-3.46), WHO clinical stage II [AOR=2.43, 95% CI:1.34-4.42] and stage III and IV [AOR=4.27, 95% CI: 2.12-8.59], had no extra medicine additional to ART (prophylaxis) had [AOR= 5.91, 95% CI: 3.31-10.56], who interrupt ART medicines [AOR=2.03, 95% CI: 1.09- 3.80] and Khat chewing [AOR=5.48, 95% CI: 2.32-12.96] when compared to their counterparts.Conclusions The overall magnitude of opportunistic infections was high when compared with other studies. Health officials and clinicians need to give attention on the strengthening of the provision if ART with prophylaxis on early-stage and adhrerence, implementation of the TB/HIV collaboration activity, and early initiation of ART to reduce opportunistic infections.
Clinical Analysis of Anti-NMDAR Encephalitis Combined with MOG Antibody in Children
Authors: Hou Chi , Li Xiaojing , Chen Wenxiong , Wu Wenlin , Tian Yang , Zhang Yani , Zhu Haixia , Zeng Yiru , Peng Bingwei , Zheng Kelu
Published: November 2019

Objective: To analyze the clinical features in children with anti-NMDAR encephalitis combined with myelin oligodendrocyte glycoprotein antibody (MOG ab).Methods: Clinical data of 7 children with anti-NMDAR encephalitis combined with MOG ab were collected in Guangzhou Women and Children’s Medical Center from January, 2016 to June, 2019.Results: Average onset age was 6.0±1.3 year-old, male to female was 2:5. Prominent symptoms in anti-NMDAR encephalitis were abnormal mental behavior (7/7), sleep disorder (6/7) and speech disorder (6/7), while in MOG ab related encephalomyelitis were encephalopathy (5/7) and paralysis (4/7). 1 case developed anti-NMDAR encephalitis 1 year after recovery from MOG ab related acute disseminated encephalomyelitis (ADEM). 4 cases developed anti-NMDAR encephalitis and MOG ab related ADEM simultaneously, with 2 cases relapsed. 2 cases were anti-NMDAR encephalitis with only MOG ab positive. 10 MRI examinations were performed in acute stage. 8/10 brain MRI showed abnormalities with multiple demyelinating lesions mainly involve subcortical white matter (7/8), cortex (6/8) and basal ganglia (5/8). 2/10 had long segment myelitis. Patients improved significantly after corticosteroid and intravenous immunoglobulin (IVIG) treatment. Patients with recurrent course (n=2) had higher MOG ab titer (1:320) and longer duration (≥12 months) compared with non-recurrent course (n=5), MOG antibody(≤1:100) (≤6 months). 3 Cases had neurological sequelae with higher cerebrospinal fluid (CSF) NMDAR antibody titer at first onset (1:320). 2 had emotional problems and 1 had epilepsy.Conclusion: Children with anti-NMDAR encephalitis combined with MOG ab were more common in girls around 6 year-old. Patients responded well to Corticosteroid and IVIG. Cases with persistent MOG ab need longer follow-up due to recurrent risk, high titer of CSF NMDAR antibody may cause neurological sequelae. Keywords: anti-NMDAR encephalitis, myelin oligodendrocyte glycoprotein antibody, children
Hypercapnia intensifies cerebral hypoxia via increasing cerebral oxygen extraction ratio: implication in neuroinflammation in hypoxemic adult rats
Authors: Ding Hong-Guang , Li Xu-Sheng , Liu Xin-Qiang , Wang Kang-Rong , Li Ya , Wen Miao-Yun , Zeng Hongke
Published: November 2019

Background: Hypoxemia is a typical symptom of acute respiratory distress syndrome (ARDS). Ventilations are always needed for correcting hypoxemia. To avoid pulmonary morbidity, the low tidal volume ventilation is often applied. The ventilation strategy will certainly result in hypercapnia. Our previous study found that hypercapnia increase neuronal death and aggravate the cognitive function of hypoxic adult rats. However, the underlying mechanism has remained unclear. This study aimed to explore whether hypercapnia would induce neuroinflammation through increasing cerebral oxygen extraction ratio in adult rats with hypoxemia. Methods: Cerebral oxygen extraction ratio (CERO2), partial pressure of brain tissue oxygen (PbtO2), and reactive oxygen species (ROS) production in brain tissue in a rat model of hypercapnia/hypoxemia were evaluated. Along with this, the oxygen consumption rate (OCR) and ROS production of BV-2 microglial cells were evaluated after 15% CO2/0.2% O2 treatment. The protein expression level of caspase-1 and IL-1β in microglia cells were detected before and after application of a ROS scavenger in vivo and in vitro. Results: PbtO2 level was elevated by hypercapnia in the hypoxemic rats in the first 1.5 h, but it was significantly decreased 2 h after ventilation. This was further evident by the increased levels of CERO2 at 3 h after ventilation. Besides, a high concentration of CO2 treatment could increase the levels of OCR in hypoxic BV-2 microglial cells in vitro. Hypercapnia markedly increased the production of ROS and the expression of caspase-1 and IL-1β in hypoxia-activated microglia both in vivo and in vitro. Pharmacological scavenging ROS inhibited the NLRP3 inflammasome activation and expression of IL-1β. Conclusion: Hypercapnia-intensified cerebral hypoxia via increasing cerebral oxygen extraction ratio may induce ROS overproduction, activate the NLRP3 inflammasome and enhance IL-1β release in hypoxia-activated microglia.
Epigenetic induction of tumor stemness via the Lipopolysaccharide-TET3-HOXB2 signaling axis in esophageal squamous cell carcinoma
Authors: Xu Fengkai , Liu Zhonghe , Liu Ronghua , Lu Chunlai , Wang Lin , Mao Wei , Zhu Qiaoliang , Shou Huankai , Zhang Kunpeng , Li Yin , Chu Yiwei , Gu Jie , Ge Di
Published: November 2019

Background: Esophageal squamous cell cancer (ESCC) is one kind of frequent digestive tumor. The inflammatory environment plays an important role in the tumorigenesis and development of ESCC. Cancer stem cells are a small group of tumor cells with stem cell characteristics, which become the potential causes of failure to tumor treatment. Methods: ELISA was performed to detect the lipopolysaccharide concentration in cancer tissues. qPCR, Western blot, FACS, Immunohistochemistry, Immunofluorescence and Dot blot were applied to detect target genes expression. CCK-8, Colony-formation, Transwell, Sphere and Xenograft were performed to investigate the function of cells, influenced by risk factors. The survival curve was drawn with the Kaplan-Meier product limit estimator. Nano-hmC-Seal-seq was applied to detect the downstream target of TET3. ChIP-qPCR was performed to demonstrate the transcriptional regulation of stem cell-associated genes by HOXB2. Results: Lipopolysaccharide concentration was significantly up-regulated in ESCC. High concentration of lipopolysaccharide stimulation induced the stemness of ESCC cells. TET3 expression was elevated with lipopolysaccharide stimulation via p38/ERK-MAPK pathway in ESCC and negatively correlated with patients’ survival. TET3 induced the stemness of ESCC cells. Nano-hmC-Seal-seq showed that TET3 overexpression led to a significant increase in 5hmC levels of HOXB2 gene region, which was thus identified as the downstream target of TET3. The binding of HOXB2 to NANOG and cMYC was veriﬁed by ChIP-qPCR. Conclusions: Lipopolysaccharide served as a tumor promotor in ESCC by inducing cancer cell stemness through the activation of a LPS-TET3-HOXB2 signaling axis, which might provide a novel therapeutic strategy for ESCC.
Targeting the USP1 dependent KDM4A protein stability as a potential prostate cancer therapy
Authors: Cui Shu-Zhong , Fan Ling-Ling , Li You-Qiang , Geng Xin-Yan , Fu De-Xue , Jiang Hao-Wu , xu songhui
Published: November 2019

Background: Prostate cancer is the most commonly diagnosed malignancy and second leading cause of cancer death in American men. The histone demethylase KDM4A is reported to be overexpressed and plays a vital in multiple cancers through controlling gene expression by epigenetic regulation of H3K9 or H3K36 methylation marks. The biological role and mechanism of KDM4A in regulating AR activity in prostate cancer, however, remain to be established. Methods: KDM4A expression in PTEN knockout mouse was determined using western blotting, Real-time PCR and immunohistochemical. Functional assays, such as cell survival, cell colony formation, anchorage-independent growth and a xenograft tumor model were used to determine the oncogenic role of KDM4A in prostate cancer cells. Association of KDM4A with USP1 and the deubiquitination assay were determined by co-immunoprecipitation, immunofluorescent staining and immunoblotting. USP1-KDM4A axis promotes AR-dependent c-Myc expression was further investigated using western blotting, chromatin immunoprecipitation and Real-time PCR. The specific USP1 inhibitor ML323 was used for assessing the role of USP1 in prostate cancer cell survival. Co-expression of KDM4A with USP1 was determined by immunohistochemical staining in 146 prostate cancer tissue samples. Results: Herein, we reported KDM4A expression was upregulation in PTEN knockout mouse prostate tissue. Depletion of KDM4A in prostate cancer cells inhibited their proliferation and survival in vivo and vitro. Further studies reveal that USP1 is a deubiquitinase that regulates KDM4A K48-linked deubiquitin and stability. Interestingly, we found c-Myc was a key downstream effector of USP1-KDM4A/AR axis in driving prostate cancer cell proliferation. Notably, upregulation of KDM4A expression with high USP1 expression were observed in 70% of prostate tumors and inhibition of USP1 promotes prostate cancer cells response to therapeutic agent_enzalutamide. Our studies propose USP1 may be an anti-cancer therapeutic target in prostate cancer. Conclusions: Our findings demonstrate that USP1 deubiquitinates and stabilizes KDM4A, which promotes recruitment of AR to the c-Myc gene enhancer and highlight USP1 potential as an anti-cancer therapeutic target in prostate cancer. Keywords: USP1; Prostate cancer; KDM4A; Deubiquitination; Tumorigenesis
Assessing the preparedness of Foundation Year 1 (FY1) doctors during the transition from medical school to the Foundation Training Programme
Authors: Michaelides Athena , Mahr Melina , Pydisetty Gaurav , Loyala Jerocin Vishani
Published: November 2019

Background: To assess how ready current FY1 doctors felt when they started their first posting as newly qualified doctors. Methods: We created an online survey where 45 FY1 doctors in South Yorkshire rated how confident they were across different domains (induction and assistantship, hospital systems, and skills) using a scale ranging from 0 (no confidence in performing task) to 5 (highly confident in performing task). Results: Responses showed that the ICE system and observations had a mean rating of 3.645 (95% CI 3.45 to 3.86), 4.425 (95% CI 4.25 to 4.6) with a standard deviation (SD) of 1.1 and 0.83 respectively. The radiological viewing platform, referral system, telephone system, and hospital notes had a mean score of 3.149 (95% CI 2.88 to 3.42), 2.341 (95% CI 2.1 to 2.58), 3.573 (95% CI 3.41 to 3.74) and 4.061 (95% CI 3.93 to 4.19), with a SD of 1.281, 1.154, 0.961 and 0.752 respectively. FY1’s wanted more training on referrals [(84.09%(n=37)) and use of phones [43.2% (n=19)]. Vital observations and diagnostic procedures scored a mean score of 3.933 (95% CI 3.75 to 4.12) and 4.251 (95% CI 4.14 to 4.36) with a SD of 1.19 and 0.944 respectively. The patient care category, the prescribing category and therapeutic procedures gave a mean score of 3.634 (95% CI 3.44 to 3.83), 4.13 (95% CI 3.96 to 4.3), 3.386 (95% CI 3.23 to 3.54) and an SD of 1.128, 0.954 and 1.253 respectively.Conclusion: Overall, junior doctors are confident in most tasks and jobs expected of them. A greater sample size would enable us to compare how different medical schools and deaneries aid this transition.
Sero - Prevalence and Risk Factors of Cattle and Human Brucellosis at Seka Chokorsa and Shebe Sonbo Jimma Zone Districts, South West Ethiopia
Authors: Tokon Ftsum Assefa , Gelalcha Benti Deresa , Moti Teferi Benti , Alemu Redeat Belaneh , Awash Hailu Degefu
Published: November 2019

Background: Brucellosis is contagious bacterial disease of major socio-economic and public health importance globally and it is also one of the priority zoonotic diseases in Ethiopia. Across-sectional epidemiological study was carried out from April 2017 to April 2018 to estimate the sero prevalence of bovine and human brucellosis and to assess the associated risk factors of brucellosis in Seka Chokorsa and Shebe Sonbo districts of Jimma zone. Results: The overall prevalence of cattle brucella infection at individual and herd level were 5.9% (95%CI: 4.1%-8.1%) and 26.6 (95%CI: 19.1%-35.3%) based on diagnosis using commercial kits of the competitive enzyme-linked Immunosorbent assay (CELISA) from Brucella abortus antibodies. Univariate logistic regression analysis at individual animal level showed that animals from large herd size and households which had a practice of introduction of new animals in their herds were 3.7 and 2.3 times more likely to be seropositive, respectively. The same scenario has been observed at herd level. Molecularly, five Brucella abortus was identified as the species affecting cattle in the study areas. From the total human serum samples tested only one serum was found to be positive for CFT and thus the prevalence is 0.42 %,( 95%CI: 0.01%-2.38%). From 238 respondents, 90% of them drink raw milk and milk products, and 70% of them also eat raw meat. Furthermore, slaughtering, assisting during delivery and poor management of aborted material is a common practice that favor transmission of the pathogen in the area. Conclusions: In conclusion, the results of this study showed that brucellosis is an important and widely distributed disease in cattle in the study areas. The finding of the infection in human indicates the public health importance of brucellosis in the area. The risk behaviors and practices observed suggests the need to design all-inclusive health programmes, such one-health approach aimed at controlling brucellosis spread in the study area.
CFTR deficiency causes cardiac dysplasia during zebrafish embryogenesis and is associated with dilated cardiomyopathy
Authors: Liu Yanyan , Lin Ziyuan , Liu Mingfeng , Liao Huijuan , Chen Yan , Zhang Xiaohu , Chan Hsiao Chang , Zhou Bin , Rao Li , Sun Huaqin
Published: November 2019

Mutations in the CFTR gene cause cystic fibrosis with myocardial dysfunction. However, it remains unknown whether CF-related heart disease is a secondary effect of pulmonary disease, or an intrinsic primary defect in the CF heart. Here, we used a zebrafish model, which lacks lung tissue, to investigate the role of CFTR in cardiogenesis during embryonic development. Our findings demonstrate that a loss of CFTR impairs cardiac development from the cardiac progenitor stage of heart development, resulting in cardiac looping defects, a dilated atrium, pericardial edema, and a decrease in heart rate. Furthermore, we found that cardiac development is perturbed in wild type embryos treated with a gating speciﬁc Cftr channel inhibitor, CFTRinh-172, at the blastula stage of development, but not with treatment at later stages. Gene expression analysis of blastulas indicated that transcript levels, including mRNAs associated with cardiovascular diseases, were significantly altered in embryos derived from cftr mutants relative to controls. To evaluate the role of CFTR in human heart failure, we performed a genetic association study on individuals with dilated cardiomyopathy and found that CFTR containing I556V mutation, which causes a channel defect, is associated with the disease. Similar to well-studied channel-defective CFTR mutants, CFTR I556V mRNA failed to restore cardiac dysplasia in mutant embryos.The present study reveals an important role for the CFTR ion channel in regulating cardiac development during early embryogenesis, supporting the hypothesis that CF-related heart disease results from an intrinsic primary defect in the CF heart.
Integrated mRNA and miRNA transcriptome analysis reveals a regulatory network for tuber expansion in Chinese yam (Dioscorea opposita)
Authors: Zhou Yun-Yi , Luo Shuzhen , Hameed Saba , Xiao Dong , Zhan Jie , Wang Aiqing , He Longfei
Published: November 2019

Background
Yam tuber is a storage organ, derived from the modified stem. Tuber expansion is a complex process, and depends on the expressions of genes that can be influenced by environmental and endogenous factors. However, little is known about the regulatory mechanism of tuber expansion. In order to identify the genes and miRNAs involved in tuber expansion, we examined the mRNAs and small RNAs in Dioscorea opposita (Chinese yam) cv. Guihuai 16 tuber during its initiation and expansion stages.
Results
A total of 14238 differentially expressed genes in yam tuber at its expansion stage were identified by using RNA sequencing technology. Among them, 5723 genes were up-regulated, and 8515 genes were down-regulated. Functional analysis revealed the coordination of tuber plant involved in processes of cell events, metabolism, biosynthesis, and signal transduction pathways at transcriptional level, suggesting that these differentially expressed genes are somehow involved in response to tuber expansion, including CDPK, CaM, CDL, SAUR, DELLA, SuSy, and expansin. In addition, 541 transcription factor genes showed differential expression during the expansion stage at transcriptional level. MADS, bHLH, and GRAS were involved in cell differentiation, division, and expansion, which may relate to tuber expansion. Noteworthy, data analysis revealed that 22 known tuber miRNAs belong to 10 miRNA families, and 50 novel miRNAs were identified. The integrated analysis of miRNA-mRNA showed that 4 known miRNAs and 11 genes formed 14 miRNA-target mRNA pairs were co-expressed in expansion stage. miRNA160, miRNA396, miRNA535 and miRNA5021 may be involved in complex network to regulate cell division and differentiation in yam during its expansion stage.
Conclusion
The mRNA and miRNA datasets presented here identified a subset of candidate genes and miRNAs that are putatively associated with tuber expansion in yam, a hypothetical model of genetic regulatory network associated with tuber expansion in yam was put forward, which may provide a foundation for molecular regulatory mechanism researching on tuber expansion in Dioscorea species.
The value of miR-155 as a biomarker for the diagnosis and prognosis of lung cancer: a systematic review with meta-analysis
Authors: Shao Chuchu , Yang Fengming , Qin Zhiqiang , Jing Xinming , Shu Yongqian , Shen Hua
Published: November 2019

Background: Recently, a growing number of studies have reported the coorelation between miR-155 and the diagnosis and prognosis of lung cancer, but results of these researches were still controversial due to insufficient sample size. Thus, we carried out the systematic review and meta-analysis to figure out whether miR-155 could be a screening tool in the detection and prognosis of lung cancer.
Methods: A meta-analysis of 13 articles with 19 studies was performed by retrieving the PubMed, Embase and Web of Science. We screened all correlated literaters until December 1st, 2018. For the diagnosis analysis of miR-155 in lung cancer, sensitivity(SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and area under the ROC curve (AUC) were pooled to evaluate the accuracy of miRNA-155 in the diagnosis of lung cancer. For the prognosis analysis of miR-155 in lung cancer, the pooled HRs and 95% CIs of miR-155 for overall survival/disease free survival/progression-free survival (OS/DFS/PFS) were calculated. In addition, Subgroup and meta-regression analyses were performed to distinguish the potential sources of heterogeneity between studies.
Results: For the diagnostic analysis of miR-155 in lung cancer, the pooled SEN and SPE were 0.82 (95% CI: 0.72-0.88) and 0.78 (95% CI: 0.71-0.84), respectively. Besides, the pooled PLR was 3.75 (95% CI: 2.76-5.10), NLR was 0.23 (95% CI: 0.15-0.37), DOR was 15.99 (95% CI: 8.11-31.52) and AUC was 0.87 (95% CI: 0.84-0.90), indicating a significant value of miR-155 in the lung cancer detection. For the prognostic analysis of miR-155 in lung cancer, up-regulated miRNA-155 expression was not significantly associated with a poor OS (pooled HR = 1.26, 95% CI: 0.66-2.40) or DFS/PFS (pooled HR = 1.28, 95% CI: 0.82-1.97).
Conclusions: The present meta-analysis demonstrated that miR-155 could be a potential biomarker for the detection of lung cancer but not an effective biomarker for predicting the outcomes of lung cancer. Furthermore, more well-designed researches with larger cohorts were warranted to confirm the value of miR-155 for the diagnosis and prognosis of lung cancer.
Fast counting with tensor networks
Authors: Kourtis Stefanos , Chamon Claudio , Mucciolo Eduardo , Ruckenstein Andrei
Published: November 2019

We introduce tensor network contraction algorithms for counting
satisfying assignments of constraint satisfaction problems (#CSPs). We
represent each arbitrary #CSP formula as a tensor network, whose full
contraction yields the number of satisfying assignments of that formula,
and use graph theoretical methods to determine favorable orders of
contraction. We employ our heuristics for the solution of #P-hard
counting boolean satisfiability (#SAT) problems, namely monotone
#1-in-3SAT and
#Cubic-Vertex-Cover, and find that they
outperform state-of-the-art solvers by a significant margin.
Carthusian symbolism in Architecture and Art: San Lorenzo of Padula
Authors: Marino Maria Fernanda García
Published: November 2019

The aim of this contribution is to demonstrate through the study of the concrete example of the Charterhouse di San Lorenzo in Padula (Province of Salerno, Italy) how and to what extent, the utopian value of the spirituality of the Carthusian monks - inspired by the model of the Desert Fathers and the Church of primitive Christianity, devoted to the practices of strict enclosure, of rigorous abstinence, of meditation, of contemplation and of prayer - has affected the definition and development of a specific iconography; both for what concerns the figurative arts, which have as a milestone the theme of martyrdom and angels (the creatures closest to God), present within the monasteries of the order, both for what interests the architectural structure of buildings. Always the same as themselves, especially for the design, distribution and function of the spaces, which as a whole and in particular, they reflect, strictly and everywhere, the immutability of the Carthusian Rule, never changed since the foundation of the order in 1084. Following the model of the first monastery, built on the Chartreuse massif, in Grenoble (France), made by St. Bruno of Cologne, new settlements were erected and spread throughout Europe, with an exponential growth that does not suffer interruptions until the end of eighteenth century and that, left a deep and unequivocal cultural mark in the territory on which they extended. The Charterhouse model, a kind of Earthly Jerusalem like an imitation of the Celestial Jerusalem, can be well included in the universe of utopian architecture, but of the possible ones, where spirituality became tangible reality and where the sacredness of space conceived and built by the monks puts us in touch today the man with sensitive and perceptible experience, the so-called hierophany.
Sacred places: spaces for a dialogue among cultures
Authors: Niglio Olimpia , Guerriero Luigi
Published: November 2019

Background. The construction of a sacred space identifies a place where men realize a direct relationship with their God, qualifying this space as the absolute center of the existence, regardless of its location and its definition.In the sacred places, the geometric-dimensional relations, that define each space, are enriched with the temporal connotation, making more explicit the inseparable relationship between the architecture and the historical process (to stay erected in front of the history, following the more convincing anthropological meaning of the building action) with the material changes of the same architecture.Results. Then, each sacred place is the center (from which an axis is inevitably outlined) of a spatial dimension that is emancipated from pure physical conditions and it forces to involve tools of unusual analysis that fit the specificity of the use (in other words, the symbolic character).The sacred place assumes the role of an instrument of synthesis (of manifesto) that allows a vision of the world ables to build the dialogue among the cultures, overcoming the limits of the individual perspectives and fitting a community program based on the sharing of the Human Values.Conclusion. Given these premises, the paper reconsiders some studies of the history of the architecture that has given specific attention to the issue of the sacred place that is also seen as material and intangible space, where men meet their God, their self and the community. The contribution also analyzes experiences of realization of sacred spaces, between the second half of the nineteenth century and the first half of the twentieth, examining religious architecture in different geographic areas and with multiple cultures. These sacred spaces have often allowed overcoming the fracture caused by colonial politics, favoring the regeneration of the meaning of the sacred places.
The Responses Of Antakya (Antioch) Churches To Cultural Shifts
Authors: Yilmaz Yonca , Zeren Mine Tanaç
Published: November 2019

Antakya (Antioch), located in the southern region of Turkey, is one of the oldest settlements in the country. Its history dates back to the prehistoric times. It has been through countless invasions throughout its history. It has been dominated by various civilizations and has been the center of many religions. The city, which was founded by Alexander the Great in the Roman period, has many routes to nearly all directions as a result of its geographical location. Due to its context, this makes the city the point of convergence of cultures. After the Roman period, Byzantine and Arab-dominated city (AC 395 — AC 963), were exposed to constant war between the Christian and Muslim communities for the domination right to the city. Today in Antakya, although the majority of the population is Muslim and Christian, the Sunni Arabs, Sunni Turks, Shia Arabs, Assyrians, Catholics, Orthodox Christians, Protestant Arabs, Arabs, Armenians, Jewish people and other minority groups all live together in harmony, thus forming the dynamics of multicultural city structure. The name “Christian” was first coined in this historic city. Antakya also hosts the Church of Saint Peter, which is believed to be one of the earliest Christian houses of worship, making it extremely valuable for Christianism. Indigenous inhabitants of Antakya have lived in the same land since the foundation of Christianity. Today, 90 percent of the Christians are Orthodox, 10 percent are Protestants and other believers, where the population of Christians are decreasing. Bearing in mind the aforementioned history and context, a research was conducted on the Orthodox Church, Antakya Protestant Church and Vakıflı Armenian Church which all still exist to this day in the city. Purpose of the research is to evaluate the structure of the churches in regards to the following parameters;-    The responses of the churches to the indigenous inhabitants-    Cultural shifts in the ever-changing sociocultural values of the society-    The city image they present.The reason behind choosing these three structures for the study is the fact that all three structures boast Christian symbolism and imagery.
Process of developing education material on water, sanitation and hygiene (WaSH) and diarrhoea prevention and testing its acceptability among tribal mothers
Authors: Jeyakumar Angeline , Godbharle Swapnil , Giri Bibek Raj , Mirzaie Zakir Hussain , Jori Chandrashekhar
Published: November 2019

The study aimed to develop education material on WaSH practices and assess its content and acceptability. Online survey of 19 posters identified two Marathi posters that were not context- or setting-specific. A three-phased evaluation study was conducted to assess (i) WaSH practices of mothers attending an ANC centre (n = 40) and (ii) performed a quantitative content analysis of education material developed on WaSH (n = 38). Focus group discussions (FGDs) were employed for qualitative content analysis (n = 10). (iii) Acceptability was derived from the scores of quantitative content analysis. Relevance of content and use of fear appeal emerged as significant characteristics using qualitative content analysis. In quantitative content analysis, the maximum score for the domains pertaining to relevance and comprehension was 5 each and for the layout was 3. The mean scores for posters 1 and 2 were 4.34 ± 0.9 and 4.00 ± 1.1 for relevance; and 4.89 ± 0.3 and 4.95 ± 0.2 for comprehension, respectively. Acceptability ranging between 68 and 100% in all three domains for both the posters indicated high acceptability. Maximum acceptability score was obtained for comprehension followed by relevance and layout for both the posters. Tribal populations can benefit from these communication aids that are context- and setting-specific. These can be adopted with relevant cultural modifications to suit similar settings.