bluuebunny/crossref_metadata_2025 huggingface dataset:
Long Noncoding RNA UCA1 Promotes Glutamine-Driven Anaplerosis of Bladder Cancer by Interacting With hnRNP I/L to Upregulate GPT2 Expression
Authors: Zhao Hua , Wu Wenjing , Li Xu , Chen Wei
Published: December 2020

Background: Glutamine-driven anaplerosis maintains the tricarboxylic acid (TCA) cycle by replenishing its carbon source of intermediates with the glutamine-derived carbons in cancer cells. Long noncoding RNA urothelial cancer associated 1 (UCA1), initially identified in bladder cancer, is associated with multiple cellular processes, including metabolic reprogramming. However, its characteristics in the anaplerosis context of bladder cancer (BLCA) remains elusive. Methods: The mechanism of UCA1 bound to and facilitated the combination of hnRNP I/L to the promoter of GPT2 gene was investigated by RNA pulldown, qRT-PCR, western blot, dual luciferase reporter assays, immunohistochemical staining, chromatin immunoprecipitation and chromatin isolation by RNA purification. Metabolomics analysis and metabolic flux analysis were conducted to assess the effects of UCA1, hnRNP I/L, and GPT2 on metabolic reprogramming of BLCA.Results: We identified UCA1 as a binding partner of heterogeneous nuclear ribonucleoproteins (hnRNPs) I and L, RNA-binding proteins with no previously known role in metabolic reprogramming. UCA1 and hnRNP I/L profoundly affected glycolysis, TCA cycle, glutaminolysis, and viability of BLCA cells. Importantly, UCA1 specifically bound to and facilitated the combination of hnRNP I/L to the promoter of glutamic pyruvate transaminase 2 (GPT2) gene, resulting in upregulated expression of GPT2 and enhanced glutamine-derived carbons in the TCA cycle. We also systematically confirmed the influence of UCA1, hnRNP I/L, and GPT2 on metabolism and proliferation via glutamine-driven anaplerosis in BLCA cells. Conclusions: Our study reveals the critical mechanism by which UCA1 forms a functional UCA1-hnRNP I/L complex that upregulates GPT2 expression to promote glutamine-driven TCA cycle anaplerosis, providing novel evidence that lncRNA regulates metabolic reprogramming in tumor cells.
Circ-0012417/ miR-29c-5p Axis Stimulates Thyroid Cancer Growth
Authors: Zhang Fan , Luo Jing , Shi Xingyuan , Liu Jiming , Chen Guo , Chen Ting , Wang Chunchuang , Lv Huizeng , Zhou Xinke
Published: December 2020

Background: There is an increasing tendency of the incidence rate of thyroid cancer. Despite the advance of widespread early diagnose and good prognosis of papillary thyroid cancer (PTC), some patients still suffered from the invasiveness and metastasis of thyroid cancer. More and more evidences demonstrated that circular RNAs (circRNAs) play important roles in tumorigenesis, tumor progression and metastasis. This study aims to identify oncogenic cirRNAs and explore its underlying molecular mechanisms in thyroid cancers.Methods: With circRNA chips in GEO database, we found that circ-0012417 was over-expressed in thyroid cancer. After silencing circ-0012417 or ectopic over-expressed circ-0012417, CCK-8 was used for detecting cell proliferation and transwell is used for examining metastasis and invasion abilities. Western Blot was used to detect changes of downstream proteins. Dual luciferase reporter assay was used to verify whether miR-29c-5p is the target of circ-0012417. Tumor xenografts in nude mice were used for further in vivo verifications. Results: Circ-0012417 is overexpressed in thyroid cancer, and silencing circ-0012417 could inhibit cancer cell proliferation, metastasis and invasion. MiR-29c-5p may be the target of circ-0012417 and inhibiting miR-29c-5p could reverse this phenomenon. And further analysis of TCGA and GTEx databases showed that EGFL7 may be the target of miR-126 and a promising thyroid cancer prognosis indicator.Conclusion: Circ-0012417 promotes thyroid cancer progression through regulating miR-29c-5p /EGFL7 pathway. Our finding provided novel therapeutic targets for thyroid cancer treatment.
Multiple Targeted Self-Emulsifying Compound RGO Reveals Obvious Antitumor Potential in Hepatocellular Carcinoma
Authors: He Sanxiu , Tian Shaorong , Le Xin , Chen Jialin , Chen Hongyi , He Xiaoqian , Mu Junhao , Xu Ke , Xiang Qin , Wu Yue , Ning Yijiao , Chen Jiong , Xiang Tingxiu
Published: December 2020

Background: Currently, the treatment for advanced hepatocellular carcinoma (HCC) is extremely limited. Ginsenoside Rg3, ganoderma lucidum polysaccharide, and Oridonin have shown great potential in anti-tumor therapy in previous studies, but low bioavailability and poor solubility seriously hinder their clinical application. Hence, new strategy for liver cancer are urgently needed. Methods: Cell viability, cell proliferation, cell migration, colony formation, tubule formation, sphere formation, and flow cytometry were used to assess the effect of a new drug, RGO-SMEDDS, (self-microemulsifying drug delivery system comprising of Rg3, ganoderma lucidum polysaccharide, and Oridonin) on HCC. Specific anti-tumor mechanisms of RGO-SMEDDS were investigated by western blot, qRT-PCR, and immunohistochemistry. Xenografts and staining with hematoxylin and eosin were used to assess the effects of RGO-SMEDDS on tumorigenesis in vivo.Results: We developed a self-microemulsifying drug delivery system (RGO-SMEDDS) for these three plant monomers. Treatment with RGO-SMEDDS resulted in induction of G2/M phase arrest and apoptosis, inhibition of migration and invasion, and suppression of cell proliferation, both in vitro and in vivo. Furthermore, RGO-SMEDDS restored immune function by suppressing the production of immunosuppressive cytokine and M2-polarized macrophages, reduced angiogenesis by down-regulation of vascular endothelial growth factor and its receptor, and attenuated stemness of HCC by inhibiting EGFR/AKT/GSK-3α/β signaling pathways. In addition to excellent anti-tumor effects, RGO-SMEDDS showed considerable safety in acute toxicity tests.Conclusion: RGO-SMEDDS exerted significant anti-tumor effects by reducing angiogenesis, remodeling immune microenvironments, and promoting apoptosis, without obvious toxicities. With these attributes RGO-SMEDDS is a promising therapy for the treatment of hepatocellular carcinoma.
Application of Auriculotemporal Nerve Block and Dextrose Prolotherapy in Exercise Therapy of TMJ Closed Lock in Adolescents and Young Adults
Authors: Zhou Hongzhi , Xue Yang , Liu Ping
Published: December 2020

Background: Temporomandibular joint (TMJ) ‘closed lock’ is a clinical condition causing TMJ pain and limited mouth opening (painful locking). Recent studies suggest an increasing prevalence of degenerative joint disease associated with the onset of TMJ closed lock in adolescents and young adults. Early interventions are recommended, but the curative effect of standard therapies remains controversial. In this retrospective study, an alternative method of non-surgical treatment of TMJ closed lock is presented, and its long-term efficacy has been observed. Methods: Forty adolescents and young adults, aged 16 to 30 years old, with distinct combination of symptoms of TMJ closed lock, were enrolled. Patients received anesthetic blockages of the auriculotemporal nerve, then performed mandibular condylar movement exercise for 10 minutes, and subsequently received hypertonic dextrose prolotherapy in retro-discal area of TMJ. Clinical assessments at baseline and at follow-up (2 weeks, 2 months, 6 months, and 5 years) included intensity and frequency of TMJ pain, mandibular range of motion, TMJ sounds, and impairment of chewing.Results: Cone beam CT images of the TMJs revealed joint space changes in all patients and degenerative bone changes in 20% (8/40) of the patients. The patients were diagnosed as having disc displacement without reduction with limited opening. Successful reduction of displaced disc had been achieved in the treatment. And pain at rest and pain on mastication had substantially decreased in all patients and mandibular function and mouth opening had significantly improved since 2 weeks’ follow-up. The overall success rate kept at a high level of 97.5% (39/40) at 6 months and 5 years’ follow-up. Conclusions: The technique combining mandibular condylar movement exercise with auriculotemporal nerve block and dextrose prolotherapy is straightforward to perform, inexpensive and satisfactory to young patients with TMJ closed lock.
Relationship Between the Accuracy of Acetabular Cup Angle and Body Mass Index in Posterolateral Total Hip Arthroplasty With CT-Based Navigation: A Retrospective Case-Control Study
Authors: Ishikura Hisatoshi , Nakamura Masaki , Nishino Hanae , Nakamura Shigeru , Tanaka Takeyuki , Kawano Hirotaka , Tanaka Sakae
Published: December 2020

Background: Precise acetabular cup placement is essential for successful total hip arthroplasty (THA). In obese patients, its accuracy is often difficult to achieve because of the thickness of the soft tissues. This study aimed to determine the relationship between the accuracy of acetabular cup angle and body mass index (BMI) in posterolateral THA using the computed tomography-based navigation (CT-navi) system.Methods: We retrospectively reviewed 145 consecutive primary THAs using the CT-navi system between January 2015 and January 2018. All surgeries were performed using cementless cups employing the posterolateral approach with the patient in the decubitus position. We compared the radiographic inclination and anteversion obtained from the angle displayed on the CT-navi screen with those measured by the postoperative CT using the three-dimensional templating software. We evaluated the relationship between the extent of errors and correlation with BMI. Statistical analyses were performed using the Student’s t-test and Spearman’s rank coefficient test.Results: In non-overweight patients (BMI < 25, 88 hips), the mean navigation errors for inclination were 2.8 ± 2.2° and for anteversion were 2.6 ± 2.3°. Meanwhile, in overweight patients (BMI ≥ 25, 57 hips), the mean navigation errors were 2.6 ± 2.4° for inclination and 2.4 ± 2.4° for anteversion. We found no significant difference between overweight and non-overweight patients in both inclination and anteversion. The Spearman’s rank correlation coefficients were -0.04 for inclination and -0.11 for anteversion, showing no correlation between the extent of errors and BMI.Conclusions: In posterolateral THA, CT-navi can aid the precise placement of the acetabular cup irrespective of a patient’s BMI.Trial registration: This trial was retrospectively registered and approved by the institutional ethics committee of Teikyo University. The registration number is 17-190, and the date of approval was March 1, 2018. URL of trial registry is: https://www.teikyo-u.ac.jp/application/files/7015/8432/1341/2016_all_syounin_1.pdf
Steroid Cell Tumours: Rare Ovarian Tumours that Cause Hyperandrogenaemia in Postmenopausal Women
Authors: zhu xiaodan , zhou linyu , jiang jian , Jiang Tian'an
Published: December 2020

Background Diagnosing hyperandrogenemia in postmenopausal women is very difficult, because it occasionally manifests as excessive hair growth or no clinical manifestations, so it is often misdiagnosed or missed diagnosis. Ovarian steroid cell tumours that cause hyperandrogenaemia in women account for approximately 0.1% of all ovarian tumours. Due to the low incidence, corresponding imaging reports are rare, so ovarian steroid cell tumours lacks typical imaging findings to differentiate it from other ovarian tumours. Therefore, we summarized its clinical and imaging characteristics through this case series ,and we also elaborated on the differential diagnosis of steroid cell tumors. We hope to help clinicians have a deeper understanding of ovarian steroid cell tumours.Case presentation we report three cases of postmenopausal women with hyperandrogenaemia.Only 1 patient showed virilization symptoms, the other two patients were completely asymptomatic. All patients underwent total hysterectomy + bilateral adnexectomy. Histological results showed one case of leyding cell tumor (case 1) and two cases of benign non-specific steroid cell tumor (case 2 and case 3). After the operation, the androgen levels of all patients returned to normal, and there was no clinical recurrence since follow-up.Conclusions Through this series of cases, we found that although virilization caused by increased serum testosterone levels is an important clinical feature of ovarian steroid cell tumors, complete asymptomatic is also one of its features. A solid, slightly hypoechoic, round or oval mass with uniform internal echo, richer blood flow in the solid part and low resistance index are typical imaging features of ovarian steroid cell tumors. Diagnosis of ovarian steroid cell tumours after menopause is challenging, but surgery can be used for both diagnosis and clear treatment.
Use of Sat Scan for Identification of Cholera Hotpots in a High-Density Suburb of Harare, Zimbabwe.
Authors: Chigumadzi Layman , Chiurunge Panashe , Ndarukwa Pisirai
Published: December 2020

Background: The cholera pandemic remains a major public health risk in developing nations most of which are in the Sub Saharan regions. However, there is limited data on near real time analysis using the Sat Scan whichIn this study, of particular concern is the spatial-temporary distribution of cholera cases obtained from the mapping and detection of cholera hotspots or clusters in Budiriro on the outbreak, which occurred in September 2018. Methods: The research study used the spatial geographical distribution approach in order to study the clusters of high diseases incidence in Budiriro high-density suburb of Harare, Zimbabwe. The participants in this study included patients from all age groups and gender who were either suspects or confirmed cases of cholera according to the line lists provided by Harare City Health Department. Data was then analysed using the Python, Geographic Information Systems (GIS) and the Sat-Scan. Since this study, is an essential part of the health-needs assessment in the identification of high-risk areas for a disease, understanding the characteristics of high-risk areas was needed to indicate areas, which required improvements in the provision of WASH programmes in order to reduce the risk of cholera outbreaks. Results: The results from this study showed significant clusters or hotspots of cholera in Budiriro for the period of the outbreak (29 September-02 October 2019). People within 0.22km and 0.55km showed a significant risk of being susceptible to cholera (p=0.001). Clusters 1-3 were considered to be hotspots (p<0.05) for cholera outbreak and correspondingly there were more cases of cholera. These hotspots were linked to contaminated water sources (HA034, HA039 and HA075). Water was contaminated from low flow rate of sewage. Conclusions: Cholera and other general infectious disease surveillance can benefit from this perspective approach by monitoring outbreaks in real-time as new data becomes available. The results emphasised on the importance of focusing surveillance on emerging and active clusters during epidemics. Further we concluded that safe water provision could reduce the risk of such outbreaks if Sat-scans could be applied in locating possible areas of contamination.
Metrological and Visual Analysis of the Status of Hypotension in Septic Shock
Authors: qianfei wang , chenxi wang , lijuan wu , jianqiang MEI , wenzhong XU , fenqiao CHEN
Published: December 2020

Background:At present, there is a lot of research in the field of septic shock and hypotension, but there is no comprehensive analysis of the current situation, hot spots and frontiers in this field，and many researchers don't know where to start..Therefore，in this study, the research status, research hotspots and frontier trends of septic shock hypotension in the past 30 years were analyzed by knowledge graph, so as to provide a reference basis for further research.Methods: We collected the literature related to hypotension in septic shock in Web Of Science (WOS) from 1991 to 2020, and made a bibliometric analysis of the literature. At the same time, we Use Excel2019 and Adobe Illustrator CC2018 software to analyze the annual volume of articles and draw bar charts and VOSviewer software to draw the relevant maps of countries, authors and institutions to explore the cooperative relationship in this field and CiteSpace software to draw keyword co-occurrence map, cluster timeline map and emergence map of keywords, and analyze the frontiers and hotspots in this field.Results: A total of 1419 articles were obtained, of which the country with the largest number of articles was the United States, and the centrality was the highest. Professor Bellomo Rinaldo in Australia has published the largest number of articles, up to 29 articles, which plays an important role in this field. In the organization cooperation graph, Univ sao Paulo cooperates closely with other agencies and publishes a large number of articles. There are high-frequency keywords such as sepsis, septic shock and hypotensio, 11 clusters such as relative adrenal insufficiency, nitric oxide and thromboxane, and high-prominence keywords of endotoxin and tumor necrosis factor.Conclusion: In the past 30 years, the volume of articles in the field of hypotension in septic shock showed a steady upward trend. Institutions in North America, Australia and Europe have made outstanding contributions to this field, but the degree of inter-country and inter-agency cooperation is worrying. Three major author cooperation groups have been formed, with close ties within the group. In the future, international exchanges and cooperation can be strengthened and the degree of cooperation in this field can be improved. Drugs for the treatment of hypotension, molecular mechanisms including endotoxin and tumor necrosis factor, and physiological and pathological mechanisms of hypotension are the research hotspots and frontiers in recent years.
Calcium-dependent serine-threonine phosphatase, calcineurin inactivation mediated by baicalein attenuates prion protein-mediated neuronal cell damage
Authors: Hong Jeong-Min , Moon Ji-Hong , Park Sang-Youel
Published: December 2020

Background: Prion diseases are a group of unvaryingly fatal neurodegenerative disorders characterized by neuronal cell death. Calcineurin and autophagy mediate prion-induced neurodegeneration, suggesting that inhibition of calcineurin and autophagy could be a target for therapy. Baicalein has been reported to exert neuroprotective effects against calcium-dependent neuronal cell death. Results: In the present study, we investigated whether baicalein attenuates prion peptide-mediated neurotoxicity and reduces calcineurin. We found that baicalein treatment inhibits prion protein-induced apoptosis. Baicalein inhibited calcium up-regulation and protected the cells against prion peptide‑induced neuron cell death by calcineurin inactivation. Furthermore, baicalein increased p62 protein levels and decrease LC3-II protein levels indicating autophagic flux inhibition and baicalein inhibited prion protein-induced neurotoxicity through autophagy flux inhibition. Conclusions: Taken together, this study demonstrated that baicalein attenuated prion peptide-induced neurotoxicity via calcineurin inactivation and autophagic flux reduction, and also suggest that baicalein may be an effective therapeutic drug against neurodegenerative diseases, including prion diseases.
Evaluation of NaCl and MgCl2 heat exchange fluids in a deep binary geothermal system in a sedimentary halite formation
Authors: Moore Kayla R , Holländer Hartmut M.
Published: December 2020

Halite formations are attractive geothermal reservoirs due to their high heat conductivity, resulting in higher temperatures than other formations at similar depths. However, halite formations are highly reactive with undersaturated water. An understanding of the geochemical reactions that occur within halite-saturated formation waters can inform decision making regarding well construction, prevention of well clogging, formation dissolution, and thermal short-circuiting. Batch reaction and numerical 3-D flow and equilibrium reactive transport modeling were used to characterize the produced NaCl-brine in a well targeting a halite-saturated formation. The potential for inhibition of precipitation and dissolution using an MgCl2-brine and NaCl+MgCl2-brine were also investigated. Within the injection well for an NaCl-brine, with heating from 70 to 120°C, the solubility of halite decreases resulting in the potential dissolution of 0.479 mol kg-1 halite at the formation. Cooling from 120 to 100°C in the production well results in precipitation of 0.196 mol kg-1 halite as well as anhydrite. Introduction of MgCl2, resulting in a common Cl- ion, into the heat exchange brine resulted in a decreased potential for dissolution by 0.290 mol kg-1 halite within the formation, as well as decreased precipitation within the production well, compared to the NaCl-brine. The halite solubility was altered by changes in pressure up to 0.045 mol kg-1. This indicates that designing and monitoring the composition of heat exchange fluids in highly saline environments is an important component in geothermal project design.
Mucosa-associated Cultivable Aerobic Gut Bacterial Microbiota among Colorectal Cancer Patients Attending at the Referral Hospitals of Amhara Regional State, Ethiopia
Authors: Siraj Yesuf Adem , Byadgelegn Melese Gebeyehu , Yassin Mensur Osman , Chekol Yohannes Zenebe
Published: December 2020

Background: Colorectal cancer (CRC) is one of the top ten causes of cancer deaths in the world. Despite an increased prevalence of colorectal cancer has been documented from developing countries, there is no any report regarding gut microbiota among colorectal cancer patients in Ethiopia. Therefore, the current study evaluated cultivable aerobic gut bacterial distributions among malignant and its adjacent normal biopsies of CRC patients.Methods: CRC patients who were under colorectal cancer resection surgery during April 2017 to February 2018 at Felege Hiwot Referral and University of Gondar Teaching Hospitals enrolled in the study. Biopsy specimens were taken from malignant and its adjacent normal-appearing tissues. Bacterial cultivation, quantification and characterization of saline washed biopsies were performed under aerobic and candle jar conditions. Differences in bacterial microbiota compositions between malignant and normal tissue biopsies were evaluated and analyzed using Microsoft excel 2010 and GraphPad Prism5 statistical software.Results: Fifteen CRC patients were participated with a mean age of 53.8 + 10.8 years old and majorities (73.3%) of patients were in between the age groups of 40 and 60 years old. The mean + SD bacterial microbiota of malignant biopsies (3.2x105 + 1.6x105 CFU/ml) was significantly fewer than that of adjacent normal tissue biopsies (4.0x105 + 2.2x105 CFU/ml). This dysbacteriosis is positively correlated with the occurrence of CRC (p=0.019). Proteobacteria (55.6%), Firmicutes (33.3%) and Fusobacteria (11.1%) were the most frequently isolated phyla from non-malignant biopsies while only Proteobacteria (58.8%) and Firmicutes (41.2%) from malignant ones. Family level differences were observed among phyla (Firmicutes and Proteobacteria) isolated from the study participants. For instance, the relative abundance of family Bacillaceae from malignant (26%) was lower than the normal biopsies (39%). On other hand, family Enterobacteriaceae was twice more abundant in malignant tissues (45%) than in its matched normal tissues (23%). Furthermore, the family Enterococcaceae (14%) of phylum Firmicutes was solely isolated from malignant tissue biopsies. Conclusion: The overall microbial composition of normal and malignant tissues was considerably different among the study participants. Further studies with culture independent analysis of mucosal microbiota will provide detail pictures of microbial composition and pathogenesis of CRC in Ethiopian settings.
Geographically extensive larval surveys reveal an unexpected scarcity of primary vector mosquitoes in a region of persistent malaria transmission in western Zambia
Authors: Cross Dónall Eoin , Thomas Chris James , McKeown Niall , Siaziyu Vincent , Healey Amy , Willis Tom , Singini Douglas , Liywalii Francis , Silumesii Andrew , Sakala Jacob , Smith Mark , Macklin Mark , Hardy Andy J , Shaw Paul W
Published: December 2020

BackgroundThe Barotse floodplains of the upper Zambezi River and its tributaries are a highly dynamic environment, with seasonal flooding and transhumance presenting a shifting mosaic of potential larval habitat and human and livestock bloodmeals for malaria vector mosquitoes. However, limited entomological surveillance has been undertaken to characterise the vector community in these floodplains and their environs. Such information is necessary as, despite substantial deployment of insecticide-treated nets (ITNs) and indoor residual spraying (IRS) against Anopheles vectors, malaria transmission persists across Barotseland in Zambia’s Western Province. MethodsGeographically extensive larval surveys were undertaken in two health districts along 102 km of transects, at fine spatial resolution, during a dry season and following the peak of the successive wet season. Larvae were sampled within typical Anopheles flight range of human settlements and identified through genetic sequencing of cytochrome c oxidase I and internal transcribed spacer 2 regions of mitochondrial and nuclear DNA. This facilitated detailed comparison of taxon-specific abundance patterns between ecological zones differentiated by hydrological controls.ResultsAn unexpected paucity of primary vectors was revealed, with An. gambiae s.l. and An. funestus representing <2% of 995 sequenced anophelines. Potential secondary vectors predominated in the vector community, primarily An. coustani group species and An squamosus. Whilst the distribution of An. gambiae s.l. in the study area was highly clustered, secondary vector species were ubiquitous across the landscape in both dry and wet seasons, with some taxon-specific relationships between abundance and ecological zones by season. ConclusionsThe diversity of candidate vector species and their high relative abundance observed across diverse hydro-ecosystems indicates a highly adaptable transmission system, resilient to environmental variation and, potentially, interventions that target only part of the vector community. Larval survey results imply that residual transmission of malaria in Barotseland is being mediated predominantly by secondary vector species, whose known tendencies for crepuscular and outdoor biting renders them largely insensitive to prevalent vector control methods.
Processing of progranulin into granulins involves multiple lysosomal proteases and is affected in frontotemporal lobar degeneration
Authors: Mohan Swetha , Sampognaro Paul J. , Argouarch Andrea R. , Maynard Jason C. , Patwardhan Anand , Welch Mackenzie , Courtney Emma C. , Zhang Jiasheng , Mason Amanda , Li Kathy H. , Huang Eric J. , Seeley William W. , Miller Bruce L. , Burlingame Alma , Jacobson Mathew P. , Kao Aimee
Published: December 2020

Background - Progranulin loss-of-function mutations are linked to frontotemporal lobar degeneration with TDP-43 positive inclusions (FTLD-TDP-Pgrn). Progranulin (PGRN) is an intracellular and secreted pro-protein that is proteolytically cleaved into individual granulin peptides, which are increasingly thought to contribute to FTLD-TDP-Pgrn disease pathophysiology. Intracellular PGRN is processed into granulins in the endo-lysosomal compartments. Therefore, to better understand the conversion of intracellular PGRN into granulins, we systematically tested the ability of different classes of endo-lysosomal proteases to process PGRN at a range of pH setpoints. Results - In vitro cleavage assays identified multiple enzymes that can process human PGRN into multi- and single-granulin fragments in a pH-dependent manner. We confirmed the role of cathepsin B and cathepsin L in PGRN processing and showed that these and several previously unidentified lysosomal proteases (cathepsins E, G, K, S and V) are able to process PGRN in distinctive, pH-dependent manners. In addition, we have demonstrated a new role for asparagine endopeptidase (AEP) in processing PGRN, with AEP having the unique ability to liberate granulin F from the pro-protein. Brain tissue from individuals with FTLD-TDP-Pgrn show increased PGRN processing to granulin F and an increased activity of AEP, in a region-specific manner. Conclusions - This study demonstrates that multiple lysosomal proteases may work in concert to liberate multi-granulin fragments and granulins. It also implicates both AEP and granulin F in the neurobiology of FTLD-TDP-Pgrn. Modulating progranulin cleavage and granulin production may represent therapeutic strategies for FTLD-Pgrn and other progranulin-related diseases.
Laboratory test ordering in inpatient hospitals: a systematic review on the effects and features of clinical decision support systems
Authors: Zare Sahar , Meidani Zahra , Shirdeli Mohammad , Nabovati Ehsan
Published: December 2020

Background: Studies have revealed inappropriate laboratory testing as a source of waste. This review aimed at evaluating the effects and features of CDSSs on physicians' appropriate laboratory test ordering in inpatient hospitals.Method: Medline through PubMed, SCOPUS, Web of Science, and Cochrane were queried without any time period restriction. Studies using CDSSs as an intervention to improve laboratory test ordering as the primary aim were included. The study populations in the included studies were laboratory tests, physicians ordering laboratory tests, or the patients for whom laboratory tests were ordered. The included papers were evaluated for their outcomes related to the effect of CDSSs which were categorized based on the outcomes related to tests, physician, and patients. The primary outcome measures were the number and cost of the ordered laboratory tests. The instrument from The National Heart Lung and Blood Institute (NIH) was used to assess the quality of the included studies. Moreover, we applied a checklist for assessing the quality and features of the CDSSs presented in the included studies. A narrative synthesis was used to describe and compare the designs and the results of included studies.Result: Sixteen studies met the inclusion criteria. Most studies were conducted based on a quasi-experimental design. The results showed improvement in laboratory test-related outcomes (e.g. proportion and cost of tests) and also physician-related outcomes (e.g. guideline adherence and orders cancellation). Patient-related outcomes (e.g. length of stay and mortality rate) were not well investigated in the included studies. In addition, the evidence about applying CDSS as a decision aid for interpreting laboratory results was rare.Conclusion: CDSSs increase appropriate test ordering in hospitals through eliminating redundant test orders and enhancing evidence-based practice. Appropriate testing and cost saving were both affected by the CDSSs. However, the evidence is limited about the effects of laboratory test CDSSs on patient-related outcomes.
Visceral adiposity index is associated with lung function impairment: A population-based study
Authors: He Sunyue , Yang Jie , Li Xiaoyong , Gu Hongxia , Su Qing , qin li
Published: December 2020

Background: The effects of visceral adiposity on decreased lung function have drawn much attention. Recently, the visceral adiposity index (VAI) has been proposed as a visceral fat distribution and dysfunction marker. However, the relationship between the VAI and lung function has not been investigated. The objective of the study was to analyze the association between the VAI and lung function and evaluate the potential of VAI as a predictor of lung function. Methods: We collected data from a population-based study of 1786 subjects aged 40 years or older. All subjects completed a questionnaire and underwent anthropometric measurements and laboratory tests. Linear and logistic regression models were developed to assess the association between the VAI and lung function. Results: The VAI was inversely related to FVC%predicted in men and negatively associated with both FVC%predicted and FEV1%predicted in women. In the linear regression analysis, the decrease in FVC%predicted associated with each 10% increase in the VAI was 1.127% in men and 1.943% in women; the decrease in FEV1%predicted associated with each 10% increase in the VAI was 0.663% in men and 1.738% in women. Further regression analysis revealed that the VAI was positively correlated with FVC and FEV1 impairment in women. Conclusions: We were the first to show a clear correlation between the VAI and lung function impairment in the Chinese population. The VAI could be a simple and reliable approach in daily practice, and individuals, especially women with a high VAI, should receive additional screening and preventive interventions for respiratory disease.
Role of ATF3 as a prognostic biomarker and correlation of ATF3 expression with macrophage infiltration in hepatocellular carcinoma
Authors: Li Lijuan , Song Shaohua , Fang Xuailin , Cao Donglin
Published: December 2020

Background: The abnormal expression of activating transcription factor 3 (ATF3), a member of the basic leucine zipper (bZIP) family of transcription factors, is associated with carcinogenesis. However, the expression pattern and exact role of ATF3 in the development and progression of hepatocellular carcinoma (HCC) remain unclear. Methods: We used UALCAN, ONCOMINE, Kaplan-Meier plotter, and cBioPortal databases to investigate the prognostic value of ATF3 expression in HCC. Results: ATF3 was found to be expressed at low levels in multiple HCC tumor tissues. Moreover, low ATF3 expression was significantly associated with clinical cancer stage and pathological tumor grade in patients with HCC. Therefore, low expression of ATF3 was significantly associated with poor overall survival in patients with HCC. Functional network analysis showed that ATF3 regulates cytokine receptors and signaling pathways via various cancer-related kinases, miRNAs, and transcription factors. ATF3 expression was found to be correlated with macrophage infiltration levels and with macrophage immune marker sets in HCC patients. Conclusions: Using data mining methods, we clarified the role of ATF3 expression and related regulatory networks in HCC, laying a foundation for further functional research. Future research will validate our findings and establish clinical applications of ATF3 in the diagnosis and treatment of HCC.
Carriage of antimicrobial-resistant bacteria in a high-density informal settlement in Kenya is associated with environmental risk-factors
Authors: Omulo Sylvia , Lofgren Eric T , Lockwood Svetlana , Mwangi Samuel T , Bigogo Godfrey , Ouma Alice , Verani Jennifer R. , Juma Bonventure , Njenga Kariuki M , Kariuki Samuel , McElwain Terry F , Palmer Guy H , Call Douglas R
Published: December 2020

Background. The relationship between antibiotic use and antimicrobial resistance varies with cultural, socio-economic, and environmental factors. We examined these relationships in Kibera, an informal settlement in Nairobi - Kenya, characterized by high population density, high burden of respiratory disease and diarrhea. Methods. Two-hundred households were enrolled in a 5-month longitudinal study. One adult (≥18 years) and one child (≤5 years) participated per household. Biweekly interviews (n=1,516) that included questions on water, sanitation, hygiene, and antibiotic use in the previous two weeks were conducted, and 2,341 stool, 2,843 hand swabs and 1,490 drinking water samples collected. Presumptive E. coli (n=34,042) were isolated and tested for susceptibility to nine antibiotics.Results. Eighty percent of presumptive E. coli were resistant to ≥3 antibiotic classes. Stool isolates were resistant to trimethoprim (mean: 81%), sulfamethoxazole (80%), ampicillin (68%), streptomycin (60%) and tetracycline (55%). Ninety-seven households reported using an antibiotic in at least one visit over the study period for a total of 144 episodes and 190 antibiotic doses. Enrolled children had five times the number of episodes reported by enrolled adults (96 vs. 19). Multivariable linear mixed-effects models indicated that children eating soil from the household yard and the presence of informal hand-washing stations were associated with increased numbers of antimicrobial-resistant bacteria (counts increasing by 0·27−0·80 log10 and 0·22−0·51 log10 respectively, depending on the antibiotic tested). Rainy conditions were associated with reduced carriage of antimicrobial-resistant bacteria (1·19 to 3·26 log10 depending on the antibiotic tested).Conclusions. Antibiotic use provided little explanatory power for the prevalence of antimicrobial resistance. Transmission of resistant bacteria in this setting through unsanitary living conditions likely overwhelms incremental changes in antibiotic use. Under such circumstances, sanitation, hygiene, and disease transmission are the limiting factors for reducing the prevalence of resistant bacteria.
The Effective Screening Tools for Detecting Hearing Loss in Elderly Population: HHIE-ST Versus TSQ
Authors: Chayaopas Nichtima , Kasemsiri Pornthep , Thanawirattananit Panida , Piromchai Patorn , Yimtae Kwanchanok
Published: December 2020

Background: Globally increasing number of elders is concerned. Hearing loss process in elderly cannot be avoided. An effective screening tool for hearing loss is essential for proper diagnosis and rehabilitation, which can improve QOL in elderly individuals. Methods: This prospective-diagnostic test study evaluates the diagnostic value of Thai version of the Hearing Handicap Inventory for Elderly Screening (HHIE-ST) and the Thai Single Question (TSQ) surveys in screening hearing disability in 1109 Thai elderly participants aged 60 years and older in communities in four provinces in Thailand. The HHIE-ST consisted of 10 selected questions from the validated HHIE-Thai version. A TSQ survey was developed to have the same meaning as an English Single Question survey. The participants answered both questionnaires, and a standard audiometry test assessed with air conduction from 250 to 8000 Hz was included as a gold standard. Results: The prevalence of hearing disability was 38.34%. The HHIE-ST achieved a sensitivity of 88.96% (95% CI 85.77-91.64) and specificity of 52.19% (95% CI 48.24-56.13) for diagnosis hearing disability in Thai elderly subjects, whereas the TSQ yielded a sensitivity of 88.73% and a specificity of 55.93%. A combined test including the HHIE-ST and TSQ achieved better performance with sensitivity of 85.29% and specificity of 60.13%. Conclusions: Either the HHIE-ST or the TSQ is a sensitive and useful tool for screening hearing disability in Thai elderly subjects. Using the HHIE-ST together with the TSQ resulted in a better screening tool for detecting moderate hearing loss elderly individuals who will benefit and recommended for hearing rehabilitation.Trial Registration: The study is registered with the following number in the Thai Clinical Trials Registry: TCTR20151015003. URL: http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1562
Electrical conductive fluid-rich zones and their influence on the earthquake initiation, growth, and arrest processes: Observations from the 2016 Kumamoto earthquake sequence, Kyushu Island, Japan
Authors: Aizawa Koki , Takakura Shinichi , Asaue Hisafumi , Koike Katsuaki , Yoshimura Ryokei , Yamazaki Ken'ichi , Komatsu Shintaro , Utsugi Mitsuru , Inoue Hiroyuki , Tsukamoto Kaori , Uyeshima Makoto , Koyama Takao , Kanda Wataru , Yoshinaga Tohru , Matsushima Nobuo , Uchida Kazunari , Tsukashima Yuko , Matsushima Takeshi , Ichihara Hiroshi , Muramatsu Dan , Teguri Yoshiko , Shito Azusa , Matsumoto Satoshi , Shimizu Hiroshi
Published: December 2020

Crustal earthquake ruptures tend to initiate near fluid-rich zones. However, it is relatively unknown whether fluid-rich zones can further promote or arrest these ruptures. We image the electrical resistivity structure around the focal area of the 2016 Kumamoto earthquake sequence by using 200 sites broad-band magnetotelluric data, and discuss its quantitative relationship to earthquake initiation, growth, and arrest processes. The ruptures that initiated along the outer edge of the low-resistivity fluid-rich zones (<30 Ωm) tended to become large earthquakes, whereas those that initiated either distal to or within the fluid-rich zones did not. The ruptures were arrested by high-temperature (>400°C) fluid-rich zones, whereas shallower low-temperature (200–400°C) fluid-rich zones either promoted or arrested the ruptures. These results suggest that the distribution of mid-crustal fluids contributes to the initiation, growth, and arrest of crustal earthquakes. The pre-failure pressure/temperature gradient (spatial difference) of the pore fluids may contribute to the rupture initiation, propagation, and arrest.
Hybrid Semantic Recommender System for Chemical Compounds in Large-Scale Datasets
Authors: Barros Márcia , Moitinho André , Couto Francisco M.
Published: December 2020

The large, and increasing, number of chemical compounds poses challenges to the exploration of such datasets. In this work, we propose the usage of Recommender Systems to identify compounds of interest to scientific researchers. Our approach consists of a hybrid recommender model suitable for implicit feedback datasets and focused on retrieving a ranked list according to the relevance of the items. The model integrates collaborative-filtering algorithms for implicit feedback (Alternating Least Squares and Bayesian Personalized Ranking) and a new content-based algorithm, using the semantic similarity between the chemical compounds in the ChEBI ontology. The algorithms were assessed on an implicit dataset of chemical compounds, CheRM-20, with more than 16.000 items (chemical compounds). The hybrid model was able to improve the results of the collaborative-filtering algorithms, by more than ten percentage points in most of the assessed evaluation metrics.
POTRET PERGESERAN RELASI GENDER DAN DAMPAKNYA BAGI KELUARGA PEKERJA MIGRAN INDONESIA (PMI)
Authors: Zuhriyah Lailatuzz , Mustofa Saiful , Syamsudin Ghinanjar Ahmad
Published: December 2020

This article examines the shift in gender relations in the context of the families of Indonesian Migrant Workers (PMI). By taking an object in Rejotangan District as the most PMI area in Tulungagung Regency, this article uses a symbolic approach to attempts to portray the process of interaction between individuals in the context of PMI families. In this case, the concept of patriarchy is no longer valid. The husband begins to play a role in the domestic sector; cooking, taking care of children and doing everything about the household. While the wife, only has a role to fulfill the family’s living, whether as a housemaid, taking care of elderly parents, or in other sectors abroad. Such matter does not only have implications for material-economic factors but also psychologically and sociologically; there is a complexity of family problems whose impact can lead to the destruction of household relations and the education of their children.
ANALISIS SOAL SEJARAH KEBUDAYAAN ISLAM MI ‎KELAS IV PERSPEKTIF HOTS
Authors: Cahayaningsih Ica Putri
Published: December 2020

Analysis of the items is adjusted to the material provided in the textbook, whether the questions available in the book or not, because in some cases it not in accordance with the questions. in addition the authors, also analyzed the items contained in the book with HOTS qualification categories based on Bloom’s Taxonomy. this study aims to describe wether the questions presented in thr studebt book (BSE) History of Islamic culture class IV curriculum 2013 published by Ministry of Religion in 2014 aew in accordance with the level HOTS category in Bloom’s Taxonomy. The data analyzed in this study are the study questions presented in the student’s book. The analysis technique used in the research is descriptive statistical analysis and with resulting data in the form of percentages. The result of the analysis in this study indicate that the questions contained in the SKI student book are presented with the proportion (1) 78% of questions in LOTS category, (2) 21% of questions in the MOTS category, and (3)1% of questions in the HOTS category. Thus, it can be concluded that the questions prsentes in the SKI student book are not ideal as matter of practice.
Extraction of DNA from a Wide Range of Objects by Treatment with Ammonium Salts
Authors: Levitin E.I. , Sviridov B.V. , Piksasova O.V. , Shustikova T.E.
Published: December 2020

Currently, simple, rapid, and efficient techniques for DNA isolation from a wide range of organisms are in demand in biotechnology and bioinformatics. A key (and often limiting) step is the cell wall disruption and subsequent DNA extraction from the disintegrated cells. We have developed a new approach to DNA isolation from organisms with robust cell walls. The protocol includes the following steps: treatment of cells or tissue samples with ammonium acetate followed by cell lysis in low-salt buffer with the addition of SDS. Further DNA extraction is carried out according to standard methods. This approach is efficient for high-molecular native DNA isolation from bacteria, ascomycetes, yeast, and mammalian blood; it is also useful for express analysis of environmental microbial isolates and for plasmid extraction for two-hybrid library screening.

express method for DNA isolation; ammonium salt treatment (в русских ключевых такой порядок), osmotic breakage of cells

This study was financially supported by the NRC "Kurchatov Institute"-GOSNIIGENETIKA Kurchatov Genomic Center.
Parent-Adolescent Communication on Sexual Issues as Predictor of Sexual-Risk Reduction behaviour among in-School Adolescents in Selected Secondary Schools in Yei River State-South Sudan
Authors: Loponi Lou Eluzai
Published: December 2020

The study investigated the parent-adolescent communication on sexual issues as predictors of sexual-risk reduction among in-school adolescents in secondary school. Teenage pregnancy and adolescent birth rates are high at 300/1000 and 158/1000 live births respectively in 2018. Frequent discussion on sexual behaviour is more likely to reduce adolescent risk-taking sexual behaviors. However, there is a paucity of evidence about adolescent parent communication in Yei River State. A cross-sectional study using both quantitative and qualitative approaches involving 156 participants to explore the parent-adolescent communication frequency and topics discussed among secondary school adolescents was carried out. Respondents were recruited from the ten functional secondary schools in Yei River state from secondary school class 1 to 4. The inclusion criteria consider secondary school adolescent aged 15 to 19, parental consent and adolescent acceptance to participate in the study. Adolescent below the age 15 and young men above 19 years of age were excluded from the study. Data was collected using semi-structured questionnaire, the date collected were coded first and analyzed suing SPSS version 21. The percentage of adolescents who had more than three sessions of communication with their parents about sexual behaviour was nearly 43% in which, majority 67% reported to have frequent discussions with their mothers and the commonly discussed topics were biological and physical development. The study concluded that a few adolescents have frequent communication with their parents on sexual behaviours. This study recommends, repeat of the current study in some states for comparison, as well as a study focusing on both out of school and school adolescent to explore more.