bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of a Novel MAP4K4-SASH1 Kinase Cascade Regulating&nbsp;Breast Cancer Tumorigenesis and Metastasis
Authors: Li Yadong , Wu Daoqiu , Hou Jing , Zhang Jing , Zeng Xing , Chen Lian , Wan Xin , Wu Zhixiong , Wang Jinyun , Wang Ke , Yang Dan , Chen Hongyu , Xu Zexi , Jia Lei , Liu Qianfan , Kuang Zhongshu , Jiang Geli , Zhang Hui , Luo Jie , Li Wei , Zou Xue , Zeng Xiaohua , Zhou Ding'an 
Published: November 2020

Abstract
Background: The SAM and SH3 domain containing protein 1(SASH1) was previously described as a candidate tumor-suppressor gene in breast cancer and colon cancer to mediate tumor metastasis and tumor growth. However，the underlying mechanisms by which SASH1 implements breast cancer tumorigenesis and the question why SASH1 is downregulated in most solid cancers remain unexplored. Methods: The expression and clinical relevance of SASH1 and mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4) were analyzed by immunohistochemistry(IHC). The bindings of SASH1 and MAP4K4 were investigated by pull down assay, nano-flow LC-MS/MS , immunoprecipitation- western blot(IP-WB) and immunofluorescence(IF). The knockdown of SASH1- and/or MAP4K4-induced cell proliferation, apoptosis, migration and invasion were investigated by flow cytometry and transwell assays. The cell proliferation and apoptosis treated by GNE-495 were assessed by flow cytometry. The in vitro regulation relationship between SASH1 and MAP4K4 were identified by in vitro kinase assay. The functional effects of the silencing of SASH1 and/or MAP4K4 on tumorigenesis and metastasis of T47D cells-xenograft tumors were assessed by HE staining and IHC .Results: SASH1 and MAP4K4 was significantly downregulated in hormone- dependent subtypes of breast cancers and SASH1 was significantly correlated with MAP4K4 in hormone-dependent subtypes. SASH1 is identified to be a novel serine/threonine protein kinase that binds to MAP4K4, and is phosphorylated by MAP4K4. SASH1 and MAP4K4 synergistically regulate cell proliferation，migration and invasion of hormone-dependent breast cancer cells and mediate liver and lung metastasis of T47D cells-xenograft tumors.Ser801 in MAP4K4 might be the serine site for MAP4K4 to phosphorylate SASH1. GNE-495， a MAP4K4-specific inhibitors by upregulating the expression of MAP4K4 and SASH1 might be a potential reagent in treating hormone-dependent breast cancers. Conclusion: Our findings characterize a novel MAP4K4-SASH1 kinase cascade to mediate the tumorigenesis and metastasis of breast cancer, which can be of targeted intervention by GNE-495.
Identification of Tumor-Suppressive miRNA-1275 as a Novel Marker for Breast Cancer (BC) by MACE-Sequencing and RT-qPCR Techniques
Authors: Majed Sevan Omer , Mustafa Suhad Asad 
Published: November 2020

Abstract
IntroductionDisruption of cellular processes in the breast by abnormally expressed miRNA is characterized to develop cancer. We aimed to determine the differential expression of coding and non-coding RNAs in formalin fixed paraffin embedded (FFPE) blocks of breast cancer (BC) tissue and normal adjacent tissue (NAT). Another aim is to determine differential expression of has-miR-1275 as novel biomarker for BC and identify its target genes using prediction sites and experimentally expression level of them via the MACE-sequencing technique. MethodsMACE-sequencing technique was utilized to analyze differential expression of coding RNAs and small RNAs (sRNAs). Among small RNAs, miRNA-1275 expression was focused and confirmed using RT-qPCR technique in 20 Kurdish cases with BC . Moreover, clinical significance of miR- 1275 and its target genes was studied in a large number of patients with BC using the data obtained from The Cancer Genome Atlas database.ResultsThe MACE-seq findings showed that 1400 sRNAs and 26843 coding RNAs were differentially expressed in FFPE of BC tissue compared to NAT. Among these sRNAs, miRNA-1275 expression was found to be decreased in BC tissue compared to NAT. The decreased expression level of which was then confirmed via RT-qPCR technique to farther prove in 20 Kurdish cases with BC . Furthermore, the correlation between the expression level of miRNA-1275 and clinical data were evaluated to be highly corrected in cases with BC (overall survival rate: P = 0.0401). However, putative target genes ( DVL3, PPP 2R2D, THSD4, CREB1, SYT7, and PRKACA) were computationally identified as direct targets of miRNA-1275 in several target predicted sites. Among coding RNAs, the expression level of these targets was increased in BC tissue compared to NAT. The levels of these targets were negatively associated with miRNA-1275 expression. Finally, the role of down-expressed miRNA-1275 and its targets in BC cells were identified to attenuated biological mechanisms; including cell growth, proliferation, movement, invasion, metastasis, and apoptosis.Conclusiondown-expressed miR-1275 , a tumor suppressor, is as a novel biomarker for early detection of breast cancer. DVL3, PPP 2R2D, THSD4, CREB1, SYT7, and PRKACA are novely identified to be targeted by miR-1275 in BC cells.
Access to Formal Maternal Health Services and Informal Supports for Resettled Refugee Mothers in the Postnatal Period: A Scoping Review Protocol
Authors: Cameron Emma Stirling , DuPlessis Benjamin , Aston Megan , Ramos Howard , Jackson Lois 
Published: November 2020

Abstract
Background: The postnatal period is a critical time when women may need access to formal maternal health services (e.g., family physicians) and informal supports (e.g., family, friends). Resettled refugee women often encounter a myriad of barriers and challenges when attempting to access these services and supports in resettlement countries, including language and communication differences, socioeconomic constraints, challenges navigating foreign healthcare systems, and reduced social support networks. This has contributed to health inequities among postnatal resettled refugee women, including low self-reported health, five-times higher rates of postpartum depression, and social isolation. The purpose of this review is to understand access to formal maternal health services and informal supports for resettled refugee women during the postnatal period. Methods: This review will be conducted in accordance with JBI methodology for scoping reviews. A comprehensive search strategy, developed with a librarian scientist, will be used to identify relevant sources. Titles, abstracts, and full texts will be evaluated against inclusion criteria. Evidence from peer-reviewed and gray literature published after 2003 will be included. This review will focus only on studies conducted in middle- and high-income resettlement countries. Information will be extracted by two independent reviewers using a screening tool. Data will be synthesized and presented narratively, with tables and figures where appropriate. Discussion: This scoping review will provide an overview of resettled refugee women’s experiences during the postnatal period, with a focus on understanding access to health services and the availability and use of informal supports. It is expected that this review will outline both the barriers and facilitators affecting resettled refugee women seeking formal and informal care during the postnatal period. Findings will help to inform policy direction and future interventions seeking to improve postnatal care for resettled refugee women.Systematic Review Registration: This scoping review protocol has been registered with the Open Science Framework database, https://osf.io/rkqj6.
Monitoring Measures in the Elimination of Malaria in Fujian, China: A Cost-Benefit Analysis
Authors: HUANG Chun-Yan , Zhang Shan-Ying , CHEN Zhu-Yun , XIE Han-Guo , OUYANG Rong 
Published: November 2020

Abstract
Background: Malaria is an insect-borne infectious disease that spreads through bites from infected Anopheles mosquitos. The disease seriously endangers human health and economic development. The study focuses on Fujian Province, China, which entered the final stage of malaria elimination stage in 2005. In order to understand the costs and benefits of malaria monitoring measures during the elimination stage, the health economics of the monitoring measures should be examined. Methods: Data on the number of cases during the malaria elimination stage (2005–2019) in Fujian Province were collected and sorted. The basic economic data were obtained from the Fujian Statistical Yearbook. Based on the fundamental theories in health economics, a cost-benefit analysis was conducted based on the data. Specifically, the cost of monitoring measures during the malaria elimination stage was calculated by economic cost and compared to the benefits, which were quantified based on economic and social benefits of the monitoring measures.Results: The total cost of monitoring measures in the malaria elimination stage was estimated at 607,878,783.36 yuan (USD 87,534,544.80). The components of the total cost were: case detection and treatment, which accounted for 66.62% of costs, health education with 13.31%, epidemic monitoring, 10.05%, supervision and assessment, 5.15%, and training and meetings took 4.87%. The total benefit of the monitoring measures in the malaria elimination stage was valued at about 116,123,417,911.81 yuan (USD 16,721,772,179.30). Direct economic benefit accounted for 22.61% of the total, while the social benefit was 77.39%. The cost-benefit analysis of the malaria elimination stage showed that the net benefit of monitoring measures was about 115,515,539,128.45 yuan (USD 16,634,237,634.50) and the benefit-cost ratio was 191.03. The monitoring cost for residents was 1.08 yuan (USD 0.16) per capita, and the benefit for residents was 206.12 yuan (USD 29.68) per capita. Conclusions: The monitoring measures conducted in the malaria elimination stage are a highly cost-effective intervention for reducing the negative impact of malaria in Fujian Province. Over the past 15 years, malaria control work has achieved excellent economic and social benefits in Fujian and the work should continue. The framework and results of this study conform to the principles of health economics and have a reference value for current malaria monitoring practices.
Exploiting the Efficacy of Tyro3 and Folate Receptors to Enhance the Delivery of Gold Nanoparticles into Colorectal Cancer Cells In Vitro
Authors: Patel Nakul Nautam , Ghali Lucy , Roitt Ivan , Munoz Leonardo Pantoja , Bayford Richard 
Published: November 2020

Abstract
Colorectal cancer (CRC) is the fourth most common cancer in the world. Due to its asymptomatic nature, CRC is diagnosed at an advanced stage where the survival rate is <5%. Besides, prognosis from CRC treatment using chemotherapy, radiotherapy and surgery often causes undesirable side-effects. As such, gold nanoparticles (GNPs) are envisaged in the field for the diagnosis and treatment of CRC. GNPs have unique physical, chemical and electrical properties at nanoscale which makes them suitable for application in biomedicine. However, for GNPs to become clinically effective, its internalisation efficiency in the cancer cells must be enhanced. Folate receptor-α (FR) are overexpressed in CRC wherein FR helps in uptake of folic acid within the cell. Tyro3, a novel tyrosine kinase receptor, drives cell proliferation and its overexpression is correlated with poor prognosis in CRC. Their upregulated expression in CRC cells relative to normal cells makes them an ideal target for GNPs using active targeting. Therefore, in this study receptors FR and Tyro3 were simultaneously targeted using specific antibody-coated GNPs in order to enhance uptake and internalisation of GNPs in CRC cells in vitro. Four different types of coated-GNPs were synthesised GNPs-PEG, GNPs-anti-FR, GNPs-anti-Tyro3 and GNPs-anti-(FR+Tyro3) and incubated (0ng – 50ng) with three CRC cell lines including CRL1790, CRL2159 and HCT116. Simultaneous targeting of these receptors by GNPs-anti-(FR+Tyro3) was found to be the most effective in internalisation in CRC cells compared with GNPs targeted singly to FR or Tyro3 (p<0.05). Besides this, results show that Tyro3 mediated similar internalisation efficacy as FR (p<0.05) in CRC using ICP-OES.
ICAT Promotes Cervical Cancer Cell Proliferation, Invasion, Migration and Epithelial‑to‑mesenchymal Transition through HPV16 E6, E7/ miR-23b-3p/ ICAT axis
Authors: Hu Jing , Sun Zijiu , Wang Hui , Ren Wei , Fang Yuting , Hu Kai , Yu Huomei , Liao Deyu , Liu Shiyan , Zhou Lan , He Tongchuan , Zhang Yan 
Published: November 2020

Abstract
Background: Human papillomavirus (HPV) 16 plays a crucial role in cervical cancer (CC) development. Previous study reported that inhibitor of β-catenin and TCF (ICAT) is upregulated in CC and promotes cervical tumor progression. Herein, we aimed to investigate the underlying molecular mechanism that HPV16 regulates the expression of ICAT and promotes the CC development. Methods: The expressions of HPV 16 E6, E7 and ICAT were modulated by small interfering RNA and recombinant adenovirus, respectively. qRT-PCR was conducted to detect the mRNA expression of HPV 16 E6, E7, ICAT and miR-23b-3p in SiHa and CasKi cells. Bioinformatics analysis was utilized to predict the potential miRNAs that could bind to the ICAT 3′ untranslated region. Then, the dual luciferase reporter assay was used to confirm that. Cell proliferation ability was detected by CCK-8 assay. Wound healing and Transwell assays were used to observe migration and invasion abilities. Protein expressions were measured with western blot. Results: Results revealed that after knocking down of HPV16 E6, E7, the expression of ICAT decreased, but the expression of miR-23b-3p increased. Besides, miR-23b-3p negatively modulated ICAT expression in HPV16 positive CC cells. Dual luciferase assays confirmed that ICAT was a target gene of miR-23b-3p. Functional experiments showed that the overexpression of miR-23b-3p suppressed malignant behaviors of SiHa and CasKi cells, such as migration, invasion and EMT. Importantly, the overexpression of ICAT counteracted the suppressive effect of miR-23b-3p on HPV16 positive cervical cancer cell. Furthermore, after the knockdown of HPV16 E6 and E7, the inhibition of miR-23b-3p could increase the ICAT expression and rescue the siRNA HPV16 E6, E7-mediated suppressive impact on the aggressiveness of SiHa and CasKi cells.Conclusions: Our study demonstrates that HPV 16 E6, E7/miR-23b-3p/ ICAT axis plays an important role in HPV16 positive CC pathogenesis, which may serve as a promising therapy target for HPV 16-associated cervical cancer.
The Axis-patella Index: A New Method for Measuring Patellar Height
Authors: Han Hua , Zhang Xiaohui 
Published: November 2020

Abstract
Background: The widely used methods for measuring patellar height are based on the anatomic landmarks of the patella and the proximal tibia. When the knee undergoes alterations in the articular surface or adjacent structures due to various diseases or operations, the accurate identification of tibial landmarks is challenging. The results of these conventional methods may be biased or even unavailable. The purpose of this study was to introduce and validate a new method, axis-patella index (API), for assessing patellar height. Methods: Patellar heights were respectively measured using the Insall–Salvati, modified Insall–Salvati, Blackburne–Peel, Caton–Deschamps, plateau-patellar angle, and axis-patella methods on the lateral radiographs of 649 knees without anatomic abnormalities. The inter- and intra-observer reliability of all methods were evaluated by calculating intraclass correlation coefficient and Bland-Altman plots. The associations between the API and the established methods were assessed using Pearson’s correlation coefficient. Results: The API was strongly correlated with the five aforementioned methods. Reliability analyses indicated high inter-observer reproducibility and intra-observer repeatability. The mean of API was approximately 1.5, hence the reference range was defined 1.2 - 1.9 according to the 95% confidence interval. Conclusions: The API, a new index of referencing the tibial shaft axis and the fibular head, providing a valid and accurate alternative for the assessment of patellar height. The reference range was 1.2 - 1.9 in radiographically normal knee.
Cloning and Expression of an Active Aspartic Proteinase Gene From Aspergillus Oryzae DRDFS13 in Pichia Pastoris
Authors: Mamo Jermen , Kostadinovska Konstantina , Kangwa Martin , Fernandez-Lahore Marcelo , Assefa Fassil 
Published: November 2020

Abstract
BackgroundPichia pastoris is a yeast widely used in expressing recombinant proteins from eukaryotic organisms. In the present study, the total RNA was extracted from a eukaryotic fungus; Aspergillus oryzae DRDFS13 and reverse transcribed into cDNA using specific primers. The gene for aspartic protease was amplified and sequenced and then cloned into pGAPZαA for further expression in P. pastoris. The recombinant yeast (P. patoris X-33Ap) was cultivated in YPD media at pH 5 and 7 for 6 days and the production of recombinant proteins was checked by total protein determination, milk-clotting activity assay, and SDS-PAGE analysis. ResultsThe gene sequence results showed 98% similarity with aspartic protease gene from A. oryzae RIB40. The aspartic protease gene cloned into pGAPZαA (later pMKAP) was successfully expressed in P. pastoris as an active extracellular protease with the highest MCA (190.47 MCU/mL) of secreted enzyme from the recombinant yeast was obtained at pH 5 and 6 days of incubation time. The major protein expressed by the recombinant P. Pastoris X-33 AP has a molecular mass between 32 and 46 kDa. When analyzed for clotting activity, the protein was able to clot skim-milk in 2 min. The clotting activity was found to be 190.47 U/mL.ConclusionThus, the milk-clotting protease extracted form the recombinant yeast in the present study could be a suitable candidate for cheese production. However, further study of the recombinant proteins need to be carried out and its application in cheese production by analyzing the organoleptic and chemical properties of the cheese produced.
A Feasibility Study to Assess Imbrasia Belina (Mopane Worm) Sensitisation and Related Respiratory Health Outcomes in a Rural Community in Gwanda District, Zimbabwe
Authors: Ndlovu Vuyelwa , Chimbari Moses , Sibanda Elopy , Ndarukwa Pisirai 
Published: November 2020

Abstract
Background: Allergic diseases are considered to be some of the fastest growing chronic conditions in Africa. Of concern is the paucity of knowledge about the local environment and its role in allergic disease development. In response to this, we explored whether Imbrasia belina, a popular indigenous edible insect commonly known as mopane worm, is a potential allergen of clinical and public health significance in Zimbabwe. This study was intended to assess the plausibility and feasibility of this hypothesis with a view to evaluate the insect’s health impact in a larger study.Methods: The study participants included both male and female villagers aged 10 years and above in Gwanda district, Zimbabwe. Eligible participants who completed the household questionnaire were referred to the local clinic for skin prick tests and to measure lung function and allergic airway inflammation. Allergen sensitization patterns were evaluated using 10 different inhalant allergen extracts including an in-house preparation of mopane worm. Lung function was measured with a Koko Legend spirometer and fractional exhaled nitric oxide levels (FeNO) (NIOX VERO) were measured in participants with at least one abnormal spirometric parameter. Data was analysed using Stata version 13 software.Results: Of the 46 eligible participants that completed the household questionnaire, 17 went to the clinic giving a response rate of 37%. Majority who completed the questionnaire were adults (91%) and the children (9%) were all female. The prevalence of sensitization to Imbrasia belina was 50% and the prevalence ranged from 22% to 72% for the other allergens including cockroach, mosquito and house dust mites. The data collection tools were safe and well tolerated by participants with no adverse events reported. Self-reported respiratory symptoms, abnormal lung function and elevated FeNO were recorded amongst participants sensitised to mopane worm.Conclusion: Pre-defined feasibility criteria were met with the exception of a lower than expected response rate for clinic data collection in this pilot study. For the main study, an increase in the sample size and more consistent community engagement will be applied to improve the response rates.
Design Principles and Traction Performance of a Novel Zero-spin Rolling Conical Traction Continuously Variable Transmission
Authors: Li Chao , Cao Xiuquan , Li Qing-tao 
Published: November 2020

Abstract
In the existing traction continuously variable transmission (CVT), half toroidal CVT (HT-CVT) is considered to have a better traction performance. However, the HT-CVT has the spin losses due to its structural limitations, which significantly influences the traction efficiency. In this paper, the kinematic qualities and contact models of a novel zero-spin rolling conical CVT (RC-CVT) are studied, and then the rollers and conical disks are compactly designed through the proposed design principles. Subsequently, the transmission efficiency is investigated by using a detailed numerical model and compared with HT-CVT. Based on these computational models and parameters, the practical spin ratio, spin momentum and traction efficiency of RC-CVT are calculated and compared with HT-CVT. The results show that the practical spin ratio and spin momentum of RC-CVT are much smaller than that of HT-CVT, and the efficiency on fixed transmission ratio is consequently higher than that of HT-CVT.