bluuebunny/crossref_metadata_2025 huggingface dataset:
Compared to plasma, bronchial washing fluid shows higher diagnostic yields for detecting EGFR-TKI sensitizing mutations by ddPCR in lung cancer
Authors: Lee Sang Hoon , Kim Eun Young , Kim Taehee , Chang Yoon Soo
Published: June 2020

Background: The rate of diagnosis of advanced lung adenocarcinoma must be improved. In this study, we compared the detection rates of EGFR-tyrosine kinase inhibitor-sensitizing mutations (mEGFRs) in bronchial washing fluid (BWF) and the plasma of patients with lung adenocarcinoma using the tissue genotype as the standard reference.Methods: Paired blood and BWF specimens were collected from 73 patients with lung cancer. The tumor EGFR mutation status was determined by genotyping of the plasma and BWF samples using droplet digital PCR (ddPCR).Results: The study cohort included 26, 10, 10, and 27 patients with stage I, II, III, and IV disease. Of the 73 cases, 35 had a wild-type EGFR, and 19 had the L858R substitution and exon 19 deletion mutations. The areas under the receiver operator characteristic curves for sensitivity vs. specificity of ddPCR were 0.895 [95% confidence interval (CI): 0.822–0.969] for BWF and 0.686 (95% CI: 0.592–0.780) for plasma (p < 0.001). The fractional abundance was higher in BWF of the mEGFR-positive cases than in the plasma (p = 0.004), facilitating easy threshold setting and discrimination between mEGFR-positive and negative cases. When genotyping results obtained using plasma and BWF were compared for early lung cancer (stages I–IIIA), the diagnostic yields were significantly higher for BWF ddPCR, and the same tendency was observed for the advanced stages, suggesting that the BWF data may reflect the genotype status in early-stage patients.Conclusions: The mEGFR genotyping results obtained using BWF showed a higher diagnostic efficacy than did those obtained using the plasma. Thus, BWF-based genotyping may be a useful substitute for that using plasma in lung cancer.
Influence of Bacterial Organic Selenium on Blood Parameters, Immune Response, Selenium Retention and Intestinal Morphology of Broiler Chickens
Authors: Dalia A. M. , Loh T. C. , Sazili A. Q. , Samsudin Anjas Asmara
Published: June 2020

Background: Several studies indicated that dietary organic selenium (Se) usually absorbed better than an inorganic source, with high retention and bioavailability. Dietary Se as an antioxidant element affects the immune system and hematological status in animals. Therefore, the aim of this study was to evaluate the effect of dietary supplementation of bacterial selenium as an organic source on hematology, immunity response, selenium retention, and gut morphology in broiler chickens. Results: The present results revealed that supplementation of inorganic Se was associated with the lowest level of RBC, HB, and PCV with significant difference than ADS18-Se. In the starter stage, both T2 and T5 were associated with the significantly highest IgG level compared to the basal diet, while all supplemented groups showed higher IgM levels compared to the control group. In the finisher phase, all Se supplemented groups showed significant (P ˂ 0.05) increases in IgG, IgA, and IgM levels compared to T1. Birds fed bacterial-Se showed high intestinal villus height and better Se retention more than sodium selenite. The organic selenium of ADS18 had a superior action in improving Se retention compared to ADS1 and ADS2 bacterial Se. Conclusion: Bacterial organic Se had a beneficial effect on the villus height of small intestine led to high Se absorption and retention. Thus, it caused a better effect of Se on hematological parameters and immunity response.
Incidence and Mode of Deployment Failure of the Fast-Fix 360™ Meniscal Repair Device
Authors: Lawrie Steven Alan , Lawrie Angus , Vertullo Christopher
Published: June 2020

Background

Meniscal repair device deployment failure is a recognised complication of all-inside meniscal repair with subsequent risk of patient harm. The Fast-Fix device has undergone design changes to reduce deployment failure since its introduction in 2001.

Purpose

The purpose of this study was to assess the incidence and mechanism of intra-operative deployment failure of the 3 rd generation Fast-fix 360™ (Smith & Nephew, Andover, USA) device.

Method

Data was prospectively collected for 106 consecutive all-inside meniscal repairs undertaken with the Fast-fix 360™ device. Patient demographics, mechanism of failure, site and type of repair were recorded.

Results

20 deployment failures occurred in 423 Fast-fix 360™ deployments, an incidence of 4.72%. Deployment failure occurred in 19 of 109 patients an incidence of 17.43%. Six different failure mechanisms occurred; anchor exiting device without trigger being initiated, anchors not holding in meniscus, both anchors simultaneously exiting device and braided suture failing. The most common failure mechanism was failure of the second anchor not holding in the meniscus.

Average cost of device failure was $75 per patient.

Conclusion

Despite design modification, deployment failure still occurs with similar modes top to the original design.
Laboratory colonization by Dirofilaria immitis alters the microbiome of female Aedes aegypti mosquitoes
Authors: Adegoke Abdulsalam , Neff Erik , Geary Amie , Husser Montana Ciara , Wilson Kevin , Norris Shawn Michael , Dharmarajan Guha , Karim Shahid
Published: June 2020

Background: The ability of blood feeding arthropods to successfully acquire and transmit pathogens of medical and veterinary importance has been shown to be interfered or enhanced by the arthropod’s native microbiome. Mosquitoes transmit bacteria, viruses, protozoan and filarial nematodes, majority of which contributes to the 17% of infectious disease cases worldwide. Dirofilaria immitis, a mosquito transmitted filarial nematodes of dogs and cats, is vectored by several mosquito species including Aedes aegypti.Methods: In this study, we investigated the impact of D. immitis colonization on the microbiome of laboratory reared female A. aegypti. Metagenomic analysis of the V3-V4 variable region of the microbial 16SRNA was used for identification of the microbial differences down to species level.Results: We generated a total of 1068 OTUs representing 16 phyla, 181 genera and 271 bacterial species. Overall, in order of abundance, Proteobacteria, Bacteroidetes, Actinobacteria and Firmicutes were the most represented phylum with D. immitis infected mosquitoes having more of Proteobacteria (71%) than uninfected mosquitoes (56.9%). An interesting finding in this study is the detection of Klebsiella oxytoca in relatively similar abundance in infected and uninfected mosquitoes, suggesting a possible endosymbiotic relationship. It has been previously shown to indirectly compete for nutrients with fungi on the domestic housefly eggs and larva. While D. immitis colonization has no effect on the overall species richness, we identified significant differences in the composition of selected bacteria genus and phylum between the two groups. We also reported distinct compositional and phylogenetic differences in the individual bacteria species when commonly identified bacteria were compared.Conclusions: In conclusion, this is the first study to the best of our knowledge to understand the impact of a filarial infection on the microbiome of its mosquito vector. Further studies is required to identify bacteria species that could play an important role in the mosquito biology. While the microbiome composition of A. aegypti mosquito have been previously reported, our study shows that in an effort to establish itself, a filarial nematode modifies and alters the overall microbial diversity within its mosquito host.
What is the level of uptake of Partner Notification Services in HIV testing in Selected Health Facilities in Gatanga Sub County, Muranga County – Kenya; a retrospective Study﻿
Authors: Kariuki Rewel , Rithaa Gilbert Koome , Elvis Oyugi , Gachathi Daniel
Published: June 2020

Background: Identification of people living with HIV is key in HIV prevention and control. Partner Notification service is a World Health Organization backed strategy of reaching out to sexual partners of people diagnosed with HIV for HIV testing. However, its adoption and success rate in Kenya remains unknown.Methods: A cross sectional facility based study was undertaken in five purposely selected health facilities in Gatanga Sub county, Muranga County, Kenya. A retrospective review of patient medical records data for HIV positive index clients and their Sexual Partners conducted. Census approach was applied to extract data for study subjects from Partner Notification Services registers for the period covering January 2017 to August 2018. Epi Info software was used for data analysis.Results: A total of 183 index clients were offered Partner notification services. The mean age of the indexed clients studied was 39(SD ±13.1). Females comprised 64 % of clients studied. Of the 183 indexed clients, 89% accepted the services and elicited 216 sexual partners for tracing. The ratio of elicited sexual partners to index client was 1.3:1. Out of the 216 sexual partners, 77% were reached and tested. A total of 46 [32%] of the sexual partners elicited and traced, tested HIV positive. The most preferred approaches were provider referral (51%) and contract referral (45%). Dual referral (4%) was the least preferred approach. Conclusions: Assisted Partner notification services is acceptable and an effective strategy of increasing HIV case identification and raising awareness to exposed sexual partners in low resource countries.
Firing activity of locus coeruleus noradrenergic neurons decreases in necdin-deficient mice, an animal model of Prader–Willi syndrome
Authors: Wu Rui-Ni , Hung Wei-Chen , Chen Ching-Tsuey , Tsai Li-Ping , Lai Wen-Sung , Min Ming-Yuan , Wong Shi-Bing
Published: June 2020

Background Prader–Willi syndrome (PWS) is a neurodevelopmental disorder characterized by multiple respiratory, cognitive, endocrine, and behavioral symptoms, such as central apnea, intellectual disabilities, exaggerated stress responses, and temper tantrums. The locus coeruleus noradrenergic system (LC-NE) modulates a diverse range of behaviors, including arousal, learning, pain modulation, and stress-induced negative affective states, which are possibly correlated with the pathogenesis of PWS phenotypes. Therefore, we evaluated the LC-NE neuronal activity of necdin-deficient mice, an animal model of PWS. Methods Heterozygous necdin-deficient mice (B6.Cg-Ndn tm1ky ) were bred from wild-type (WT) females to generate WT (+m/+p) and heterozygotes (+m/−p) animals, which were examined of LC-NE neuronal activity, developmental reflexes and plethysmography. Results On slice electrophysiology, LC-NE neurons of Ndn tm1ky mice with necdin deficiency showed significantly decreased spontaneous activities and impaired excitability, which was mediated by enhanced A-type voltage-dependent potassium currents. Ndn tm1ky mice also exhibited the neonatal phenotypes of PWS, such as hypotonia and blunt respiratory responses to hypercapnia. Conclusions LC-NE neuronal firing activity decreased in necdin-deficient mice, suggesting that LC, the primary source of norepinephrine in the central nervous system, is possibly involved in PWS pathogenesis.
The considerations, experiences and support needs of family members making treatment decisions for patients admitted with major stroke: a qualitative study.
Authors: Visvanathan Akila , Mead Gillian , Dennis Martin , Whiteley William , Doubal Fergus , Lawton Julia
Published: June 2020

Background Treatment decision-making by family members on behalf of patients with major stroke can be challenging because of the shock of the diagnosis and lack of knowledge of the patient’s treatment preferences. We aimed to understand how, and why, family members made certain treatment decisions, and explored their information and support needs. Method Semi-structured interviews with family members (n=24) of patients with major stroke, within two weeks of hospital admission. Data were analysed thematically. Results Families’ approach to treatment decision-making lay on a spectrum according to the patient’s state of health pre-stroke (i.e. patient’s prior experience of illness and functional status) and any views expressed about treatment preferences in the event of life-threatening illness. Support and information needs varied according to where they were on this spectrum. At one extreme, family members described deciding not to initiate life-extending treatments from the outset because of the patients’ deteriorating health and preferences expressed pre-stroke. Information from doctors about poor prognosis was merely used to confirm this decision. In the middle of the spectrum were family members of patients who had been moderately independent pre-stroke. They described the initial shock of the diagnosis and how they had initially wanted all treatments to continue. However, once they overcame their shock, and had gathered relevant information, including information about poor prognosis from doctors, they decided that life-extending treatments were no longer appropriate. Many reported this process to be upsetting and expressed a need for psychological support. At the other end of the spectrum were family members of previously independent patients whose preferences pre-stroke had not been known. Family members described feeling extremely distressed at such an unexpected situation and wanting all treatments to continue. They described needing psychological support and hope that the patient would survive. Conclusion The knowledge that family members’ treatment decision-making approaches lay on a spectrum depending on the patient’s state of health and stated preferences pre-stroke may allow doctors to better prepare for discussions regarding the patient’s prognosis. This may enable doctors to provide information and support that is tailored towards family members’ needs.
Bone mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury
Authors: zhou song , Qiao Yu-ming , Liu Yong-guang , Liu Ding , Hu Jian-min , Liao Jun , Li Min , Guo Ying , Fan Li-pei , Li Liu-Yang , Zhao Ming
Published: June 2020

Background: Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect; however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow mesenchymal stem cells (BMSCs) for AKI treatment.Results: We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated SIRT1 and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did.Conclusions: Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.
Knowledge, attitude, motivation and planning of breastfeeding: A cross-sectional study among Jordanian women
Authors: khasawneh wasim , Kheirallah Khalid , Mazin Mai , Abdulnabi Sanaa
Published: June 2020

Background In Jordan, the rate of exclusive breastfeeding is declining. The trend variation in breastfeeding practice is determined by different factors including antenatal women’s attitude and planning which are affected by their awareness and the support they receive. This study aims to assess knowledge, attitude, support, and planning of breastfeeding among Jordanian women.Methods A face-to-face cross sectional semi-structured questionnaire survey was conducted among healthy women in the antenatal clinic and postpartum ward at three hospitals in Northern Jordan during the period August 2019 to December 2019. Data were collected about demographic characteristics, women’s knowledge and attitude towards breastfeeding, antenatal and postnatal support and counseling, and feeding planning. Customized scales were utilized to assess knowledge and attitude. Factors associated with planning to breastfeed were reported.Results 660 women completed the survey questionnaire. The majority were 20 to 35 years of age, 10% were primiparous, and 30% were employed. 78% were knowledgeable about breastfeeding benefits and aware of WHO recommendations. 72% had a positive attitude towards breastfeeding. More than half received support from their husbands to breastfeed their infants, while less than 20% received any counseling from their obstetric providers. 97% reported their intention to breastfeed, and more than half indicated their willingness to breastfeed exclusively. With multilogistic regression modelling, predictors of EBF planning include: primiparity (AOR 1.79 95% C.I 1.1, 3.25), positive attitude (AOR 1.80 95% C.I 1.05, 3.1) and positive husband’s support (AOR 1.92 95% C.I. 1.18, 3.15). Barriers include women’s employment (AOR 0.43 95% C.I. 0.26, 0.70) and low birth weight (AOR 0.46 95% C.I. 0.25, 0.84)Conclusion Jordanian women are highly knowledgeable about breastfeeding benefits, and they exhibit a positive attitude towards breastfeeding resulting in a very high percentage intending to breastfeed their infants. Limited counseling about breastfeeding is a major gap in antenatal care. As intentions might not reflect the actual practice after delivery, gaps and barriers affecting the determinants of successful breastfeeding should be identified, and corrective tools should be implemented accordingly. Allocating a specific time for antenatal or postnatal counseling and support is expected to promote breastfeeding practice in our population.
Perinatal listeriosis patients at a maternity hospital in Beijing, China, during 2013 – 2018
Authors: Li Chunyun , Zeng Huihui , Ding Xin , Chen Yi , Liu Xiaowei , Zhou Li , Wang Xin , Cheng Yumei , Hu Shanshan , Cao Zheng , Liu Ruixia , Yin Chenghong
Published: June 2020

Background: Listeriosis is a rare but severe foodborne infectious disease. Perinatal listeriosis is extremely prone to causing septicaemia, central nervous system (CNS) infection, and serious adverse pregnancy outcomes (abortion and neonate death). This research reports perinatal listeriosis cases over the course of six years at Beijing Obstetrics and Gynecology Hospital (BOGH), which is the largest maternity hospital in China.Methods: We retrospectively searched all the laboratory confirmed pregnancy-associated listeriosis cases during Jan 1, 2013 to Dec 31, 2018. The clinical manifestations, laboratory results, perinatal complications and outcomes (follow-up for half a year after birth) were investigated.Results: In BOGH, 12 perinatal listeriosis cases were diagnosed based on Listeria monocytogenes positive culture, including 10 single pregnancies and 2 twin pregnancies, and the incidence of which is 13.7/100,000 deliveries. Among those cases, four pregnant women and four newborns had septicaemia, and two of the neonatal septicaemia also got CNS infection. All the maternal patients recovered. For the fourteen offsprings, there were 8 newborns and 6 aborted fetuses, with two newborns died and 6 survived among the 8 newborns, and none of survivors had sequelae. The feto-neonatal fatality ratio is 57.1%.Conclusions: Perinatal listeriosis is associated with high mortality, which has become a public health concern. Subsequently, further researches about perinatal listeriosis among a wider range of population are needed to strengthen the epidemiological understanding of listeriosis in China.
Effects of strontium ions with potential antibacterial activity on in vivo bone regeneration
Authors: Baheiraei Nafiseh , Eyni Hossein , bakhshi Bita , Najafloo Raziyeh
Published: June 2020

Background: Bioactive glasses (BGs) have attracted added attention in the structure of the scaffolds for bone repair applications. Different metal ions could be doped in BGs to induce specific biological responses. Among these ions, strontium (Sr) is considered as an effective and safe doping element with promising effects on bone formation and regeneration.Methods: In this experiment, we evaluated the antibacterial activities of the gelatin-BG (Gel-BG) and Gel-BG/Sr scaffolds in vitro. The osteogenic properties of the prepared scaffolds were also assessed in rabbit calvarial bone defects for 12 weeks. Alizarin Red, Hematoxylin & Eosin (H&E) and Masson’s Trichrome staining were performed to assess bone regeneration and the obtained results were compared with those without Sr. Also, histomorphometric data were obtained to evaluate the new bone, residual graft, and connective tissue.Results: Both scaffolds showed in vivo bone formation during 12 weeks with the newly formed bone area in Gel-BG/Sr scaffold was higher than that in Gel-BG scaffolds after the whole period. Based on the histological results, Gel-BG/Sr exhibited acceleration of early-stage bone formation in vivo. The results of antibacterial investigation showed that although both Gel-BG/Sr and Gel-BG effectively inhibited the growth of Escherichia coli (E. coli) but, only Gel-BG/Sr structure could lead to a 3 log reduction in Staphylococcus aureus (S. aureus). Conclusions: Our results confirmed that Sr doped BG is a favorable candidate for bone tissue engineering with superior antibacterial activity and bone regeneration capacity compared with similar counterparts having no Sr ion.
Association between dietary patterns and cognitive ability in 10-15 years old Chinese children: Evidence from the 2010 China Family Panel Studies
Authors: Wang Tiantian , Cao Shiyi , Li Dandan , Chen Fan , Jiang Qingqing , Zeng Jing
Published: June 2020

Background: At present, limited information is available concerning the association between dietary patterns and cognitive ability during childhood and adolescence, especially in regards to the epidemiological studies in China. Therefore, This study aimed to analyze the association between dietary patterns and cognitive ability in 10 to 15 year-old Chinese children. Methods: The dietary information, cognitive ability and sociodemographic data of 2029 children were retrieved from the 2010 China Family Panel Studies (CFPS). Dietary patterns were assessed by principal component analysis (PCA). The association between dietary patterns and cognitive ability was determined using Ordinal-Logistic regression models. Results: Three dietary patterns were identified, namely, ‘High protein’, ‘High fat’ and ‘High salt-oil’. Following adjustment for gender, age, nationality, household registration, school types, parents’ education level, family learning environment, annual household income and family size, we found that an increase in ‘High protein’ pattern score was significantly associated with higher scores of mathematics test (OR=1.62, CI: 1.23~2.15; P=0.001), but not with those of vocabulary test (OR=1.21, CI: 0.93~1.58; P=0.149). Besides, an increase of ‘High fat’ pattern score was significantly associated with lower score of mathematics (OR=0.76, CI: 0.59~0.98; P=0.031) and vocabulary (OR=0.77, CI: 0.61~0.97; P=0.029) test. However, there was no significant association between ‘High salt-oil’ pattern and the score of mathematics (OR=0.99, CI:0.77~1.27; P=0.915) and vocabulary (OR=0.93, CI:0.73~1.18; P=0.544) test.Conclusions: The findings of this study indicate that ‘High protein’ pattern is positively associated with cognitive ability in Chinese children, while ‘High fat’ pattern exhibits a negative association.
MiR-21-3p regulation FGFR1/FGF21/PPARγ pathway induces atrial fibrosis by targeting FGFR1 in diabetes
Authors: Pan Jian-an , Lin Hao , Yu Jian-ying , Zhang Hui-li , Zhang Jun-feng , Wang Chang-qian , Gu Jun
Published: June 2020

Background: A relationship between the abundance of epicardial adipose tissue (EAT) and the risk of atrial fibrosis and atrial fibrillation (AF) in diabetes mellitus (DM) has been reported. And previous studies have shown that MicroRNA-21 (miR-21) is a regulatory factor in atrial fibrosis and AF. The aim of this study was to examine the role of different subtypes of miR-21 in EAT browning and atrial fibrosis under hyperglycemia conditions.Methods: In vivo, C57BL/6 wild type (WT) and miR-21 knockout (KO) mice were used to establish the diabetic model by intraperitoneal injection of streptozotocin (STZ). In vitro, the EAT adipocytes from miR-21 KO mice were cultured and transfected with miR-21-3p mimic or miR-21-5p mimic and co-cultured with atrial fibroblasts in both HG or LG conditions. The browning of EAT and the fibrosis of fibroblasts were assessed by western blotting, immunofluorescence, Masson staining, and ELISA. The gain- and loss-of-function experiments were used to identified fibroblast growth factor receptor 1 (FGFR1) as the target gene of miR-21-3p.Results: In patients with DM and/or AF, serum hsa-miR-21-3p, instead of hsa-miR-21-5p, was significantly up-regulated. And miR-21 KO clearly ameliorated the atrial fibrosis in the diabetic mice. miR-21-3p as a key regulator that controls EAT browning and participates in atrial fibrosis under hyperglycemia conditions. Moreover, our gain- and loss-of-function experiments showed that FGFR1, as a direct target of miR-21-3p identified a regulatory pathway in EAT adipocytes. Conclusions: MiR-21-3p regulated EAT browning and participated the process of hyperglycemia-induced atrial fibrosis by targeting FGFR1.
Evaluation of commercial veterinary probiotics containing enterococci for transferrable vancomycin resistance genes
Authors: Berreta Ana , Baumgardner Rachel M , Kopper Jamie Jennifer
Published: June 2020

Objective: Vancomycin resistant enterococci (VRE) are of significant public health concern. The identification of VRE in livestock and food has increased. The objective of this study was to determine if the transferrable vancomycin resistance genes vanA and vanB were present in probiotics marketed for use in animals that claimed to contain Enterococcus spp. Results: Of the 40 products selected, Enterococcus spp. DNA was successfully extracted from 36 products. Of these 36 products with enterococcal DNA, 2 (6%) had a PCR product consistent with vanA which was confirmed by sequencing. None of the products appeared to contain vanB.
RalB degradation by dihydroartemisinin induces autophagy and IFI16/caspase-1 inflammasome depression in the human Laryngeal squamous cell carcinoma
Authors: Shi Xinli , Li Shenghao , Wang Li , Li Hui , Li Zhen , Wang Weiyi , Bai Jing , Sun Yajing , Li Jianchun , Li Xiaoming
Published: June 2020

Background Interferon-inducible 16 (IFI16) /caspase-1 inflammasome activates and secretes IL-1β. However, whether the IFI16 inflammasome involved in human Laryngeal squamous cell carcinoma is still unclear. Autophagy directly removed inflammasome components and limited early IL-1β production. RalB is required for the crosstalk between inflammasome and autophagy in macrophages. Dihydroartemisinin (DHA), the main derived ingredient of artemisinin, has a variety of biological activities. The mechanism of DHA in regulation the crosstalk between IFI16 inflammasome and autophagy by inhibiting RalB expression was analyzed in order to provide clues for new therapeutic methods in laryngeal cancer. Methods The expression of IFI16 was analyzed by Oncomine and GEPIA databases and detected by Western blot and immunohistochemistry. The relationship between IFI16 inflammasome and autophagy was investigated by transmission electron microscopy, immunofluorescence assay, etc. in Hep-2, Cal-27 and HeLa cells with DHA treatment. Hep-2 cell xenograft tumor in nude mice were used to assess the effect of DHA on laryngeal cancer. Results The study was firstly reported that IFI16 was overexpressed and positively correlated with caspase-1 in laryngeal carcinoma tissues. DHA alone or in combination with cisplatin significantly inhibited inflammasome activation and reduced IL-1β production in the xenograft tumor microenvironment of Hep-2 cell xenograft tumor in nude mice. Mechanistically, we found that DHA degraded RalB by inhibiting USP33 expression, leading to triggered autophagy. Meanwhile, enhanced autophagy can reduce the expression of RalB and USP33. Therefore, DHA depresses RalB, resulting in formation a positive feedback loop between USP33 and autophagy. Further, DHA promotes autophagy, which suppresses the IFI16/caspase-1 inflammasome activation and IL-1β production. Conclusions Therefore, our findings demonstrate that DHA may act as a RalB inhibitor to regulate the crosstalk between autophagy and IFI16/caspase-1 inflammasome, which inhibits IL-1β production in tumor microenvironment.
Predicting the Treatment Response of Certolizumab for Individual Adult Patients with Rheumatoid Arthritis: Protocol for An Individual Participant Data Meta-Analysis
Authors: Luo Yan , Chalkou Konstantina , Yamada Ryo , Funada Satoshi , Salanti Georgia , Furukawa Toshi A.
Published: June 2020

Background A model that can predict treatment response for a patient with specific baseline characteristics would help decision-making in personalized medicine. The aim of the study is to develop such a model in the treatment of rheumatoid arthritis (RA) patients who receive certolizumab (CTZ) plus methotrexate (MTX) therapy, using individual participant data meta-analysis (IPD-MA).Methods We will search Cochrane CENTRAL, PubMed, and Scopus as well as clinical trial registries, drug regulatory agency reports, and the pharmaceutical company websites from their inception onwards to obtain randomized controlled trials (RCTs) investigating CTZ plus MTX compared with MTX alone in treating RA. We will request the individual-level data of these trials from an independent platform (http://vivli.org). The primary outcome is efficacy defined as achieving either remission (based on ACR-EULAR Boolean or index-based remission definition) or low disease activity (based on either of the validated composite disease activity measures). The secondary outcomes include ACR50 (50% improvement based on ACR core set variables) and adverse events. We will use a two-stage approach to develop the prediction model. First, we will construct a risk model for the outcomes via logistic regression to estimate the baseline risk scores. We will include baseline demographic, clinical and biochemical features as covariates for this model. Next, we will develop a meta-regression model for treatment effects, in which the stage-one risk score will be used both as a prognostic factor and as an effect modifier. We will calculate the probability of having the outcome for a new patient based on the model, which will allow estimation of the absolute and relative treatment effect. We will use R for our analyses, except for the second stage which will be performed in a Bayesian setting using R2Jags.Discussion This is a study protocol for developing a model to predict treatment response for RA patients receiving CTZ plus MTX in comparison with MTX alone, using a two-stage approach based on IPD-MA. The study will use a new modeling approach, which aims at retaining the statistical power. The model may help clinicians individualize treatment for particular patients.Systematic review registration PROPSPERO registration number pending (ID#157595).
The effects of family, society and national policy support on treatment adherence among newly diagnosed tuberculosis patients: a cross-sectional study
Authors: Chen Xu , Du Liang , Wu Ruiheng , Xu Jia , Ji Haoqiang , Zhang Yu , Zhu Xuexue , Zhou Ling
Published: June 2020

Background: Non-adherence to tuberculosis (TB) treatment is the most important cause of poor TB treatment, and improving support for TB patients is a primary priority for governments, but there has been little research on the effects of family, social and national policy support factors on TB treatment adherence. The current study evaluated the treatment adherence of newly diagnosed TB patients in Dalian, northeast of China, and determined the effects of family, society, national policy support factors on treatment adherence. Methods: A cross-sectional survey was conducted among newly diagnosed TB patients treated at the outpatient department of Dalian Tuberculosis Hospital from September 2019 and January 2020. Data were collected using questionnaire that measured medication adherence, family support, social support, and national policy support and so on. Differences between groups were assessed using the chi-square test and Fisher’s exact tests. Ordinal logistic regression analysis was used to determine the predictors of adherence. Results: A total of 481 newly diagnosed TB patients were recruited, of whom 45.7% had good adherence, and 27.4% and 26.8% had moderate and low adherence, respectively. Patients with family members' frequent supervision of medication (OR:0.34, 95% CI:0.16-0.71), family members' often spiritual encouragement(OR:0.14, 95% CI:0.03-0.80), good doctor-patient relationship (OR:0.58, 95% CI:0.38-0.88), more TB-related knowledge (OR:0.49, 95% CI:0.33-0.72) and high need for TB treatment policy support (OR:0.39, 95% CI:0.22-0.67) performed satisfactory medication adherence. However, patients with a college degree or higher (OR:1.78, 95% CI:1.10-2.88) were more likely to have a lower adherence.Conclusions: Our findings suggested that non-adherence was high in newly diagnosed TB patients. Family members' frequent supervision of medication and spiritual encouragement, good doctor-patient relationship and TB-related knowledge, high need for policy support contributed to high adherence. It is recommended to strengthen the training of medical staff and the health education of patients and their families, increase the financial support for improve adherence.
Spatial Estimation of Soil Erosion Using RUSLE Modeling: A case study of Dolakha District, Nepal
Authors: Thapa Pawan
Published: June 2020

Background: In the mountainous areas, soil erosion causes the topsoil loss which decreases fertility in the agricultural land. Spatial estimation of soil erosion essential for an agriculture-dependent country like Nepal for developing erosion control plans. This study was conducted for estimation of soil erosion impacts on Dolakha using the Revised Universal Soil Loss Equation (RUSLE) model, also analyzes the effect of Land Use and Land Cover (LULC) on soil erosion.Results: The soil erosion rate had been categorized into 6 erosion classes based on the erosion severity, and 5.01% of the areas was found to be under extreme severe erosion risk (> 80 Mg ha-1yr-1) that should be addressed by decision-maker for reducing its rate and consequences. Followed by 10 % areas were classified under high to severe with the rate of soil loss range from 10 to 80 Mg ha-1yr-1. While 15% and 70% of areas remained in moderate and low-risk zone respectively. The results suggest this district northeastern part suffers from a high soil erosion risk due to steep slope.Conclusions: The result produces a spatial distribution of soil erosion over Dolakha, which can be applied for conservation and management planning processes, at the policy level, by land-use planners and decision-makers.
Statistical Joint Modeling on Longitudinal Body Weight and CD4 Cell Progression with Survival Time-to-Death Predictors on HIV/AIDS Patients in Mekelle General Hospital, Ethiopia.
Authors: Gebrerufael Gebru , Asfaw Zeytu , Melese Dessie
Published: June 2020

Background

This study assessed the impact of repeated biomarker measurements of statistical joint modeling on survival time-to-death and determines potential predictors of HIV/AIDS patients on ART in Mekelle General Hospital Ethiopia.
Methods

A retrospective cohort study was conducted among HIV/AIDS patients who were under ART follow-up during September 11, 2013 - September 5, 2016 at Mekelle General Hospital, Ethiopia. The two repeated biomarkers of longitudinal measurements and survival outcome with separate

univaraite
longitudinal modeling approach and statistical joint modeling approach were used to fit simultaneously. A total of 216 HIV/AIDS patients were selected by using systematic random sampling technique from ART follow-up.
Results

The relationship between the two biomarkers CD4 cell and body weight with risk for survival time-to-death were statistical insignificant. Thus, death is less probable to occur in HIV/AIDS patients with higher value of CD4 cell count and body weight progression. In event process the sub-model, Baseline CD4, Fair and Good Adherence, HIV/TB (yes) and Sex (male) were significant factors of risk to short survival Time-to-Death on HIV/AIDS patients. In the 1st longitudinal process sub-model, Baseline CD4, Ambulatory functional status, HIV/TB (yes), Time*Ambulatory functional status, Time*Working functional status and Time*Baseline CD4 were the significant factors of

\sqrt{CD4 cell }
count progression. Moreover, In 2nd longitudinal process sub-model, visit Time of follow-up, Age, Sex (male), Baseline weight, Time*Ambulatory and Time*Working functional status were the significant factors of log 10(body weight) progression.
Conclusion

Both governmental and non-governmental stakeholders should pay special attention for HIV positive adults, especially for those who had developed HIV/TB, male, bedridden functional status, poor adherence and lower Baseline CD4 cell count progression so that mortality due to HIV/AIDS optimally reduced.
Prevalence and Associated Factors of Intestinal Parasites in Ethiopian Ortodox Tewahido Church Religious Students, Ethiopia
Authors: Addisu Ayenew , Gebre Habtamu , Tesfaye Sara , Zewdu Mola , Birhanie Meseret
Published: June 2020

Background

Intestinal parasitic infections are the most serious medical and public health problems in developing countries. In Ethiopia, intestinal parasites are among the top ten causes of morbidity, especially in children. The aim of this study was to assess the prevalence and associated factors of intestinal parasites among Ethiopian Orthodox church school students in Gondar town, northwest Ethiopia.
Method:

an institutional-based cross-sectional study was conducted to assess the prevalence and associated factors of intestinal parasites among religious students in Gondar town from February 2019 to April 2019, northwest Ethiopia. A total of 360 participants were selected by the random sampling technique.
Results

In this study, a total of 360 Orthodox Tewahido church school students were participated. The over all parasite prevalence, 24.7% was relatively low compared with previous studies conducted in other localitie in Ethiopia. The predominanat parasites were A. lumbricoides S. mansoni and hookworm with (11.4%), (4.4%) and (3.6%) prevalence respectively, A significant association was observed among participants with habits of frequent swiming with 2.3 times higher probability of acquaring infections, but there was no association with gender, age, finger nail status, the habit of eating uncooked vegetables/ fruits, source of drinking water and proper toilet utilization.
Conclusion

In general, the prevalence of intestinal parasite infections was high and calls for intervention actions on Orthodox Tewahido church students. Moreover, swimming frequency and habits had a significant association. Since the prevalence was high, improvement in awareness and enhancing health seeking behavior of the students, deworming and health education need to be focused on.
Clinical features and neuropsychiatric comorbidities in pediatric patients with tic disorders
Authors: Park Eu Gene , Kim Young-Hoon
Published: June 2020

Background
Tic disorders are childhood-onset neuropsychiatric disorders characterized by multiple motor or vocal tics with frequent comorbidities and a broad spectrum of phenotypic presentations. In this study, we aimed to investigate the clinical characteristics and comorbid neuropsychiatric conditions in pediatric patients with tic disorders.
Methods
We retrospectively reviewed the medical records of 119 pediatric patients (89 males, 30 females) who were diagnosed with tic disorders according to the Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-Ⅴ) at Uijeongbu St. Mary’s Hospital, Republic of Korea, between January 2012 and July 2019. Statistical comparisons were performed using Fisher’s exact test, Pearson’s chi-square test, Student’s t-test, and the Kruskal-Wallis test. Spearman’s rank correlation coefficient was used to conduct correlational analyses.
Results
The mean age of tic onset was 6.9 years (range, 1–14) and the mean age at diagnosis was 8 years (range, 1–17). The mean lag between tic onset and diagnosis was 13.3 months (range, 0.25–132). The most common, first-presenting tics were eye blinking (50.4%), followed by jaw or lip movement (29.4%) and throat clearing (29.4%). Thirty-seven (31.1%) patients had at least one co-occurring neuropsychiatric disorder at the time of tic diagnosis. Subtypes of tic disorders, types of first-presenting tics, and presence of neuropsychiatric comorbidities were not associated with tic severity. Tic severity was associated with greater functional impairment and tic noticeability (P < 0.05). A relatively shorter time to diagnosis was associated with tic severity (Spearman’s ρ = − 0.147, P = 0.110).
Conclusions
The evolving nature of tic expression and severity, high prevalence of neuropsychiatric comorbidities, and associated functional impairments emphasize the importance of comprehensive assessment during the disease course for determining and prioritizing goals of treatment.
Overexpression of miR-146a-5p alleviate SDF1-induced cartilage degradation through repression TRAF6 mediated p38-MAPK signal pathway
Authors: Wang Guoliang , Yang Xiao , Xiang Yaoyu , He Lu , Jia Di , Li Yanlin
Published: June 2020

Background : Previous study have revealed that miR-146a-5p has a role in osteoarthritis (OA) development, here, we aim to further explore the underlying mechanism of miR-146a-5P in OA both in vitro and in vitro . Methods : RT-PCR was used to detect the level of miR-146a-5p in OA patients. Primary chondrocytes were treated with SDF-1 to induce an OA model in vitro , and an IL-1β mediated OA model in rats were also used. Gain- or loss- of function assays of miR-146a-5p and TRAF6 were conducted to determine their roles in regulating the proliferation, apoptosis and cartilage degradation of chondrocytes. Results : MiR-146a-5p was overexpressed in OA patients while downregulated in SDF-1 treated chondrocytes. Functionally, miR-146a-5p considerably accelerated the proliferation, inhibited apoptosis and limited ECM degradation of SDF-1 induced chondrocytes. However, TRAF6 upregulation had the opposite effects. Moreover, miR-146a-5p also inhibited OA progression in vivo. Mechanistically, miR-146a-5p targeted at the 3’UTR of TRAF6 and relieved TRAF6 mediated p38-MAPK/NF-κB activation. Conclusions : MiR-146a-5p exerted protective effects chondrocytes against SDF-1 or IL-1β induced OA by regulating the proliferation, apoptosis and ECM degradation of chondrocytes by regulating the TRAF6/ p38-MAPK signaling pathway.
A Bibliometric Analysis of Folate Receptor Research: A comprehensive bibliometric analysis of the entire field of Folate Receptor Research
Authors: Didion Cari , Henne Walter
Published: June 2020

Background
The objective of this study is to conduct a comprehensible bibliometric analysis of the entire field of folate receptor research.
Methods
A Web of Science search was performed on folate receptor or folate binding protein (1969-to June 28, 2019). The following information was examined: publications per year, overall citations, top 10 authors, top 10 institutions, top 10 cited articles, top 10 countries, cc-author collaborations and key areas of research.
Results
In total, 3248 documents for folate receptor or folate binding protein were retrieved for the study years outlined in the methods section search query. The range was 1 per year in 1969 to 264 for the last full year studied (2018). A total of 123,720 citations for the 3,248 documents retrieved represented a mean citation rate per article of 38.09 and range of 1667 citations (range 0 to 1667). Researchers in 71 countries authored publications analyzed in this study. The US was the leader in publications and had the highest ranking institution. The top 10 articles have been cited 7270 times during the time frame of this study. The top cited article had an average citation rate of 110 citations per year. Network maps revealed considerable co-authorship among several of the top 10 authors.
Conclusion
Our study presents several important insights into the features and impact of folate receptor research. To our knowledge, this is the first bibliometric analysis of folate receptor.
The Axin2-snail Axis Promotes Bone Invasion by Activating Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma
Authors: An Yin-Zhe , Cho Eunae , ling Junqi , Zhang Xianglan
Published: June 2020

Background: In bone-invasive oral squamous cell carcinoma (OSCC), cancer-associated fibroblasts (CAFs) infiltrate into bony tissue ahead of OSCC cells. In the present study, we aimed to investigate the role of the Axin2-Snail axis in the biological behavior of CAFs and bone invasion in OSCC.Methods: The clinicopathological significance of Axin2 and Snail expression was investigated by immunohistochemistry in an OSCC cohort containing 217 tissue samples of patients with long-term follow-up. The influence of the Axin2-Snail axis on the biological behavior of OSCC cells and CAFs was further investigated both in vitro and in vivo.Results: Axin2 expression is significantly associated with Snail expression, status of desmoplasia, and bone invasion in patients with OSCC. In multivariate analysis, lymph node metastasis, desmoplasia, Axin2, and Snail expression were independent poor prognostic factors in our cohort. Supportively, OSCC cells demonstrated attenuated oncogenic activity as well as decreased expression of Snail and various cytokines after Axin2 knockdown in vitro. Among the related cytokines, C-C motif chemokine ligand 5 and interleukin 8 have a strong influence on the biological behavior of CAFs in vitro. Moreover, both the desmoplastic reaction and osteolytic lesions in the calvaria were predominantly decreased after Axin2 knockdown in OSCC cells in vivo using BALB/c athymic nude mice xenograft model. Conclusions: Oncogenic activities of the Axin2-Snail axis are not limited to the cancer cells themselves, but rather extend to CAFs by regulation of cytokine-mediated cancer-stromal interaction, with further implications for bone invasion as well as poor prognosis of OSCC.