bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Genomics Reveals a Convergent Signature on the Vitamin D Receptor (VDR) in Herbivorous Mammals
Authors: Wang Ziming , Liu Zhijin , Wang Xiaochen , Tan Xinxin , Qi Jiwei , Shen Ying , Zhou Xuming , Li Ming
Published: May 2021

Background: Dietary adaptation is one of hot topics in adaptive evolution of mammals. Herbivorous mammals generally digest structural carbohydrates (such as cellulose and hemicellulose) via intestinal microbial fermentation. However, the mechanism by which the host supports the intestinal fermentation capacity is still not well understood. To address this question, we conducted convergent amino acid scanning to identify candidate genes involving intestinal fermentation across mammalian phylogeny. Results: Among 4886 one-to-one orthologous genes, we found that 122 genes showed a significant increase of convergent signature in two foregut-fermenting families (Cercopithecidae: Rhinopithecus roxellana, Bovidae: Bos taurus and Ovis aries ) and particularly, in the vitamin D receptor (VDR), a convergent cysteine to serine substitution at amino acid 410 (VDR C410S) occurred in 14 mammalian families with intestinal fermentation capacity. As a critical role of VDR in the regulation of intestinal microbes and adaptive immunity, we employed phylogenetically independent contrast analysis to test whether the evolution of the VDR gene influenced intestinal fermentation and found this convergent amino acid substitution (VDR C410S) possess significant positively correlations with the intestinal fermentation capacity and the dietary components (plant parts except for fruits, seeds and nectar) consumed by 107 mammalian species, which indicated VDR have a positive impact on the herbivorous adaptation of intestinal fermentation. Conclusions: Our results suggest that nuclear receptor gene VDR involved in intestinal adaptive immune show rapid adaptive fixation of convergent amino acid substitutions (C410S) among herbivorous mammals with convergent methodology.
Screening of Iranian Tarragon Accessions Based on Physiological and Phytochemical Responses Under Water Deficit: Applications for Development and Breeding
Authors: Mumivand Hasan , Ebrahimi Amin , Shayganfar Alireza , Khoshro Hamid Hassaneian
Published: May 2021

In this study, screening of tarragon accessions based on physiological and phytochemical traits was investigated under water deficit. The compounding impacts of water deficit * accessions significantly altered the chlorophyll and carotenoid contetnt, malondialdehyde, electrolyte leakage, superoxide dismutase, catalase and ascorbate peroxidase. The HPLC analyse revealed the presence of chlorogenic, syringic, ferulic, vanilic, chicoric and p-coumaric acids as major phenolic acids, while quercetin and herniarin were detected as the predominant flavonoid and coumarin compounds in the extracts. The quality and quantity of tarragon secondary metabolites were impacted by water deficit, suggesting that drought stress either increased the amounts of some common compounds or introduced some new compounds that were not present under normal conditions. In some genotypes, the content of some secondary metabolites in tarragon had the highest values under severe water deficit stress. The results indicated that Hamadan, Varamin and Estahbanat accessions could be introduced as tolerant accessions. Due to the very different response of tarragon accessions to water deficit and the existence of diversity between these accessions, the findings of the present study could be an effective step in identifying and achieving homogeneous, drought-tolerant and high-yield potential accessions, and may help tarragon breeding programs and development of cultivation.
A Comprehensive Study on Knowledge, Attitude and Practices Concerning Dengue Fever Among Inhabitants of Dhaka, Bangladesh
Authors: Haque Md Ariful , Ying Xiong , Qazi Tariq Siraj , Jami Sayed Abdulla , Hussein Dahir , Antora Rifath Jahan , Tong Wu , Mobarak Siam Al , Bhuiyan Md Rifat Al Mazid , Jiayu Xiao
Published: May 2021

Background

Each year around the globe, thousands of people are affected by Dengue fever. Dhaka is a very highly populated city. The rate of Dengue transmission in Dhaka is increased over the year. Authority takes numerous steps to reduce the Dengue transmission. Nevertheless, without proper Knowledge of folks on Dengue government may not alone prevent Dengue. In these circumstances, this paper will find out the Knowledge, Attitude and Practice among Dhaka people. This study will help policymakers access the KAP among the people and set goals to improve the Dengue prevention program.
Methods

This study determines 57 questions under three components. Preliminary data were collected from Dhaka dwellers throughout the internet survey using convenience sampling is a non-chance sampling method. The mean value of variables and Standard deviation (SD) is used to investigate the characteristics of the Socio-demographic profile of the sample. The data were analyzed using the Pearson correlation and regression method.
Results

The study finds that in Dhaka, urban people have much better KAP of Dengue than people who live in the countryside area. Between Male and Female at Dhaka, male does have much better KAP rather than women. Gender influences the practice level regarding DHF but does not affect the Knowledge and Attitude towards DHF. That means people's Income can change the knowledge level on DHF. People affected by Dengue fever at any stage of life have a better understanding of KAP than people do who are never affected by Dengue fever. People affected by Dengue fever at any stage of life have a better understanding of KAP than people do who are never affected by Dengue fever.
Conclusion

This study will help the dengue prevention in Dhaka and will help to increase the KAP towards the general people
Perceived Knowledge Gap of Public Health Officer in Ethiopia
Authors: Ashengo Biniyam Altamo , Soklaridis Sophie
Published: May 2021

Background: Ethiopia has been training health officers as non-physician clinicians to meet the urgent public health service needs including preventive and health promotion as well as curative services. However, to date there is a lack of evidence of whether the curriculum content of the program meets the needs of the community. The purpose of this study was to explore the perception among health officers on whether the curriculum prepared them with what they need to know for practice when deployed to district hospitals and rural health centersMethod: A qualitative research design was used to explore health officer’s perceptions on the curriculum for clinical practice. The study was conducted in Dale district, Sidama region, southern Ethiopia. Data collection was done using semi-structured interview guide with open ended questions. The interview guide were developed using the first author’s experience as a health officer who recently graduated the program. All public health officers training graduates in the Dale districts, included in the study. Data analysis was done following a thematic analysis approach. The data was analyzed using ATLAS.ti qualitative data analysis software. Result: The study revealed a major curriculum-related gap which contributed to the perceived knowledge gap of public health officers. The main gap identified was the disproportional time allocation for very crucial courses of basic sciences and clinical practice during training. In addition the curriculum lacked a strict monitoring system of its implementation. Conclusion: Based on the result most participants believed the course content of the curriculum was very strong and crucial for public health officers. Some weakness of the curriculum were also identified which created the perceived knowledge gap of public health officers. The main weakness in the curriculum was that some of the courses were not proportionally allocated with adequate time for course contents like that of basic science and clinical courses.
Identification of inflammation related miRNA, lncRNA and mRNA in synovial tissue of knee osteoarthritis patients
Authors: qiao linghui , wang guancheng , han jie , liu yang , gu yanglin
Published: May 2021

Osteoarthritis is one of the most common chronic diseases in the elderly, which has caused a heavy burden to the family and society. At present, the clinical treatment can only be total joint replacement, but is hard to prevent the degeneration of cartilage tissue. The molecular mechanism of OA, especially the role of inflammation in disease progression, has been reported, but it is still unclear.Here, we first collected synovial tissues of 8 OA patients and 2 RA patients as controls, and detected the expression profiles of lncRNA, miRNA and mRNA in tissues by RNA-seq technology, and tried to find out the differentially expressed genes and key pathways in OA patients.Compared with the control group, 343 mRNAs, 270 lncRNAs and 247 miRNAs were significantly up-regulated, 232 mRNAs, 109 lncRNAs and 157 miRNAs were significantly down regulated. Then we predicted the targeted mRNAs of dysregulated lncRNAs. Through pathway enrichment and functional annotation of these target genes, we identified 12 differentially expressed transcripts related to inflammation, including CHST11, ALDH1A2, TREM1, IL-1β, IL-8, CCL5, LIF and miR-146a-5p, miR-335-5p, as well as lncRNA GAS5, LINC02288 and LOC101928134.In this study, we identified the differential expression of inflammation related genes and ncRNA in synovial tissue. These differentially expressed transcripts may indicate the network of ceRNA net in synovial tissue and its effect on OA progression. Our research will help to explore the pathogenesis and key therapeutic targets of OA.
Systematic Analysis of the Relationship Between Ovarian Cancer Prognosis and Alternative Splicing
Authors: Zhang Di , Zou Dan , Deng Yue , Yang Lihua
Published: May 2021

Background: Ovarian cancer(OC) is the gynecological tumor with the highest mortality rate, effective biomarkers are of great significance in improving its prognosis. In recent years, there have been many studies on alternative splicing (AS) events, and the role of AS events in tumor has become a focus of attention.Methods: Data were downloaded from the TCGA database and Univariate Cox regression analysis was performed to determine AS events associated with OC prognosis. Eight prognostic models of OC were constructed in R package, and the accuracy of the models were evaluated by the time-dependent receiver operating characteristic (ROC) curves. Eight types of survival curves were drawn to evaluate the differences between the high and low risk groups. Independent prognostic factors of OC were analyzed by single factor independent analysis and multi-factor independent prognostic analysis. Again, Univariate Cox regression analysis was used to analyze the relationship between splicing factors(SF) and AS events, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis were performed on OS-related SFs to understand the pathways.Results: Univariate Cox regression analysis showed that among the 15,278 genes, there were 31,286 overall survival (OS) related AS events, among which 1524 AS events were significantly correlated with OS. The area under the time-dependent receiver operating characteristic curve (AUC) of AT and ME were the largest and the RI was the smallest ,which were 0.757 and 0.68 respectively. The constructed models have good value for the prognosis assessment of OC patients. Among the eight survival curves, AP was the most significant difference between the high and low risk groups, with a P value of 1.61e−1.The results of single factor independent analysis and multi-factor independent prognostic analysis showed that risk score calculated by the model and age could be used as independent risk factors. According to univariate COX regression analysis ,109 SFs were correlated with AS events and adjusted in two ways: positive and negative.Conclusions: SFs and AS events can directly or indirectly affect the prognosis of OC patients. It is very important to find effective prognostic markers to improve the survival rate of OC.
Sequential Multiple Assignment Randomized Trial (SMART) To Identify Optimal Sequences Of Telemedicine Interventions For Improving Initiation of Insulin Therapy: A Simulation Study
Authors: Yan Xiaoxi , Matchar David B. , Goel Aastha , Sivapragasam Nirmali , Ansah John P. , Chakraborty Bibhas
Published: May 2021

Background: To examine the value of a Sequential Multiple Assignment Randomized Trial (SMART) design compared to a conventional randomized control trial (RCT) for telemedicine strategies to support titration of insulin therapy for Type 2 Diabetes Mellitus (T2DM) patients new to insulin. Methods: Microsimulation models were created in R using a synthetic sample based on primary data from 63 subjects enrolled in a pilot study of a smartphone application (App), Diabetes Pal compared to a nurse-based telemedicine strategy (Nurse). For comparability, the SMART and an RCT design were constructed to allow comparison of four (embedded) adaptive interventions (AIs). Results: In the base case scenario, the SMART has similar overall mean expected HbA1c and cost per subject compared with RCT, for sample size of n = 100 over 10000 simulations. SMART has lower (better) standard deviations of the mean expected HbA1c per AI, and higher efficiency of choosing the correct AI across various sample sizes. The differences between SMART and RCT become apparent as sample size decreases. For both trial designs, the threshold value at which a subject was deemed to have been responsive at an intermediate point in the trial had an optimal choice (i.e., the sensitivity curve had a U-shape). SMART design dominates the RCT, in the overall mean HbA1c (lower value) when the threshold value is close to optimal. Conclusions: SMART is suited to evaluating the efficacy of different sequences of treatment options, in addition to the advantage of providing information on optimal treatment sequences.
WITHDRAWN: Sodium-glucose Cotransporter 2 Inhibitors and Anemia Among Diabetic Patients in Real Clinical Practice: a Retrospective Observational Study.
Authors: Murashima Miho , Tanaka Tomohiro , Ide Atsuki , Ono Minamo Tomohiro , Mizuno Masashi , Suzuki Taisei , Hamano Takayuki
Published: May 2021

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were reported to increase hemoglobin levels in short-term clinical trials. Whether it is also true in real clinical practice is unknown. Methods: This is a retrospective cohort study. Inclusion criterion was diabetics who visited our outpatient clinic from January 2019 to August 2020. Exposure of interest was the use of SGLT2i. Outcomes were hemoglobin levels. For the cross-sectional analyses, non-linear regression models were fitted with restricted cubic splines to investigate the association between hemoglobin levels and estimated glomerular filtration rate (eGFR) for users and non-users of SGLT2i. For the case-control study, cases (anemia defined as hemoglobin <120 g/L for men, <110 g/L for women or the use of erythropoiesis stimulating agents) and controls were matched by age, sex, and eGFR. Results: Among 2063 diabetics, 723 were on SGLT2i. In the cross-sectional analyses, hemoglobin levels were higher among SGLT2i users compared with non-users at eGFR >15 mL/min/1.73m2. For the case-control study, 197 cases and controls were matched. Conditional logistic regression showed that the use of SGLT2i was associated with significantly lower prevalence of anemia (OR: 0.35 [0.21-0.58]). Adjusted mean differences (95% CIs) in hemoglobin levels between users and propensity score-matched non-users of SGLT2i were 7.0 (3.0-10.0) g/L at 6 months. Among SGLT2i users, odds of increase in 6-month hemoglobin were similar across eGFR categories except for eGFR <15 mL/min/1.73m2.Conclusions: The use of SGLT2i was associated with higher hemoglobin levels and lower prevalence of anemia in real clinical practice.
Modelling Conditional Volatility of NIFTY 50
Authors: NERLEKAR VARSHA SHRIRAM , Nerlekar Shriram
Published: May 2021

The present study demonstrates modelling of conditional volatility of NIFTY 50 using GARCH (1,1) model. The daily returns data of the Indian stock market index NIFTY 50 is used for the period ranging from April 2010- March 2020. The data is analysed using R software. The study estimates and interprets the results arrived in the summary output of the R environment and demonstrates how to forecast the volatility of the returns based on the estimated parameters. Extracting the time series of conditional volatilities is also demonstrated in the study.
Evaluation of Mental Health First Aid training program in Bangladesh: A modified Delphi study
Authors: Huque Akib Ul , Kawser Umme , Rahman Monira , Gnani Shamini , Rao Mala , Baskin Cleo , Mallick Pauroma Preety , Armstrong Stephanie
Published: May 2021

BackgroundBangladesh, like other low-resource countries, faces a shortage of a trained mental health workforce to meet its population's mental health needs adequately. The ongoing COVID-19 pandemic has further aggravated this. Mental health first aid (MHFA) is an internationally recognized training program that has been operating in Bangladesh since 2015. It offers a potential way to reduce the mental health treatment gap and skills shortage by training laypeople to help support individuals with mental health issues. The present study evaluated the effectiveness of MHFA training in Bangladesh. MethodsAn online modified Delphi study was conducted consisting of two rounds of a self-administered survey and a consensus workshop. A five-step logic framework was used to develop questionnaire statements (n=111) that consisted of 'general,' 'I,' and 'social impact' statements around the seven MHFA aims. The statements were constructed in English and adapted in Bangla. The expert panel consisted of 20 participants trained in the MHFA program. Participants anonymously stated their opinion on 111 round-1 statements and then on 27 low agreement statements in round-2. The consensus workshop facilitated a group discussion where participants explained their views on the low consensus items. ResultsThe consensus ranged from 61.5% (Aim 3: Promote recovery of good mental health) to 100% (Aim 7: To improve own health and well-being) with an overall consensus of 83.8%. 'Social impact' items produced the most (50%) disagreements. Participants' comments reflected 12 themes of MHFA's effectiveness in fostering and promoting mental health individually and socially. There were nine themes of disagreement reflecting individual, sociocultural, and political barriers to the implementation of MHFA in Bangladesh. Participants made recommendations for the MHFA and mental health initiatives in Bangladesh to increase mental health awareness, acceptance, and support in society.Conclusion﻿MHFA training offers Bangladesh and other low-and-middle-income countries a potential solution to tackle mental health burden at individual and societal levels and the additional challenges that the COVID-19 pandemic poses to mental health.
Serum Periostin and Cognitive Impairment in Ischemic Stroke Patients: a Prospective Cohort Study
Authors: Li Guangzong , Li Jie , Zhu Chen , Ye Jing , Wang Bin , Luo Xiaojing , Liu Mei
Published: May 2021

Background. Recent evidence suggest elevated periostin is associated with cardiovascular diseases. The aim of this study was to investigate the relationship between serum periostin and post-stroke cognitive impairment (PSCI) at 3 months. Methods. In this prospective cohort study, we enrolled patients with ischemic stroke and hospitalized within 7 days of symptoms onset from January 2019 to January 2020. Serum periostin levels were measured using enzyme-linked immunosorbent assay after admission. Cognitive function assessment was performed at 3-month follow-up visit using the Montreal Cognitive Assessment (MoCA). We defined the PSCI as total MoCA score < 25. Results. A total of 315 ischemic stroke patients were enrolled for the study. PSCI was observed in 173 patients, which accounted for 54.9% (95% confidence interval [CI] 52.1%–57.7%) of the cohort. Serum periostin levels were higher in patients with PSCI than in those without PSCI (median 19.6 vs 14.8 ng/mL; P = 0.001). In logistic regression analysis, the highest quartile of periostin levels were significantly correlated to PSCI (odds ratio [OR], 9.69; 95% CI, 5.06–25.61; P = 0.001), as compared with the lowest quartile. This association remained significant after adjustment for age, gender, educational years, stroke severity, and vascular risk factors. Subgroup analyses further confirmed these results. Furthermore, restricted cubic spline regression demonstrated a linear association between periostin levels and PSCI (P = 0.001 for linearity).Conclusions. This study found that higher serum periostin levels are associated with an increased risk of PSCI at 3 months after ischemic stroke onset.
Presenting Climate Projection Ensembles as Mean and Reasonable Worst Case, with Application to EURO-CORDEX Precipitation
Authors: Jewson Stephen , Messori Gabriele , Barbato Giuliana , Mercogliano Paola , Mysiak Jaroslav , Sassi Maximiliano
Published: May 2021

Users of ensemble climate projections have choices with respect to how they interpret and apply the ensemble. A simplistic approach is to consider just the ensemble mean and ignore the individual ensemble members. A more thorough approach is to consider every ensemble member, although for complex impact models this may be unfeasible. Building on previous work in ensemble weather forecasting we explore an approach in-between these two extremes, in which the ensemble is represented by the mean and a reasonable worst case. The reasonable worst case is calculated using Directional Component Analysis (DCA), which is a simple statistical method that gives a robust estimate of worst-case for a given linear metric of impact, and which has various advantages relative to alternative definitions of worst-case. We present new mathematical results that clarify the interpretation of DCA and we illustrate DCA with an extensive set of synthetic examples. We then apply the mean and worst-case method based on DCA to EURO-CORDEX projections of future precipitation in Europe, with two different impact metrics. We conclude that the mean and worst-case method based on DCA is suitable for climate projection users who wish to explore the implications of the uncertainty around the ensemble mean without having to calculate the impacts of every ensemble member.
Pesticides and Pesticide-Related Products in Ambient Air in Germany
Authors: Kruse-Plaß Maren , Hofmann Frieder , Wosniok Werner , Schlechtriemen Ulrich , Kohlschütter Niels
Published: May 2021

BackgroundTree bark measurements conducted between 2014 and 2017 in a biosphere reserve have indicated the presence of pesticides from conventional agriculture in ambient air in Germany. In the present study, we quantified pesticides and related substances in ambient air at 69 sites using passive air samplers and ventilation filter mats. It is, to our knowledge, so far the most comprehensive dataset on pesticides and their related products in ambient air in Germany. ResultsSamples were collected in 2019 and analysed for over 500 substances, of which 109 were detected, including 28 that are not approved for use in Germany. In each sampling site, we detected one to 36 substances, including at locations such as national parks and forests, where the presence of pesticides is not expected, e.g., on the highest mountain top in the national park “Harz” (13 substances) and in the "Bavarian Forest" (six substances). Glyphosate was detected in every sample. More than half of passive air samplers contained chlorothalonil, metolachlor, pendimethalin, terbuthylazine, prothioconazole-desthio, dimethenamid, prosulfocarb, flufenacet, tebuconazole, aclonifen, chlorflurenol, hexachlorobenzene (HCB), and γ-hexachlorocyclohexane (ɣ-HCH). Filter mats also contained boscalid. The statistical analysis showed that landscape classification and agricultural intensity were the primary factors influencing the number of substances detected in ambient air. Location, such as protected areas or regions of organic farming, had only a small effect on the number of substances recorded. Long-range transport likely accounts for the findings and active sampling of ambient air will probably detect more pesticides and higher concentrations than passive air sampler data presently suggest. ConclusionsAirborne pesticide mixtures are ubiquitous in Germany, which is particularly concerning for glyphosate, pendimethalin, and prosulfocarb. Deposition of these pesticides on organic products may disqualify them from the market, resulting in economic damage to farmers. Air concentrations of pesticides are a relevant issue and must be reduced.
Cimifugin Suppresses NF-κB Signaling to Prevent Osteoclastogenesis and Periprosthetic Osteolysis
Authors: Duan Juan , Hu Xuantao , Li Tao , Dou Pengcheng
Published: May 2021

Background: Aseptic loosening of prosthesis (ALP) is one of the most common long-term complication of knee and hip arthroplasty. Wear paticle-induced osteoclastogenesis and subsequent periprosthetic osteolysis accounts for the morbidity of ALP. Here, we investigate cimifugin (CIM), a natural extract from Cimicifuga Racemosa and Saposhnikovia Divaricata, as a bone protective drug in treatment of ALP.Method: First, we deployed cell viability and osteoclast formation assays to detect the effect of noncytotoxic CIM on osteoclast differentiation in vitro. Bone slice resorption evaluation and F-actin ring immunofluorescence assays were adopted to measure bone-resorbing function affected by CIM. Then, we introduce quantitative real-time polymerase chain reaction (qRT-PCR) analysis to further identify the repressed osteoclastogenesis by CIM in gene expression level. To reveal underlying mechanism of findings above, we used Western blotting and luciferase reporter gene assay to determine the regulation manner of CIM in NF-κB and MAPKs signaling pathways. Moreover, Ti particle-induced murine calvarial osteolysis model and following histomorphometric analysis via micro-CT and immunohistochemical staining were used to demonstrate the effect of CIM on periprosthetic osteolysis in vivo. Result: CIM administration dose-dependently inhibited both bone marrow-derived macrophages (BMMs) and RAW264.7 cells derived osteoclastogenesis and bone resorption pit formation in vitro, which further supported by reduced expression of F-actin and osteoclast specific genes. According to the Western blotting analysis, inhibition of IkBa phosphorylation in NF-κB signaling pathway, not the phosphorylation of MAPKs, was detected as the suppressive effect of CIM on osteoclastogenesis. In vivo animal experiment demonstrated that CIM alleviated Ti particle-induced bone erosion and osteoclast accumulation in murine calvaria. Conclusion: The current study for the first time proved that CIM could dose-dependently inhibit RANKL-induced osetoclastogenesis via suppressing NF-κB signaling pathway in vitro and prevent periprosthetic osteolysis in vivo. These findings suggest the potential therapeutic use of CIM in ALP.
The evolution of pelvic canal shape and rotational birth in humans
Authors: Stansfield Ekaterina , Fischer Barbara , Mitteroecker Philipp
Published: May 2021

The human foetus needs to rotate when passing through the tight birth canal because of the complex shape of the pelvis. In most women the upper part, or inlet, of the birth canal has a round or mediolaterally oval shape, which is considered ideal for parturition, but it is unknown why the lower part, or outlet, of the birth canal has a pronounced anteroposteriorly oval shape. Here we show that the shape of the lower birth canal affects the ability of the pelvic floor to resist pressure exerted by the abdominal organs and the foetus. Based on a series of finite element analyses, we found that the highest deformation, stress and strain occur in pelvic floors with a circular or mediolaterally oval shape, whereas an anteroposterior elongation increases pelvic floor stability. This suggests that the anteroposterior oval outlet shape is an evolutionary adaptation for pelvic floor support. For the pelvic inlet, by contrast, it has long been assumed that the mediolateral dimension is constrained by the efficiency of upright locomotion. But we argue that upright stance limits the anteroposterior dimension of the inlet. A deeper inlet requires greater pelvic tilt and lumbar lordosis, which compromises spine health and the stability of upright posture. These different requirements on the pelvic inlet and outlet have led to the complex shape of the human pelvic canal and to the evolution of rotational birth.
Smoking and Dementia Status Among Older Americans: A Mendelian Randomization Analysis
Authors: Fu Mingzhou , Faul Jessica D. , Jin Yuan , Ware Erin B. , Bakulski Kelly M.
Published: May 2021

Smoking is associated with dementia, but causality has not been well-established. Given smoking has a strong genetic component, we used genetic predisposition to smoking, based on a genome-wide association study (GWAS) from the GWAS & Sequencing Consortium of Alcohol and Nicotine use, as an instrumental variable. In a Mendelian randomization framework, we assessed the relationships between smoking and impaired cognitive status using the 2010 wave of the Health and Retirement Study. Cognitive status was assessed using cognition tests and categorized in three levels (normal cognition, cognitive impairment-non dementia, dementia). Smoking status was self-reported and classified into never, former, and current smoking. We used multivariable logistic regressions, Wald-type ratio estimators, and two-sample Mendelian randomization methods to examine associations and infer causal relationships. Among European genetic ancestry participants (n = 8741), current smoking was associated with cognitive impairment (OR = 1.62, 95%CI: 1.29, 2.01) relative to normal cognition. Two-sample Mendelian randomization results showed an inferred causal effect of smoking initiation on late-onset Alzheimer’s type dementia (MR-Egger: OR = 1.021, 95%CI: 1.017, 1.025). We observed no association between current smoking and dementia, or between former smoking and any cognitive status. No associations between smoking status and cognitive status were observed in the African genetic ancestry sample (n = 2501). Smoking behavior can give rise to cognitive impairment; therefore, promotion of smoking cessation is also important for brain health. Studies on dose and duration of smoking on cognition are critically needed, as well as continued research in non-European genetic ancestry study samples.
Chronic Hepatitis C Pathogenesis: Immune Response in The Liver Microenvironment and Peripheral Compartment
Authors: Rios Daniela Alejandra , Casciato Paola Cecilia , Caldirola María Soledad , Gaillard María Isabel , Giadans Cecilia , Ameigeiras Beatriz , De Matteo Elena Noemí , Preciado María Victoria , Valva Pamela
Published: May 2021

Background: Chronic hepatitis C pathogenesis is not defined yet, so immune cell populations and cytokines in liver and peripheral blood (PB) were evaluated to elucidate their role in liver disease. B, CTL, Th, Treg, Th1, Th17 and NK cells localization and frequency were evaluated on liver biopsies by immunohistochemistry, while frequency, differentiation, and functional status on PB by flow cytometry. TNF−α, IL−23, IFN−γ, IL−1β, IL−6, IL−8, IL−17A, IL−21, IL−10 and TGF−β expression were quantified in fresh liver biopsy by RT-qPCR and in plasma by CBA/ELISA. Results: Liver CTL and Th1 at lobular area inversely correlated with viral load (r=−0.469, p=0.003 and r=−0.384, p=0.040). Treg correlated with CTL and Th1 at lobular area (r=0.784, p<0.0001; r=0.436, p=0.013). Th17 correlated with hepatic IL-8 (r=0.52, p<0.05) and both were higher in advanced fibrosis cases (Th17 p=0.0312, IL-8 p=0.009). Hepatic cytokines were higher in severe hepatitis cases (IL−1β p=0.026, IL−23 p=0.031, IL−8 p=0.002, TGF−β p=0.037). Peripheral NK (p=0.008) and NK Dim (p=0.018) were diminished while NK Bright (p=0.025) were elevated in patients vs donors. Naïve Th (p=0.011) and CTL (p=0.0007) were decreased, while activated Th (p=0.0007) and CTL (p=0.0003) were increased. IFN−γ production and degranulation activity in NK and CTL were normal. Peripheral cytokines showed an altered profile, particularly elevated IL−6 (p=0.008) and TGF−β (p=0.041). Conclusions: HCV-specific and non-specific hepatic CTLs favored damage. Treg could not prevent fibrogenesis triggered by Th17 and IL-8. Peripheral T-lymphocyte differentiation stages shift, elevated cytokines levels and NK-cell count decrease would contribute to global disease.
Modelling Based Analysis and Optimization of Simultaneous Saccharification and Fermentation for the Production of Lignocellulosic-Based Xylitol
Authors: Hidayatullah Ibnu Maulana , Setiadi Tjandra , Kresnowati Made Tri Ari Penia
Published: May 2021

Simultaneous saccharification and fermentation (SSF) configuration offers an efficient used of the reactor. In this configuration, both the hydrolysis and fermentation processes are conducted simultaneously in a single bioreactor and the overall process may be accelerated. Problems may arise if both processes have different optimum conditions, and therefore process optimization is required. This paper presents the development of mathematical model over SSF strategy implementation for producing xylitol from hemicellulose component of lignocellulosic materials. The model comprises of the hydrolysis of hemicellulose and the fermentation of hydrolysate into xylitol. The model was simulated for various process temperature, prior hydrolysis time, and inoculum concentration. Simulation of the developed kinetics model shows that the optimum SSF temperature is 36oC, whereas conducting a prior hydrolysis at its optimum hydrolysis temperature will further shorten the processing time and increase the xylitol productivity. On the other hand, increasing the inoculum size will shorten the processing time further. For an initial xylan concentration of 100 g/L, the best condition is obtained by performing 21-hour prior hydrolysis at 60oC, followed by SSF at 36oC by adding 2.0 g/L inoculum, giving 46.27 g/L xylitol within 77 hours of total processing time.
AMT Starting Control as a Soft Starter Using a Novel Data-Driven Method
Authors: Li Yunxia
Published: May 2021

To improve the starting quality of automated mechanical transmission (AMT) as a soft starter for belt conveyors, a novel data-driven method is proposed. By analyzing the common soft-starting acceleration curves, a segmented acceleration curve is proposed as the soft-starting acceleration curve for AMT. A modified model free adaptive control (MFAC) method with jerk compensation is proposed as a data-driven method to control the AMT output shaft’s angular acceleration, which consists of a MFAC algorithm and a jerk compensation algorithm. Simulation comparisons are analyzed between the modified MFAC method with jerk compensation, the prototype MFAC method, and the proportion integration differentiation (PID) method. Results indicate better control of the modified MFAC method with jerk compensation on the AMT output shaft’s angular acceleration than the other two methods. It also has excellent properties of small tracking error and small shock, providing a novel approach for AMT as a soft starter.
FABP4 Might be an Indicator of the Status of Tumor Microenvironment in Colorectal Cancer
Authors: Ning Lijun , Yan Yuqing , Tong Tianying , Gao Ziyun , Cui Zhe , wang zhenhua
Published: May 2021

Background: As tumor microenvironment (TME) play an indispensable role in tumorigenesis of colorectal cancer, this study performs a bunch of bioinformatics analysis to identify the indicator of the status of TME in Colorectal cancer (CRC). Results: In the presented study, we applied CIBERSORT and ESTIMATE computational methods to calculate the proportion of tumor-infiltrating immune cells (TICs) and the amount of immune and stromal components in 444 COAD-READ cases from The Cancer Genome Atlas (TCGA) database. The differentially expressed genes (DEGs) were analyzed by COX regression analysis and protein–protein interaction (PPI) network construction. Then, fatty acid-binding protein four ( FABP4 ) was determined as a predictive factor by the intersection analysis of univariate COX and PPI. Further analysis revealed that FABP4 expression was positively correlated with the clinical pathologic characteristics (clinical stage, distant metastasis) and negatively correlated with the survival of CRC patients. Gene Set Enrichment Analysis (GSEA) showed that the genes in the high-expression FABP4 group were mainly enriched in immune-related activities. In the low-expression FABP4 group, the genes were enriched in metabolic pathways. CIBERSORT analysis for the proportion of TICs revealed that NK cell, CD4 + T cells and CD8 + T cells were negatively correlated with FABP4 expression, suggesting that FABP4 might be a potential prognostic factor of CRC patients. Conclusion: Our study has developed a new biomarker (FABP4) that can predict the status of tumor microenvironment in Colorectal cancer. Keywords: FABP4, tumor microenvironment, ESTIMATE, CIBERSORT, colorectal cancer
Upmodulation of Unfolded Protein Response and ER Stress-Related IL-23 Production in M1 Macrophages From Ankylosing Spondylitis Patients
Authors: Rezaiemanesh Alireza , Mahmoudi Mahdi , Amirzargar Ali Akbar , Vojdanian Mahdi , Babaie Farhad , Mahdavi Jila , Jamshidi Ahmad Reza , Nicknam Mohammad Hossein
Published: May 2021

Background

The inflammatory interleukin (IL)-23/IL-17 axis plays an important role in the pathogenesis of ankylosing spondylitis (AS), but with an unknown regulatory mechanism. The aim of this study was to investigate the role of endoplasmic reticulum (ER) stress and autophagy pathway in the expression of IL-23 in peripheral blood-derived macrophages in AS patients.
Methods

Peripheral blood samples were obtained from 15 AS and 15 healthy control subjects. MACS was used to isolate monocytes from PBMCs. Then, M-CSF was used to differentiate monocytes to M2 macrophages. IFN-γ and/or LPS was used to activate macrophages and M2 polarization toward M1 macrophages. Thapsigargin was used to induce ER stress and 3-MA to inhibit autophagy. The purity of extracted monocytes and macrophage markers was evaluated by flow cytometry. mRNA expression of HLA-B and-B27, ER stress-related genes, autophagy-related genes, and IL-23p19 was performed using RT-qPCR. Soluble levels of IL-23p19 were measured using ELISA.
Results

Significant increase in mRNA expression of HLA-B, HLA-B27, BiP, XBP1, CHOP, and PERK mRNAs was observed in macrophages of AS patients before and after stimulation with IFN-γ and LPS. No significant change in autophagy gene expression was detected. mRNA and soluble levels of IL-23p19 demonstrated a significant increase in macrophages of AS patients compared to healthy subjects. ER stress induction led to a significant increase in IL-23p19 in macrophages. Inhibition of autophagy had no effect on IL-23 expression.
Conclusion

ER stress, unlike autophagy, in macrophages of AS patients is associated with increased IL-23 levels.
A Practical Approach for Geographic Prioritization and Targeting of Insecticide-Treated Net Distribution Campaigns During a Public Health Emergency
Authors: Young Alyssa , Eaton Will , Worges Matt , Hiruy Honelgn , Maxwell Kolawole , Audu Bala Mohammed , Marasciulo Madeleine , Nelson Charles , Tibenderana James , Abeku Tarekegn A.
Published: May 2021

BackgroundThe use of data in targeting of malaria control efforts is becoming increasingly adopted by national malaria control programmes and is essential for optimal use of resources. This is especially important during public health emergencies such as the COVID-19 pandemic which resulted in reallocation of funding towards containment efforts. This work provides a practical mechanism for prioritizing geographical areas for insecticide-treated net (ITN) distribution during a public health emergency or situations of limited resources. We adopt a GIS-based weighted approach to categorize and rank administrative units based on data inputs that are widely available and can be applied in various country contexts where Plasmodium falciparum transmission is reported. MethodsP. falciparum-specific intervention and prevailing risk factors were used to rank administrative units in Nigeria for prioritization during ITN distributions. Each factor was assigned a unique weight and was multiplied by a value, typically ranging from 1 to 4, based on natural groupings inherent in the data, or the presence or absence of a given intervention. Risk scores for each factor were then summated to generate a composite unique risk score for each administrative unit. This risk score was then translated into a prioritization map which ranks each administrative unit from low to high priority in terms of ITN distribution targeting in situations of limited resources. ResultsA major component that influenced the prioritization scheme was previous ITN depth of coverage, as obtained and spatially interpolated from DHS survey data. The geospatial heterogeneity found among input risk factors suggests that a range of variables and covariates — outside of those that characterize malaria transmission exclusively — should be considered when using data to inform ITN distributions. The approach resulted in identification of regions that should be prioritized in upcoming ITN distributions. ConclusionThe presented approach provides a tool for prioritizing regions for ITN distributions. It serves as a base upon which a wider range of vector control interventions could be targeted. Its value added can be found in its potential for application in multiple country contexts, expediated timeframe for producing outputs, and its use of systematically collected malaria indicators in informing prioritization.
The Combination of Bacillus Subtilis wt55 with AiiO-AIO6 Improve the Resistance of Zebrafish to A. Veronii Infection by Simple Collocation Rather Than B. Subtilis Quorum-Quenching Recombinant Expression Strain
Authors: Yao Yuan-Yuan , Xia Rui , Yang Ya-Lin , Gao Chen-Chen , Zhang Feng-Li , Hu Juan , Hao Qiang , Ran Chao , Zhang Zhen , Zhou Zhigang
Published: May 2021

Disease problems will seriously restrict the sustainable development of aquaculture, and the environmental-friendly prevention strategies are urgently needed. Probiotics and quorum-quenching enzyme are innovative strategies to control bacterial diseases. The bacteriostatic effect of B. subtilis wt55 strain and quenching enzyme AiiO-AIO6 in vitro showed wt55 inhibit the growth of A. veronii, but AiiO-AIO6 did not. Therefore simple combination of B. subtilis wt55 strain and AiiO-AIO6 was used to evaluate potential synergistic effect. The results showed this combination could significantly reduce the number of invasive A. veronii in gut after challenge, corresponding to the lower intestinal alkaline phosphatase activity. In vitro co-culture experiments showed this combination could inhibit the growth of A. veronii. Direct immersion of germ-free zebrafish proved AiiO-AIO6 did not directly regulate the innate immune response of the host, but wt55 did it, and the combination of wt55 and AiiO-AIO6 could significantly reduce the expression of NF-κB and proinflammatory cytokine IL-1β, increase the expression of lysozyme gene. The gut microbiota induced by either experimental diet was transferred to germ-free zebrafish, and the results showed that intestinal microbiota also plays a regulatory role. The gut microbiota from combination group could significantly inhibit the expression of IL-1β and NF-κB, and increased the expression of TGF-β and lysozyme. Given the effectiveness of this combination, a B. subtilis quorum-quenching recombinant expression strain in which AiiO-AIO6 was surface displayed on the spores and secreted by vegetative cells was built. The results showed that the survival rate after challenge was lower than that of the group treated with AiiO-AIO6 or wt55 alone, and the expression of proinflammatory cytokine IL-1β and NF-κB were significantly higher. Our study demonstrated the effectiveness of B. subtilis and AiiO-AIO6 simple combination and established an efficient B. subtilis expression system.
The BMMSCs Derived From Juvenile Macaques Have the Ability to Promote Thymus Regeneration in Aged Macaques
Authors: WANG Yan-ying , ZHU Gao-hong , LI Gong-hua , KONG Qing-peng , Long-bao LV , SU Yu-lin , HU Jian-wei , WEI Wei , WANG Qiang , HE Jie , WANG Jin-xiang , TIAN Chuan , LI Ye , ZHU Xiang-qing , pan xinghua
Published: May 2021

BackgroundThe thymus gland is an important central immune organ in the human body and plays an indispensable role in the immune system. Aging thymic atrophy is critical factors leading to immune function decline and senile debilitation in aged people. Immune function decline is one of the important mechanisms of aging. Some research reports indicated that Stem cell therapy have the ability to promote tissue regeneration，but reverse thymus atrophy or promote atrophy thymus regenerate by stem cells need to be confirmed further. MethodsThe elderly macaque models were systematic screened and the thymus structure and function were evaluated by imaging and histopathology methods. The juvenile BMMSCs were injected into macaque models body by intravenous infusion. The effects of thymus tissue structure and expression of related factors were investigated by using imaging, histopathology,cell and molecule observation and measurement techniques. To explore the mechanism of juvenile BMMSC on thymus atrophy in aging rhesus macaques, the gene transcription profile of thymus tissue were sequencing and analyzed by bioinformatic methods. .ResultsThrough PET-CT observation, the thymus tissue density gradually increased after treatment, CT value gradually increased, SUVmax >1;The percentage of CD3+T cells in peripheral blood increased first and then decreased, CD3+CD4+T cells increased slowly, and CD3+CD8+T cells increased first, then decreased and then increased. By detecting Tregs in peripheral blood, the percentage of Tregs in peripheral blood showed a trend of decreasing first and then increasing after treatment (P< 0.05).The levels of thymosin α and thymosin II in peripheral blood were analyzed by ELISA method. It was found that thymosin α was firstly increased and then decreased after BMSC infusion, and the levels of thymosin Ⅱ were firstly increased and then decreased.The area of thymus parenchyma increased, and the boundary between skin and medulla appeared. Some thymus tissues were regenerated and changed to normal structure.The cortical and medullary junction structure and dense thymus structure gradually appeared in the elderly treatment group.The degree of thymus tissue fibrosis was reduced, and the deposition of collagen fiber was reduced. Apoptosis cells decreased significantly in the elderly treatment group compared with the elderly group. BMMSCs inhibited the expression of genes related to aging and apoptosis.Conclusion﻿Transplantation BMMSC derived from juvenile macaques can poromote thymus regeneration, reverse thymus atrophy by regulating gene transcription profiles in aged macaques.
Application of the Concave Arc Surface Collision Detection Method to Virtual Assembly
Authors: shi xin , Tian Li
Published: May 2021

Exact location calculation between each part of a parallel groove clamp when connecting a power line with a jumper is addressed in this paper. The relative location between a concave clamp and convex power line cannot be measured directly in live-line manipulation. We propose a concave arc surface collision detection method embedded in motion simulation. The relative location between irregular concave parts in the manipulation process can be obtained. The method is found to be computationally less expensive than convex partitioning collision detection techniques. This research provides a foundation for further study on robot hand manipulation with irregular assembly.