bluuebunny/crossref_metadata_2025 huggingface dataset:
Modelling for Anaemia and Malnutrition in Children Less Than Five Years of Age in Lesotho: A Case Study of a Cross-Sectional Dataset Using Multivariate Joint Model.
Authors: Gaston Rugiranka Tony , Ramroop Shaun , Habyarimana Faustin
Published: April 2021

Background

Anaemia and malnutrition remain jointly a serious health issue worldwide especially in developing countries. In Lesotho, the prevalence of anaemia and malnutrition remains highly significant especially among children less than five years of age.
Objectives

The primary objective of the present study was to determine the association between anaemia and malnutrition, and identify the associated factors with the two diseases among children less than five years of age in Lesotho.
Methods

The present study was cross-sectional and used secondary data from the 2014 Lesotho Demographic Health Survey (LDHS). The study considered a total number of 3112 children and utilized a multivariate joint model under the scope of the generalized linear mixed model (GLMM) for the data analysis.
Results

The prevalence of anaemia and stunting in children less than five years of age were 51% and 43% respectively. The multivariate results revealed that there is a strong relationship between anaemia and malnutrition. In addition, the results indicated that education, residence, wealth index and childbirth weight have a significant effect on stunted or malnourished child, while child with fever and diarrhoea have a significant effect on anaemia. Lastly, child’s age has a significant effect on both stunting and anaemia.
Conclusion

The study indicated a strong association between anaemia and stunting or malnutrition in the long-term, and controlling one disease should result in reducing the other. The socio-economic, geographical and demographic variables have a significant impact on improving stunting and anaemia. Thus, improving nutrition in children less than five years, especially those from rural area and having a birthweight less than 2500g, and educating the mothers to take their children to the health care facility when they have fever and diarrhoea, especially those from poor background, would contribute immensely to the reduction of malnutrition and anaemia in children from Lesotho.
The Effect of Ofloxacin in Men With Elevated Prostate Specific Antigen
Authors: Rabani Seyedhossein , Mousavizadeh Ali , Rabani Seyed Mohammadreza
Published: April 2021

Background: Antibiotic prescription is a common practice in men with elevated serum prostate specific antigen. The thought is that if patients were to have a drop in, or normalization of their PSA, we can be able to avoid unnecessary prostate biopsy. The aim of this study was to evaluate the effect of ofloxacin in men with elevated PSA.Methods: 224 men with elevated PSA from the base of 4 ng/ml were enrolled in this study. Exclusion criteria were age less than 50 or greater than 75, history of allergy to fluoroquinolones, cases with history of recent prostate manipulation, men on 5 alpha reductase inhibitors, and known cases of prostate cancer. After a duration of 10 days ofloxacin 200 mg twice a day orally, PSA level was rechecked.Results: Mean age was 61.18 year. Mean PSA level before administering antibiotic was 26.3 ng/ml (-21.9 +97.4). In 120 patients (53.57%) a significant drop in serum PSA was detected so prostate biopsy was not done and in the remainder 104 patients (46.43%), Prostate biopsy was done that showed 65 adenocarcinomas of prostate and 39 benign prostate hyperplasia. Conclusions: This study showed in a patient with active urinalysis (pyuria) and normal rectal examination, trans rectal ultrasonography and prostate biopsy should be post ponded and antibiotic be started. If significant drop in serum PSA was seen, antibiotic should be continued to avoid unnecessary biopsies, otherwise, no benefit in asymptomatic men with normal urinalysis, but elevated PSA.
Global and regional health and food security in a Half Earth world
Authors: Henry Roslyn , Arneth Almut , Jung Martin , Rabin Sam , Rounsevell Mark , Visconti Piero , Warren Frances , Alexander Peter
Published: April 2021

Global biodiversity is rapidly declining and goals to halt biodiversity loss, such as the Aichi Biodiversity Targets, have not been achieved. To avoid further biodiversity loss and aid recovery some have argued for the protection of 50% or 30% of the Earth’s terrestrial land surface. We use a state of the art global land use model, LandSyMM, to assess global and regional human health and food security outcomes when potential area based strategies for conserving biodiversity are modelled. We find diet and weight changes in strictly enforced 30% and 50% land protection scenarios, cause an additional 5.1 million deaths in 2060. At a regional level, South Asia and Sub-Saharan Africa experience high levels of underweight-related mortality, causing an additional 200,000 deaths in these regions alone. Developed regions in contrast are less affected by protection measures. Our results highlight that radical measures to protect areas of biodiversity value may jeopardise food security and human health in the most vulnerable regions of the world.
FGF21 Ameliorates Hepatic Fibrosis by Multiple Mechanisms
Authors: Meng Fanrui , Khoso Mir Hassan , Kang Kai , He Qi , Cao Yukai , Jiang Xinghao , Xiao Wei , Li Deshan
Published: April 2021

Previous study reports that FGF21 could ameliorate hepatic fibrosis, but its mechanisms have not been fully investigated. In this study, three models were used to investigate the mechanism by which FGF21 alleviates liver fibrosis. CCL4 and DMN were respectively used to induce hepatic fibrosis animal models. Our results demonstrated that liver index and liver function were deteriorated in both models. HE and Masson’s staining showed that the damaged tissue architectonics were observed in the mice of both models. Treatment with FGF21 significantly ameliorated these changes. ELISA analysis showed that the serum levels of IL-1β, IL-6 and TNF-α were significantly elevated in both models. However, administration of FGF21 significantly reduced these inflammatory cytokines. RT-PCR and Western blot analysis showed that mRNA and protein expression of collagenI, α-SMA and TGF-β were significantly decreased by treatment with FGF21. PDGF-BB stimulant was used to establish the experimental cell model in HSCs. RT-PCR and Western blot analysis demonstrated that the expression of collagenI and α-SMA were significantly upregulated by this stimulant in model group. Interestingly, our results showed that mRNA and protein expression of leptin were also significantly induced in PDGF-BB treated HSCs. Administration of FGF21 could significantly reduce leptin expression in a dose dependent manner and these effects were reversed in siRNA (against β-klotho) transfected HSCs. Furthermore, the leptin signaling pathways related protein p-ERK/t-ERK, p-STAT3/STAT3 and TGF-β were significantly downregulated by FGF21 treatment in a dose dependent manner. The expression of SOCS3 and Nrf-2 were enhanced by treatment with FGF21. The underlying mechanism may be that FGF21 regulates leptin-STAT3 axis via Nrf-2 and SOCS3 pathway in activated HSCs.
Th17 Cell Differentiation Induced by Cytopathogenic Biotype BVDV-2 in Bovine PBLCs
Authors: Li Yanping , Liu Tingli , Chen Guoliang , Wang Liqun , Guo Aimin , Li Zhi , Pan Li , Mao Li , Luo Xuenong
Published: April 2021

Background: Bovine viral diarrhea virus (BVDV) is a major pathogen that causes bovine viral diarrhea/mucosal disease (BVD-MD), which has become a global infectious disease due to its wide spread and the lack of effective treatment. The process of BVDV infection is complex. Once infected, host immune cells are activated and modulated. As a major immune cell, peripheral blood lymphocyte cells (PBLCs) are the primary target of BVDV. In order to further understand the mechanism of BVDV- host interaction, the expression profiles of host lymphocytes mRNAs associated with BVDV infection were investigated by transcriptomic sequencing analysis. Results: The transcriptomic sequencing analysis was performed on bovine PBLCs infected with CP BVDV-2 GS2018 after 12 h of infection. Gene expression profiling demonstrated that 1,052 genes were differentially expressed in GS2018 infected PBLCs compared with the control group. Of these genes, 485 genes were up-regulated and 567 were down-regulated. 19 differential expressed genes (DEGs) were selected for validation using quantitative real-time PCR and the results were consistent with the results of RNA-Seq. Gene ontology enrichment and KEGG pathway analysis showed that 1052 DEGs were significantly enriched in 16 pathways, including cytokine-cytokine receptor interaction, IL17 signaling pathway, PI3K-Akt signaling pathway, MAPK signaling pathway and TNF signaling pathway. PPI network analysis showed that IL17A, IFN-γ and TNF-α interacted with various proteins and may play crucial roles in BVDV-2 infection. Of note, we confirmed that GS2018 induced Th17 cell differentiation in PBLCs and persistently increased the expression levels of IL17A. In turn, the replication of GS2018 was inhibited by IL17A. Conclusion: In this study, the transcription changes of DEGs related to host immune responses in bovine PBLCs were caused by CP BVDV-2 infection. In particular, the effector molecules IL17A of Th17 cells were significantly up-regulated, which inhibited viral replication. These results will contribute to exploration and further understanding of the host immune response mechanism and interaction between host and BVDV-2.
Utilization of HIV Testing and Counselling Services By Women With Disabilities During Antenatal Care in Uganda: Analysis of 2016 Demographic and Health Survey
Authors: Zandam Hussaini , Akobirshoev Ilhom , Nandakumar Allyala , Mitra Monika
Published: April 2021

Background: HIV testing and counselling during antenatal care (ANC) is critical for eliminating mother-to-child transmission of HIV. We investigated disparity in utilization of HIV testing and counselling services (HTC) between women with and without disabilities in Uganda.Methods: We conducted a retrospective study using the nationally representative 2016 Uganda Demographic and Health Survey. The study sampled 10,073 women between age 15-49 who had a live birth in the last 5 years. We estimated unadjusted and adjusted odds ratio for receiving pre-test HIV counselling, obtaining an HIV test result, and post-test HIV counselling by disability status using logistic regressions.Results: We found that women with disabilities were less likely to receive pre-test HIV counselling (59.6 vs 52.4), obtain an HIV test result (68.2 vs 61.4), receive post-test HIV counselling (55.5 vs 51.6), and all HTC services (49.2 vs 43.5). From the regression analysis, women with disabilities were less likely to receive pre-test counselling [AOR = 0.83; CI = 0.74, 0.93] and obtain an HIV test result [AOR = 0.88; CI = 0.78, 0.99].Conclusions: Our findings revealed that women with disabilities are less likely to receive HTC service during ANC and highlighted the need for disability-inclusive HIV and reproductive health services. Government, non-governmental organizations, and other stakeholders should consider funding inclusive campaigns and identifying other mechanisms for disseminating health information and behavioral interventions to women with disabilities.
Herbicidal Properties of Antihypertensive Drugs: Calcium Channel Blockers
Authors: Abdullah HANNAN SAFIYYAH TAN SIAN HUI , Chia Poh Wai , Omar Dzolkhifli , Chuah Tse Seng
Published: April 2021

Herbicide resistance is a worldwide problem in weed control. This prompts researchers to look for new modes of action to slow down the evolution of herbicide-resistant weeds. This research aims to determine the herbicidal action of thiazolo[3,2-a]pyrimidines derivatives, which are well known as antihypertensive drugs. The phytotoxic effects of ten compounds were investigated using leaf disc discoloration test and seed germination bioassay. At concentrations of 125 to 250 mg/L, the 5-(3-Fluoro-phenyl)-7-methyl-5H-thiazolo[3,2-a]pyrimidine-6-carboxylic acid ethyl ester (c) was highly active against Oldenlandia verticillata and Eleusine indica. At application rates of 1.25 to 2.5 kg ai/ha, formulated c demonstrated selective post-emergence and pre-emergence herbicidal activity against O. verticillata, E. indica and Cyperus iria. In the crop tolerance test, formulated c outperformed the commercial herbicide diuron, with aerobic Oryza sativa being the most tolerant, followed by Zea mays, and Brassica rapa. The addition of calcium chloride partially nullified compound c's inhibitory effects on weed shoot growth, indicating that it has potential as a calcium channel blocker. Compound c acted by triggering electrolyte leakage without affecting photosystem II. These findings imply that c could be explored further as a template for developing new herbicides with novel modes of action.
The Construction of Polygenic Risk Scores for Breast Cancer Based on LightGBM and Multiple Omics Data
Authors: Ma Baoshan , Pan Jianqiao , Hou Xiaoyu , Li Chongyang , Xiong Tong , Gong Yi , Song Fengju
Published: April 2021

Background: Breast cancer accounts for a large proportion of cancer-related deaths in women. Polygenic risk score (PRS) derived from single nucleotide polymorphisms (SNP) data can evaluate the individual-level genetic risk of breast cancer and has been widely applied for risk stratification. However, standalone SNP data used for PRS may not provide satisfactory prediction accuracy. Additionally, current PRS models based on linear regression have insufficient power to leverage non-linear effects from thousands of associated SNPs.Methods: In this study, the multiple omics data (DNA methylation data, miRNA data, mRNA data and lncRNA data) and clinical data of breast invasive carcinoma (BRCA) were collected from The Cancer Genome Atlas (TCGA). First, we developed a novel PRS model utilizing single omic data and a machine learning algorithm (LightGBM). Subsequently, we built a combination model of PRS derived from each omic data to explore whether multiple omics data can further improve the prediction accuracy of PRS. Finally, we performed association analysis and prognosis prediction of breast cancer to evaluate the utility of the PRS generated by our method.Results: Our PRS model based on single omic data and LightGBM algorithm achieved better predictive performance than the linear models and other machine learning models. Moreover, the combination of the PRS derived from each omic data can efficiently strengthen prediction accuracy. The analysis of prevalence and the associations of the PRS with phenotypes including case-control and cancer stage status indicated that the risk of breast cancer increases with the increases of PRS. The survival analysis also suggested that PRS for the cancer stage is an effective prognostic metric of breast cancer patients.Conclusion: Our proposed model expanded the current definition of PRS from standalone SNP data to multiple omics data and outperformed the state-of-the-art PRS models, which may provide a powerful tool for diagnostic and prognostic prediction of breast cancer.
Tribological Properties of a Self-Repairing Material: Functionalized Graphene/montmorillonite Nanosheets Lubricant Additives
Authors: Li Yujunwen , Yang Rui , Lei Wu , Hao Qingli
Published: April 2021

The functionalized graphene/montmorillonite (FG/MTT) nanosheets were synthesized through chemically bonding by a simple, green method, which has remarkable dispersion stability in oil and its lubricating performance was evaluated by a four-ball tribometer. The test results show that FG/MTT has a preeminent lubricant property when the concentration is 0.4 mg/ml. Compared with the bare oil sample, its average friction coefficient (FC) and wear scar diameter (WSD) decrease by 50.4 % and 13.2 %, respectively. The synergistic effect between FG and MTT was further explored by comparing the lubricant mechanism of the different additives. After synthetically analyzing worn surface by means of scanning electron microscopy and X-ray photoelectron spectroscopy, the lubrication mechanism of the FG/MTT nanocomposite as oil additive is discussed and postulated: The FG/MTT with weak interlayer adhesion is filled between the friction pairs to avoid contact and clinging of some asperities, and the sliding between the layers plays a role in lubrication. Furthermore, FG/MTT will react with the surface of the friction pair to form a repair layer composed of Fe2O3, SiC, SiO2, and aluminosilicate, mending the grinding surface and promoting the hardness after friction.
An explainable supervised machine learning predictor of acute kidney injury after adult deceased donor liver transplantation
Authors: Zhang Yihan , Yang Dong , Liu Zifeng , Chen Chaojin , Ge Mian , Li Xiang , Luo Tongsen , Wu Zhengdong , Shi Chenguang , Wang Bohan , Huang Xiaoshuai , Zhang Xiaodong , Zhou Shaoli , Hei Ziqing
Published: April 2021

Background: Early prediction of acute kidney injury (AKI) after liver transplantation (LT) facilitates timely recognition and intervention. We aimed to build a risk predictor of post-LT AKI via supervised machine learning and visualize the mechanism driving within to assist clinical decision-making.Methods: Data of 894 cases that underwent liver transplantation from January 2015 to September 2019 were collected, covering demographics, donor characteristics, etiology, peri-operative laboratory results, co-morbidities and medications. The primary outcome was new-onset AKI after LT according to Kidney Disease Improving Global Outcomes guidelines. Predicting performance of five classifiers including logistic regression, support vector machine, random forest, gradient boosting machine (GBM) and adaptive boosting were respectively evaluated by the area under the receiver-operating characteristic curve (AUC), accuracy, F1-score, sensitivity and specificity. SHapley Additive exPlanations (SHAP) method was applied to evaluate feature importance and explain the predictions made by ML algorithms.Results: 430 AKI cases (55.1%) were diagnosed out of 780 included cases. The GBM model achieved the highest AUC (0.76, CI 0.70 to 0.82), F1-score (0.73, CI 0.66to 0.79) and sensitivity (0.74, CI 0.66 to 0.8). High preoperative indirect bilirubin, low intraoperative urine output, long anesthesia time, low preoperative platelets, and graft steatosis graded NASH CRN 1 and above were revealed by SHAP method the top 5 important variables contributing to the diagnosis of post-LT AKI made by GBM model.Conclusions: Our GBM-based predictor of post-LT AKI provides a highly interoperable tool across institutions to assist decision-making after LT.
Study on the correlation between mental health and socio-demographics of patients in five designated treatment hospitals in China during the COVID-19 outbreak : a cross-sectional survey
Authors: Liang Zhonghuan , Ou Xiuli , Li Jieming , He Gang , Xu Qingdong , Li Fuquan , Li Yongyi , Wang Mingying , Liang Runzhi
Published: April 2021

Purpose

The global epidemic of 2019 Novel Coronavirus Diseases (COVID-19) has caused many psychological problems. At present, there are few studies on the mental health status and correlation of COVID-19 patients.
Methods

During the peak period of COVID-19 outbreak in China, COVID-19 patients from 5 designated hospitals with new coronary pneumonia were selected by convenient sampling method. Symptom Checklist 90 (SCL-90) were investigated by either a convenient online questionnaire at: WJX.cn as a data collecting platform or an equivalent paper questionnaire.
Results

It showed that the positive detection rate of SCL-90 in the COVID-19 patients was 29.83%. The most common mental health problem was anxiety (28.3%), and the top three prominent mental health problems are depression (9.4%), interpersonal sensitivity (9.4%), paranoia ideation (7.7%). Compared with the Chinese adult norm, there were significant differences in the SCL-90 total score and somatization, depression, anxiety, and phobic anxiety dimension (P < 0.05). The main influencing factors of mental health of COVID-19 patients are the number of confirmed cases nationwide, sex, marital status and psychological intervention.
Conclusion

The mental state of some groups is relatively low, which leads to depression and anxiety more easily. In particular, the most vulnerable group was found to be unmarried women who have a high occurrence rate of mental health problems. We need to pay particular attention to high risk groups, and support patients with increased susceptibility, which will require timely assessment by mental health care professionals.
A bioactivated in vivo assembly (BIVA) nanotechnology fabricated NIR probe for small pancreatic tumor intraoperative navigation imaging
Authors: Li Li-Li , Ren Han , Zhao Xiao-Xiao , Hou Dayong , Yao Haodong , Zhao Lina , Xu Wanhai , Wang Hao
Published: April 2021

Visual intraoperative navigation depends on the optical technique for real-time imaging of the boundary of tumor. However, the fluorescence probes now enable for bioimaging are usually lack of tumor specificity and poor imaging window, which limited the further clinical applications. Here, we report a bioactivated in vivo assembly (BIVA) nanotechnology, which provides a universal optical probe delivery system to enhance the targeting specificity, region accumulation and continuous imaging window of the probe. Based on the coupling of BIVA domain and probe, BIVA probe exhibits a synergy mechanism of active targeting and assembly induced retention, which improved the targeting efficiency. In addition, the tumor surface specific nanofiber assembly significantly increases the accumulation of the probe at tumor boundary. The PEGylation of the BIVA probe extended the blood circulation time for 110 min, and the area under the curve (AUC 0-120 h) of tumor was significantly increased by 3.6 times compared with the active targeting probe. As the dynamic assembly difference between tumor and background further enlarges the metabolic difference, we obtained a delayed imaging window between 8-96 hours with better signal-to-background ratio (SBR > 9 times). Our BIVA probe can be used for imaging of small-size (d < 2 mm) orthotopic pancreatic tumors in vivo. The high specificity and sensitivity of the BIVA probe will further benefit the intraoperative navigation imaging in clinical.
Camrelizumab combined with sorafenib versus sorafenib alone in patients with advanced hepatocellular carcinoma: a retrospective study
Authors: Liu Qinqin , Li Jing , You Nan , Wu Ke , Peng Xuehui , Wang Zheng , Liang Wang , Zhu Yinan , Zheng Lu
Published: April 2021

Background: Few studies have evaluated the efficacy and safety of immunotherapy and targeted therapy in combination. The present study aimed to compare camrelizumab plus sorafenib versus sorafenib alone in patients with advanced hepatocellular carcinoma using a propensity score analysis.Patients and methods: Between January 2019 and January 2021, a total of 100 patients with advanced HCC in the Second Affiliated Hospital of Army Medical University were retrospectively analyzed. Of the patients involved, 35 patients received combined camrelizumab plus sorafenib treatment, and 65 patients received sorafenib monotherapy. After 1:1 propensity score matching (PSM), 34 patients were included in each group. The progression-free survival (PFS), overall survival (OS), treatment response and the relevant adverse effects (AEs) were evaluated.Results: The combined-therapy group showed significantly improved overall response rate (ORR) than the sorafenib-only group (before PSM, P=0.037; after PSM, P=0.010), but no difference was noted in disease control rate (DCR) (before PSM, P=0.695; after PSM, P=1.000). The median PFS was significantly longer in the combined-therapy group than the sorafenib-only group (before PSM, P=0.041; after PSM, P=0.043). However, the two groups exhibited comparable median OS (before PSM, P=0.135; after PSM, P=0.105). Although The incidence of thrombocytopenia after PSM was significantly higher in the combined-therapy group than in the sorafenib-only group, most of the AEs could be easily controlled after treatment.Conclusion: The combination treatment of camrelizumab with sorafenib showed promising efficacy with acceptable safety for the management of advanced HCC.
Florigen Governs Shoot Regeneration
Authors: Kutsher Yaarit , Fisler Michal , DORON-FAIGENBOIM Adi , Reuveni Moshe
Published: April 2021

It is widely known that during the reproductive stage (flowering), plants do not root well. Most protocols of shoot regeneration in plants utilize juvenile tissue. Adding these two realities together encouraged us to study the role of florigen in shoot regeneration. Mature tobacco tissue that expresses the endogenous tobacco florigen mRNA regenerates poorly, while juvenile tissue that does not express the florigen regenerates shoots well. Inhibition of Nitric Oxide (NO) synthesis reduced shoot regeneration as well as promoted flowering and increased tobacco florigen level. In contrast, the addition of NO (by way of NO donor) to the tissue increased regeneration, delayed flowering, reduced tobacco florigen mRNA. Ectopic expression of florigen genes in tobacco or tomato decreased regeneration capacity significantly. Overexpression pear PcFT2 gene increased regeneration capacity. During regeneration, florigen mRNA was not changed. We conclude that florigen presence in mature tobacco leaves reduces roots and shoots regeneration and is the possible reason for the age-related decrease in regeneration capacity.
Determination of the Optimal Coverage for Heavy-Duty-Axle Gears in Shot Peening
Authors: Yan Hongzhi , Zhu Pengfei , Chen Zhi , Zhang Hui , Zhang Yin , Zhang Yu
Published: April 2021

Pitting and wear often appear on heavy-duty-axle gears due to their harsh working conditions, such as high torques, high loads and poor lubrication. Shot peening is a popular surface strengthening method for gears. In order to ensure complete coverage during shot peening, 100%~200% coverage is usually prescribed for most gears. However, it is difficult to effectively improve the contact fatigue and wear resistance of heavy-duty-axle gears. Generally, increasing shot peening coverage can heighten the compressive residual stress for prolonging the service lifetime of gears. Whereas, high coverage levels may cause the deterioration of surface roughness, thus increase the noise and vibration of gears. To address this issue, this paper deals with the determination of optimal coverage for heavy-duty-axle gears by experimental tests. The influence of shot peening coverage on the surface integrity of gears is analyzed in terms of residual stress, microhardness, surface morphology and dislocation density. The results show that the maximum compressive residual stress increases first and then keeps stable with the increase of coverage, and the maximum value is −1172.10 MPa. The microhardness peak increases obviously in the beginning and then slowly rises with the increase of coverage, and the maximum value is 747.5 HV1.0. The surface roughness (Ra) decreases initially and then enhances with the increase of coverage, and the minimum value is 0.99 μm under the coverage of 1000%. The dislocation density increases with the increase of coverage, and the maximum value is 3.70×1016 m-2. Numerous damages (microscalings, spallings) occur on the treated gear tooth flank affecting the residual stress distribution and roughness under high coverage levels. Taking into consideration of service lifetime, working noise and economic efficiency, the coverage of 1000% is the optimal coverage for heavy-duty-axle gears in shot peening.
The Influence of the Pharmacists’ Training on the Patients’ Education in the Field of Inhalation Techniques in Community Pharmacies in Poland
Authors: Waszyk-Nowaczyk Magdalena , Targosz Patrycja , Guzenda Weronika , Byliniak Michał , Plewka Beata , Dąbrowiecki Piotr , Michalak Michał , Bąbol Aneta , Szapel Karol , Bielas Marzena , Żabiński Jerzy
Published: April 2021

Background: Following the example of other countries, it is very important to educate patients on the correct use of inhalers by properly trained healthcare professionals, including pharmacists.Objectives: The aim of the study was to assess the quality and comprehensiveness of professional advice given by pharmacists on the use of inhalers, which was determined by the pharmacists’ level of training. Methods: The study was conducted from June 2019 to March 2020. 150 pharmacists from Poznan and Warsaw (Poland) were involved. Before the study began, the professional education of 240 pharmacists was conducted in Warsaw to implement standard operating procedures. The study used the model of a mystery patient.Results: The conversation with a trained pharmacist lasted on average 5.5 minutes, with an untrained one - 3.0 minutes. Placebo inhalers were used more often by trained pharmacists during patients’ education. 10.3% of untrained pharmacists did not provide any education. Additionally, untrained employees quality of advice were assessed on an average of 3.5 points, while trained ones - 7.6 points. Conclusions: This study has shown that there is a need for professional training among pharmacists in Poland, which translates into better patient education in the field of inhalation techniques.
MiR-1246 regulates the PI3K/AKT signaling pathway by targeting PIK3AP1 and inhibits thyroid cancer cell proliferation and tumor growth
Authors: Li Jingyan , Zhang Zhanlei , Hu Jieting , Wan Xiaoting , Huang Wei , Zhang Hong , Jiang Ningyi
Published: April 2021

One of the most prevalent forms of endocrine malignancies is thyroid cancer. Herein, we explored the mechanisms whereby miR-1246 is involved in thyroid cancer. Phosphoinositide 3-kinase adapter protein 1 (PIK3AP1) was identified as a potential miR-1246 target,with the online Gene Expression Omnibus (GEO) database. The binding between miR-1246 and PIK3AP1 and the dynamic role of these two molecules in downstream PI3K/AKT signaling were evaluated. Analysis of GEO data demonstrated significant miR-1246 downregulation in thyroid cancer, and we confirmed that overexpression of miR-1246 can inhibit migratory, invasive, and proliferative activity in vivo, and tumor growth in vitro. Subsequent studies indicated that miR-1246 overexpression decreased the protein level of PIK3AP1 and the phosphorylation of PI3K and AKT, which were reversed by PIK3AP1 overexpression. At the same time, overexpression of PIK3AP1 also reversed the miR-1246 mimics-induced inhibition proliferative, migratory, and invasive activity while promoting increases in apoptotic death, confirming that miR-1246 function was negatively correlated with that of PIK3AP1. Subsequently, we found that the miR-1246 mimics-induced inhibition of PI3K/AKT phosphorylation, was reversed by the PI3K/AKT activator IGF-1. miR-1246 mimics inhibited proliferative, migratory, and invasive activity while promoting increases in apoptotic death, which were reversed by IGF-1. Furthermore, miR-1246 agomir can inhibit tumor growth in vivo. We confirmed that miR-1246 affects the signaling pathway of PI3K/AKT via targeting PIK3AP1, and inhibits the development of thyroid cancer. Thus, miR-1246 is a new therapeutic target for thyroid cancer.
Optimization of Culture Media for T Cell Expansion: T Cell Expansion Is a Bottle Neck in Adoptive T Cell Therapy
Authors: Rahimmanesh Ilnaz , Khanahmad Hossein
Published: April 2021

Adoptive T cell therapy is a promising treatment strategy for cancer immunotherapy. The methods used for the expansion of high numbers of T cells are essential steps for adoptive cell therapy. In this study, we evaluated the expansion, proliferation, activation, and anti-tumor response of T lymphocytes, in presence of different concentrations of interleukin-2, phytohemagglutinin, and insulin. Our results showed that supplemented culture media with an optimized concentration of phytohemagglutinin and interleukin-2 increased total fold expansion of T cells up to 500-fold with about 90% cell viability over 7 days. The quantitative assessment of Ki-67 in expanded T cells showed a significant elevation of this proliferation marker. In addition, the proportion of CD4+ and CD8+ cells were evaluated using flow cytometry, and data showed that both cells were present in the expanded population. Finally, we assessed the activation and tumor cytotoxicity of expanded T cells against target cells. Overexpression of CD107a, as a functional marker of T cell degranulation on expanded T cells and their ability to induce cell death in tumor cells, was observed in the co-cultured experiment. Based on these data we have developed a cost-effective and rapid method to support the efficient expansion of T cells for adoptive cell therapy.
Investigation of Interaction Between the Spike Protein of SARS-CoV-2 and ACE2-Expressing Cells Using an In Vitro Cell Capturing System
Authors: Shang Yuning , Chen Feixiang , Li Shasha , Song Lijuan , Gao Yunzhen , Yu Xinhua , Zheng Junfeng
Published: April 2021

Background: The Interaction between severe acute respiratory syndrome coronavirus 2 ( SARS-CoV-2 ) spike protein with Angiotensin converting enzyme 2 (ACE2) on the host cells is a crucial step for the viral entry and infection. Therefore, investigating the molecular mechanism underlying the interaction is of great importance for the prevention of the infection of SARS-CoV-2. In this study, we aimed to establish a virus-free in vitro system to study the interaction between the spike protein and host cells of SARS-CoV-2.Results: Our results show that ACE2-overexpressing HEK293T cells are captured by immobilized spike protein, and the cell capturing process can be inhibited by the receptor binding domain of the spike protein or antibodies against S protein. Furthermore, spike protein variant with D614G mutant show a higher cell capturing ability than wild type spike protein. In addition, the captured cells can be eluted as living cells for further investigation.Conclusions: This study provides a new in vitro system for investigating the interaction between SARS-CoV-2 and host cells and purifying ACE2-expressing cells.
Circulating LncRNAs Landscape as Potential Biomarkers in Breast Cancer
Authors: Pourramezan Zahra , Attar Fatemeh Akhavan , Yusefpour Maryam , Azizi Masoumeh , Oloomi Mana
Published: April 2021

The delay in diagnosis and treatment of breast cancer results in low survival rates and high mortality. Thus, it is essential to characterize new therapeutic targets and prognostic breast cancer biomarkers. The rising evidence suggested that long non-coding RNAs (lncRNAs) expression levels are deregulated in human cancers and can use as biomarkers for the rapid diagnosis of breast cancer. In the present study, a Quantitative Real-time polymerase chain reaction (qRT-PCR) technique was used to measure twenty oncogenic and tumor suppressor lncRNAs expression levels in whole blood samples of breast cancer patients and normal controls. Blood samples from 30 healthy women and 30 female breast cancer patients were collected. Then cDNA was synthesized from the extracted RNA blood. The expression level of lncRNAs measured and analyzed by LinReg PCR and REST software and the correla­tion between lncRNAs dysregulation and clinical characteristics and prognosis were also analyzed by SPSS software. The comparison between the expression levels of lncRNAs in the blood samples of breast cancer patients compared with healthy individuals revealed that some lncRNAs (MEG3, NBAT1, NKILA, GAS5, EPB41L4A-AS2, ZFAS1, MVIH, Z38, and BC040587) were down regulated. In contrast, other lncRNAs (H19, SPRY4-IT1, UCA1, AC026904.1, CCAT1) were up-regulated, significantly. It was shown that the expression levels of NKILA, NBAT1, and ZFAS1 lncRNAs were related to tumor size, and BC040587expression level related to age, node metastasis, tumor size, and grade (P<0.05). The association between H19 and SPRY4-IT1 lncRNAs with HER-2 was confirmed statistically (P<0.05). Our data highlighted the correlation of BC040587, H19, and SPRY4-IT1 lncRNAs with clinicopathological traits in breast cancer patients suggesting their future applications as novel biomarkers and therapeutic targets in breast cancer. In conclusion, circulating lncRNAs could consider as the prognostic and predictive markers in breast cancer.
Expression of Spred2 in the Urothelial Tumorigenesis of the Urinary Bladder
Authors: Oda Shinsuke , Fujisawa Masayoshi , Chunning Li , Ito Toshihiro , Yamaguchi Takahiro , Yoshimura Teizo , Matsukawa Akihiro
Published: April 2021

Aberrant activation of the Ras/Raf/ERK-MAPK pathway is involved in the progression of cancer, including urothelial carcinoma; but the negative regulation remains unclear. Here, we investigated pathological expression of Spred2 (Sprouty-related EVH1 domain-containing protein 2), a negative regulator of the Ras/Raf/ERK-MAPK pathway, and the relation to ERK activation and a cell proliferation marker Ki67 index in various categories of 275 urothelial tumors obtained from clinical patients. In situ hybridization demonstrated that Spred2 mRNA was highly expressed in high-grade non-invasive papillary urothelial carcinoma (HGPUC) and carcinoma in situ (CIS), and the expression was decreased in invasive urothelial carcinoma (IUC). Immunohistochemically, membranous Spred2 expression, important to interact with Ras/Raf, was preferentially found in HGPUC. Interestingly, membranous Spred2 expression was decreased in CIS and IUC relative to HGPUC, while ERK activation and Ki67 index were increased. HGPUC with membranous Spred2 expression correlated significantly with lower levels of ERK activation and Ki67 index as compared to those with negative Spred2 expression. Thus, our pathological findings suggest that Spred2 negatively regulates cancer progression in non-invasive papillary carcinoma possibly through inhibiting Ras/Raf/ERK-MAPK pathway, but this regulatory mechanism is lost in CIS and IUC. Spred2 appears to be a key regulator in the progression of non-invasive bladder carcinoma.
Assessment of water quality status of hemodialysis treatment plants in Baghdad, Iraq
Authors: Raad Yasamen , Al-Naseri Saadi , Imran Natheer , Jaafar Mahdi
Published: April 2021

The chemical quality of the water used for dialysis fluid is a crucial factor for patients receiving dialysis. Therefore, strict monitoring of the quality of water is necessary in order to prevent complications and to guarantee the safety and health of patients. The current study aimed to determine the chemical water quality used in hemodialysis treatment plants and compare it to standards of the Association for advancement of medical instrumentation (AAMI) and International Organization for Standardization (ISO) in four hospitals in Baghdad. This cross-sectional study is performed in four seasons in 2019. This research was conducted on samples of dialysis water. Samples were tested by the spectrometry system (AA-7000, Shimadzu, Japan) and colorimeters DR890 for free chlorine. Microsoft 2010 was used for statistical analyses. Based on the results of the research, all concentrations of chemical compounds were within accepted international standards except free chlorine. Also, there were no significant differences between the measured parameters in the dialysis water at four treatment plants during the study period at (P < 0.05). The assessment of water quality hemodialysis showed that these hemodialysis treatment plants were not significantly contaminated and that the quality of the water met the AAMI and ISO standards.
The relationship between the visceral adiposity index and carotid atherosclerosis in different genders and age groups
Authors: Cao Jing , Liu Shengpeng , Yang Q. , Zhang Y. , Huang J. , Zeng Y.
Published: April 2021

Objective: We aimed to investigate the possible relationship between visceral adiposity index (VAI) and carotid atherosclerosis(CAS) in different genders and age groups in China. Methods: This study was an observational cross-sectional study and included 1996 participants who were health examination population .From January 2018 to June 2019, people over 18 years old who had physical examinations were included in the study. Each participant completed a standard questionnaire, anthropometric measurements, ultrasonic examination ,and provided blood samples for biochemical measurements. Regression models were utilized to evaluate the correlation between VAI and the CAS risk. An ROC curve was utilized to predict VAI diagnostic efficacy for carotid atherosclerosis. Result: After adjusting for potential risks, high-VAI subjects had an increased OR of having CAS in women aged>44 years[OR= 3.09,95% Confdence interval (95%CI)=1.64⑶5.82, p <0.001]. In females, the AUC and sensitivity specificity were [(0.595, 76.68% and 39.85%, all females), (0.575, 78.51% and 30.37%, age ≤44), (0.609, 84.71% and 40.46%, age >44). When compared with traditional obesity indices(BMI, WC, and HC) , the predictive ability of VAI was stronger in females >44.The same relationships in males were not signifcant. Conclusions: The VAI were associated with an increased risk of CAS,and it could be selected as new and simple predictors of CAS for middle-aged and elderly women(age >44)in China .
Quantum Phases of Time Order in Many-Body Ground States
Authors: Guo Tie-Cheng , You Li
Published: April 2021

Understanding phases of matter is of both fundamental and practical importance. Prior to the widespread appreciation and acceptance of topological order, the paradigm of spontaneous symmetry breaking, formulated along the Landau-Ginzburg-Wilson (LGW) dogma, is central to understanding phases associated with order parameters of distinct symmetries and transitions between phases. This work proposes to identify ground state phases of quantum many-body system in terms of time order, which is operationally defined by the appearance of nontrivial temporal structure in the two-time auto-correlation function of a symmetry operator (order parameter). As a special case, the (symmetry protected) time crystalline order phase detects continuous time crystal (CTC). Time order phase diagrams for spin-1 atomic Bose-Einstein condensate (BEC) and quantum Rabi model are fully worked out. Besides time crystalline order, the intriguing phase of time functional order is discussed in two non-Hermitian interacting spin models.
MIR31 May Mediate Multiple Biology Processes To Promote Vocal Fold Wound Healing
Authors: Wang Haizhou , Xu Wen
Published: April 2021

The aim of this study was to explore the role of MIR31 in vocal fold wound healing (VFWH) and its possible mechanism. MIR31 expression was studied in rat vocal fold tissue at multiple time points (1, 4, and 8 weeks) after vocal fold injury. Co-expression analysis, pathway analysis, and literature-based network analysis were conducted to explore the possible mechanism underlying the relationship between MIR31 and VFWH. MIR31 expression was significantly elevated after vocal fold injury (p<5.65e-5), which also presented decreased expression in the late stage of VFWH process compared to the early and middle stages (p<5.40e-3). MIR31 also presented strong co-expression with 17 VFWH-significant genes (absolute value of ROH∈(0.63, 0.83)), which were mainly involved in collagen production. Literature-based network analysis showed that MIR31 could suppress two inhibitors (gene SMAD1 and HDAC2) of wound healing and activate one promoter (adenosine triphosphate). MIR31 could also mediate multiple biology processes that were associated with wound healing, including keratinocyte proliferation, collagen production, and inflammation. This study supports a strong association between MIR31 and the process of vocal fold wound healing, which may be related to collagen synthesis and other biological processes that need further study.
Lack of social touch increases anxiety and alters social behaviors in mice
Authors: Ma Yu-Kai , Zeng Pei-Yun , Chu Yu-Hsin , Lee Chih-Lin , Cheng Ching-Chuan , Chen Chen-Hung , Su Yu-Shan , Lin Kai-Ti , Kuo Tsung-Han
Published: April 2021

The importance of social interactions has been reported in different animal species. During the pandemic, although people can communicate through other sensory cues, social touch is mostly prohibited under different levels of social distance policies, which inspired us to explore the necessity of physical contact in mouse social interaction. In this study, we first conducted a long-term observation showing that pair-housed mice in a standard laboratory cage spent nearly half the day in direct physical contact with each other. Furthermore, isolation experiments demonstrated that, even with access to other sensations, prevention of social touch for one month significantly induced anxiety levels, changed social behaviors and increased interleukin-6 cytokine in the hippocampus and the serum of mice. Our study demonstrated the necessity of social touch for the maintenance of mental health in mice. This information could have important implications for human social interactions, especially the social policies during a pandemic crisis.
Components of perinatal palliative care: a systematic review protocol
Authors: Dombrecht Laure , Chambaere Kenneth , Beernaert Kim , Roets Ellen , De Keyser Mona De Vilder , De Smet Gaëlle , Roelens Kristien , Cools Filip
Published: April 2021

Background When a severe diagnosis is made before or shortly after birth, perinatal palliative care can be provided to support the infant, parents and involved healthcare providers. However, since this is a relatively new and evolving field of study, a large variation exists amongst perinatal palliative care initiatives internationally. The field currently lacks a systematic overview of effectiveness and working components of such initiatives.Methods A systematic search will be conducted in MEDLINE, Embase, CENTRAL, CINAHL, PsycInfo and Web of Science. We will include quantitative and qualitative study designs examining the effect of perinatal palliative care compared to regular care provided on pain and/or symptom relief, quality of care for, and quality of life of fetuses/infants, parents, family members and involved healthcare providers; and quantitative and qualitative study designs describing the components of care included in existing perinatal palliative care initiatives. Three independent authors will review titles and abstracts and screen full texts against eligibility criteria. Two standardized scales will be used to assess the quality of included studies: one for quantitative research from the NHS Centre of Reviews and Dissemination guidelines for observational studies and for quantitative research, and one for qualitative research from Hawker critical appraisal tool for evaluating qualitative and mixed research. One reviewer will carry out full data extraction and quality assessment, and a 20% random sample will be extracted and assessed by two independent reviewers. An overview table of all identified perinatal palliative care initiatives, including their components and their (preliminary) effectiveness and measured outcome variables when applicable, will be construed. Our protocol adheres to the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) checklist for study protocols.Discussion This systematic review will provide a comprehensive overview of palliative care programs in the perinatal period and their working components. This will aid the construction of a reliable and valid perinatal palliative care intervention with the aim of developing and piloting a Perinatal Palliative Care program within the existing perinatal healthcare setting, in order to provide the best possible care for fetuses and neonates with a life-limiting diagnosis, their families, and involved healthcare providers.