bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Characteristics and CT Manifestations of 143 Patients With 2019 Novel Coronavirus Disease (COVID-19) in Taizhou City, Zhejiang, China
Authors: Kuang Yani , He Susu , Lin Shuangxiang , Zhu Rui , Zhou Rongzhen , Ying Shuying , Li Renzhan , Lin Haiyong , Zhang Zhibang , Pang Peipei , Ji Wenbin
Published: May 2020

Background In December 2019, the first case of pneumonia associated with the SARS-CoV-2 was found in Wuhan and rapidly spread throughout China, so data are needed on the affected patients. The purpose of our study was to find the clinical manifestations and CT features of COVID-19.Methods All patients with COVID-19 in Taizhou city were retrospectively included and divided into non-severe group and severe group according to the severity of the disease. The clinical manifestations, laboratory examinations and imaging features of COVID-19 patients were analyzed, and the differences between the two groups were compared.Results A total of 143 laboratory-confirmed cases were included in the study, including 110 non-severe patients and 33 severe patients. The median age of patients was 47 (range 4–86 years). Fever (73.4%) and cough (63.6%) were the most common initial clinical symptoms. Between two groups of cases, the results of aspartate transaminase, creatine kinase and lactate dehydrogenase, serum albumin, CPR, glomerular filtration rate, amyloid protein A, fibrinogen, calcitonin level and oxygen partial pressure, red protein, IL – 10, absolute value of CD3, CD4, CD8 were different, and the difference was statistically significant (P < 0.05). On admission, the CT showed that the lesions were mostly distributed in the external lung or under the pleura (135 cases (98%)), and most of lesions presented as patchy (81%), heterogeneous (73%) and mixed density (63%) shadow. Consolidation (68% vs 41%), bronchial inflation signs (59% vs 41%), and bronchiectasis (71% vs 39%) were more common in the severe group.Conclusions Most of the cases of COVID-19 in Taizhou have mild symptoms and no death. In addition to clinical symptoms, some laboratory tests (such as absolute values of CD4 and CD8) and CT findings can be used to assess the severity of the disease.
Reputation-Based Dynamic Contract Incentive Mechanism in Mobile Crowdsourcing Network
Authors: Wu Minghu , Wan Qixuan , Zheng Xuan , Jiang Yuhan , Zhao Nan
Published: May 2020

Mobile crowdsourcing network is a promising technology utilizing the mobile ter- minal’s sensing and computing capabilities to collect and process data. However, because the mobile users (MUs) have selfish characteristics, the MUs only aim at maximizing their benefits. Therefore, how to design an appropriate long-term incentive mechanism for the service provider (SP) in dynamic environments is an urgent problem. In this work, we investigate the reputation-based dynamic contract for mobile crowdsourcing network. A two-period dynamic contract is first investi- gated to deal with the asymmetric information problem in the long-term crowd- sourcing tasks. Reputation strategy is introduced to attract the MUs to complete the long-term tasks. The incentives of the contract and the implicit incentives of the reputation strategy are used together to encourage MUs to complete the long-term crowdsourcing tasks. The optimization strategy is formulated by adjust- ing the reputation coefficient to maximize the SP’s utility. The impact of MUs’ risk attitude and reputation impact factors on the incentive mechanism is studied through experiments. Numerical simulation results demonstrate that the optimal reputation-based contract design scheme is efficient in the Mobile crowdsourcing networks.
Elevated Circulating Levels of N-Acetyl-Seryl-Aspartyl-Lysyl-Proline ( AcSDKP) Involved in Pancreatic Cancer Development
Authors: Susanto Hendra , Purnomo Jerry Dwi Trijoyo , Chen Chang-Chiang , Wang Chih-Hong
Published: May 2020

Background: Pancreatic cancer is the fourth leading cause of patient mortality with poor early prognosis. Lack of symptoms as early detection of this cancer has become the major problem for its clinical investigation. Thymosin β-4 (Tβ4) has been associated with angiogenesis and metastasis in pancreatic cancer. Recently, N-Acetyl-Seryl-Aspartyl-Lysyl-Proline (AcSDKP), a cleavage and active form of Tβ4, is suggested related to systemic alteration to patients and involve in the Pancreatic Ductal Adenocarcinoma (PDAC) progression. However, the way this systemic change affected PDAC development is still not fully elucidated. This case-control study was conducted to evaluate the level of AcSDKP in health and pancreatic cancer patients during the progression of pancreatic cancer development. Methods: We analyzed 105 patients, including 15 healthy subjects and 90 pancreatic cancer subjects. The levels of AcSDKP were analyzed by Enzyme-Linked Immunosorbent Assay (ELISA) kit. Proliferation rate analysis was conducted using MTS assay in AsPC, HPAC, and PANC-1 cell line pre-treated by prolyl oligopeptidase (POP) inhibitor and AcSDKP polypeptide. Results: Compared to healthy patients (0.73 ± 0.13), the levels of AcSDKP significantly increased in pancreatic cancer subjects (1.34 ± 0.14). AcSDKP induced pancreatic cell proliferation while inversely inhibited with POP inhibitor by in vitro analysis. Moreover, levels of AcSDKP were strongly positively correlated with pancreatic cancer status (r = 0.278, p = 0.026), betatrophin (r = 0.270, p = 0.025), ALP (r = 0.267, p = 0.034), ALT (r = 0.336, p = 0.007), and AST (r = 0.255, p = 0.042), while inversely correlated with cholesterol levels (r = - 0.250, p = 0.046). Furthermore, in univariate and multivariate binary logistic regression analysis, the levels of AcSDKP showed a strong association with pancreatic cancer [(p = 0.031, OR±95%CI = 3.342 (1.117-10.002)] and [(p = 0.024, OR±95%CI = 4.324 (1.030-18.148)]. Quintile analysis showed that the level of AcSDKP has a strong association with betatrophin [(p = 0.033, OR±95%CI = 5.623 (1.142-24.266)]. Conclusions: AcSDKP can contribute to the progression of pancreatic cancer incidence and may indirectly be associated with liver lipid metabolism hormone as well as tumor cell proliferation. AcSDKP might be a potential additional predictor for pancreatic cancer.
Exploring the zoonotic potential of Mycobacterium bovis using variant calling approaches
Authors: Banerjee Ruma , Balamurugan Muthukumar , Joshi Rajendra
Published: May 2020

BackgroundMycobacterium tuberculosis var. bovis is one of the causative agents of Tuberculosis primarily known to infect cattle and is a member of the Mycobacterium Tuberculosis Complex. M.bovis is zoonotic and infects human and other animals resulting in immense economic losses globally. M.bovis is often misdiagnosed and becomes a challenge for treatment and recovery, as M.bovis is intrinsically resistant to certain antibiotics. Hence, the need for accurate diagnostics for zoonotic tuberculosis. ResultsIn order to discern the differences which lie between M.tuberculosis and M.bovis isolates we collected a global collection of M.bovis isolates from NCBI and carried out variant identification studies keeping M.tuberculosis as the reference. Clustering approaches like Principal component analysis and distance-based UPGMA methods helped to segregate isolates into different clusters of homogeneous and heterogeneous populations, which were further analyzed for variant identification. Methods like Joint Variant Calling using population-based studies was adopted for the M.bovis strains, which helped to discern high confidence polymorphisms for each set of populations. Four different variant callers were used to predict SNPs present in their genomic regions. Based on the predicted SNPs, M.bovis samples isolated from New-Zealand were identified as a heterogeneous fast evolving population, whereas the UK samples were identified as a slow evolving homogeneous population. The core-SNP identified for each population revealed the “fixed” mutations present within the populations, whereas, the total-SNP for heterogeneous population indicated presence of clonal subpopulations. A methodology for assignment of genomic coordinates to the reference SNP cluster id of M.tuberculosis entries in dbSNP was also developed and implemented, which helped to identify the percentage of known variants in a population. ConclusionsPopulation-specific studies for global collection of M.bovis samples aided in identification of SNPs responsible for zoonosis. The core-SNP set identified across global M.bovis isolates provide a rationale for further studies to the underlying host-tropism along with aiding in as a robust genetic biomarker for distinguishing M.bovis form M.tuberculosis in addition to the already known RDs. The variation profile reported in this study can serve as potential biomarkers for identification of M.bovis isolates and provide a rationale for further studies to the underlying host-tropism.
Differences in radiological and functional outcomes between cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament after multi-level laminoplasty
Authors: Yu Dongwoo , Kim Sang Woo , Jeon Ikchan
Published: May 2020

Objective

The purpose of this study was to compare the radiological and functional outcomes between patients with cervical spondylotic myelopathy (CSM) and ossification of the posterior longitudinal ligament (OPLL) after multi-level laminoplasty.
Methods

This study included 75 patients (32 with CSM and 43 with OPLL) with preserved cervical sagittal balance who underwent multi-level laminoplasty for cervical myelopathy. The radiological outcomes were analyzed using the following parameters: C2–C7 Cobb angle in neutral (C27AN), flexed (C27AF), and extended (C27AE) neck postures; C2–C7 range of motion (C27ROM); T1 slope (T1S); and C2–C7 sagittal vertical axis (C27SVA). The functional outcomes were analyzed using the modified Japanese Orthopedic Association (mJOA) score, Nurick grade, and recovery rate. The radiological and functional outcomes between the two groups were evaluated 12-months postoperatively.
Results

C27AF, C27ROM, and C27SVA in the CSM group and C27ROM in the OPLL group decreased significantly (p < 0.05). There was a significant difference in ΔC27SVA between the two groups (9.41 ± 17.06 mm vs. 1.10 ± 17.15 mm, p < 0.05). However, there were no significant intra- or intergroup changes and differences in C27AN (p > 0.05). The functional outcomes including mJOA score (p = 0.251), Nurick grade (p = 0.316), and recovery rate (p = 0.435) showed no significant intergroup differences.
Conclusions

Although there were no significant differences in functional outcomes between the two groups, the CSM group showed a greater deterioration in sagittal balance with an increase of C27SVA than the OPLL group after multi-level laminoplasty.
Construct validity and differential item functioning of the PHQ-9 among health care workers: Rasch Analysis approach
Authors: Jiraniramai Surin , Wongpakaran Tinakon , Angkurawaranon Chaisiri , Jiraporncharoen Wichuda , Wongpakaran Nahathai
Published: May 2020

Background The Patient Health Questionnaire (PHQ-9) is a widely used self-report questionnaire to screen depression. Its psychometric property has been tested in many populations including health care workers. We used Rasch measurement theory to examine the psychometric properties of PHQ-9 regarding item difficulty, item fit and the differences between subgroups of respondents classified by sex, age, education and alcohol user status, based on the same overall location of participants.Methods In total, 3,204 health care workers of Maharaj Nakorn Chiang Mai Hospital participated and were administered the PHQ-9. Rating scale Rasch measurement modeling was used to examine the psychometric properties of the PHQ-9.Results The data fitted well to the Rasch model and no violations of the assumption of unidimensionality were observed. All 9 items could form a unidimensional construct of overall depressive severity. Suicidal ideation was the least endorsed while sleep problem was the most. No disordered category and threshold of the rating response were observed. No locally dependent items were observed. No items were found to show differential item functioning across age, sex, education and alcohol consumption. The item-person Wright map showed that the PHQ-9 did not target well with the sample, and a wide gap suggesting few or no items exist to differentiate participants at a certain ability level among the PHQ-9 items.Conclusion The PHQ-9 can be used as a screening questionnaire for major depressive disorder as its psychometric property was verified based on Rasch measurement model. The findings are generally consistent with related studies in other populations. However, the PHQ-9 may be unsuitable for assessing depressive symptoms among health care workers who have low levels of depression.
Comparative genome analysis of Bacillus okhensis Kh10-101T reveals insights into adaptive mechanisms for halo-alkali tolerance
Authors: Krishna Pilla Sankara , Raghunathan Sarada , Jogadhenu Shyam Sunder Prakash
Published: May 2020

Background: Bacillus okhensis, isolated from saltpan near port of Okha, India, was initially reported to be a halo-alkali tolerant bacterium.We previously sequenced it’s 4.86 Mb genome, here we analyze its genome and physiological responses to high salt and high pH stress. Results: B. okhensis is a halo-alkaliphile with optimal growth at pH 10 and 5% NaCl. 16S rDNA phylogenetic analysis resulted in habitat based segregation of 106 Bacillus species into 3 major clades with all alkaliphiles in one clade clearly suggesting a common ancestor for alklaliphilic Bacilli. We observed that B. okhensis has been adapted to survive at halo-alkaline conditions, by acidification of surrounding medium using fermentation of glucose to organic acids. Comparative genome analysis revealed that the surface proteins which are exposed to external high pH environment of B. okhensis were evolved with relatively higher content of acidic amino acids than their orthologues of B. subtilis. It posess relatively more genes involved in the metabolism of osmolytes and sodium dependent transporters in comparison to B. subtilis. Growth of B. okhensis is Na+ dependent, with a minimum requirement of 4% NaCl at neutral pH but 0.5% NaCl is enough at pH 10. It tolerated sudden increase of salt concentration of its medium, and exhibited an elongated cellular phenotype. But, could not tolerate a sudden shift of pH from 7 to 11, and cell envelope got damaged, confirming the pH regulation through cell wall reinforcement is key to survival at high-pH condition. We observed that hydroxyl ions damage the cell, but not Na+ ions, becuase at high pH Na+ ions were not accumulated inside. Conclusion: B. okhensis uses acidification of the external medium and pH dependent cell wall reinforcement to survive sodic environments. Interestingly, its growth is highly Na+ dependent and the genome encodes for a high proportion of acidic amino acids in majority of surface proteins in comparison to their orthologues of B. subtilis, a direct evidence of adaptive evolution.
The worldwide contribution of medical students during the COVID-19 pandemic: quantitative and qualitative research
Authors: Blom Iris Martine , Whyatt Gemma , Viva Inês , Martin Anastasia
Published: May 2020

Background

One of the biggest concerns regarding the COVID-19 pandemic is the extreme demand for health care workers and health systems. Medical students possess a range of skills and attributes that can help the declining workforce. This paper aims to provide an overview of the roles medical students have taken during this pandemic worldwide and provide insights to work towards establishing safe, efficient and useful roles during the progression of the pandemic.
Methods

A comprehensive questionnaire was distributed through social media using platforms and networks that involved medical students worldwide. Analysis of the data included both quantitative and qualitative methods. Qualitative data of multiple-choice questions was done to calculate the percentage of countries in which students played a role during the pandemic, whether they were paid, and if medical education was suspended. Furthermore, we identified the different roles medical students had across the globe. Qualitative analysis was performed on blank space questions to gain more insights regarding the roles of medical students across different countries.
Results

144 responses were reported from 47 countries and 81 different universities, representing all United Nations Regions. The role of medical students was most reported as providing medical assistance, namely in 61.7% of countries. Other reported roles were helplines, no role, logistical assistance, testing, baby-sitting, awareness, triage and supporting a physician at home. In 7.5% of the countries where students are performing services, it is reported these are paid services. In 45.7% (n = 37) of all universities, medical schools have been suspended with no reported (online) alternative for classes or exams.
Conclusions

Our results show that medical students have the capability to contribute in many different ways during this pandemic. In most cases, roles are unpaid and many reports show that there is no clarity on whether their roles will count towards their educational credits. It is crucial to develop adequate protocols and statements, so medical students can contribute to the best of their capacity and in a safe, ethical and healthy manner during the pandemic, for which additional research and collaboration between institutions is needed.
Identification of a Four-miRNA Risk Score Model and Hub Genes as a Novel Potential Prognostic Biomarker in Patients with Glioma
Authors: xu jianguang , Li Si-Si , Lu Ye-Chen , Hua Xu-Yun , Wu Jia-Jia , Ding Dao-Fang , Ma Zhen-Zhen
Published: May 2020

Background Novel biomarkers for malignant glioma are urgently needed due to the poor prognosis of this cancer. Numerous discoveries have demonstrated that microRNAs (miRNAs) participate in the occurrence and progression of glioma. The objective of this study is to explore new biomarkers related to glioma prognosis by bioinformatic analysis.Methods The miRNA, mRNA expression profiles and relevant clinical information were extracted from TCGA database. Differently expressed miRNAs (DEMs) and differently expressed mRNAs/genes (DEGs) were screened, and a risk score comprising four miRNAs was constructed. We evaluated and tested the model accuracy through the ROC curve and a survival status analysis. Four-miRNA nomography were performed to quantitatively and visually evaluate the model. The potential biological functions of those network genes were performed through KEGG pathways and Gene Ontology (GO) terms analysis. Furthermore, survival analysis and the clinical information was used to verify whether the hub genes are associated with prognosis. The CGGA and GEPIA database were used to verified the accuracy of these analysis. To investigate the potential functions of those hub genes in glioma, we performed GSEA and GSVA.Results The results of univariate Cox regression showed that twenty miRNAs were significantly associated with overall survival of glioma. Multivariate Cox regression analyses were performed to screen four miRNAs (hsa-miR-744-5p, hsa-miR-1249-3p, hsa-miR-3677-3p and hsa-miR-10b-3p). The estimated area under the receiver operating characteristic (ROC) curve (AUC) were 0.902, 0.896 and 0.907 for groups train, test and entire, respectively, indicating that the model had a significant ability to predict survival in glioma patients. Furthermore, univariate and multivariate Cox regression were performed using relevant clinical factors associated with glioma, showed that the model could act as an independent prognostic factor. CGGA and GEPIA database were used to verified the accuracy of these hub genes. GSEA and GSVA revealed that the lower expressions of these hub genes were most closely associated with vascularization and tumor proliferation.Conclusions In conclusion, the four-miRNA risk score model and these hub genes may represent a novel prognostic marker to predict the survival of patients with glioma.
Circ_0002232 Acts as a Potential Biomarker for AML and Reveals a Potential ceRNA Network of Circ_0002232/miR-92a-3p/PTEN
Authors: Deng Zhao-qun , Su Xiao-yu , Zhu Xin , Zhao Qian , Ke Jin-ming , Wu De-long , Yi Yun-yun , Yi Jing , Lin Jiang , Qian Jun
Published: May 2020

Background: PTEN, known as a classical tumor suppressor, has been reported to be down-expressed in acute myeloid leukemia (AML) and affected the progression of AML patients. Our research was aimed to investigate the expression level of circ_0002232, one of circular RNAs of PTEN, reveal the clinical significance and potential ceRNA interaction network in AML of it.Methods: Circ_0002232 expression in 117 AML patients and 48 controls was detected by using Real-time quantitative PCR.Results: Compared with controls, circ_0002232 was notably low-expressed in AML (P < 0.001). According to the result of receiver operating characteristic curve, circ_0002232 expression could distinguish AML patients from controls (P < 0.001). There were significant differences in patients’ age (P = 0.002), FAB classifications (P = 0.025), white blood cell count (P = 0.034) and platelet count (P = 0.047) between low-expressed circ_0002232 group and high-expressed circ_00022332 group. Moreover, there was a positive correlation between circ_0002232 expression and patients’ age (Pearson r = 0.256, P = 0.0053). Interestingly, we found that patients in low-expressed circ_0002232 group had better overall survival both in whole AML (P = 0.019) and non-APL AML (P = 0.044). Remarkably, the expression of circ_0002232 was positively correlated with PTEN (Pearson r = 0.769, P < 0.001). Furthermore, there was a negative correlation in AML between circ_0002232 and miR-92a-3p (Pearson r=-0.262, P = 0.032), miR-92a-3p and PTEN (Pearson r=-0.358, P = 0.019). Interaction prediction websites revealed that circ_0002232 might regulate the expression of PTEN through sponging miR-92a-3p and affect the process of AML.Conclusions: Circ_0002232, one of circRNAs of PTEN, was remarkably down-regulated in AML and could act as a promising biomarker for the diagnosis of AML. In addition, there might be a potential ceRNA interaction network of circ_0002232/miR-92a-3p/PTEN in AML.
Fraction exhaled nitric oxide and IOS as potential biomarkers for HDM immunotherapy in patients with allergic rhinitis and asthma
Authors: Zhou Jun , Du Wei , Xu Guofang , Wang Ping , Tao Yi , Sun Lin , Peng Bo , Dai Ranran , Tang Wei
Published: May 2020

Background：Allergen specific immunotherapy (AIT) is the only potential disease-modifying treatment of house dust mite (HDM) allergic asthma and rhinitis. The conventional treatment procedure lasted for 3 years, but biomarkers indicating early efficacy from this long-term treatment has not been well illustrated. In this single arm, observation study, we evaluated non-invasive airway inflammation parameters such as Exhaled nitric oxide (FeNO), nasal NO levels (FnNO), and small airway function parameter-impulse oscillometry system (IOS) as well as serum parameters Dermatophagoides pteronyssinus (Derp) specific IgG4 and sIgG4/IgE ratio as potential biomarkers for AIT.Methods：Patients with mild allergic asthma concomitant with allergic rhinitis were treated with subcutaneous immunotherapy of Der p extract. Clinical evaluations including symptom score and medication score, small airway function of spirometer and non-invasive airway inflammation parameters from the nose (FnNO) and lung (FeNO) were collected before and after half year and one year of AIT. Serum Derp specific IgE and IgG4 measurement data were also collected. Results：Symptoms and medication score of patients were alleviated both after half and one-year HDM immunotherapy according to VAS (visual analogue score) and medication score. Improved small airway function (evaluated through IOS) and reduced non-invasive airway allergic inflammation parameters both from the nose (FnNO) and lung (FeNO) were achieved after half and one year AIT. As to serum biomarkers, Der p specific IgG4 increased and Der P specific IgE/IgG4 decreased significantly after one year treatment.Conclusions: One year HDM subcutaneous allergen immunotherapy improved allergic symptoms and reduced medication score in patients with allergic asthma concomitant with rhinitis. Non-invasive airway inflammation parameters such as FeNO and FnNO and small airway function parameter IOS are potential biomarkers for evaluating early efficacy of AIT. Derp specific IgG4 as well as IgE/IgG4 ratio maybe good therapeutic predictors to reflect the efficacy of AIT in the first year of treatment.
Syngas production by chemical-looping gasification of waste activated carbon with iron-based oxygen carrier
Authors: Li Xiao , An Mei , Wu Man , Li Jinshuai , Zhang Xiuli , Wu Jilai , Yuan Sijie , Guo Qingjie
Published: May 2020

Waste activated carbon (WAC), as a typical solid waste, can be utilized by chemical looping gasification (CLG) technology with an iron-based oxygen carrier to produce valuable synthesis gas products. A series of experiments on WAC of the CLG process were carried out in a fixed-bed reactor. The operation parameters involving the OC/WAC mole ratio, steam flow rate and reaction temperature during WAC CLG reactions were investigated in detail. Further, the cyclic performance within 10 cycles was also discussed. Fresh and other representative oxygen carrier samples were analyzed by X-ray diffraction (XRD) and scanning electron microscopy (SEM) characterization methods. The results showed that the optimal OC/WAC mole ratio, steam flow rate and reaction temperature were determined to be 0.15, 0.10 mL/min, and 950 °C, respectively, to obtain high-quality syngas with relatively high carbon conversion. The iron-based oxygen carrier exhibited a stable cyclic performance during the multiple tests, following the reaction path of Fe2O3→Fe0.98O in the individual reduction process. Moreover, the iron-based oxygen carrier could be oxidized almost to its initial state after 10 redox tests, and no obvious sintering and agglomeration phenomena were observed. The WAC of CLG presents a new approach for the comprehensive utilization and disposal of solid waste, especially with low volatile feedstocks.
Efavirenz Based First Line Anti-Retroviral Drugs Disrupts Follicular Development-Evidence From Animal And Human Studies
Authors: Ohihoin Aigbe , Ohihoin Esther Ngozi , Iranloye Bolanle Olubusola , Olarenwaju Oladeji , Okafor Arinze , Oji Kalu , Kalejaiye Olufunto , Bakare Airat , Ujomu Ifeoma , Aina Olugbemiga , Ajibaye Shola , Okechukwu Ada , Kiladejo-Aderoba Adekemi , Medobi Frank , Ezechi Oliver , Taylor-Robinson Simon
Published: May 2020

INTRODUCTION: Interventions to eliminate mother to child transmission of HIV has led to very low vertical transmission rate, however there are genuine concerns on long term effect of anti-retroviral drugs on future reproductive functions of females. There is currently paucity of information regarding the effect of anti-retroviral agents such as Tenofovir, Efavirenz and Lamivudine on the ovarian reserve of patients receiving anti-retroviral drugs. METHODOLOGY: 1. ANIMAL STUDY: A total of 25 female Wistar rats, weighing between 150g to 170g were obtained and kept in the experimental animal house of the Nigerian Institute of Medical Research (NIMR) in Lagos, Nigeria. They were kept in clean cages at a temperature of 28 o C HUMAN STUDY: Women within the reproductive age range of 15-45 years were grouped into A, B and C categories. Group A was made up of HIV positive patients already on efavirenz based anti-retroviral therapy. Group B were HIV positive patients who were naïve to antiretroviral drugs at the time of recruitment. Group C participants were HIV negative women within the reproductive age range not being managed for Infertility. RESULTS: ANIMAL STUDY : The mean count of antral follicles was significantly lower in the group that received efavirenz (p=0.00). The corpus luteal count was significantly higher in the control group than study groups (p=0.033) HUMAN STUDY: Average value of FSH is significantly higher in the HIV positive group who had antiretroviral medications when compared to HIV negative group. (P=0.039).Antral follicular count was significantly reduced in the group that received anti retrovirals (ARV). P=0.009 CONCLUSION: Evidence from this animal and human study, tend to suggest that efavirenz based antiretroviral medication disrupts follicular development.
Network pharmacology-based mechanistic investigation of Jinshui Huanxian formula acing on idiopathic pulmonary fibrosis
Authors: Liu Tiantian , Xu Pengli , Qi Shuishui , Ke Shaorui , Hu Qin , Zhao Peng , Li Jiansheng
Published: May 2020

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease with high incidence rate, morbidity and mortality. Jinshui Huanxian formula (JHF) is an empirical formula for the pathogenesis of lung-kidney qi deficiency and phlegm-blood stasis in pulmonary fibrosis. The purpose of this study is to explore the pharmacological mechanism of JHF action in IPF therapy by network interaction analysis.
Methods

The main active components and corresponding target genes of JHF were predicted using various databases. Two sets of IPF disease genes were obtained from the DisGeNET database and GEO database. Two sets of drug targets for IPF treatment were collected and the overlapping genes between disease genes and drug targets were analyzed. The target genes of JHF were intersected with the differentially expressed genes of IPF to obtain the predicted targets of JHF acting on IPF. The functions and pathways of predicted targets acting on IPF were analyzed by using DAVID and KEGG pathway database. Finally, the resulting drug target mechanisms were validated in a rat model of pulmonary fibrosis.
Results

494 active compounds and 1304 corresponding targets were screened. Intersection analysis showed that 4 genes were common genes of JHF targets, IPF disease genes and anti-IPF drugs in KEGG database, and these genes were targeted by several compounds of JHF respectively. 72 JHF targets were closely related with IPF, and were thus considered therapeutically relevant. The targets were screened and participated in the regulation of IPF through 18 pathways. The molecular functions of targets included regulation of oxidoreductase activity, kinase regulator activity, phosphotransferase activity and transmembrane receptor protein kinase activity. In vivo experiments showed that JHF could alleviate the degree of pulmonary fibrosis, including the decrease of collagen deposition and epithelial-mesenchymal transition.
Conclusions

This study explored the mechanisms of JHF from a systematic point of view, trying to identify the specific target pathways acing on IPF. Pharmacological network with in vivo validation explained the potential roles and mechanisms of JHF in IPF therapy.
SPINK7 Expression Changes Accompanied by HER2, P53 and RB1 may be Potential Biomarkers to Predict Oral Squamous Cell Carcinoma at Molecular Level
Authors: Penachiotti Gina , Valdez Fabio , González-Arriagada Wilfredo A , Montes Hector F , Parra Judith , Guida Valeria , Gómez Silvina E , Guerrero-Gimenez Martin E , Fernandez-Muñoz Juan M , Zoppino Felipe CM , Carón Rubén W , Ezquer Marcelo E , Fernández-Ramires Ricardo , Bruna Flavia A.
Published: May 2020

Background. The oral squamous cell carcinoma (OSCC) affects more than 300,000 patients annually worldwide with a high morbidity rate (37.8%). Several tumor biomarkers have been suggested to anticipate outcome but results were poor. Changes of SPINK7 and associated proteins in precancerous oral lesions could lead to genomic instability and promote oncogenesis. Our aim was to evaluate SPINK7as apotential molecular biomarkerpredictive of OSCC stages, compared with well-known molecules altered in cancer: HER2,TP53, RB1, NFKB and CYP4B1. Methods.Oral biopsies from patientswith dysplasia (n=33), less invasive(n=28) andhighly invasiveOSCC (n=18) were collected. 20 cases with a clinical suspicion but normal mucosa confirmedwere included ascontrol. Gene expression of SPINK7, P53,RB, NFKBand CYP4B1 were quantified by qPCR.SPINK7 levels were correlated with a cohort of 330 patients from the TCGA. Also,SPINK7, HER2, TP53, and RB1, were evaluated by immunohistofluorescence. One-way Kruskal-Wallis test and Dunn's post-hocwith a p<0.05 significance were used to data analyze.Results.In OSCC, SPINK7wasdown regulated andP53, RB, NFKB and CYP4B1were up regulatedrespect tothe others groups (p<0.001). Also,SPINK7 expressionwasdiminished in patients of TCGA(p=2.10e-6). In less invasive OSCC,SPINK7 and HER2 proteinswere decreasedandTP53 and RB1 significantly increasedrespect todysplasia and highly invasivegroups (p<0.05).Conclusion. Our results suggest that SPINK7changes accompanied of HER2, P53 and RB1 can be used to classify the molecular stage of epithelial oral lesion inthe OSCC, allowing a more accuratediagnosis to molecular and histopathological level.
An autonomous economical and efficient ureteroscopic irrigation system
Authors: Wang Tengteng , Chen Xiude , Xia Qinghua , Zhang Qi , Jin Xunbo
Published: May 2020

Background

In recent years, the minimally invasive technique for treating nephrolithiasis has been developed rapidly. Particularly, the flexible ureteroscopy has been extensively applied. For flexible ureteroscopy lithotripsy, the perfusion equipment is necessary to ensure a clear intraoperative field of view. This study was aimed to prepare a set of economical and efficient ureteroscopic irrigation system by some commonly used devices in clinical diagnosis and treatment practice.
Methods

In this study, according to requirements of the endoscopic surgery, the infusion apparatus, infusion apparatus extension tube, three-way plug valve, Luer one-way valve, ordinary syringe, and negative pressure spring were used to assemble the irrigation system with different functions.
Results

The autonomous perfusion device realized the real-time conversion of manual injection, continuous perfusion or negative pressure suction. The entire equipment has many advantages, including easily accessible raw materials, low cost, simple assembly process, easy operation, strong controllability, effective control ability for the intrarenal pressure, and high safety.
Conclusions

The commonly used medical devices were applied to assemble the autonomous ureteroscopic irrigation system, which is flexible, simple and cost-effective and thus can be applied in flexible ureteroscopic surgery.
Lathosterol in plasma measures cholesterol synthesis and identifies the efficiency of dietary phytosterols in reducing the plasma cholesterol concentration
Authors: Nunes Valeria Sutti , Ilha Angela Oliveira Godoy , Ferreira Guilherme Silva , Bombo Renata Paula Assis , Afonso Milessa Silva , Machado Roberta Marcondes , Nakandakare Edna Regina , Quintão Eder Carlos Rocha , Lottenberg Ana Maria Maria
Published: May 2020

Background

Because the plasma campesterol/cholesterol ratio does not differ between groups that absorb different amounts of cholesterol measured by the gold standard isotopic procedure we investigated whether the intestinal absorption of phytosterols (PS) depends on the body's cholesterol synthesis rate.
Methods

38 volunteers (58 ± 12 years; low-density lipoprotein cholesterol (LDL-C) ≥ 130 mg/dL) were randomly assigned to consume 400 mL/day of soy milk or soy milk + PS (1.6 g/day) for 4 weeks in a double-blind, placebo-controlled, cross-over study. Blood samples were collected and markers of phytosterol (PS) absorption and non-cholesterol sterol synthesis precursors measured.
Results

PS treatment reduced plasma total cholesterol concentration (-5,5%, p < 0.001), LDL-C (-7.6%, p < 0.001), triglycerides (-13.6%, p < 0.0085), and apolipoprotein B (apo B) (-6.3%, p < 0.008), without changing high density lipoprotein cholesterol (HDL-C concentration). The lathosterol-to-cholesterol ratio in serum predicted the serum cholesterol response to PS feeding where high basal cholesterol synthesis was associated with lack of response of plasma cholesterol to PS in the diet. Cholesterol synthesis being elevated in the placebo phase in non-responders to dietary PS indicated they were resistant to further synthesis rise, whereas responders, because they have lower synthesis rate than non-responders in the placebo phase, are capable expanding synthesis under the effect of alimentary PS.
Conclusions

responders absorbed more PS than non-responders likely resulting from responders delivering less endogenous cholesterol than non-responders into the intestinal lumen that facilitates greater absorption of PS by the intestine.
The Diagnostic and Prognostic Value of MiR-92a in Gastric Cancer
Authors: Guo Hanxu , Wang Yuhang , Li Yongtian , Wang Zishu
Published: May 2020

Background: miR-92a been proposed to have a significant role in the diagnosis andprognosis of different types of tumors, but the potential impact of its expression is still controversial due to the sample size. We conducted the meta-analysis to figure out whether miR-92a could be used as a detecting tool and prognosis of gastric cancer.Method: A literature search was performedby retrieving Web ofScience, PubMed, EMBASE, ChineseNational Knowledge Infrastructure (CNKI), VIP(Technology of Chongqing databases) and Wanfang databases (last update by February2020). The sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the ROC curve (AUC) were pooled to explore the diagnostic performance of miR-92a.The pooled HRs and 95%CIs of miR-92a for overall survival (OS) were calculated to explore the prognostic performance of miR-92a. Subgroup and meta-analysis were further carried out to explore the heterogeneity.Results: 10 articles with12 studies were included. The pooled SEN and SPE were 0.76 (95% CI 0.64–0.85) and 0.79 (95% CI 0.63–0.90).Besides, the pooled PLR and NLR were3.7(95% CI 1.8–7.5)and 0.30 (95% CI 0.18–0.50), and the pooled DOR was 12(95% CI4–38). AUC was 0.84 (95% CI: 0.81–0.87), indicating asignificant value of miR-92a in the gastric cancer detection. For the prognostic analysis of miR-92a in gastric cancer, the univariate and multivariate data’s poor OS were 1.46(95% CI0.87-2.45) and 1.46(95% CI0.90-2.39).Conclusions: The present meta-analysis demonstrated that miR-92a could be a potential biomarker for thedetection of gastric cancer.Furthermore,high expression of miR-92a has a negative association with the survivalof patients, suggesting its potential as a prognostic indicator in gastric cancer.
Non-coplanar VMAT improves plan quality for locoregional radiotherapy of left-sided breast cancer with internal mammary nodes
Authors: Xu Yuan , Ma Pan , Hu Zhihu , Tian Yuan , Men Kuo , Wang Shulian , Xu Yingjie , Dai Jianrong
Published: May 2020

Purpose A planning study was performed to evaluate the feasibility of non-coplanar volume modulated arc therapy (ncVMAT) for locoregional radiotherapy of left-sided breast cancer with internal mammary nodes. Methods and materials Ten patients with left-sided breast cancer after breast conserving surgery were retrospectively studied. The planning target volumes (PTV) were contoured encompassing the whole breast/chestwall, internal mammary nodes (IMN) and supraclavicular nodal (SCN) region. For each patient, ncVMAT plan with 4 partial arcs composing of two coplanar arcs and two non-coplanar arcs with couch rotating to 90˚ was generated. The prescription dose was normalized to cover 95% of PTV with 50 Gy delivering in 25 fractions. For each ncVMAT plan, dosimetric parameters were compared with coplanar VMAT (coVMAT) plan optimizing with identical coplanar beam angle arrangement. Results With ncVMAT, the mean conformity index of the whole PTV increased from 0.82±0.02 to 0.86±0.01 (p=0.005), and there was no significant difference for the homogeneity index. The mean coverage of internal mammary target volume (PTVimn) with ncVMAT increased from 88.77±3.07% to 91.67±3.84% comparing with coVMAT (p=0.005). Meanwhile, the V55 in PTVscn and PTVimn decreased significantly from 5.76±6.03%, 13.73±7.77% to 2.94±3.93%, 3.75±3.36%, separately (p<0.01). For organs at risk, the average V30, V20, V10, V5 and Dmean of heart decreased from 5.13±3.22%, 12.18±7.29%, 33.98±15.73%, 72.03±16.79% and 10.47±2.97 Gy to 4.86±2.54%, 9.35±5.43%, 25.16±12.42%, 62.27±13.18% and 9.08±2.34 Gy, separately (p<0.01). Furthermore, ncVMAT significantly reduced the mean V20, V10, V5, Dmean of left lung, and V10, V5, Dmean of contralateral lung (p<0.01). A better sparing of LAD descending coronary artery and right breast were also shown with ncVMAT (p<0.01). Conclusions Compared to coVMAT, ncVMAT provides better conformity, lower V55 in PTVscn and PTVimn, better coverage of PTVimn, better dose sparing in heart, bilateral lung, LAD and right breast for locoregional radiotherapy of left-sided breast cancer with internal mammary nodes, which potentially increase the local control in IMN and reduce the risk of deleterious effects.
Quantification of Ovarian Granulosa Cells and Different Level Follicles in the Mouse Ovary Using Stereology Method, for Potential Application in 3D Bioengineered Ovary.
Authors: Zheng Jiahua , Zhang Jingkun , Tian Yanpeng , Song Yanbiao , Yang Zhengwei , Huang Xianghua
Published: May 2020

Background Stereology is an accurate method to obtain 3D quantitative information of microstructure based on the comprehensive observation of two-dimensional sections. Three-dimensional bioprinting of bioink to rebuild a bioengineered ovary has been proved to be a promising technique in preserving fertility. Fully understand the structure of the ovary, the distribution of the main cells and the numerical density of cells using stereology method is of great significance to the computer 3D reconstruction technology.Results The Cavalieri method gave the estimations that the ovary was (2.49 ± 0.32)mm3, the volume fraction of cortex, medulla, follicles and ovarian granulosa cells ( OGCs ) were 86.80%±2.82%, 13.20%±2.82%, 5.60%±0.25% and 81.19%±2.57%, respectively. From exact counts on serial sections, OGCs, primordial, preantral and antral follicles numerical density were estimated at ( 2.11 ± 0.28 ) × 106/mm3, 719.57 ± 18.04/mm3, 71.84 ± 3.93/mm3 and 17.29 ± 3.54/mm3, respectively. We estimated that there would be (2.11 ± 0.28) × 109 OGCs, (719.57 ± 18.04) × 103 primordial follicles, (71.84 ± 3.93) × 103 preantral follicles, (17.29 ± 3.54) × 103 antral follicles in one milliliter 3D bioink when 3D encapsulated mice ovarian constructs. The total number of the three stages follicles per ovary were 1791.74 ± 5.77, 178.88 ± 1.26, 43.04 ± 1.13, and the respective total number of OGCs and follicles per ovary were (5.26 ± 0.09) × 106, 2013.66 ± 8.16.Conclusions OGCs and follicles can be accurately measured using either the optical or physical disector. The application of these approaches for the study of 3D bioengineered ovary may contribute to a deeper understanding of the artificial ovary.
FXR expression in a rat model of hilar cholangiocarcinoma
Authors: Zhang Meng-yu , Wang Jie-ping , he Kai , Xia Xian-ming
Published: May 2020

Background: To develop a rat model of hilar cholangiocarcinoma and detect Farnesyl X receptor (FXR) expression in hilar cholangiocarcinoma tissues of this model, in order to provide a new method for the treatment of hilar cholangiocarcinoma.Methods: Forty male Wistar rats (body weight, 185 ± 5 g) were randomly divided into two groups (n = 20 each) as follows: The control group was fed a standard diet, and the experimental group was injected by cholangiocarcinoma QBC939 cell suspension along the hilar bile duct into the bile duct bifurcation with microsyringe. Every day note the rats’ mental state, diet, and fur condition. At 4 weeks, one rat of the experimental group was sacrificed, and we recorded changes in hilar bile duct size, texture, and form. This procedure was repeated at 6 weeks. After 6 weeks, hilar cholangiocarcinoma developed only in the experimental group, thereby establishing an experimental model for studying QBC939-induced hilar cholangiocarcinoma. Tumor formation was confirmed by pathological examination, and hilar bile duct tissues were harvested from both the groups. A real-time polymerase chain reaction assay and an immunohistochemical assay were used to analyze the expression of FXR in hilar cholangiocarcinoma and normal hilar bile duct tissues.Results: From the second week, the rats in experimental group began to eat less, and their body mass decreased compared with controls. After 6 weeks, we detected hilar cholangiocarcinoma in 17 rats (85%) in the experimental group. In the experimental group, we found that the levels of total cholesterol, total bilirubin, and direct bilirubin were higher compared with those of the control group. Simultaneously, muddy stones emerged from the bile ducts of rats in the experimental group. The FXR/Gapdh mRNA ratio in hilar cholangiocarcinoma and normal hilar bile duct tissues differed markedly. Light microscopy revealed a granular pattern of FXR expression which reacted with the anti-FXR antibody. Each section was randomly divided into six regions, with 80 cells were observed in every region. Sections with >10% positive cells were designated positive,Sections with <10% positive cells were designated negative. Each group included 4,800 cells. In the experimental group, 1,196 cells (24.9%) were positive and 3,538 cells (73.7%) were positive in the control group, and this difference was statistically significant.Conclusion: FXR expression significantly decreased in hilar cholangiocarcinoma of rats than in those of controls, suggesting that drugs targeting FXR may be a new strategy for hilar cholangiocarcinoma.
Timing of immune checkpoint inhibitors for metastatic patients over 75 years of age: the earlier the better
Authors: Landre Thierry , Guetz Gaetan Des , Chouahnia Kader , Fossey-Diaz Virginie , Culine Stéphane
Published: May 2020

Background The impact of ageing on Immune Checkpoint Inhibitors (ICIs) effectiveness remains controversial. However, data from clinical studies do not show any difference between patients over 65 years and those under 65 years. We focused our study on patients over 75 and looked at the potential impact of timing in the use of ICIs. Methods We performed a meta-analysis of published randomized control trials (RCTs) concerning ICIs versus standard therapy in patients with advanced solid tumors. Overall Survival (OS) among the older (≥75 years) was compared with that of younger patients (< 75 years). Hazard ratios (HRs) with their 95% confidence interval (CI) were collected and pooled. Results Fifteen phase III studies evaluating anti-PD-1(nivolumab or pembrolizumab), anti-PD-L1 (atezolizumab or avelumab) or anti-CTLA-4 (ipilimumab) were included. Patients were enrolled for Non-Small-Cell-Lung-Cancer, Renal-Cell-Carcinoma, Melanoma, Head-and-Neck-Squamous-Cell-Carcinoma or Gastric Cancer. Eight studies assessed treatment in first-line setting and seven in the second line. The median age was 64 years, with 906 patients over 75 years of age and 5233 youngers. In first-line setting, HRs for death were 0.78 (95% CI: 0.61-0.99) in patients ≥75 years versus 0.84 (95% CI: 0.71-1.00) in younger. In second line setting, HRs for death were 1.02 (95% CI: 0.77-1.36) in patients ≥75 years versus 0.68 (95% CI: 0.61-0.75) in younger with a statistically significant difference observed between subgroups (p interaction = 0.009). Conclusions ICIs appears to be effective in patients over 75 years of age. However, the survival benefit is mainly observed in first-line treatment.