bluuebunny/crossref_metadata_2025 huggingface dataset:
METİN SADELEŞTİRME BAĞLAMINDA YÖNETİM KİTAPLARI ÜZERİNE KARŞILAŞTIRMALI BİR İNCELEME: İŞLETME ORGANİZASYONU VE SEVKU İDARESİ (1959) VE İŞLETME ORGANİZASYONU VE YÖNETİMİ (1963)
Authors: ÖZKUL Ahmet Sait , ŞATIRER Hüseyin
Published: June 2020

Bu çalışmada, Mehmet Oluç tarafından 1959 tarihinde yayımlanan “İşletme Organizasyonu ve Sevku İdaresi” adlı ders kitabı ve aynı kitabın 1963 tarihinde “İşletme Organizasyonu ve Yönetimi” adıyla yayımlanan ikinci baskısı, “metin sadeleştirme” bağlamında değerlendirilmektedir. Çalışmada, Amerikan işletmecilik ve yönetim bilgisinin Türkiye’de 1950’lerle birlikte etkili olduğu dönemde, “yönetim eğitiminde kullanılan dilin sadeleşmesi” meselesinin de ortaya çıktığı görülmektedir. Bu noktada Türkiye’de işletme ve yönetim alanındaki dilsel olguların, hangi etkenlere bağlı olarak değişime uğradığını tespit etmek önem arz etmektedir. Çünkü Oluç’un bu iki kitabında; gerek yayımlandıkları tarihler itibariyle yönetim alanına artan ilgi gerekse dil sadeleşmesinin, işletmecilik ve yönetim alanına yansıması hakkında önemli ipuçları bulunmaktadır. Çalışmada doküman inceleme yöntemi kullanılmıştır. Bu bağlamda kitaplar, toplam kelime ve bölüm sayıları açısından incelenmiştir. Daha sonra ise içeriklerinde yapılan değişiklikler açısından karşılaştırılmıştır. İşletmecilik ve yönetim eğitimi alanında 1950’lerde kullanılan kelime/terimlerin 1960’lardaki değişimi, incelenen kitaplar bağlamında tablolaştırılmıştır. Oluç’un kitabının birinci ve ikinci baskısı arasında; dil sadeleşmesi açısından önemli değişiklikler bulunmaktadır. İncelenen kitaplarda; yapılan metin sadeleştirmesi neticesinde, hem içerikte yer alan genel dilsel olguların hem de işletmecilik ve yönetim yazınında kullanılan terimlerin değişime uğradığı tespit edilmiştir
Role of Female Reproductive Hormones in Musicians' Dystonia
Authors: Rosset-Llobet Jaume , Pascual-Leone Álvaro , Fàbregas-Molas Sílvia
Published: June 2020

Musicians’ dystonia is an occupational focal dystonia affecting men more often than women. METHODS: We identified all patients presenting with musicians’ dystonia and prospectively collected data on reproductive and menstrual history from the women with musician’s
dystonia and female musicians without dystonia. RESULTS: 149 men and 23 women (13.37%) with musician’s dystonia where identified. We did not identify any effect of contraceptive hormones, pregnancy, or menstrual phases on dystonia symptoms, but as compared with women without dystonia,
those with musician’s dystonia reported oligomenorrhea and menometrorrhagia significantly less frequently. CONCLUSIONS: Our data reinforce the relation between sex hormones variations and musicians’ dystonia. This link should be further explored to identify mechanisms and assess
whether certain hormonal interventions might protect from the manifestation of dystonia.
RELATIONSHIP BETWEEN THE PERCEPTION AND SKILLS OF STUDENT BASIC SCIENCE PROCESS IN THE USE OF M-MODULE IN BASIC PHYSICS PRACTICUM
Authors: Samosir Sofia Christine , Gurning Lidia
Published: June 2020

This study aims to determine the relationship between perception and basic science process skills through the use of the m-module in basic physics practicum II. This research is a quantitative study using correlational design. data collection instruments used in the form of perception questionnaire instruments and observation sheets to measure students' science process skills. This study used a sample of 36 physics students at Universitas Jambi. The results of the study will be analyzed using descriptive statistics and inferential statistics. The results of this study indicate that students give a good perception of the use of the m-module in basic physics practicum II. Flat mirror material is proven from the value of the perception of 63.9% in the good category according to a predetermined range. And the basic science process skills of students are in a good category with a percentage of 50.0%. Pearson correlation results show the number 0.756 and sig 0.05 which is 0.00, this shows that there is a strong relationship between perceptions and students' science process skills in using the m-module. This means that a high perception will result in high science process skills.
Modern Features of Hepatitis a Epidemic Process in Large City of European Russia
Authors: Zalesskikh A. A. , Bystrova Т. N. , Polyanina A. V.
Published: June 2020

Purpose of the studywas to characterize modern features of hepatitis A epidemic process in large city of European Russia and optimization of epidemic surveillance of the infection.

Materials and methods. Hepatitis A incidence data were analyzed in long-term period 1968–2017. Etiologic structure of acute viral hepatitis was identified by both incidence data and extended set of viral hepatitis markers in patients with jaundice (n = 144). Anti-HAV prevalence rate was studied in population of N. Novgorod by immuno-enzyme method in 2014 and 2017 (n = 1728, age: 1–60 years old).

Results and discussion. Share of hepatitis A in etiology of acute viral hepatitis did not significantly change in 2007–2017, if compared to 1994–2006 (50,8 ± 9,2% and 56,1 ± 13,3% respectively, р > 0,05), but it varies greatly depending on the phase of epidemic process of the infection. Modern period is characterized by 9 times reduction of the incidence rate and extension of epidemic cycle up to 10 years. Age structure of morbidity in modern conditions is defined by age groups of children 3–14 years old. Seasonal variability of the incidence rate was reduced in non-epidemic phase of epidemic process and in age group of adults. Anti-HAV antibodies were detected in 30,9 ± 1,9% of the city population in 2014, and this rate was even lower in 2017 (24,8 ± 1,6%). This data indicates that non-epidemic phase seroprevalence in modern conditions has decreased when compared to former period (from 51,5 ± 1,9% in 1998, p < 0,001). These changes primarily affect group of adults 30–59 years old.

Conclusion. Presented characteristics of hepatitis A epidemic process play crucial role in the risk assessment of hepatitis A in modern period and must be implemented as first step in optimization of epidemic surveillance of hepatitis A.
Validation of the French translation of the Dutch Residency Educational Climate Test
Authors: Majbar Anass Mohammed , Majbar Yassin , Benkabbou Amine , Amrani Laila , Bougtab Abdeslam , Mohsine Raouf , Souadka Amine
Published: June 2020

Background The learning environment is one of the most influential factors in training of medical residents. The Dutch Residency Educational Climate Test (D-RECT) is one of the strongest instruments for measuring the learning environment. However, it has not been translated in French. The objective of this study is the psychometric validation of the DRECT French version.Material and methods After translation of the D-RECT questionnaire into French, residents of five Moroccan hospitals were invited to complete the questionnaire between July and September 2018. Confirmatory factor analysis was used to evaluate the validity of the construct using the standardized root mean square residual (SRMR), the root mean square error approximation (RMSEA), the Comparative Fit Index (CFI) and the Tucker- Lewis Index (TLI). Fidelity analysis was analysed using Internal consistency and temporal stability.Results During the study period, 211 residents completed the questionnaire. Confirmatory factor analysis showed an adequate model fit with the following indicators: SRMR = 0.058 / RMSEA = 0.07 / CFI = 0.88 / TLI = 0.87. The French translation had a good internal consistency (Cronbach alpha score > 0.7 for all subscales) and a good temporal stability (correlation score between two measurements = 0.89). Conclusion This French version has an acceptable validity of the construct, a good internal consistency and good temporal reliability, and may be used to evaluate the learning climate. Additional research is necessary in other french-speaking contexts, in order to confirm these results.
Liquid Based Cytology for the Detection of Cervical Intraepithelial Lesions among Women in Jimma Town, Ethiopia
Authors: Tesfaw Getnet , Ahmed Yesuf , Gedefaw Lealem , Dube Lamessa , Godu Samson , Eshetu Kirubel , Nigussie Mesfin , Hailekiros Haftamu , Joloba Moses , Goba Gelila Kidane , Abdissa Alemseged
Published: June 2020

Background: Cervical cancer is the second leading type of female cancer in Ethiopia. Screening is primarily conducted using visual inspection with 5% acetic acid (VIA). Liquid-based cytology (LBC) has not yet been used in Ethiopia.Method: Women aged 21-65 years were tested using LBC and VIA for the detection of cervical dysplasia. Logistic regression analysis was conducted to identify associated factors. Cohen’s K test was conducted to test agreement between LBC and VIA. Results: Forty-two percent (n=188) of 448 participants were 31 to 40 years of age and only two participants were above 60. Of the 448 participants, 419 (93.5%) were tested with LBC, 294 (65.6%) VIA and 272 (60.7%) with both LBC and VIA. Among women screened using LBC, 305(72.8%) were negative for intraepithelial lesion or malignancy (NILM), 97 (23.2%) had low grade squamous intraepithelial lesion (LSIL) and 17 (4.1%) high grade squamous intraepithelial lesion (HSIL). Presence of cervical lesions was generally lower in younger and older aged women. Majority, 39(40%) with LSIL and 10 (59%) of women with HSIL were 41-50 years old. Women aged 51-60 years were more likely to have abnormal intraepithelial lesions compared to women aged 21-30 (AOR= 20.9,95%CI=[7.2-60.9], p=0.00). Out of 47 (10.8%) HIV-patients,14(32.56%) had intraepithelial lesion of which 10(23.3%) and 4(9.3%) had LSIL and HSIL, respectively. Among women screened with VIA, 18 (6.1%) were positive. Among the 272 (60.7%) women screened using both LBC and VIA, 6 (2.2%) were positive on both LBC and VIA. The level of agreement between the two tests was weak and statistically significant (kappa value=0.155, p=0.006). Conclusion: LBC detected high cervical squamous intra-epithelial lesions in our setting. VIA was a less reliable predictor of cervical squamous intra-epithelial lesions than LBC. Evaluating diagnostic accuracy of both LBC and VIA against histological endpoint should be completed before adopting either screening modalities.
Comparative Study of Imaging and Histology of Sacroiliac Joint in Normal Rats Based on IVIM-DWI and DCE-MRI
Authors: Qin Jian , Yao Qianqian , Ge Xubo , Zhu Jianzhong , Yin Zhaoliang , Li Xiaoqian , Li changqin
Published: June 2020

Background : There are few reports describing the relationship between functional MRI findings and histology of normal sacroiliac joint (SIJ). Furthermore, the histology of SIJ is difficult to access, so animal models have special value. Aims:We undertook this study to explore the changes of parameters of Intravoxel Incoherent Motion Diffusion Weighted Imaging(IVIM-DWI), Dynamic Contrast Enhanced Magnetic Resonance Imaging(DCE-MRI) and compare them with histology in the SIJ of normal rats in different ages.Methods: Thirty 7 week-old male wistar rats were included in the study. The parameters of IVIM-DWI and DCE-MRI in bone marrow and the joint space of SIJ were measured respectively at 8, 13, 18, 23, 28 and 33 weeks, then histological specimen of the SIJ were examined with light microscopy. One-way ANOVA were used for statistical analysis. Results: The values of D in the sacral and iliac bone marrow of normal rats in different age groups decreased with the increase of age, and ANOVA indicated a significant difference in D values among different age groups(P＜0.005). The normal values of D*, f, Fenh(%), Senh(%/s) in the sacral bone marrow, the iliac bone marrow and in the joint space in SIJ of normal rats were obtained. In six groups of rats with different weeks of age, the histology of the SIJ surface was smooth and clear, the cartilage cells were intact, and no thickening or pannus formation was found. Conclusions: The range of IVIM-DWI and DCE-MRI parameters of the sacral and iliac bone marrow and of the synovial area of the joint space in normal rats were obtained. These parameters in normal rats can be used in future research to compare them to the same parameters in animal models or patients with SIJ diseases.This study can be a guide for future research in SIJ diseases.
The Feasibility of Implementing High-Intensity Interval Training in Cardiac Rehabilitation Settings: A Retrospective Analysis
Authors: Way Kimberley , Vidal-Almela Sol , Keast Marja-Leena , Hans Harleen , Pipe Andrew L. , Reed Jennifer L.
Published: June 2020

Background: Cardiovascular disease is the leading cause of death worldwide. Notwithstanding the well-known benefits of cardiac rehabilitation (CR), adherence to CR remains low, particularly in women. High-intensity interval training (HIIT) has received specific attention as an emerging exercise-training paradigm that addresses frequently cited barriers to CR (i.e. lack of motivation/enjoyment and time, perceiving exercise regime as tiring/boring) and improves cardiovascular risk factors. Previous studies have examined the safety of HIIT in CR; there is little evidence on the feasibility of HIIT in CR. The aims of this study were to evaluate the feasibility of HIIT within a CR setting and examine the sex differences regarding the feasibility of such programming. Methods: Patients attended an on-site HIIT CR program (10-minute warm-up, 25 minutes of interspersed high [HI - 4 minutes at 85-95% HRpeak] and low [LO - 3 minutes at 60-70% HRpeak] intervals, 10-minute cool-down) twice weekly for 10 weeks. Heart rate (HR) and the Borg rating of perceived exertion (RPE) scale (6-20 points) were recorded at each session. Feasibility was assessed by: (1) attendance and compliance: the number of sessions attended and the compliance to the prescribed HI and LO HR ranges; (2) the patient experience: patients’ perceived effort, program difficulty, if the program was challenging and satisfying; and, (3) safety. Descriptive statistics were used to report the means and their variations. Mann-Whitney U tests and Chi-square analyses were performed to examine sex-differences. Results: A total of 151 patients (33% women, 57.5 ± 9.1 years) attended the HIIT program and completed 16±5 classes with a low attrition rate (11.3%). Most patients met or exceeded the prescribed target HR for the HI (80%) and LO (84%) intervals, respectively. Patients reported a “somewhat hard” RPE for HI (14 ± 2) and “very light” for LO (10 ± 2) intervals. All patients were satisfied with the program and found it challenging. Most patients found HIIT to be difficult (7 ± 2 points, scale range 0-10 points), yet safe (97%). Three vasovagal episodes occurred and more women dropped-out of the program than men (p<0.01). Conclusions: HIIT is a feasible, safe and well-received exercise paradigm in a CR setting.
Virtual Screening of DPP-4 Inhibitors Using QSAR-Based Artificial Intelligence and Molecular Docking of Hit Compounds to DPP-8 and DPP-9 Enzymes
Authors: Hermansyah Oky , Bustamam Alhadi , Yanuar Arry
Published: June 2020

Background: Dipeptidyl Peptidase-4 (DPP-4) inhibitors are becoming an essential drug in the treatment of type 2 diabetes mellitus, but some classes of these drugs have side effects such as joint pain that can become severe to pancreatitis. It is thought that these side effects appear related to their inhibition against enzymes DPP-8 and DPP-9. Objective: This study aims to find DPP-4 inhibitor hit compounds that are selective against the DPP-8 and DPP-9 enzymes. By building a virtual screening workflow using the Quantitative Structure-Activity Relationship (QSAR) method based on artificial intelligence (AI), millions of molecules from the database can be screened for the DPP-4 enzyme target with a faster time compared to other screening methods. Result: Five regression machine learning algorithms and four classification machine learning algorithms were used to build virtual screening workflows. The algorithm that qualifies for the regression QSAR model was Support Vector regression with R 2 pred 0.78, while the classification QSAR model was Random Forest with 92.21% accuracy. The virtual screening results of more than 10 million molecules from the database, obtained 2,716 hit compounds with pIC50 above 7.5. Molecular docking results of several potential hit compounds to the DPP-4, DPP-8 and DPP-9 enzymes, obtained CH0002 hit compound that has a high inhibitory potential against the DPP-4 enzyme and low inhibition of the DPP-8 and DPP-9 enzymes. Conclusion: This research was able to produce DPP-4 inhibitor hit compounds that are potential to DPP-4 and selective to DPP-8 and DPP-9 enzymes so that they can be further developed in the DPP-4 inhibitors discovery. The resulting virtual screening workflow can be applied to the discovery of hit compounds on other targets.
Patient-specific instrument-assisted minimally invasive internal fixation of calcaneal fracture for rapid and accurate execution of a preoperative plan: A retrospective study
Authors: Wang Chenggong , Xu Can , Li Mingqing , Li Hui , Xiao Han , Zhong Da , Liu Hua
Published: June 2020

Background: Traditional methods for minimally invasive internal fixation (MIIF) of calcaneal fractures require extensive intraoperative fluoroscopy, and fracture recovery is usually not ideal. We developed a new surgical procedure using digital surgical simulation and constructed a patient-specific instrument (PSI) for calcaneal fracture that we used during the operation. This study investigated whether PSI-assisted MIIF of calcaneal fracture enables rapid and accurate execution of the preoperative plan. Methods: We retrospectively analyzed patients with Sanders type III or IV fresh calcaneal fractures who had undergone PSI-assisted MIIF at our hospital from January 2016 to December 2018. We analyzed perioperative data including intraoperative fluoroscopy time, concurrence of internal fixation actual usage (IFAU) with the preoperative plan, surgery time, and complications. We also compared pre- and postoperative actual measurements from X-ray radiographs and computed tomography images including Böhler, Gissane, and calcaneus valgus angles; subtalar joint width; and calcaneal volume overlap ratio with the preoperative design. All patients had been followed up and their American Orthopedic Foot and Ankle Score (AOFAS) score was available. Results: Mean intraoperative fluoroscopy time was 3.95±1.78 h; IFAU in 16 patients (16 feet) was the same as the preoperative plan; mean surgery time was 28.16±10.70 min; and none of the patients developed complications. Böhler, Gissane, and calcaneus valgus angles and subtalar joint width did not differ between pre- and postoperative plans; however, the actual preoperative values of each of these parameters differed significantly from those measured postoperatively. The calcaneal volume overlap ratio with the preoperative design was 91.2%±2.3%. AOFAS scores increased with time, with significant differences in the score at each time point. Conclusions: The newly developed PSI-assisted calcaneal fracture MIIF method can rapidly and accurately execute the preoperative plan.
Comparison of the gluteus medius strength between obese and eutrophic individuals: a cross-sectional study
Authors: Fenato Rafael Ratti , Araujo Allan Cezar Faria , Guimarães Ana Tereza Bittencourt
Published: June 2020

Background: The hip abductor muscles play an important role in stabilizing the pelvis during gait, with its main function being performed by the gluteus medius. Gluteus medius insufficiency is associated with biomechanical alterations and musculoskeletal disorders. Due to being overweight and a possible muscle mass decrease, maintaining the abductor muscular function can be a great challenge for the obese. However, it is still unclear whether the musculature of obese individuals manages to compensate for these alterations. Therefore, the aim of this study was to compare the gluteus medius strength between obese and normal weight individuals using a digital hand-held dynamometer.Methods: Twenty-five obese (BMI > 35 kg / m2) participated in the study, being matched in gender, age, and height with normal weight individuals. The gluteus medius strength was measured by a single examiner using a belt-stabilized hand-held digital dynamometer on the knee of individuals positioned in lateral decubitus. Three measurements were recorded with rest intervals, considering only the highest value measured for each limb for analysis. The difference between pairs was calculated and the data distribution pattern was assessed using the Shapiro-Wilk test (p < 0.05), and the matrices of the variables were standardized and analyzed using the principal component analysis (PCA).Results: For the strength variables (Newtons) on both sides, no statistical differences were detected between the groups (p > 0.05). However, statistical differences were detected in these variables between the groups (p < 0.05) when normalizing the measurements in relation to individuals' weights (Newtons / kilograms). The PCA indicates that both strength in absolute values and normalized by weight are reduced in obese individuals.Conclusions: These findings indicate that obese individuals have the same or lower strength (PCA) to move more mass, which may suggest a relative weakness that induces functional limitation.Trial registration: The study was approved by the UNIOESTE Human Research Ethics Committee (#1.180.202) in July 2015.
An unlabeled probe based real time PCR and modified semi nested PCR as molecular tools for analysis of chloroquine resistant in Plasmodium vivax isolates from Afghanistan
Authors: Mosawi Sayed Hussain , Dalimi Abdolhossein , Safi Najibullah , Fotouhi-Ardakani Reza , Ghaffarifar Fatemeh , Sadraei Javid
Published: June 2020

Background: Plasmodium vivax isolate resistance to Chloroquine (CQ) has been reported from many endemic regions in the world. P. vivax is responsible for 95% of malaria cases in Afghanistan and CQ is the first-line treatment given for treatment of vivax malaria. The pvmdr-1 and pvcrt-o (K10 insertion) genes are the possible markers for CQ-resistance P. vivax isolates. There have been no studies done on the presence or absence of molecular markers for CQ-resistance P. vivax in Afghanistan. In the present work, we aimed to evaluate the frequency of mutations in the pvmdr-1 and K10 insertion in the pvcrt-o genes of P. vivax.Methods: P. vivax isolates were collected from Laghman, Baghlan and Khost provinces. For investigation of polymorphisms of desired regions in pvmdr-1 and pvcrt-o genes, sequencing was applied on the PCR products. We developed a new asymmetric qPCR and melting analysis assay based on unlabeled probe for scanning of K10 insertion in pvcrt-o gene. Results: The analysis of sequencing data of the pvmdr-1 gene showed wild type Y976 and K997 and mutant M958 and L1076 in 33 isolates from three provinces and submitted in GenBank (accession number MK419882-MK419914)Of 36 samples that evaluated for K10 insertion in pvcrt-o, 2/18(11%), 0/10(0%) and 0/8(0%) isolates from Laghman, Baghlan and Khost province possessed K10 insertion, respectively, that confirmed by either sequencing and unlabeled probes and submitted in GenBank (accession number MK292011-MK292046).Conclusion: Two samples with K10 insertion and 33 samples with pvmdr1 polymorphism, indicating on the possibility of CQ resistance P. vivax populations in Afghanistan. Furthermore, unlabeled probes are simple and inexpensive alternative tools for screening of P. vivax mutations.
A cross country comparison for the burden of cardiovascular disease attributable to tobacco exposure in China, Japan, USA and world
Authors: Wu Xiaomei , Zhu Bo , Xu Shuang , Bi Yifei , Liu Yong , shi jingpu
Published: June 2020

Background Tobacco exposure (TE) is the major contributor for CVD mortality, but few published studies on CVD mortality attributable to TE have analyzed the potential reasons underlying long-term trends in China. Our study sought to find the potential reasons and compared CVD mortality attributable to TE in China, Japan, the United States of America (USA), and the world between 1990 and 2017.Methods The mortality data in China, Japan, the USA, and the world were obtained from Global Burden of Disease Study 2017 (GBD 2017). Joinpoint regression was used to assess the trend magnitude and directions over time for CVD mortality, while the age-period-cohort method was used to analyze the temporal trends of CVD mortality according to age, period, and cohort.Results A significant downward trend was found in the age-standardised mortality rate (ASMR) of CVD attributable to smoking in four regions. China had the smallest decline and the Chinese ASMR became the highest in 2017. All the annual net drifts in the four regions were negative and the local drifts were below zero. The longitudinal age curves of CVD mortality attributable to smoking increased in four regions, with China having the largest increase. The period or cohort RRs indicated a decline, and China had the smallest decline. The researchers further analyzed the IHD and stroke trends, finding that the morality and period or cohort RR of IHD in China was always at a high level.Conclusions CVD mortality attributable to TE declined in four regions, and was highest in China. The proportion of IHD mortality attributable to TE was similar to stroke, which significantly changed the traditional cognition of CVD composition, but the control measure was not sufficient for IHD in China.
FNDC5/Irisin improves the therapeutic efficacy of bone marrow-derived mesenchymal stem cells for myocardial infarction
Authors: Deng Jingyu , Zhang Ning , Wang Yong , Yang Chao , Wang Yabin , Xin Chao , Zhao Jinming , Jin Zhitao , Cao Feng , Zhang Zheng
Published: June 2020

Background: The beneficial functions of bone marrow mesenchymal stem cells (BM-MSCs) decline with decreased cells survival, limiting their therapeutic efficacy for myocardial infarction (MI). Irisin, a novel myokine which is cleaved from its precursor fibronectin type III domain-containing protein 5 (FNDC5), is believed involved in a cardioprotective effect but little was known on injured BM-MSCs and MI repair yet. Here, we investigated whether FNDC5 or irisin could improve the low viability of transplanted BM-MSCs and increase their therapeutic efficacy after MI. Methods: BM-MSCs, isolated from dual-reporter firefly luciferase and enhanced green fluorescent protein positive (Fluc+– eGFP+) transgenic mice, were exposed to normoxic condition and hypoxic stress for 12 h, 24 h, and 48 h, respectively. In addition, BM-MSCs were treated with irisin (20 nmol/L) and overexpression of FNDC5 (FNDC5-OV) in serum deprivation (H/SD) injury. Furthermore, BM-MSCs were engrafted into infarcted hearts with or without FNDC5-OV. Results: Hypoxic stress contributed to increased apoptosis, decreased cells viability and paracrine effects of BM-MSCs while irisin or FNDC5-OV alleviated these injuries. Longitudinal in vivo bioluminescence imaging and immunofluorescence results illustrated that BM-MSCs with overexpression of FNDC5 treatment (FNDC5-MSCs) improved the survival of transplanted BM-MSCs, which ameliorated the increased apoptosis and decreased angiogenesis of BM-MSCs in vivo. Interestingly, FNDC5-OV elevated the secretion of exosomes in BM-MSCs. Furthermore, FNDC5-MSCs therapy significantly reduced fibrosis and alleviated injured heart function. Conclusions: The present study indicated that irisin or FNDC5 improved BM-MSCs engraftment and paracrine effects in infarcted hearts, which might provide a potential therapeutic target for MI.
Overexpression of HOXA10 is associated with unfavorable prognosis of acute myeloid leukemia
Authors: Guo Chao , Ju Qian-qian , Zhang Chun-xia , Gong Ming , Li Zhen-ling , Gao Ya-yue
Published: June 2020

Background HOXA family genes were crucial transcription factors involving cell proliferation and apoptosis. While few studies have focused on HOXA10 in AML. We aimed to investigate the prognostic significance of HOXA10. Methods We downloaded datasets from GEO and BeatAML database, to compare HOXA expression level between AML patients and controls. Kaplan-Meier curves were used to estimate the impact of HOXA10 expression on AML survival. The differentially expressed genes, miRNAs, lncRNAs and methylated regions between HOXA10-high and -low groups were obtained using R (version 3.6.0). Accordingly, the gene set enrichment analysis (GSEA) was accomplished using MSigDB database. Moreover, the regulatory TFs/microRNAs/lncRNAs of HOXA10 were identified. A LASSO-Cox model fitted OS to clinical and HOXA10-associated genetic variables by glmnet package. Results HOXA10 was overexpressed in AML patients than that in controls. The HOXA10-high group is significantly associated with shorter OS and DFS. A total of 1219 DEGs, 131 DEmiRs, 282 DElncRs were identified to be associated with HOXA10. GSEA revealed that 12 suppressed and 3 activated pathways in HOXA10-high group. Furthermore, the integrated regulatory network targeting HOXA10 was established. The LASSO-Cox model fitted OS to AML-survival risk scores, which included age, race, molecular risk, expression of IKZF2/LINC00649/LINC00839/FENDRR and has-miR-424-5p. The time dependent ROC indicated a satisfying AUC (1-year AUC 0.839, 3-year AUC 0.871 and 5-year AUC 0.813). Conclusions Our study identified HOXA10 overexpression as an adverse prognostic factor for AML. The LASSO-COX regression analysis revealed novel prediction model of OS with superior diagnostic utility.
Correlation between immune-related adverse events and prognosis in patients with various cancers treated with anti PD-1 antibody.
Authors: Matsuoka Hiroshi , Hayashi Takahiro , Takigami Karen , Imaizumi Kazuyoshi , Shiroki Ryoichi , Ohmiya Naoki , Sugiura Kazumitsu , Kawada Kenji , Sawaki Akira , Maeda Koutarou , Ando Yousuke , Uyama Ihiro
Published: June 2020

Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) are used for the treatment of various cancer types. However, immune-related adverse events (irAEs) occur in patients treated with ICIs. Several small-scale studies have reported the onset of irAEs and therapeutic effects of ICIs. Here we report a large-scale retrospective study covering a wide range of cancers. We evaluated irAEs and the therapeutic effects of ICIs and determined whether irAEs could be predicted.Methods: This study included patients treated with the anti-PD-1 antibodies nivolumab or pembrolizumab at Fujita Health University Hospital between December 2015 and March 2019. We retrospectively reviewed the electronic medical records for age, cancer type, pre-treatment blood test data, presence or absence of irAE onset, type and severity of irAEs, outcome of irAE treatment, response rate, progression-free survival and overall survival.Results: Two hundred-eighty patients received ICIs. The overall incidence of irAEs was 41.1% (115 patients), and the incidence of severe irAEs of grade 3 and higher was 2.8% (eight patients). The most common irAEs were skin disorders, thyroid disorders and interstitial pneumonia. Patients with irAEs were significantly older than those without irAEs (69.7 versus 66.0 years, P=0.02). The objective response rate (ORR) in patients with irAEs was 30.4%, which was significantly higher than in patients without irAEs (12.7%; P<0.01). Both the median overall and progression-free survival were significantly longer in patients with irAEs. Based on the blood test data obtained before ICI therapy, hypothyroidism, thyroid-stimulating hormone levels and thyroglobulin antibody levels were associated with the onset of irAEs. In many patients with irAEs of Common Terminology Criteria for Adverse Events Grade 3 or higher, re-administration of ICIs was difficult, and their outcomes were poor. In contrast, many patients with irAEs of a lower grade were able to resume ICI therapy.Conclusion: Although the onset of irAEs was difficult to be predicted based on pre-treatment tests. It appeared that the continuation of ICI therapy, along with early detection and adequate control of irAEs, might contribute to the improved prognosis of patients.
Is Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy Indicated in Hepatobiliary Malignancies?
Authors: Leigh Natasha , Solomon Daniel , Pletcher Eric , Labow Daniel M. , Magge Deepa R. , Sarpel Umut , Golas Benjamin J.
Published: June 2020

Background: Hepatopancreaticobiliary malignancies with peritoneal carcinomatosis exhibit poor survival with current therapies; hepatocellular carcinoma 11 months with sorafenib, pancreaticobiliary 9-14 months with systemic chemotherapy. However, limited data exist on the utility of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in these patients. Methods: We retrospectively reviewed our institutional hepatopancreaticobiliary malignancies with peritoneal carcinomatosis which underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy from 2007-2017 and analyzed perioperative and oncologic outcomes. Results: 17 patients were included; 9 hepatocellular carcinoma, 8 pancreaticobiliary (4 cholangiocarcinoma, 3 gallbladder, 1 pancreatic). PCI, number of organs resected, completeness of cytoreduction and 30-day morbidity were equivalent. Hepatocellular carcinoma received significantly less neoadjuvant therapy (11%, p=0.008), though adjuvant therapy rates were similar. At a median follow-up of 15 months, progression-free survival was similar amongst all cohorts. However, overall survival was longer in hepatocellular carcinoma (42 months vs. cholangiocarcinoma 19 months, gallbladder 8 months, pancreatic 15 months, p=0.206) with 59% 3-year overall survival (vs. 0% cholangiogarcinoma, 0% gallbladder, 0% pancreatic).Conclusions: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy may offer a survival benefit in select hepatocellular carcinoma patients with peritoneal carcinomatosis, though has dubious utility in pancreaticobiliary malignancies.
The establishment of a rheumatoid arthritis primate model in Macaca fascicularis
Authors: Na Hyun Sik , Lee Seon-young , Min Hong Ki , Park Wan-je , Lee Jung-hwan , Cho Ka-hee , Hong Shin-hee , Kim Dae-hoon , Jhun Jooyeon , Choi Jeong-Won , Kim Sung-Min , Kwok Seung-Ki , Cho Mi-La , Park Sung-Hwan
Published: June 2020

Background: Rheumatoid arthritis (RA) is a long-term autoimmune disorder that mostly affects the joints and leads to the destruction of cartilage. An RA model in non-human primates is especially useful because of their close phylogenetic relationship to humans in terms of cross-reactivity to compounds developed using modern drug technologies.Methods: We used a collagen-induced arthritis (CIA) model in Macaca fascicularis. CIA was induced by the immunization of chicken type II collagen. Swelling was measured as the longitudinal and transverse axes of 16 proximal interphalangeal joints. Results: A new system for visual evaluation was created, with a perfect score of 16. Individual behavioral analysis was also conducted. Serum was collected once a week after the first immunization. Blood chemistry and inflammatory cytokine parameters were higher in the CIA group than in the wild type group. Conclusion: In conclusion, we established CIA in M. fascicularis, and the results can be used for drug evaluation models.
The protective effects of liguzinediol on congestive heart failure induced by myocardial infarction and its relative mechanism
Authors: Chen Qi , Zhang Dini , Bi Yunhui , Zhang Weiwei , Zhang Yuhan , Meng Qinghai , Li Yu , Bian Huimin
Published: June 2020

Background: Heart failure (HF) is one of the most common causes of cardiovascular diseases in the world. Currently, the drugs used to treat HF in the clinic may cause serious side effects. Liguzinediol, 2, 5-dimethyl-3, 6-dimethyl-pyrazine, is a compound synthesized after the structural modification of ligustrazine (one active ingredient of Szechwan Lovage Rhizome). We aimed to observe the effects of liguzinediol on preventing HF and explore the related mechanisms.Methods: The ligation of left anterior descending coronary artery was operated to established the myocardial infarction (MI) model in Sprague–Dawley rats. Cardiac functions were recorded by echocardiography and hemodynamics. The changes in the Renin-Angiotensin-Aldosterone System (RAAS), inflammation, and oxidative stress were detected by radioimmunoassay and Elisa kits. Western blot and real-time PCR were applied to determine the expressions of the TGF-β1/Smads pathway.Results: Firstly, liguzinediol enhanced the systolic and diastolic functions of the heart in MI rats. Liguzinediol improved ventricular remodeling by reducing myocardial cell necrosis, as well as reducing collagen deposition and myocardial fibrosis. Then, liguzinediol suppressed the activation of RAAS, inhibited the synthesis of pro-inflammation factors, and reduced oxidative stress. In the end, liguzinediol also down-regulated the expressions of the TGF-β1/Smads pathway.Conclusions: Liguzinediol could alleviate HF caused by MI in rats, and the protective effect was associated with the regulation of the TGF-β1/Smads pathway.
FRET-based Tau seeding assay does not represent prion-like templated assembly of Tau filaments
Authors: Kaniyappan Senthilvelrajan , Tepper Katharina , Biernat Jacek , Chandupatla RamReddy , Hübschmann Sabrina , Irsen Stephan , Bicher Sandra , Klatt Christoph , Mandelkow Eva-Maria , Mandelkow Eckhard
Published: June 2020

Tau aggregation into amyloid fibers based on the cross-beta structure is a hallmark of several Tauopathies, including Alzheimer Disease (AD). Trans-cellular propagation of Tau with pathological conformation has been suggested as a key disease mechanism. This is thought to cause the spreading of Tau pathology in AD by templated conversion of naive Tau in recipient cells into a pathological state, followed by assembly of pathological Tau fibers, similar to the mechanism of nucleated polymerization proposed for prion pathogenesis. In cell cultures, the process is often monitored by a FRET assay where the recipient cell expresses the Tau repeat domain (TauRD) with a pro-aggregant mutation, fused to GFP-based FRET pairs. Since the size of the reporter GFP (barrel of ~3nm x 4nm) is ~7 times larger than the β-strand distance (0.47nm), this points to a potential steric clash. Hence, we investigated the influence of the GFP tag on Tau or TauRD aggregation. Using biophysical methods (light scattering, atomic force microscopy (AFM), and scanning-transmission electron microscopy (STEM)), we found that the assembly of TauRD-GFP was severely inhibited and incompatible with that of Alzheimer filaments. These observations argue against the hypothesis that the propagation of Tau pathology in AD is caused by the prion-like templated aggregation of Tau protein, transmitted via cell-to-cell spreading of Tau. Thus, even though the observed local increase of FRET in recipient cells may be a valid hallmark of a pathological reaction, our data argue that it is caused a process distinct from assembly of TauRD filaments.
The Mental Impact of COVID-19 Outbreak: A Population-Based Survey in Iran
Authors: Shahriarirad Reza , Erfani Amirhossein , Ranjbar Keivan , Bazrafshan Amir , Mirahmadizadeh Alireza
Published: June 2020

Objective: Disease outbreak not only carries the risk of death to the public due to the infection, it also endures an unbearable psychological impact on the mental health of the individuals. This study aims to explore and evaluate the burden of psychological problems on the Iranian general population during the outbreak of COVID-19.Method: A cross-sectional web-based survey was conducted among the general population of Iran age 15 and above. Demographic variables, depression, and anxiety symptoms were evaluated using the Patient Health Questionnaire-9 and General Anxiety Disorder-7 questionnaires.Results: Among the 8591 participants, the mean age was 34.37 (±11.25) years and 66.4% were female while 33.6% were male. Based on our results, 1295 (15.07%) and 1733 (20.17%) of the general population had depression and anxiety respectively. Based on the demographic variables, Among the risk factors for both anxiety and depression, one could name female gender, whereas getting information about the disease from medical journals and articles, being older and being married were considered as protective factors. In terms of depression, being a non-healthcare worker was a risk factor. On the other hand, for anxiety, having higher education was a protective factor while a higher number of individuals in a household was considered as a risk factor.Conclusions: This study identified a major mental health problem in the Iranian population during the time of the COVID-19 outbreak. Therefore, establishing a targeted mental health support program during the time of public emergencies, such as the disease outbreak, is advised.
Evaluation and utility of mitochondrial ribosomal genes for molecular systematics of parasitic nematodes
Authors: Chan Abigail Hui En , Chaisiri Kittipong , Morand Serge , Saralamba Naowarat , Thaenkham Urusa
Published: June 2020

Background Molecular advances have accelerated our understanding of nematode systematics and taxonomy. However, comparative analyzes between various genetic markers have led to discrepancies in nematode phylogenies. This study aimed to evaluate the suitability of using mitochondrial 12S and 16S ribosomal RNA genes for nematode molecular systematics. Methods To study the suitability of mitochondrial 12S and 16S ribosomal RNA genes as genetic markers for nematode molecular systematics, we compared them with the other commonly used genetic markers, nuclear internal transcribed spacer 1 and 2 regions, nuclear 18S and 28S ribosomal RNA genes, and mitochondrial cytochrome c oxidase subunit 1 gene. After that, phylum-wide primers for mitochondrial 12S and 16S ribosomal RNA genes were designed, and parasitic nematodes of humans and animals from 75 taxa with 21 representative species were inferred through phylogenetic analyzes. Phylogenetic analyzes were carried out using maximum likelihood and Bayesian inference algorithms. Results The phylogenetic relationships of nematodes based on the mitochondrial 12S rRNA gene supported the monophyly of nematodes in clades I, IV, and V, reinforcing the potential of this gene as a genetic marker for nematode systematics. In contrast, the mitochondrial 16S rRNA gene only supported the monophyly of clades I and V, providing evidence that the 12S rRNA gene is more suitable for nematode molecular systematics. In this study, subclades of clade III containing various nematode families were not monophyletic when the 16S or 12S rRNA gene was used as the genetic marker. This is similar to the phylogenetic relationship revealed by previous studies using whole mitochondrial genomes as genetic markers. Conclusions This study supports the use of the 12S rRNA gene as a genetic marker for studying the molecular systematics of nematodes to understand intra-phyla relationships. Phylum-wide primers for nematodes using mitochondrial ribosomal genes were prepared, which may enhance future studies. Furthermore, sufficient genetic variation in the mitochondrial 12S and 16S rRNA genes between species also allowed for accurate taxonomy to species level, revealing the potential of these two genes as genetic markers for DNA barcoding.
WITHDRAWN: IL-10-producing B cells regulated 1,3-β-glucan induced Th responses in coordinated with Treg
Authors: Liu Fangwei , Lu Yiping , Zeng Xinning , Chen Jie
Published: June 2020

Background: Repeated exposure to fungi contaminated dust can lead to multiple adverse effect on lung, such as hypersensitivity pneumonitis, granuloma even irreversible fibrosis. 1,3-β-glucan, as the major cell wall component of fungi, was considered as its exposure biomarker. Existing studies showed that series of Th response were involved in 1,3-β-glucan induced hypersensitivity pneumonitis, in which macrophages, regulatory T cells (Treg) and IL-10 producing B cells were reported to participate. The reciprocal interaction among those critical immune cells in 1,3-β-glucan induced inflammation were not investigated yet.Results: To clarify the regulatory mechanism of IL-10 producing B cells on Th and Treg, current study set up a primary cell co-culture system. Anti-CD22 antibody was injected intraperitoneally to generate IL-10 producing B cells deficiency mouse model. Cells were isolated and purified from different groups’ mice. Flow cytometry was used to check the phenotype of different cell subtypes. CBA assay and realtime PCR were used to examine the levels of multiple cytokines. Our results indicated that IL-10 producing B cells were involved in modulating 1,3-β-glucan induced inflammatory response. The modulation of IL-10 producing B cells on Th response after 1,3-β-glucan treatment was independent on cell-cell contact. What’s more, the modulation pattern of IL-10 producing B cells might be impaired without Treg response.Conclusions: IL-10-producing B cells regulated 1,3-β-glucan induced Th responses in coordinated with Treg.
Health services utilization and out-of-pocket (OOP) expenditures in public and private facilities in Pakistan: An empirical analysis of 2013-14 OOP Health Expenditure Survey
Authors: Khalid Faraz , Raza Wajeeha , Hotchkiss David R. , Soelaeman Rieza H.
Published: June 2020

Background As low- and middle-income countries (LMICs) progress towards achieving Universal Health Coverage (UHC), there is an increasing focus on measuring both out-of-pocket (OOP) expenditure and health services utilization within countries. While there have been several reforms to improve health services coverage and financial protection in Pakistan, there is limited empirical research comparing OOP expenditure and health services utilization between public and private facilities and exploring their determinants. In this paper, we have addressed this gap by using the 2013-2014 OOP Expenditure Survey Methods Our study is based on data from nationally representative household survey that includes 7,969 encounters from 4,293 households. In our analysis, we examined factors associated with two outcome variables; the sector where care was sought (public or private) and OOP expenditures. To investigate factors associated with the sector where care was sought, we fitted multivariate models stratified by type of care (i.e., inpatient and outpatient). Next, we fitted multivariate linear regression models to identify determinants of OOP expenditures stratified by type of care.Results  Our bivariate analysis shows that most encounters (82.5%) were in the private sector, and 85% of encounters were for outpatient visits. Expenditures on medicines and vaccines account for the largest proportion of OOP expenditures, followed by diagnostic tests and transportation. We found that the probability of seeking outpatient care in the private sector was higher for men, richer individuals, residents of Punjab and Sindh provinces, and households of smaller sizes. For inpatient care, we found that rural households and females with reproductive health concerns were more likely to seek private sector care. Importantly, our study found no significant difference in OOP expenditures between public and private facilities for both inpatient and outpatient visits. However, there were differences in OOP expenditures by sociodemographic factors. Conclusions This is the first study that has comprehensively investigated how healthcare utilization and OOP expenditures vary by sector, type of care, and socio-economic characteristics in Pakistan. Its findings will be useful for federal and provincial health ministries in planning and monitoring the impact of the next phase of their social health protection programs and supply side reforms.