bluuebunny/crossref_metadata_2025 huggingface dataset:
Modulation of steroidogenesis by Actaea racemosa and vitamin C combination, in letrozole induced polycystic ovarian syndrome rat model: Promising activity without the risk of hepatic adverse effect
Authors: Azouz Asmaa A. , Ali Sara E. , Abd-Elsalam Reham M. , Emam Shimaa R. , Galal Mona K. , Elmosalamy Sherif H. , Alsherbiny Muhammad , Hassan Bardes B. , Li Chun Guang , Badawy Shymaa A. El
Published: November 2020

Background: Complementary remedies such as the Chinese herb ‘Sheng Ma’ (Black cohosh; Actaea racemosa ‘AR’) are being sought to overcome the shortcomings of conventional hormonal and surgical therapies developed for treatment of polycystic ovary syndrome (PCOS). However, the AR hepatotoxicity urges a cautionary warning to be labeled on its products as recommended by the United States Pharmacopeia, where four out of seven hepatotoxic cases in Sweden were possibly associated with black cohosh products.Methods: We investigated the effects, safety, and molecular targets of black cohosh ethanolic extract and/or vitamin C on ovarian functionality and oxidative response in hyperandrogenism-induced PCOS rats. A well-established rat model using oral letrozole, daily, for 21 days was employed then rats received the AR extract with and without vitamin C for 28 days. The hormonal evaluation, antioxidant status, histopathological examination, immunohistochemical analysis, cell proliferation, and the expression ratio of the aromatase (Cyp19α1) gene were evaluated. Additionally, a holistic profiling of AR arsenal of secondary metabolites was performed using ultra high-performance liquid chromatography (UHPLC) coupled with quadrupole high resolution time of flight mass spectrometry (QTOF-MS).Results: Beneficial effects were exerted by AR in PCOS rats via the improved antioxidant status, hormonal profile, lipid profile, glucose level, liver functions, and the induced Ki-67 expression in the granulosa, theca cell layers and interstitial stromal cells. Notably, the combination of AR with vitamin C was not only more effective in reversing the dysregulated levels of testosterone, luteinizing hormone, and mRNA level of Cyp19α1 gene in the PCOS rat, but also safer. The combination regulated both ovarian and hepatic MDA and GSH levels with histological improvement observed in the liver and ovaries. In addition, the untargeted metabolomic profiling enabled the identification of 61 metabolites allocated in five major chemical classes.Conclusion: This study demonstrated the benefit of the combination between AR and vitamin C in mitigating the reproductive and metabolic disorders of PCOS with the elimination of AR hepatotoxic risk.
Disability, Frailty and Depression in the Community-dwelling Elderly with Osteosarcopenia
Authors: Park Ki-Soo , Lee Gyeong-Ye , Seo Sung-Hyo , Seo Young-Mi , Yoo Jun-Il
Published: November 2020

Background: The purpose of this study was to investigate the prevalence of osteosarcopenia in the over 60-year-old community and to evaluate whether osteosarcopenia is associated with disability, frailty and depression.Methods: This study was performed using the baseline data of Namgaram-2, which was developed to study the relationship between the prevalence of musculoskeletal disorders and activity limitations in the elderly in rural areas. Among the 1010 surveyed subjects, 885 study subjects who were 60 years or older and had all necessary tests performed were selected. The Kaigo-Yobo checklist was completed for diagnosis of frailty and the degree of disability in everyday life was evaluated by World Health Organization Disability Assessment Schedule (WHODAS). To understand the symptoms of depression in the elderly, the Geriatric Depression Scale-Short Form-Korean (GDSSF-K) was used. The Asian Working Group for Sarcopenia (AWGS 2019) were applied in this study. Sarcopenia was defined as SMI less than 7.0 kg/m2 in men and less than 5.4 kg/m2 in women. The maximum grip strength was used as a reference level, for men below 28 kg and for women below 18 kg. Osteopenia was measured using data from dual energy X-ray absorptiometry (DEXA) and osteopenia was diagnosed when the T-score was less than -1.0.The study subjects were divided into four groups: the normal group, in which both sarcopenia and osteopenia were undiagnosed, osteopenia only, sarcopenia only and the osteosarcopenia group, which was diagnosed with both sarcopenia and osteopenia.Results: Of the 885 subjects over 60 years old evaluated, the normal group comprised 34.0%, the only osteopenia group 33.7%, the only sarcopenia group 13.1%, and the osteosarcopenia group 19.2%. WHODAS, Kaigo-Yobo, and GDSSF scores were statistically significantly higher in the osteosarcopenia group compared the other groups.Conclusions: Osteosarcopenia is a relatively common disease group in the elderly community that may cause deterioration of health outcomes. Therefore, when evaluating osteopenia or sarcopenia in the elderly, management of those in both disease groups should occur together.
Is There a Health Inequality in Gambling Related Harms? A Systematic Review
Authors: Raybould Jodie , Larkin Michael , Tunney Richard
Published: November 2020

Background: Here we present a systematic review of the existing research into gambling harms, in order to determine whether there are differences in the presentation of these across demographic groups such as age, gender, culture, and socioeconomic status, or gambling behaviour categories such as risk severity and play frequency. Primary and Secondary Outcome Measures: Inclusion criteria were: 1) focus on gambling harms; 2) focus on harms to the gambler rather than affected others; 3) discussion of specific listed harms and not just harms in general terms. Exclusion criteria were: 1) research of non-human subjects; 2) not written in English; 3) not an empirical study; 3) not available as a full article.Methods: We conducted a systematic search using the Web of Science and Scopus databases in August 2020. Assessment of quality took place using Standard Quality Assessment Criteria.Results: A total of 59 studies published between 1994 and 2020 met the inclusion criteria. These were categorised into thematic groups for comparison and discussion. There were replicated differences found in groups defined by age, socioeconomic status, education level, ethnicity and culture, risk severity, and gambling behaviours. Conclusion: Harms appear to be dependent on specific social, demographic and environmental conditions that suggests there is a health inequality in gambling related harms. Further investigation is required to develop standardised measurement tools and to understand confounding variables and co-morbidities. With a robust understanding of harms distribution in the population, Primary Care Workers will be better equipped to identify those who are at risk, or who are showing signs of Gambling Disorder, and to target prevention and intervention programmes appropriately.
Comparing two treatment approaches for patients with type 1 diabetes during aerobic exercise: a randomised, crossover study
Authors: Vartak Varun , Chepulis Lynne , Driller Matt , Paul Ryan
Published: November 2020

In a randomised, counterbalanced, crossover design, eight men with type 1 diabetes (T1D; mean ± SD age: 27.6 ± 11.4 years) reduced insulin (INS) by 50% of their normal dose or consumed carbohydrates equivalent to 1 g of carbohydrate/kg of their body weight without the usual insulin bolus (CARBS) over two sessions, held a week apart. Each session included standardised meals, a 45-minute treadmill-walk at 7.24 km.h-1 and a six-minute walk test (6MWT). Rate of perceived exertion (RPE), blood glucose, blood ketone and blood lactate measures were taken before, during and immediately after the aerobic exercise. The distance covered in metres and the predicted VO2 max (mL⋅kg−1⋅min−1) were also calculated for the 6MWT. Participants completing the INS intervention spent more time in normoglycaemia (242 ± 135 min vs 88 ± 132 min; P < 0.01) and less time in hyperglycaemia (41 ± 95 min vs 154 ± 125 min; P = 0.01) as compared to the CARBS intervention. Mild hypoglycaemia occurred in two participants during INS and no participants during CARBS. Furthermore, there was no significant difference for blood lactate, ketone, RPE, distance covered and predicted VO2 max between interventions. Based on this pilot study, INS intervention appears to be the best approach for maintaining blood glucose levels in those with T1D during aerobic exercise, though this does need evaluating in other groups, including women, children and those with sub-optimal glycaemic control. Trial registration: ACTRN12619001397101p. Registered 09 September 2019, http://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378264
Radiological evaluation of malignant pleural mesothelioma - defining distant metastatic disease
Authors: Collins Dearbhaile Catherine , Sundar Raghav , Constantidinou Anastasia , Dolling David , Yap Timothy Anthony , Popat Sanjay , O’Brien Mary E , Banerji Udai , de Bono Johann Sebastian , Lopez Juanita Suzanne , Tunariu Nina , Minchom Anna
Published: November 2020

BackgroundMalignant pleural mesothelioma (MPM) is traditionally characterized by local destructive spread of the pleura and surrounding tissues. Patient outcomes in MPM with distant metastatic dissemination are lacking.MethodsIn this retrospective study, we reviewed a cohort of 164 MPM patients referred to a Phase I trials unit, aiming to describe identified metastatic sites, and correlate with clinical outcomes. Results67% of patients were diagnosed with distant metastatic disease with a high incidence of bone (19%), visceral (14%), contralateral lung (35%) and peritoneal metastases (22%). Peritoneal metastases were more likely in epithelioid versus biphasic/ sarcomatoid MPM (p=0.015). Overall survival was 23.8 months with no statistical difference in survival between those with distant metastases and those without.ConclusionsThis report highlights the frequency of distant metastases and encourages further radiological investigations in the presence of symptoms. In particular, given the relatively high incidence of bone metastases, bone imaging should be considered in advanced MPM clinical workflow and trial protocols. The presence of distant metastases does not appear to have prognostic implications under existing treatment paradigms. This cohort of MPM patients gives an indication of patterns of metastatic spread that are likely to become prevalent as prognosis improves with emerging treatment paradigms.
Effectiveness of blended learning versus lectures alone on ECG analysis and interpretation by medical students
Authors: Viljoen Charle Andre , Millar Rob Scott , Manning Kathryn , Burch Vanessa Celeste
Published: November 2020

BackgroundMost medical students lack confidence and are unable to accurately interpret ECGs. Thus, better methods of ECG instruction are being sought. Current literature indicates that the use of e-learning for ECG analysis and interpretation skills (ECG competence) is not superior to lecture-based teaching. We aimed to assess whether blended learning (lectures supplemented with the use of a web application) resulted in better acquisition and retention of ECG competence in medical students, compared to conventional teaching (lectures alone).MethodsTwo cohorts of fourth-year medical students were studied prospectively. The conventional teaching cohort (n=67) attended four hours of interactive lectures, covering the basic principles of Electrocardiography, waveform abnormalities and arrhythmias. In addition to attending the same lectures, the blended learning cohort (n=64) used a web application that facilitated deliberate practice of systematic ECG analysis and interpretation, with immediate feedback. All participants completed three tests: pre-intervention (assessing baseline ECG competence at start of clinical clerkship), immediate post-intervention (assessing acquisition of ECG competence at end of six-week clinical clerkship) and delayed post-intervention (assessing retention of ECG competence six months after clinical clerkship, without any further ECG training). Diagnostic accuracy and uncertainty were assessed in each test.ResultsThe pre-intervention test scores were similar for blended learning and conventional teaching cohorts (mean 31.02±13.19% versus 31.23±11.52% respectively, p=0.917). While all students demonstrated meaningful improvement in ECG competence after teaching, blended learning was associated with significantly better scores, compared to conventional teaching, in immediate (75.27±16.22% vs 50.27±17.1%, p<0.001; Cohen’s d=1.58), and delayed post-intervention tests (57.70±18.54% vs 37.63±16.35%, p<0.001; Cohen’s d=1.25). Although diagnostic uncertainty decreased after ECG training in both cohorts, blended learning was associated with better confidence in ECG analysis and interpretation.ConclusionBlended learning achieved significantly better levels of ECG competence and confidence amongst medical students than conventional ECG teaching did. Although medical students undergo a significant attrition of ECG competence without ongoing training, blended learning also resulted in better retention of ECG competence than conventional teaching. Web applications encouraging a stepwise approach to ECG analysis and enabling deliberate practice with feedback may, therefore, be a useful adjunct to lectures for teaching Electrocardiography.
LINC00665 enhances tumorigenicity of endometrial carcinoma by interacting with high mobility group AT-hook 1  
Authors: Cai Yixuan , Hao Min , Chang Yue , Liu Yun
Published: November 2020

Background: Endometrial carcinoma is a frequently diagnosed cancer among females. LncRNAs are reported to be associated with various cancers. Their biological roles in endometrial carcinoma progression is an emerging scientific area. LINC00665 can exert a significant role in many cancers. However, its potential function in endometrial carcinoma is still poorly known.Method: qRT-PCR was carried out to test expression of LINC00665 and HMGA1. Western blot analysis was carried out to detect protein expression of HMGA1. Cell proliferation was evaluated using Cell Counting Kit-8 (CCK-8) and EdU assay. Flow cytometry assay was used to determine cell apoptosis and cell cycle. Wound healing and transwell invasion assay was carried out to test cell migration and invasion. Immunohistochemical staining and HE staining were conducted to assess Ki-67 and tumor growth respectively.Results: Expression of LINC00665 in clinical endometrial carcinoma tissues and cells was obviously up-regulated. Loss of LINC00665 could repress endometrial carcinoma cell viability, induce cell apoptosis and block cell cycle in G1 phase. KLE and HHUA cell migration and invasion ability were depressed by LINC00665 shRNA. Decrease of LINC00665 suppressed endometrial carcinoma tumorigenicity in vivo. RIP assay proved that LINC00665 directly bound with HMGA1 protein. shRNA of HMGA1 obviously restrained endometrial carcinoma cell growth and cell invasion.Conclusions: LINC00665 might promote endometrial carcinoma progression by positively modulating HMGA1.
The impact of COL1A1 and COL6A1 expression on hypospadias and penile curvature severity
Authors: Yuri Prahara , Gunadi  , Lestari Rahmadani Puji , Fardilla Firly Putri , Setyaningsih Wiwit Ananda Wahyu , Arfian Nur , Dachlan Ishandono
Published: November 2020

Background: Hypospadias, the most frequent congenital male external genitalia abnormality, is usually associated with curvature of the ventral penis, i.e. chordee. Abnormality of darto tissue has been suggested as the pathophysiology of chordees. Collagen is one of the most abundant fibrous proteins within the extracellular matrix. In this study, we determined the expression of collagen 1 (COL1A1) and COL6A1 in patients with hypospadias and associated them with the severity of penile curvature.Methods: We included 60 children <18 years old, consisting of 20 distal hypospadias, 20 proximal hypospadias patients, and 20 controls in our institution from 2017 – 2020. The expression of COL1A1 and COL6A1 in darto tissue was determined by reverse-transcriptase polymerase chain reaction (qPCR). The penile curvature severity was classified as mild (<30 degrees), moderate (30-60 degrees), and severe (>60 degrees).Results: qPCR showed that COL1A1 and COL6A1 expression was significantly downregulated in the distal (0.88 (0.38-2.53) and 0.54 (0.16-4.35), respectively) and proximal 0.76 (0.33-2.57) and 0.57 (0.18-1.38), respectively) hypospadias groups compared to controls (1.85 (0.24-4.61) and 0.93 (0.17-4.06), respectively) with p-values of 0.024 and 0.018, respectively. Furthermore, there was a moderate correlation between COL1A1 and COL6A1 expression (r=0.458, p<0.0001). Interestingly, COL1A1 and COL6A1 were also significantly downregulated in the moderate and severe chordee groups compared to the mild chordee groups, with p-values of 0.003 and 0.037, respectively.Conclusions: Aberrant COL1A1 and COL6A1 expression might affect abnormalities in darto tissue and penile curvature severity in hypospadias patients.
Transcriptome analysis and differential gene expression profiling of two contrasting quinoa genotypes in response to salt stress
Authors: Shi Pibiao , Gu Minfeng
Published: November 2020

Background: Soil salinity is one of the major abiotic stress factors that affect crop growth and yield, which seriously restricts the sustainable development of agriculture. Quinoa is considered as one of the most promising crops in the future for its high nutrition value and strong adaptability to extreme weather and soil conditions. However, the molecular mechanisms underlying the adaptive response to salinity stress of quinoa remain poorly understood. To identify candidate genes related to salt tolerance, we performed reference-guided assembly and compared the gene expression in roots treated with 300 mM NaCl for 0, 0.5, 2, and 24 h of two contrasting quinoa genotypes differing in salt tolerance.Results: The salt-tolerant (ST) genotype displayed higher seed germination rate and plant survival rate, and stronger seedling growth potential as well than the salt-sensitive (SS) genotype under salt stress. An average of 38,510,203 high-quality clean reads were generated. Significant Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were identified to deeper understand the differential response. Transcriptome analysis indicated that salt-responsive genes in quinoa were mainly related to biosynthesis of secondary metabolites, alpha-Linolenic acid metabolism, plant hormone signal transduction, and metabolic pathways. Moreover, several pathways were significantly enriched amongst the differentially expressed genes (DEGs) in ST genotypes, such as phenylpropanoid biosynthesis, plant-pathogen interaction, isoquinoline alkaloid biosynthesis, and tyrosine metabolism. 117 DEGs were common to various stages of both genotypes, identified as core salt-responsive genes, including some transcription factor members, like MYB, WRKY and NAC, and some plant hormone signal transduction related genes, like PYL, PP2C and TIFY10A, which play an important role in the adaptation to salt conditions of this species. The expression patterns of 21 DEGs were detected by quantitative real-time PCR (qRT-PCR) and confirmed the reliability of the RNA-Seq results.Conclusions: We identified candidate genes involved in salt tolerance in quinoa, as well as some DEGs exclusively expressed in ST genotype. The DEGs common to both genotypes under salt stress may be the key genes for quinoa to adapt to salinity environment. These candidate genes regulate salt tolerance primarily by participating in reactive oxygen species (ROS) scavenging system, protein kinases biosynthesis, plant hormone signal transduction and other important biological processes. These findings provide theoretical basis for further understanding the regulation mechanism underlying salt tolerance network of quinoa, as well establish foundation for improving its tolerance to salinity in future breeding programs.
LncRNA HOXA-AS2 promotes glioblastoma carcinogenesis by targeting miR-885-5p/RBBP4 axis
Authors: Shou Jixin , Gao Haidong , Cheng Sen , Wang Bingbing , Guan Haibo
Published: November 2020

Background: LncRNA HOXA-AS2 has been found in the literature to deteriorate glioblastoma. However, its regulatory mechanism is yet to be fully investigated. Our study focused chiefly on the interaction and role of the HOXA-AS2/miR-885-5p/RBBP4 axis in the development of glioblastoma. Methods: qRT-PCR analysis was performed to detect the expression of lncRNA, miRNA and mRNA in glioblastoma tissues and cells. Dual-luciferase assay, RIP assay and RNA pull-down assay were later carried out to reveal the interactions among HOXA-AS2, miR-885-5p and RBBP4. After that, CCK-8 assay, BrdU assay, nude mice xenografting assay, western blot assay, and flow cytometry were carried out to analyze the effect of the HOXA-AS2/miR-885-5p/RBBP4 axis on glioblastoma samples. Results: HOXA-AS2 and RBBP4 were found to be overexpressed in glioblastoma. Experimental results showed that HOXA-AS2 and RBBP4 contributed to the tumorigenesis of glioblastoma cells. However, miR-885-5p was observed to be downregulated in glioblastoma. Findings also indicated that HOXA-AS2 could negatively regulate miR-885-5p, thereby enhancing RBBP4 expression. Conclusion: Overall, HOXA-AS2 promoted the tumorigenesis of glioblastoma by targeting and regulating miR-885-5p to induce the expression of RBBP4.
Proline-rich protein 11 overexpression is associated with a more aggressive phenotype and poor overall survival in ovarian cancer patients
Authors: zhan yu , wu xueyuan , zheng gang , jin jingjing , li chaofu , yu guanzhen , li wenfeng
Published: November 2020

Background: The proline-rich protein 11 (PRR11) is a newly identified oncogene associated with a poor prognosis in several human cancers. Nonetheless, research on its role in ovarian cancer (OC) remains largely understudied. Therefore, this study aims to evaluate the expression levels of PRR11 protein and its role in human ovarian cancer. Methods: Immunohistochemistry analysis was used to evaluate the expression levels of PRR11 protein in human samples obtained from 49 patients diagnosed with OC and subjected to curative surgery in the First Affiliated Hospital of Wenzhou Medical University between 2007 and 2015. Results: In total, 57.1% of the primary OC tumor tissue evaluated demonstrated overexpression of PRR11. Meanwhile, survival analysis showed that the overall survival (OS) of patients presenting overexpression of PRR11 was significantly lower than the OS of the patients with negative PRR11. In subsequent experiments, it was found that silencing the expression of PRR11 expression inhibited the proliferation of tumor cells and the migration of cells in vitro. Further, cells subjected to PRR11 knockdown exhibited a decrease in tumor growth in vivo. The downregulation of PRR11 was coupled with a decrease in N-cadherin and downregulation in the expression of early growth response protein 1 (EGR1).Conclusions: The findings suggest that PRR11 might be considered as a potential target for prognostic assessment and gene therapy strategies for patients diagnosed with OC.
Factors associated with the recruitment of foreign nurses in Japan: A nationwide study of hospitals
Authors: Hirano Yuko , Tsubota Kunio , Ohno Shun
Published: November 2020

Background: Nurse migration under bilateral agreements is a recent global trend, although lack of consultation with the health industries has led to challenges in the recruitment of foreign nurses by hospitals. To analyze the prevailing perception of hospitals on the Economic Partnership Agreement (EPA), under which Japan opened the doors to foreign nurses, we surveyed hospitals that are yet to employ foreign nurses. Methods: An anonymous questionnaire was developed and distributed to eligible hospitals; it assessed managers’ perception of Japan’s policy on the recruitment of foreign nurses and their intentions to hire foreign nurses under the EPA (hereafter called EPA nurses). We randomly selected 1,879 hospitals, or 22% of the hospitals in Japan (n = 8,540), with more than 20 beds. We used descriptive statistics, a Chi-square test, and logistic regression analysis to identify the predictors and developed a model to predict the likelihood of their intention to recruit EPA nurses in the future. Results: In total, 432 hospitals were eligible for further analysis (response rate: 22.9%). Half (50%) of the hospital managers were considerably interested in Japan’s policy on recruiting EPA nurses, although only 20% intended to recruit EPA nurses in the future. Willingness to recruit EPA nurses was associated with the degree of interest in the policy (OR 9.38; 95% CI 4.42–19.90) and managers’ perception of EPA nurses (OR 5.32, 95% CI 2.38–11.89). Conclusions: To attract more hospitals to recruit foreign nurses, it is essential for the Japanese government and the sending countries to review their EPA systems. Utilizing returning nurses to assist language acquisition by the forthcoming EPA nurses could be a provisional solution. For a more fundamental solution, long-term provision, from prior to their migration until their return migration, is needed to encourage brain circulation, as opposed to brain drain, between sending and receiving countries.
Persistently higher serum sCD40L levels are associated with outcome in septic patients
Authors: Liang Yingjian , Zhu Chengrui , Sun Yini , Li Zhiliang , Wang Liang , Liu Yina , Li Xin , ma xiaochun
Published: November 2020

Background: Soluble CD40 ligand (sCD40L) exhibits proinflammatory and procoagulant effects. Recent data indicated that sCD40L plays a significant role in septic patients. The aim of the present study was to determine sCD40L changes in surgical patients without sepsis (SWS) and in surgical sepsis patients (SS) during the first three days at intensive care unit(ICU) admission and to observe the association between sCD40L and mortality.
Methods: Time changes in sCD40L levels were assessed for 3 days after ICU admission in 49 patients with SS and compared with 19 SWS patients. Serum sCD40L concentration was detected by ELISA. Survival at 28 days was used as the endpoint.
Results: SS had significantly higher sCD40L levels than SWS and control patients. We observed an association between sCD40L levels ≥1028.75 pg/ml at day 2 and 28-day mortality (odds ratio = 7.888; 95% confidence interval = 1.758 to 35.395; P= 0.007). We could not discover any significant differences in gender, presence of septic shock, site of infection, length of stay in the ICU, PaO2/FiO2 ratio, incidence of AKI, ARDS, or type of surgery between nonsurvivors and survivors.
Conclusions: Septic patients show persistently higher circulating sCD40L levels in the first three days at ICU admission, and the serum sCD40L levels are associated with the mortality of patients with sepsis; thus, serum sCD40L could be usedas a reliable biomarker and therapeutic target in sepsis.
Nutritional and Inflammatory Measures Predict Survival of Patients with Stage IV Colorectal Cancer
Authors: Takamizawa Yasuyuki , Shida Dai , Boku Narikazu , Nakamura Yuya , Ahiko Yuka , Yoshida Takefumi , Tanabe Taro , Takashima Atsuo , Kanemitsu Yukihide
Published: November 2020

Background: This study aimed to evaluate the prognostic impact of nutritional and inflammatory measures (controlling nutritional status (CONUT) score, prognostic nutritional index (PNI), and modified Glasgow prognostic score (mGPS)) on overall survival (OS) in patients with stage IV colorectal cancer (CRC).Methods: Subjects were 996 patients with stage IV CRC who were referred to the National Cancer Center Hospital between 2001 and 2015. We retrospectively investigated correlations between OS and CONUT score, PNI, and mGPS. Multivariate analyses were performed using Cox proportional hazards regression models.Results: After adjusting for known factors (age, gender, BMI, ECOG performance status, location of primary tumor, CEA levels, histological type, M category, and prior surgical treatment), all three measures were found to be independent prognostic factors for OS in patients with stage IV CRC (CONUT score, p<0.001; PNI, p<0.001; mGPS, p<0.001). Significant differences in OS were found between low CONUT score (0/1) (n=614; 61%) and intermediate CONUT score (2/3) (n=276; 28%) (hazard ratio (HR)=1.20, 95% confidence interval (CI): 1.02-1.42, p=0.032), and intermediate CONUT score and high CONUT score (≥4) (n=106; 11%) (HR=1.30, 95% CI: 1.01-1.67, p=0.045). Significant differences in OS were found between mGPS=0 (n=633; 64%) and mGPS=1 (n=234; 23%) (HR=1.84, 95% CI: 1.54-2.19, p<0.001), but not between mGPS=1 and mGPS=2 (n=129; 13%) (HR=1.12, 95% CI: 0.88-1.41, p=0.349). Patients with low PNI (<48.0) (n=443; 44%) showed a significantly lower OS rate than those with high PNI (≥48.0) (n=553; 56%) (HR=1.39, 95% CI: 1.19-1.62, p<0.001).Conclusions: CONUT score, PNI, and mGPS were found to be independent prognostic factors for OS in patients with stage IV CRC, suggesting that nutritional and inflammatory status is a useful host-related prognostic indicator in stage IV CRC.
Knowledge, attitudes and practices of the Chinese public with respect to coronavirus disease (COVID-19): An online cross-sectional survey
Authors: Gao Huiming , Hu Rujun , Yin Ling , Yuan Xiaoli , Tang Hao , Luo Lan , Chen Mei , Huang Di , Wang Ying , Yu Anyong , Jiang Zhixia
Published: November 2020

Background: Coronavirus disease (COVID-19) has become a pandemic. The knowledge, attitudes, and practices (KAP) of the public play a major role in the prevention and control of infectious diseases. The objective of the present study was to evaluate the KAP of the Chinese public and to assess potential influencing factors related to practices.Methods: A cross-sectional online survey was conducted in China in February 2020 via a self-designed questionnaire comprising 33 questions assessing KAP.Results: For the 2,136 respondents from 30 provinces or municipalities in China, the accurate response rate for the knowledge section ranged from 72.7% to 99.5%, and the average was 91.2%. Regarding attitude section, the percentage of positive attitudes (“strongly agree” and “agree”) ranged from 94.7% to 99.7%, and the average value was 98.0%. The good practices (“always” and “often”) results ranged from 76.1% to 99.5%, and the average value was 96.8%. The independent samples t-test revealed that gender and ethnic differences had no effect on knowledge, attitude or behaviour (P>0.05). However, knowledge was associated with age (t=4.842, p<0.001), marital status (t=-5.323, p<0.001), education level (t=8.441, p<0.001), occupation (t=-10.858, p<0.001), and place of residence (t=7.929, p<0.001). Similarly, attitude was associated with marital status (t=-2.383, p=0.017), education level (t=2.106, p=0.035), occupation (t=-4.834, p<0.001), and place of residence (t=4.242, p<0.001). The multiple linear regression analysis results showed that the factors influencing practices were knowledge (t=-3.281, p=0.001), attitude (t=18.756, p<0.001), occupation (t=-3.860, p<0.001), education level (t=3.136, p=0.002), and place of residence (t=3.257, p=0.001).Conclusions: The Chinese public exhibited a good level of knowledge of COVID-19, a positive attitude, and high adherence to good practices. COVID-19-related knowledge, attitudes and practices were affected by age, marital status, education level, occupation, and place of residence to varying degrees. In addition, practices were affected by knowledge and attitudes towards COVID-19.
Preoperative prognostic factors associated with postoperative delirium in older people undergoing surgery: protocol for a systematic review and individual patient data meta-analysis
Authors: Buchan Tayler A , Sadeghirad Behnam , Schmutz Nayeli , Goettel Nicolai , Foroutan Farid , Couban Rachel , Mbuagbaw Lawrence , Dodsworth Benjamin T
Published: November 2020

Background: Early identification of patients at risk for postoperative delirium is essential because adequate well-timed interventions could reduce the occurrence of delirium and the related detrimental outcomes.Methods: We will conduct a systematic review and individual patient data (IPD) meta-analysis of prognostic studies evaluating the predictive value of risk factors associated with an increased risk of postoperative delirium in elderly patients undergoing elective surgery. We will identify eligible studies through systematic search of MEDLINE, EMBASE, and CINAHL from their inception to May 2020. Eligible studies will enroll older adults (³ 50 years) undergoing elective surgery and assess pre-operative prognostic risk factors for delirium and incidence of delirium measured by a trained individual using a validated delirium assessment tool. Pairs of reviewers will, independently and in duplicate, screen titles and abstracts of identified citations, review the full texts of potentially eligible studies. We will contact chief investigators of eligible studies requesting to share the IPD to a secured repository. We will use one-stage approach for IPD meta-analysis and will assess certainty of evidence using the GRADE approach.Discussion: Since we are using existing anonymized data, ethical approval is not required for this study. Our results can be used to guide clinical decisions about the most efficient way to prevent postoperative delirium in elderly patients. Systematic review registration: CRD42020171366
Improvement of stem cell-derived exosome release efficiency by surface modified nanoparticles
Authors: Park Dong Jun , Yun Wan Su , Kim Woo Cheol , Park Jeong-Eun , Lee Su Hoon , Ha Sunmok , Choi Jin Sil , Key Jaehong , Seo YoungJoon
Published: November 2020

Background: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSC-derived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules. Results: The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We determined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation. Conclusions: It was concluded that the nanoparticles we developed were transported to the lysosome by clathrin-mediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors.
Evaluation of curcumin and copper acetate against Salmonella Typhimurium infection, intestinal permeability, and cecal microbiota composition in broiler chickens
Authors: Leyva-Diaz Anaisa A. , Hernandez-Patlan Daniel , Solis-Cruz Bruno , Adhikari Bishnu , Kwon Young Min , Latorre Juan D. , Hernandez-Velasco Xochitl , Fuente-Martinez Benjamin , Hargis Billy M. , Lopez-Arellano Raquel , Tellez Guillermo
Published: November 2020

Background: Interest in the use of natural feed additives as an alternative to antimicrobials in the poultry industry has increased in recent years because of the risk of bacterial resistance. One of the most studied groups are polyphenolic compounds, given their advantages over other types of additives and their easy potentiation of effects when complexes are formed with metal ions. Therefore, the objective of the present study was to evaluate the impact of dietary supplementation of copper acetate (CA), curcumin (CR), and their combination (CA-CR) against Salmonella Typhimurium colonization, intestinal permeability, and cecal microbiota composition in broiler chickens through a laboratory Salmonella infection model. S. Typhimurium recovery was determined on day 10 post-challenge by isolating Salmonella in homogenates of the right cecal tonsil (12 chickens per group) on Xylose Lysine Tergitol-4 (XLT-4) with novobiocin and nalidixic acid. Intestinal integrity was indirectly determined by the fluorometric measurement of fluorescein isothiocyanate dextran (FITC-d) in serum samples from blood obtained on day 10 post-S. Typhimurium challenge. Finally, microbiota analysis was performed using the content of the left caecal tonsil of 5 chickens per group by sequencing V4 region of 16S rRNA gene.Results: The results showed that in two independent studies, all experimental treatments were able to significantly reduce the S. Typhimurium colonization in cecal tonsils (CT, P< 0.0001) compared to the positive control (PC) group. However, only CA-CR was the most effective treatment in reducing S. Typhimurium counts in both independent studies. Furthermore, the serum fluorescein isothiocyanate dextran (FITC-d) concentration in chickens treated with CR was significantly lower when compared to PC (P= 0.0084), which is related to a decrease in intestinal permeability and therefore intestinal integrity. The effect of dietary treatments in reducing Salmonella was further supported by the analysis of 16S rRNA gene sequences using Linear discriminant analysis effect size (LEfSe) since Salmonella was significantly enriched in PC group (LDA score > 2.0 and P<0.05) compared to the other groups. In addition, Coprobacillus, Eubacterium, and Clostridium were significantly higher in the PC group compared to other treatment groups. On the contrary, Fecalibacterium and Enterococcus in CR, unknown genus of Erysipelotrichaceae at CA-CR, and unknown genus of Lachnospiraceae at CA were significantly more abundant respectively.Conclusions: CR treatment was the most effective treatment to reduce S. Typhimurium intestinal colonization and maintain better intestinal homeostasis which might be achieved through modulation of cecal microbiota.
Enriched environment ameliorates adult hippocampal neurogenesis deficits in Tcf4 haploinsufficient mice
Authors: Braun Katharina , Häberle Benjamin M. , Wittmann Marie-Theres , Lie Dieter Chichung
Published: November 2020

Background: Transcription factor 4 (TCF4) has been linked to human neurodevelopmental disorders such as intellectual disability, Pitt-Hopkins Syndrome (PTHS), autism, and schizophrenia. Recent work demonstrated that TCF4 participates in the control of a wide range of neurodevelopmental processes in mammalian nervous system development including neural precursor proliferation, timing of differentiation, migration, dendritogenesis and synapse formation. TCF4 is highly expressed in the adult hippocampal dentate gyrus – one of the few brain regions where neural stem / progenitor cells generate new functional neurons throughout life.Results: We here investigated whether TCF4 haploinsufficiency, which in humans causes non-syndromic forms of intellectual disability and PTHS, affects adult hippocampal neurogenesis, a process that is essential for hippocampal plasticity in rodents and potentially in humans. Young adult Tcf4 heterozygote knockout mice showed a major reduction in the level of adult hippocampal neurogenesis, which was at least in part caused by lower stem/progenitor cell numbers and impaired maturation and survival of adult-generated neurons. Interestingly, housing in an enriched environment was sufficient to enhance maturation and survival of new neurons and to substantially augment neurogenesis levels in Tcf4 heterozygote knockout mice.Conclusion:The present findings indicate that haploinsufficiency for the intellectual disability- and PTHS-linked transcription factor TCF4 not only affects embryonic neurodevelopment but impedes neurogenesis in the hippocampus of adult mice. These findings suggest that TCF4 haploinsufficiency may have a negative impact on hippocampal function throughout adulthood by impeding hippocampal neurogenesis.
The fibronectin type-III (FNIII) domain of ATF7IP contributes to efficient transcriptional silencing mediated by the SETDB1 complex 
Authors: Shinkai Yoichi , Tsusaka Takeshi , Fukuda Kei , Shimura Chikako , Kato Masaki
Published: November 2020

Background: The histone methyltransferase SETDB1 (also known as ESET) represses genes and various types of transposable elements, such as endogenous retroviruses (ERVs) and integrated exogenous retroviruses, through a deposition of trimethylation on lysine 9 of histone H3 (H3K9me3) in mouse embryonic stem cells (mESCs). ATF7IP (also known as MCAF1 or AM), a binding partner of SETDB1, regulates the nuclear localization and enzymatic activities of SETDB1 and plays a crucial role in SETDB1-mediated transcriptional silencing. In this study, we further dissected the ATF7IP function with its truncated mutants in Atf7ip knockout (KO) mESCs.Results: We demonstrated that the SETDB1-interaction region within ATF7IP is essential for ATF7IP-dependent SETDB1 nuclear localization and silencing of both ERVs and integrated retroviral transgenes, whereas its C-terminal fibronectin type-III (FNIII) domain is dispensable for both these functions; rather, it has a role in efficient silencing mediated by the SETDB1 complex. Proteomic analysis identified a number of FNIII domain-interacting proteins, some of which have a consensus binding motif. We showed that one of the FNIII domain-binding proteins, ZMYM2, was involved in the efficient silencing of a transgene by ATF7IP. RNA-seq analysis of Atf7ip KO and WT or the FNIII domain mutant of ATF7IP-rescued Atf7ip KO mESCs showed that the FNIII domain mutant re-silenced most de-repressed SETDB1/ATF7IP-targeted ERVs compared to the WT. However, the silencing activity of the FNIII domain mutant was weaker than that of the ATF7IP WT, and some of the de-repressed germ cell-related genes in Atf7ip KO mESCs were not silenced by the FNIII domain mutant. Such germ cell-related genes are targeted and silenced by the MAX/MGA complex, and MGA was also identified as another potential binding molecule of the ATF7IP FNIII domain in the proteomic analysis. This suggests that the FNIII domain of ATF7IP acts as a binding hub of ATF7IP-interacting molecules possessing a specific interacting motif we named FAM and contributes to one layer of the SETDB1/ATF7IP complex-mediated silencing mechanisms.Conclusions: Our findings contributed to further understanding the function of ATF7IP in the SETDB1 complex, revealed the role of the FNIII domain of ATF7IP in transcriptional silencing, and suggested a potential underlying molecular mechanism for it.
A randomized, open-label, adaptive, proof-of-concept clinical trial of modulation of host thromboinflammatory response in patients with COVID-19: the DAWn-Antico study
Authors: Vanassche Thomas , Engelen Matthias M , Thillo Quentin Van , Wauters Joost , Gunst Jan , Wouters Carine , Vandenbriele Christophe , Rex Steffen , Liesenborghs Laurens , Wilmer Alexander , Meersseman Philippe , Berghe Greet Van den , Dauwe Dieter , Verbeke Geert , Thomeer Michiel , Fivez Tom , Mesotten Dieter , Ruttens David , Heytens Luc , Dapper Ilse , Tuyls Sebastiaan , De Tavernier Brecht , Verhamme Peter
Published: November 2020

Background The peak of the global COVID-19 pandemic has not yet been reached and many countries face the prospect of a second wave of infections before effective vaccinations will be available. After an initial phase of viral replication, some patients develop a second illness phase in which the host thrombotic and inflammatory responses seems to drive complications. Severe COVID-19 disease is linked to high mortality, hyperinflammation, and a remarkably high incidence of thrombotic events. We hypothesize a crucial pathophysiological role for the contact pathway of coagulation and the kallikrein-bradykinin pathway. Therefore, drugs that modulate this excessive thromboinflammatory response should be investigated in severe COVID-19.Methods In this adaptive, open-label multicenter randomized clinical trial we compare low molecular weight heparins at 50 IU anti-Xa/kg twice daily - or 75 IU anti-Xa twice daily for intensive care (ICU) patients - in combination with aprotinin to standard thromboprophylaxis in hospitalized COVID-19 patients. In the case of hyperinflammation, the interleukin-1-receptor antagonist anakinra will be added on top of the drugs in the interventional arm. In a pilot phase, the effect of the intervention on thrombotic markers (D-dimer) will be assessed. In the full trial, the primary outcome is defined as the effect of the interventional drugs on clinical status as defined by the WHO ordinal scale for clinical improvement. Discussion In this trial we target the thromboinflammatory response at multiple levels. We intensify the dose of low molecular weight heparins to reduce thrombotic complications. Aprotinin is a potent kallikrein pathway inhibitor that reduces fibrinolysis, activation of the contact pathway of coagulation, and local inflammatory response. Additionally, aprotinin has shown in vitro inhibitory effects on SARS-CoV-2 cellular entry. Because the excessive thromboinflammatory response is one of the most adverse prognostic factors in COVID-19, we will add anakinra, a recombinant interleukin-1 receptor antagonist, to the regimen in case of severely increased inflammatory parameters. This way, we hope to modulate the systemic response to SARS-CoV-2 and avoid disease progressions with a potentially fatal outcome. Trial registration This trial is registered in the EU Clinical Trials Register. Registration number: 2020-001739-28. Registered on 2020-04-10.
Incidence and risk factors for trocar-site incisional hernia detected by clinical and ultrasound examination. A prospective observational study​
Authors: Ciscar Ana , Badia Josep Maria , Novell Francesc , Bolivar Santiago , Mans Esther
Published: November 2020

BACKGROUND: Trocar site incisional hernia (TSIH) is the most frequent complication associated with laparoscopic surgery. Few studies currently describe its incidence or risk factors. The aim of this report is to determine the real incidence of TSIH and to identify risk factors. METHODS: A cross-sectional prospective study was performed including consecutive patients who underwent a laparoscopic procedure during a four months period. All the patients were assessed both clinically (TSIHc) and by an ultrasonographic examination (TSIHu). The main variable studied was the incidence of TSIH. A multivariate analysis was performed to identify risk factors. RESULTS: 76 patients were included. 27.6% of patients were clinically diagnosed as having TSIH (TSIHc) but only 23.7% of those cases were radiologically confirmed (TSIHu). In the logistic regression analysis, age > 70 years (OR 3.462 CI 1.14 - 10.515, p = 0.028) and body mass index (BMI) ≥30 Kg / m2 (OR 3.313 CI 1.037-10.588, p = 0.043) were identified as risk factors for TSIH. The size of the trocar also showed statistically significant differences (p <0.001). Mean follow-up time was 34 months.CONCLUSIONS: TSIH is under-diagnosed due to the lack of related symptomatology and the inadequacy of the postoperative follow-up period. We detected discrepancies between the clinical and ultrasonographic examinations. TSIHu should be considered as the gold standard for the diagnosis of TSIH. Risk factors such as age, BMI and size of the trocar were confirmed. Patients should be followed-up for a minimum of 2 years.TRIAL REGISTRATION: The study has been registered in Clinicaltrials.gov, under registration number: NCT04410744.