bluuebunny/crossref_metadata_2025 huggingface dataset:
COVID-19 Pandemic Readiness Status of West Africa
Authors: Lokossou Virgil Kaussi , Kaburi Basil Benduri , Bandoh Delia Akosua , Ouendo Edgard-Marius , Ouédraogo Aboubacar , Aseidu-Bekoe Franklin , Akoriyea Samuel Kaba , Sombié Issiaka , Johnson Ermel , Somé Donmozoun Télesphore , Kenu Ernest
Published: July 2020

Background

From the onset of COVID-19 pandemic in late December 2019, countries have been stepping up their pandemic preparedness and response activities in accordance with WHO recommendations. Informed by the recent lessons learned from the West Africa Ebola Virus Disease outbreak, and subsequent investments made in public health emergency preparedness and response in the Economic Community of West African States (ECOWAS) region, the West Africa Health Organisation (WAHO) is providing regional leadership in the COVID-19 pandemic preparedness and response. We assessed the COVID-19 pandemic readiness status of West Africa.
Methods

We conducted survey of all 15 ECOWAS member states between February 27 and March 15, 2020. We purposively selected a minimum of two respondents from each of the 15 ECOWAS member states – interviewing 37 in all using an interviewer-administered questionnaire based on the nine item WHO national capacity review tool for novel corona virus (nCOV). We also reviewed reports of COVID-19 pandemic preparedness meetings and trainings organized by WAHO. We performed a thematic analysis on the data and described the strengths and weaknesses of the ongoing pandemic readiness efforts of West Africa.
Results

Overall, the strengths of pandemic readiness of the region were: capacity to test 86.7% (13/15) of member states; functional incident management systems (100%); rapid response teams 100%, and at least two of the three tiers of field epidemiology workforce (100%). Within the region also, there existed good cross-border collaborations among member states, active participation of health ministers of member states in regional coordination meetings and decision making. Member states described the numbers of qualified biomedical scientists/technicians, field epidemiologists, risk communicators, and COVID-19 case management teams as inadequate. None of the member states had stockpiles of COVID-19 test kits, laboratory supplies, and personal protective equipment.
Conclusion

ECOWAS member states are taking appropriate COVID-19 pandemic preparedness measures in all pillars towards a regional response. Rather than a total lack, there are insufficiencies in numbers of skilled workforce, logistics, and supplies. Governments of member states are supportive of the coordination and technical direction of WAHO and WHO.
‘It benefits patient care’: The value of practice-based IPE in healthcare curriculums
Authors: O'Leary Noreen , Salmon Nancy , Clifford Amanda M.
Published: July 2020

Background
Practice-based interprofessional education (IPE) is essential to prepare students for collaborative working. Pockets of practice-based IPE have been integrated into healthcare curriculums in some regions. Yet practice-based IPE is not globally valued as a key element of healthcare curriculums. As students and clinical educators are key stakeholders, this study presents a case example of their experiences in a country where practice-based IPE is at an emergent stage. Their experiential knowledge will generate important insights into how practice-based IPE is perceived and experienced. This learning can be applied, both locally and beyond, by stakeholders seeking to embed practice-based IPE in their placement curriculums.
Methods
A qualitative case study was conducted at a school of allied health and partner placement sites in Ireland. Data collection comprised two participant observations, 13 interviews and 12 document analyses. Inductive thematic analysis and deductive framework analysis, underpinned by activity theory and Hofstede’s cultural dimensions, informed data analysis and interpretations.
Results
The overarching theme was establishing the value of practice-based IPE, illustrated in three sub-themes: articulating expectations, conceptualising practice-based IPE and integrating interprofessionalism. First, overt articulation of practice-based IPE learning outcomes within regulatory standards and assessment processes would enhance its value within practice education. Second, clearer conceptualisation of what constitutes practice-based IPE is required. Participants indicated varying conceptualisations regarding why and how to implement practice-based IPE. Highlighting how practice-based IPE improved patient care and safety created a clear rationale for implementation. It was also helpful to demonstrate how adaptations to existing practice education models, rather than entirely new models, could achieve meaningful practice-based IPE. Third, integrating interprofessionalism at placement sites is required. Varying levels of professional engagement were noted, perpetuating stereotypes. Creating educator networks and embedding practice-based IPE in organisational strategy enhances its status and broadens engagement.
Conclusions
Adoption of these recommendations could enhance the value of practice-based IPE and optimise student preparation for collaborative working. Practice-based IPE remains a complex model and the trajectory of embedding in healthcare curriculums will differ globally. National and international longitudinal stakeholder data is needed to refine what type of practice-based IPE is most impactful on future collaborative practice.
Prevalence and Risk Factors of Coronary Heart Disease in Chinese Patients with type 2 Diabetes Mellitus, 2013-2018
Authors: Wang Chenchen , Xie Zuoling , Huang Xi , Wang Zheng , Shangguan Haiyan , Wang Shaohua
Published: July 2020

Background: Coronary heart disease (CHD) is the most common cause of death in patients with type 2 diabetes (T2DM). We aim to estimate the prevalence of CHD and cardiovascular risk factors in Chinese diabetic inpatients.Methods: A total of 66536 diabetic inpatients from 2013 to 2018 were investigated, demographic and clinical data were gathered from 30693 patients with T2DM. The age-standardized prevalence of CHD was calculated on the basis of data from Chinese population census in 2010. Multiple imputation was used to impute missing values and logistic regression analysis was used to analyze the risk factors.Results: The crude prevalence of CHD was estimated to be 23.5% and a standardized prevalence was 13.9% (16.0% in men and 11.9% in women). More than half of diabetic patients with CHD have 4 or above of the 5 traditional risk factors, which is much higher than 38.96% of diabetic patients (p<0.01). Multivariate regression analysis showed that diabetes duration, hypertension, smoking, underweight, overweight, obesity, hypoglycemia were significantly associated with a higher risk of CHD (all p<0.05). The odds ratio of CHD in patients having 3, 4, or 5 CHD risk factors were 2.35 (95%CI 1.81- 3.04), 2.96 (95%CI 2.28- 3.85), and 5.29 (95%CI 4.04- 6.93), compared with diabetes patients without any other risk factors.Conclusions: The prevalence of CHD was rather high in Chinese T2DM inpatients, aggregation of CHD risk factors was more seriously, hierarchical CHD prevention strategies based on risk factors are needed for them.
Disparities in Child Survival in Ethiopia: Evidence From Nationally Represented Data
Authors: Geda Nigatu Regassa , Feng Cindy Xin , Whiting Susan J. , Janzen Bonnie , Lepnurm Rein , Henry Carol J.
Published: July 2020

The authors have withdrawn this preprint due to author disagreement.
Changes in physical activity, sedentary behaviour and body composition: longitudinal analysis in the PREDIMED-Plus trial
Authors: Galmes-Panades Aina M , Konieczna Jadwiga , Varela-Mato Veronica , Abete Itziar , Babio Nancy , Fiol Miquel , Paz Jose Antonio de , Casas Rosa , Olbeyra Romina , Ruiz-Canela Miguel , Galindo Antoni Palau , Castañer Olga , Martín-García Arturo , Estruch Ramon , Vidal Josep , Buil-Cosiales Pilar , Wärnberg Julia , Salas-Salvado Jordi , Martinez J Alfredo , Romaguera Dora
Published: July 2020

Background:The optimal distribution between physical activity (PA) levels and sedentary behaviour (SB) for the greatest benefits for body composition among older adults with overweight/obesity and chronic health conditions remains unclear. We aimed to determine the prospective association between changes in PA and in SB with concurrent changes in body composition. To examine whether reallocating inactive time into different physical activity levels was associated with 12-month change to body composition in older adults.Methods: A subsample (n=1564) of men and women (age: 55-75 years) with overweight/obesity and metabolic syndrome from the PREDIMED-Plus trial was included in the present analysis. Participant’s were followed-up at 6- and 12-months. Physical Activity and SB were assessed using validated questionnaires. Out of 1564 participants, 388 wore an accelerometer to objectively measure inactive time and PA over a 7-day period. At each time point, participants body composition was measured using dual-energy X-ray absorptiometry (DXA). Standard covariate-adjusted and isotemporal substitution modelling were applied to linear mixed-effects models.Results:Increasing 30 minute of total PA and MVPA were associated with significant reductions in body fat (β -0.07% and -0.08%) and VAT (-13.9g, and -15.6g) at 12-months (all p-values <0.001). Reallocating 30 minute of inactive time to MVPA was associated with reductions in body fat and VAT, and with an increase in muscle mass and muscle-to-fat mass ratio (all p-values <0.001).Conclusions:At 12 months, increasing total PA and MVPA and reducing total and TV-viewing SB were associated with improved body composition in participants with overweight or obesity, and metabolic syndrome. This was also observed when reallocating 30 minute of inactive time by total PA, LPA and MVPA, with the greatest benefits observed for MVPA.Trial registration: The trial was registered at the International Standard Randomized Controlled Trial (ISRCTN: http://www.isrctn.com/ISRCTN89898870) with number 89898870 and registration date of 24 July 2014, retrospectively registered.
Molecular and clinical characterization of CCT2 expression at transcriptional level via 2994 samples of breast cancer
Authors: Liu Qiang , Qi Yihang , Wang Xiangyu , Kong Xiangyi , Fang Yi , Wang Jing
Published: July 2020

BackgroundMolecular chaperones play important roles in regulating various cellular processes and malignant transformation. Expression of some subunits of molecular chaperonen CCT/TRiC complex have been reported to be correlated with cancer development and patient survival. However, little is known about the expression and prognostic significance of Chaperonin Containing TCP1 Subunit 2 (CCT2), a gene encoding a molecular chaperone that is a member of the chaperonin containing TCP1 complex (CCT), also known as the TCP1 ring complex (TRiC).MethodThrough the Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) databases, we systematically reviewed a total of 2994 cases with transcriptome data and analyzed the functional annotation of CCT2 by Gene ontology (GO) and KEGG analysis. Univariate and multivariate survival analysis were performed to investigate the prognostic value of CCT2 in breast cancer.ResultsWe found CCT2 was significantly upregulated in various tumors. In breast cancer, CCT2 expression was significantly upregulated in HER2-positive (HER2+) group, and more malignant group. In addition, we investigated correlations between CCT2 and other CCT members. Interestingly, almost all CCTs expression were positively correlated with each other, but not CCT6B. Survival analysis suggested that CCT2 overexpression was independently associated with worse prognosis of patients with breast cancer, especially in luminal A subtype.ConclusionIn summary, our results revealed that CCT2 might be involved in regulating cell cycle pathway, and independently predicted worse prognosis in breast cancer patients. These findings may expand understanding of potential anti-CCT2 treatments. To our knowledge, this is the largest and most comprehensive study characterizing the expression pattern of CCT2 together with its prognostic values in breast cancer.
Psychological factors affecting the association between a lifestyle behavior intervention and depressive symptoms in low-income overweight and obese mothers with young children: a secondary data analysis
Authors: Robbins Lorraine B. , Chang Mei-Wei , Ling Jiying , Brown Roger
Published: July 2020

Background Psychological factors mediating the effect of lifestyle behavior interventions on mothers’ depressive symptoms are unclear. Using data from a community-based lifestyle behavior intervention, this secondary analysis examined whether autonomous motivation, coping self-efficacy, and emotional coping mediated the association between the intervention and depressive symptoms in low-income overweight and obese mothers with young children.Methods This 16-week intervention had 2 components: Mothers watched 10 video lessons in Digital Video Disc (DVD) format at home and joined 10 peer support group teleconferences (every week in weeks 1–4; then every other week in weeks 5–16). All participants completed reliable and valid measures of autonomous motivation, coping self-efficacy, emotional coping and depressive symptoms via phone at baseline and immediately after the intervention. To assess effect size, proportion of maximum possible (POMP) scores were calculated. To test mediation effects, composite indicator structural equation modeling was performed.Results The intervention significantly alleviated depressive symptoms (p = 0.015, POMP = -4.31%). While the intervention had no influence on autonomous motivation, it significantly increased coping self-efficacy (p < 0.001, POMP = 7.4%) and emotional coping (p = 0.003, POMP = 3.81%). Coping self-efficacy significantly and negatively mediated the association between the intervention and depressive symptoms (p = 0.002, POMP = -2.53%). However, autonomous motivation and emotional coping were not significant mediators.Conclusions To help this target population alleviate depressive symptoms, clinicians may consider teaching these women practical strategies that can be applied to daily life to boost coping self-efficacy.
Development And Validation Of Models To Predict Cesarean Delivery Among Low-Risk Nulliparous Women At Term: A Retrospective Study In China
Authors: Sun Fangcan , Han Bing , Wu Fangfang , Shen Qianqian , Shen Minhong , Chen Youguo
Published: July 2020

Background: Cesarean delivery after failure of trial of labor is associated with adverse maternal and perinatal outcomes. A prediction algorithm to identify women with high risk of an emergency cesarean could help reduce morbidity and mortality associated with labor. The objective of the present study was to derive and validate a simple model to predict cesarean delivery for low-risk nulliparous women in Chinese population.Methods: This retrospective study analyzed the low-risk nulliparous women with singleton cephalic full-term fetus delivered in two medical centers. After the clinical data of the women who delivered at the tertiary referral center (n=6 551) was collected and was used univariate and multivariable logistic regression analysis, the prediction model was fitted. We performed external validation using data from nulliparous who delivered from another hospital(secondary referral center, n=7 657). A new nomogram was established based on the development cohort to predict the cesarean. The ROC curve, calibration plot and decision curve analysis were used to assess the predictive performance. Results: The cesarean delivery rates in the development cohort and the external validation cohort were 8.79% (576/6 551) and 7.82% (599/7 657). Multivariable logistic regression analysis showed that maternal age, height, BMI, weight gained during pregnancy, gestational age, induction method, meconium-stained amniotic fluid and neonatal sex were independent factors affecting cesarean outcome. Because sex of the fetuses were unknown until they born(China's Fertility Policy), we established two prediction models according to fetal sex was involved or not. The AUC was 0.782 and 0.774, respectively. The Hosmer-Lemeshow goodness-of-fit test showed that these two models fitted well. Decision curve analysis demonstrated that the models were clinically useful. And internal validation using Bootstrap method showed that these prediction models perform well. On the external validation set, the AUC were 0.775 and 0.775, respectively. The calibration plots for the probability of cesarean showed a good correlation. The online web server was constructed based on the nomogram for convenient clinical use.Conclusions: Both two models established by these factors have good prediction efficiency and high accuracy, which can provide the reference for clinicians to guide pregnant women to choose an appropriate delivery mode.
Prevalence of Coronavirus Disease 2019 in Rheumatic Patients and Evaluation of The Effect of Disease-Modifying Anti-Rheumatic Drugs
Authors: Moradi Soroush , Mohammadi Somayeh , Vafaeimanesh Jamshid , Mohseni Mohaddeseh , Mahdavi Hossein , Aryannejad Armin , Masoumi Maryam
Published: July 2020

Background: One of the most controversial issues among rheumatologists is the best approach to managing a rheumatic patient (RP) with coronavirus disease 2019 (COVID-19).Objectives: This study aims to evaluate the prevalence of COVID-19 in RPs and compare it to thegeneral population (healthy individuals). Besides, it assesses the incidence of COVID-19 based on rheumatologic diseases (RDs) categories and immunosuppressive (IS) drug history.Methods: In a cross-sectional study, all RPs of the rheumatology clinic of Shahid BeheshtiHospital, Qom, Iran were included (the case group), and the prevalence of COVID-19 was compared to that in healthy individuals (the control group), between December 1, 2019, andFebruary 29, 2020. Qom city was the first city in Iran in which COVID-19 was identified and spread rapidly. The participants were recruited from hospital records for the case group and QomHealth Network’s database for the control group.Results: The prevalence of COVID-19 is significantly less in RPs than in the healthy population.Moreover, patients who were under treatment with biologic diseas-modifying anti-rheumatic drugs(DMARDs) and IS drugs had milder symptoms in the case of COVID-19. Two RPs died from COVID-19, both of whom had granulomatosis and polyangiitis (GPA).Conclusion: The prevalence of COVID-19 in the RPs was lower than the general population, which was determined to be associated with more adherence to the quarantine and social distancing rules by RPs. Besides, using leflunomide (a DMARD) and IS drugs might have a protective effect against severe COVID-19.
Protein over-expression in Escherichia coli triggers adaptation analogous to antimicrobial resistance
Authors: James Jack , Yarnall Benjamin , Koranteng Andy , Gibson Jane , Rahman Tahmina , Doyle Declan Anthony
Published: July 2020

Background
The E. coli pET system is the most widely used protein over-expression system worldwide. It relies on the assumption that all cells produce target protein and it is generally believed that integral membrane protein (IMP) over-expression is more toxic than their soluble counterparts.
Results
Using GFP-tagged proteins, high level over-expression of either soluble or IMP targets results in > 99.9% cell loss with survival rate of only < 0.03%. Selective pressure generates three phenotypes: large green, large white and small colony variants. As a result, in overnight cultures, ~ 50% of the overall cell mass produces no protein. Genome sequencing of the phenotypes revealed genomic mutations that causes either the loss of T7 RNAP activity or its transcriptional downregulation. The over-expression process is bactericidal and is observed for both soluble and membrane proteins.
Conclusions
We demonstrate that it is the act of high-level over-expression of all exogenous proteins in E. coli that sets in motion a chain of events leading to > 99.9% cell death. These results redefine our understanding of protein over-production and link it to the adaptive survival response seen in the development of antimicrobial resistance.
Validation of 4 Estimating Methods to Evaluate 24-hour Urinary Sodium Excretion for Young Adults in China by Different Seasons
Authors: Gong Weiyi , Zhang Zechen , Liang Jufeng , Zhang Jiguo , Ma Yuxia
Published: July 2020

Background: 24-hour urine sample collection is regarded as the gold standard for sodium intake evaluation, but the implementation can be difficult. To validate and evaluate the accuracy and feasibility of estimating sodium intake by four methods of Kawasaki, INTERSALT, Tanaka and Sun’s equations. Methods: 274 healthy volunteers aged 18-25y were enrolled in this study. 24-hour urine samples as well as timed (morning, afternoon, evening and overnight) urine samples were randomly collected. The sodium intake were estimated by 4 published equations—Kawasaki, INTERSALT Tanaka and Sun’s. The consistencies between estimated sodium intake and real measured values of 24-hour urine sodium excretion were compared by Bland-Altman plots in each of the methods. Taking the variability of sodium excretion in different seasons into account, this study was conducted separately in summer (end of June 2017) and fall (end of November 2017). Results: The 24-h urinary sodium analysis result indicated an average daily sodium intake of 3043.0±1223.3mg in summer, and 3563.7±1370.0mg in the fall. Compared with autumn, the average daily reduction in sodium was about 520.7 mg. From the group level, the mean bias (estimated value - measured value) of the INTERSALT method with morning specimens (-39.7 mg ) was the smallest in summer. The mean bias of Tanaka method for prediction of morning specimens (-149.8 mg ) was the smallest in autumn. For the individual level, the correlation between 24-hour urinary sodium excretion and Sun’s methods was low, with a correlation coefficient of 0.406 in summer and 0.476 in the fall. Correlation coefficients between Kawasaki, INTERSALT, Tanaka methods and 24-hour urinary sodium excretion, respectively was in the range of 0.48-0.64. The correlation coefficient of Kawasaki method was the highest in summer (0.612) while that of Tanaka method with the afternoon specimens was the highest in the autumn (0.635). Conclusions: Estimation of sodium intakes among young adults using the 4 methods have varying degrees of bias and volatility in different times and seasons.
Expression of Catechol O methyl transferase (COMT) with the contrasting effects of 17β estradiol (E2): Implications for the mechanism of estrogen-induced ovarian carcinogenesis.
Authors: El-Etreby Nour Mohamed , Osman Eman Medhat , Badawy Nehal Abd El Latif El , Nour Hoda Abd El Hamid
Published: July 2020

Background
Epidemiological data show that induction of ovarian cancer is related to estrogen exposure and metabolism. In addition catechol metabolites of estrogen also contribute to carcinogenesis. O methylation by Catechol O methyl transferase (COMT) is a phase II metabolic inactivation pathway for catechol estrogens. The goal of the present study was to investigate the role of COMT level in ovarian carcinogenesis with the contrasting effects of 17 β estradiol level.
Subjects and methods
Our study was conducted on 80 subjects divided into 30 patients with malignant ovarian tumors ,30 patients with benign ovarian tumors and 20 healthy controls. Tissue and serum levels of COMT and 17 17 β estradiol were determined using ELISA
Results
According to our results COMT inhibition in the malignant group was detected as high as 7.1 pmol/L E2 in serum and 15.6 pmol/L E2 in tissue homogenate. This inhibition was absent in the benign group as high as 7.53 pmol/L E2 in serum and as high as 14.9 pmol/L E2 in tissue homogenates.
Conclusions
Our results provide evidence for the protective effect of COMT in benign ovaries against neoplastic transformation. This supports the notion that targeting the metabolism of estrogen can be an another way to reduce ovarian cancer risk.
Study on the Characteristics of Gut Microbiota in Chronic Hepatitis B Patients with Damp Heat Syndrome and Liver Depression and Spleen Deficiency Syndrome
Authors: Jiang Kaiping , Jiang Qunfang , Mo Xiaoai , Li Jianhong , Hu Hongtao , Huang Qinghua , Guo Wenqiang , Qiu Tengyu , Ren Jian , Zhang Lei , Xie Youqing , Huang Kaizhou
Published: July 2020

Background: To explore the potential biological characteristics of traditional Chinese medicine(TCM) syndromes in CHB patients is of great significance to improve the level of TCM treatment.This study was designed to explore the characteristics of gut microbiota in CHB patients with two most common TCM Syndromes.Methods: According to the diagnostic criteria of Western medicine, TCM and screening exclusion criteria, 65 cases of CHB patients with damp heat syndrome and 28 cases of CHB patients with liver depression and spleen deficiency syndrome were finally included in the study. All the basic information was gathered and the fresh fecal samples were collected for 16S rDNA sequencing. 16S rDNA of gut microbiota was sequenced using Illumina hiseq 2500 high-throughput sequencing platform.Based on the optimized sequence, OTU clustering analysis and taxonomic annotation were carried out. Results: The difference in relative abundance of gut microbiota was significant between damp heat syndrome and liver depression and spleen deficiency syndrome in CHB patients. Cyanobacteria was only found in damp heat syndrome.The relative abundance of Erysipelotrichia and Subdoligranulum were higher in liver depression and spleen deficiency syndrome,while the relative abundance of Rhodospirillales, Alphaproteobacteria,and Lachnospira were higher in the damp heat syndrome.LEfSe analysis showed that Lachnospira,Olsenella and Subdoligranulum had significant difference in species among the two TCM syndromes.Conclusions: The different characteristics of gut microbiota in the two TCM syndromes of CHB patients may play an important role in syndrome formation of TCM,which provides a new field of vision for the accurate diagnosis and treatment of TCM.
Upregulation of RBM24 Exacerbates Bladder Cancer Progression by Formatting Runx1t1/TCF4/miR-625-5p Feedback Loop
Authors: Yin Yue-Wei , Liu Kai-Long , Lu Bao-Sai , Li Wei , Niu Ya-Lin , Zhao Chen-Ming , Yang Zhan , Guo Ping-Ying , Qi Jin-Chun
Published: July 2020

Background: RNA-binding motif protein 24 (RBM24) acts as a multifunctional determinant of cell fate, proliferation, apoptosis, and differentiation during development through regulation of pre-mRNA splicing and mRNA stability. It is also implicated in carcinogenesis, but the functions of RBM24 in bladder cancer (BC) remains unclear.Methods: Cell viability was examined by colony forming and MTT assays. Real-time quantitative PCR (RT-qPCR) and western blot analysis were used to detect the protein and mRNA levels. Co-immunoprecipitation (CoIP) and proximity ligation assay (PLA) were used to determine the protein-protein interaction. Chromatin immunoprecipitation (ChIP), RNA immunoprecipitation (RIP), and oligo pull-down assays were used to verify DNA/RNA–protein interactions. Luciferase assay analysis was used to detect effects on transcription factor activity.Results: In the present study, we revealed that RBM24 was upregulated in BC tissues. Importantly, we found that higher level of RBM24 was correlated with poor prognosis in BC patients. Overexpression of RBM24 promoted while depletion of RBM24 inhibited BC cell proliferation in vivo and in vitro. Mechanically, RBM24 positively regulated Runx1t1 expression in BC cells by binding to and enhancing Runx1t1 mRNA stability. Runx1t1 in turn promoted RBM24 expression by interacting with TCF4. Furthermore, Runx1t1 in turn promoted RBM24 expression by interacting with the transcription factor TCF4 and depressing transcription of miR-625-5p, which directly targets and normally suppresses RBM24 expression. RBM24-regulated BC cells proliferation was moderated via the Runx1t1/TCF4/miR-625-5p feedback loop.Conclusions: In summary, these results indicate that a RBM24/Runx1t1/TCF4/miR-625-5p positive feedback loop plays a key role in BC oncogenesis. Disruption of this pathway may be a potential therapeutic strategy for BC treatment.
Expression of Cancer testis Antigens in Tumor-adjacent Normal Liver Predicts Post-resection Recurrence of Hepatocellular Carcinoma
Authors: Noordam Lisanne , Ge Zhouhong , Özturk Hadiye , Doukas Michail , Mancham Shanta , Boor Patrick P.C. , Carrascosa Lucia Campos , Zhou Guoying , Bosch Thierry P.P. van den , Pan Qiuwei , IJzermans Jan N.M. , Bruno Marco J. , Sprengers Dave , Kwekkeboom Jaap
Published: July 2020

Background: High recurrence rates after resection of hepatocellular cancer (HCC) with curative intent and lack of effective therapy for advanced disease impair clinical outcomes of HCC. Cancer/testis antigens (CTAs) are suitable targets for cancer immunotherapy if selectively expressed in tumor cells. The aims of this study were to establish a panel of CTAs that are frequently and selectively expressed in tumors of HCC-patients, and to investigate whether CTAs might be expressed in tumor-free liver tissues of HCC-patients.Methods: Surgically-resected tumor and paired tumor-free (TFL) tissues of HCC patients (n=100), healthy livers (n=21), and other healthy tissues (n=22 different tissues) were assessed for mRNA expression of 49 carefully selected CTAs by RT-qPCR. Protein expression of 5 CTAs was determined by immunohistochemistry (n=78).Results: Twelve CTAs were expressed at mRNA level in ≥10% of HCC-tumor tissues and not in healthy tissues except testis. In tumors, mRNA and protein of ≥ 1 CTA was expressed in 78% and 71% of HCC-patients, respectively. In TFL, CTA mRNA and protein expression was found in 45% and 30% of HCC-patients, respectively. Interestingly, CTA expression in TFL was an independent negative prognostic factor for HCC-recurrence and survival after tumor resection.Conclusions: We established a novel panel of 12 testis-restricted CTAs expressed in tumors of most HCC-patients, that can be safely used for immunotherapeutic targeting of HCC. The increased risk of HCC recurrence in patients with CTA expression in TFL suggests that CTA-expressing (pre-)malignant cells may be a source of HCC recurrence. Therefore, immunotherapeutic targeting of these antigens should be considered as adjuvant therapy to prevent HCC-recurrence after tumor resection. Lay summary:Expression of multiple defined cancer testis antigens in non-cancerous liver tissue is associated with significantly increased cancer-recurrence and worse patient survival after tumor resection. We propose that immunotherapeutic targeting of these antigens may prevent HCC recurrence after tumor resection.
Tanshinone IIA Inhibits Epithelial-to-mesenchymal Transition Through Regulating β-arrestin1 Mediated β-catenin Signaling Pathway in Colorectal Cancer
Authors: Song Qing , Yang Liu , Han Zhifen , Wu Xinnan , Li Ruixiao , Zhou Lihong , Liu Ningning , Sui Hua , Cai Jianfeng , Wang Yan , Ji Qing , Li Qi
Published: July 2020

Background: Tanshinone IIA (Tan IIA) is a major active ingredient extracted from Salvia miltiorrhiza, which has been proved to inhibit metastasis of various cancers including colorectal cancer (CRC). However, the detailed mechanisms of Tan IIA against CRC metastasis are not well explored. Epithelial-to-mesenchymal transition (EMT) exerts an important regulatory role in CRC metastasis, and our previous mechanism studies demonstrated that β-arrestin1 could regulate CRC EMT partly through β-catenin signaling pathway. Therefore, in this work we investigated whether Tan IIA could regulate CRC EMT through β-arrestin1-mediated β-catenin signaling pathway in vivo and in vitro.Methods: The nude mice tail vein metastasis model was established to observe the effect of Tan IIA on CRC lung metastasis in vivo. The lung metastasis was evaluated by living animal imaging and hemaoxylin-eosin staining. The migratory ability of CRC cells in vitro were measured by transwell and wound healing assays. The protein expression and cellular localization of β-arrestin1 and β-catenin were characterized by immunofluorescence staining and western blot. The β-catenin signaling pathway related proteins and EMT associated proteins in CRC cells were detected by western blot and immunohistochemistry. Results: Our results showed that Tan IIA inhibited the lung metastases of CRC cells in vivo and extended the survival time of nude mice. In vitro, Tan IIA increased the expression of E-cadherin, decreased the secretion of Snail, N-cadherin and Vimentin, thus suppressed EMT and the migratory ability of CRC cells. Further study found the mechanism involving in Tan IIA regulating EMT and metastasis, referring to the suppression of β-arrestin1 expression, reduction of β-catenin nuclear localization, thereby the decreased activity of β-catenin signaling. Conclusion: Our data revealed a new mechanism of Tan IIA on the suppression of EMT and metastasis in CRC via β-arrestin1-mediated β-catenin signaling pathway, and provided support for Tan IIA as anti-metastatic agents in CRC.
Extending the global-direction stencil with "face-area-weighted centroid" to unstructured finite volume discretization from integral form
Authors: Kong Lingfa , Dong Yidao , Liu Wei , Zhang Huaibao
Published: July 2020

Accuracy of unstructured finite volume discretization is greatly influenced by the gradient reconstruction. For the commonly used k-exact reconstruction method, the cell centroid is always chosen as the reference point to formulate the reconstructed function. But in some practical problems, such as the boundary layer, cells in this area are always set with high aspect ratio to improve the local field resolution, and if geometric centroid is still utilized for the spatial discretization, the severe grid skewness cannot be avoided, which is adverse to the numerical performance of unstructured finite volume solver. In previous work, we explored a novel global-direction stencil and combine it with face-area-weighted centroid on unstructured finite volume methods from differential form to realize the skewness reduction and a better reflection of flow anisotropy. Note, however, that the differential form is hard to achieve higher-order accuracy, and in order to set stage for the method promotion on higher-order numerical simulation, in this research, we demonstrate that it is also feasible to extend this novel method to the unstructured finite volume discretization in integral form. Numerical examples governed by linear convective, Euler and Laplacian equations are utilized to examine the correctness as well as effectiveness of this extension. Compared with traditional vertex-neighbor and face-neighbor stencils based on the geometric centroid, the grid skewness is almost eliminated and computational accuracy as well as convergence rate is greatly improved by the global-direction stencil with face-area-weighted centroid. As a result, on unstructured finite volume discretization from integral form, the method also has a better numerical performance.
Dosimetric comparison of helical tomotherapy, volume-modulated arc therapy, and fixed-field intensity-modulated radiation therapy in nasopharyngeal and cervical cancers
Authors: Yu Deyang , Lu Shan , Wang Lei , Hu Xueyuan , Li Xin , Bai Yanling , Zhang Yunyan , Yang Shanshan
Published: July 2020

Background: To compare the dosimetric parameters of different radiotherapy plans, helical tomotherapy(HT), volume-modulated arc therapy (VMAT), and fixed-field intensity-modulated radiation therapy (FF-IMRT) for nasopharyngeal carcinoma (NPC) and cervical cancer (CC).Methods: A total of 15 patients with NPC and 15 patients with CC were chosen for retrospective analysis and replanned for HT, VMAT, and FF-IMRT. The prescribed doses of the planning target were 2.12/69.96 Gy, 1.8/59.4 Gy for NPC and 1.8/45 Gy for CC, respectively. The dosimetric parameters of the planning target, organs at risk (OARs), and the efficiency of radiation delivery were assessed and compared using the paired-samples t-test.Results: Compared with VMAT and FF-IMRT, HT plans significantly improved the mean conformity index (CI) and homogeneity index (HI). For the OARs, the HT plans reduced the maximum doses of most organs, such as brainstem, spinal cord, and optic nerves in NPC, and significantly reduced the volume of the high-dose region in NPC and the V30 and V40 of small bowel, rectum, and bladder in CC. However, VMAT evidently reduced the treatment time and improved the efficiency of radiation delivery than HT.Conclusions: For NPC and CC, results showed that HT and VMAT possessed better homogeneity and conformity of the target and better sparing of OARs compared with the conventional FF-IMRT, and HT achieved the best effect. VMAT had the shortest radiation delivery time. The results of this study can provide guidance for the selection of appropriate radiation technologies for patients with NPC and CC who are undergoing concurrent chemoradiotherapy.
Proton re-irradiation of unresectable recurrent head and neck cancers
Authors: Gordon Konstantin , Gulidov Igor , Semenov Alexey , Golovanova Olga , Koryakin Sergey , Makeenkova Tatyana , Ivanov Sergey , Kaprin Andrey
Published: July 2020

Purpose: This study presents a retrospective analysis (efficacy and toxicity) of outcomes in patients with unresectable recurrence of previously irradiated head and neck cancers, treated with proton therapy.Methods: From November 2015 to January 2020, 30 patients with in-field recurrence of head and neck cancer, who were not suitable for surgery, due to medical contraindications, tumor localization or extent, received re-irradiation with intensity-modulated proton therapy (IMPT). Sites of retreatment included the aerodigestive tract (60%) and base of the skull (40%). The median total dose of prior radiotherapy was 55.0 Gy. The median time to the second course was 38 months. The median re-irradiated tumor volume was 158.1 cm3. Patients were treated with 2.0, 2.4 and 3.0 GyRBE per fraction, with a median EQD2 of 57.6 Gy (α/β=10). Radiation-induced toxicity was recorded according to the RTOG/EORTC criteria.Results: The 1- and 2-years LC, RFS, and OS were 52.6/21.0, 21.9/10.9 and 73.4/8.4%, respectively, with a median follow-up time of 21 months. The median overall survival was 16 months. Acute grade 3 toxicity was observed in 1 patient (3.3%). There were 5 late severe side effects (16.6%), with one death associated with re-irradiation.Conclusion: Re-irradiation with a proton beam can be considered a safe and efficient treatment even for a group of patients with unresectable recurrent H&N cancers.
Adiponectin and 8-epi-PGF2α as intermediate influence factors in weight reduction after legumes consumption: a 12-week randomized controlled trial
Authors: Han Youngmin , Lee Jong Ho , Kim Minjoo
Published: July 2020

Background and Aims:

The current nutritional intervention study was designed to determine the effect of legume on body weight in obese subjects.
Methods

Randomized controlled study of 12 weeks with 383 participants (body mass index ≥ 25 kg/m2) was enrolled for the study. The intervention program consisted of replacing 1/3 refined rice intake with legumes three times per day as a carbohydrate source in high fat diet group. In contrast, low fat diet group was recommended to eat as their usual diet.
Results

In high fat diet group, intake of energy and carbohydrate were lower, while the intake of fat and protein were higher. Mean weight loss at 12 weeks was 2.87 ± 0.21 kg and 0.17 ± 0.11 kg in the high fat diet group and low fat diet group, respectively, and was significantly different between groups (P < 0.001). HDL-cholesterol and adiponectin were increased, while glucose, insulin, triglyceride, HOMA-IR index, and 8-epi-PGF2α were decreased at 12 weeks in the high fat diet group compared with baseline.
Conclusions

The conclusion is that the consumption of legumes may accelerate weight loss accompanied by regulation of adiponectin and 8-epi-PGF2α in obese subjects. Also, increases in plasma adiponectin induced by a larger amount of weight loss may relate to greater activation of insulin resistance.
Trial registrations:

NCT04392882 (Registered 19 May 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04392882?cond=NCT04392882&draw=2&rank=1)
Clinicopathologic Significance of TROP2 and Phospho-TROP2 in Gastric Cancer
Authors: Kushiyama Shuhei , Yashiro Masakazu , Yamamoto Yurie , Sera Tomohiro , Sugimoto Atsushi , Nishimura Sadaaki , Togano Shingo , Kuroda Kenji , Yoshii Mami , Tamura Tatsuro , Toyokawa Takahiro , Tanaka Hiroaki , Muguruma Kazuya , Nakada Hiroshi , Ohira Masaichi
Published: July 2020

Background: Trophoblast cell-surface antigen 2 (TROP2) is a transmembrane glycoprotein expressed in epithelial cells. TROP2 overexpression has been reported to be correlated with malignant progression in most carcinomas, but TROP2 showed a tumor-suppressive function in some types of cancers. We currently developed a novel antibody against phospho-TROP2 (pTROP2). Since the function of TROP2 is controversial, we then aimed to clarify the clinicopathologic significance of TROP2 and pTROP2 expression in human gastric cancer (GC) in this study.Methods: We retrospectively analyzed the cases of 704 GC patients who underwent gastrectomy. The expressions of TROP2 and pTROP2 in each tumor were evaluated by immunohistochemistry. We analyzed the correlation between the GC patients' clinicopathologic features and the TROP2 and pTROP2 expression in their tumors.Results: Overexpression of TROP2 and that of pTROP2 were identified in 330 (46.9%) and 306 (43.5%) of the 704 GC patients, respectively. TROP2 overexpression was significantly correlated with the histological intestinal type, high tumor invasion depth (T3/T4), lymph node metastasis, lymphatic invasion, and venous invasion. In contrast, pTROP2 overexpression was significantly correlated with intestinal type, low tumor invasion depth (T1/2), no lymph node metastasis, and no lymphatic invasion. TROP2 overexpression was significantly associated with poorer overall survival (p<0.01, log rank), whereas pTROP2 overexpression was significantly associated with better overall survival (p<0.01, log rank).Conclusion: TROP2, but not pTROP2, might be associated with the metastatic ability of GC, resulting in poor prognoses for GC patients.
A Comparative Study of Chronic Subdural Hematoma in Patients With and Without Head Trauma
Authors: Ou Yunwei , Yu Xiaofan , Liu Xiaojuan , Jing Qian , Liu Baiyun , Liu Weiming
Published: July 2020

Background: Clinical features in chronic subdural hematomas (CSDH) patients with and without history of head trauma are not clear. Here, we seek to investigate difference of clinical characteristics in CSDH patients with and without head trauma.Methods: Retrospectively collected clinical characteristics of CSDH patients, who were performed exhaustive drainage strategy in burr-hole craniostomy from August 2011 to May 2019. Divided patients into trauma and no trauma groups. Chi-square test or t-test was used to analyze differences of clinical characteristics between two groups. Multiple linear regression analysis was performed to analyze relationships between clinical characteristics and reduction of hematoma cavity and length of hospital stay in CSDH patients with trauma.Results: 1,307 CSDH patients were collected. 805 patients occurred history of head trauma, 502 patients without it. Mean age of patients with trauma was 64.0 ± 16.1 years, while 61.5 ± 17.9 years in patients without trauma (p=0.010). More patients occurred hypertension in without trauma group than trauma group (40.2% vs 32.9%, p=0.007). Dizziness occurred in 29.2% patients with trauma, 23.1% in patients without trauma (p=0.016). Reduction of hematoma cavity after surgery in patients without trauma was less than ones with trauma (p=0.002). Length of hospital stay in patients with trauma was 7.9 ± 4.5 days, which was longer than patients without trauma (7.3 ± 3.7 days, p=0.016). No significantly different densities of hematoma on CT, complications, mortality, recurrence rate and outcome were found between two groups.Conclusion: Pathogenesis and some clinical characteristics occur differences in CSDH patients with and without trauma, but if we choose an optimal treatment method, such as our exhaustive drainage, and we can achieve the same effect.
Blood Metabolomic Profiling Predicts Postoperative Gastrointestinal Function Of Colorectal Surgical Patients Under The Guidance Of Goal-Directed Fluid Therapy
Authors: Xie Tao , Jiang Zhengyu , Wen Cen , Shen Du , Bian Jinjun , Liu Shanshan , Deng Xiaoming , Zha Yanping
Published: July 2020

Background: Postoperative gastrointestinal function influences postoperative recovery and hospital stay length for patients undergoing colorectal surgery. Goal-directed fluid therapy (GDFT) restricts fluid administration to an amount required to prevent dehydration. Although the fluid management of GDFT could decrease the incidence of postoperative complications in patients who undergo high-risk surgery, certain patients may not respond to GDFT. Thus, to achieve optimal treatment, identification of patients suitable for GDFT is necessary. Accordingly, in this study, we evaluated the predictive capacity of metabolomics profiling for postoperative recovery after surgery for colorectal cancer.Methods: Metabolomic profiling of 48 patients with colorectal cancer who underwent surgery was performed. Patients were divided into delayed- and enhanced-recovered groups based on gastrointestinal function within 72 hours, and the results of -omics analysis showed differential serum metabolites between the two groups of patients in the postanesthesia care unit 24 hours after surgery. A support vector machine model was applied to evaluate the curative effects of GDFT in different patients.Results: Four metabolites, oleamide, ubiquinone-1, acetylcholine, and oleic acid, were found to be highly associated with postoperative gastrointestinal function and could serve as potential biomarkers. Moreover, four pathways were found to be highly related to postoperative gastrointestinal recovery. Among these, the vitamin B6 metabolism pathway may be a common pathway for improving postoperative recovery in various diseases.Conclusion: Our findings proposed a novel method to predict postoperative recovery of gastrointestinal function based on metabolomic profiling and suggested the potential mechanisms contributing to gastrointestinal function after surgical resection of colorectal cancer under the fluid management of GDFT. Trial registration: Chinese Clinical Trial Registry, ChiCTR1800015899, Registered 27 April 2018, http://www.chictr.org.cn/showproj.aspx?proj=26623