bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing a New Tool for Determining the Difficulty of Laparoscopic Bariatric Surgery
Authors: Kabir Ali , Abbas Syed Imran , Moradi Marziyeh , Pazouki Abdolreza
Published: August 2020

Background: Recommendations for candidates of bariatric surgery are available but they seldom give guidance to help a specific patient. The purpose of this study is to develop a new tool for determining the difficulty of laparoscopic bariatric surgery before surgery. Methods: This was a mixed method study. After a comprehensive search, semi structure interview and focus group discussions (FGD) with surgeons, and operating room personnel and department, initial draft of the questionnaire was prepared. We used Delphi method to achieve a group consensus of national and international surgeons. Finally, after several times of review and modification of the designed questions, a final questionnaire was prepared. Content and face validity, reliability and internal consistency (using Cronbach’s alpha) were determined.Results: Final questionnaire has 31 questions consist of I. Factors related to surgeon: experience(four questions), and exposure(one question), II. Factors related to patient: anatomy(eleven questions), and comorbidities(two questions), patient’s position(one question), and others(one question), III. Factors related to instruments and operation room, quantity(two questions), and quality(one question), IV. Factors related to other personnel: anesthesia team(six questions), and other personnel(two questions). Cronbach’s alpha was 0.98 for the whole questionnaire and between 0.86 and 0.97 for the four subscales. Conclusions: The psychometrics analysis indicated that it is valid and reliable for determining the difficulty of laparoscopic bariatric surgery. We recommend using this questionnaire for different settings either need to know difficulty of a bariatric surgery before a surgery or as an independent variable in various research projects.
Investigating Association Between Participation in Co-curricular Activities and Student’s Academic Output at Secondary Level
Authors: Sarwat Yusra , Nadeem Hamid Ali , Sahar Namood-e
Published: August 2020

Educational experiences are necessary for ensuring student’s growth, skill development, and a successful life. The educational experiences are governed by the student’s learning outcomes. Co-curricular activities also form a significant part of student’s life and are found to play a vital role in the academic as well as personal growth and development of children. The present research studied the role of co-curricular activities in student’s learning outcomes at secondary level. The results support association between both variables as assessed by Murphy’s student survey questionnaire. Findings could help to provide evidence for importance of curricular activities to the policy makers so it can be made a part of student’s learning outcomes.﻿
Veno-venous-ECMO as a Platform to Evaluate Lung Lavage and Surfactant Replacement Therapy in an Animal Model of Severe ARDS
Authors: Qaqish Robert , Watanabe Yui , Galasso Marcos , Summers Cara , Ali Aadil , Takahashi Mamoru , Gazzalle Anajara , Liu Mingyao , Keshavjee Shaf , Cypel Marcelo , Sorbo Lorenzo Del
Published: August 2020

Background: There are limited therapeutic options directed at the underlying pathological processes in acute respiratory distress syndrome (ARDS). Experimental therapeutic strategies have targeted the protective systems that become deranged in ARDS such as surfactant. Although results of surfactant replacement therapy (SRT) in ARDS have been mixed, questions remain incompletely answered regarding timing and dosing strategies of surfactant. Furthermore, there are only few truly clinically relevant ARDS models in the literature. The primary aim of our study was to create a clinically relevant, reproducible model of severe ARDS requiring extracorporeal membrane oxygenation (ECMO). Secondly, we sought to use this model as a platform to evaluate a bronchoscopic intervention that involved saline lavage and SRT. Methods: Yorkshire pigs were tracheostomized and cannulated for veno-venous ECMO support, then subsequently given lung injury using gastric juice via bronchoscopy. Animals were randomized postinjury to either receive bronchoscopic saline lavage combined with SRT and recruitment maneuvers (treatment, n=5) or recruitment maneuvers alone (control, n=5) during ECMO.Results: PaO2/FiO2 after aspiration injury was 62.6 ±8 mmHg and 60.9 ±9.6 mmHg in the control and treatment group, respectively (p=0.95) satisfying criteria for severe ARDS. ECMO reversed the severe hypoxemia. After treatment with saline lavage and SRT during ECMO, lung physiologic and hemodynamic parameters were not significantly different between treatment and controls. Conclusions: A clinically relevant severe ARDS pig model requiring ECMO was established. Bronchoscopic saline lavage and SRT during ECMO did not provide a significant physiologic benefit compared to controls.
Implementing a mixed methods Human Factors approach to design and rehearse management of unplanned extubation in critically ill adult patients
Authors: Lang Alexandra Rosewall , Baxendale Bryn , Atkinson Sarah , Velzen Jeena , Blanks Thomas , Ansari Umair , Kane Mark , Miles Giulia , DeBeer Thearina , Gill Steven
Published: August 2020

Background: Unplanned extubation (UE), the unintentional dislodgement of a patient’s artificial airway; indwelling endotracheal tube or tracheostomy, occurs infrequently in the critical care setting but is a high risk incident and requires appropriately skilled staff and clear management plans to manage and ensure a positive outcome for the patient. Within the current guidance on management of UE, there is superficial consideration of the systems view and limited practical advice about the integration of systems thinking into management of these situations. Method: This paper reports the findings of a multidisciplinary Human Factors (HF) study to understand ‘work as done’ in being prepared and responding to UE in practice. Multiple methods were triangulated to take a systems perspective on these situations. The methods included development of a hierarchical task analysis (HTA), 21 expert interviews, 50 equipment familiarity audit surveys and three in situ simulation exercises. Results: The study identified key areas of focus for redesign of environment and accessibility of equipment and organisation of resources. It was established that difficulties in identifying individual competency and team skill mix appropriate to the scenario requirements undermined people’s non-technical skills and that decision making could be negatively impacted as a result. Conclusion: The HF approach has provided the critical care team with an improved understanding of the work involved in being prepared or responding to UE and a visual task breakdown which can be used for identifying and testing new ways of working, different environments, technological interventions and using simulation to rehearse for performance. The findings will inform future changes to practice, design of work and the development of a mastery learning programme to support individual and team capabilities in responding to UE so that staff are able to consider this infrequent scenario in context of the wider system.
Treatment of sepsis-related Acute Respiratory Distress Syndrome with Vasoactive Intestinal Peptide
Authors: Youssef Jihad G. , Said Sami , Youssef George , Javitt Matthew J. , Javitt Jonathan C
Published: August 2020

Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsisMethods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery.Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients.Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.Registration: This clinical trial was registered with www.clinicaltrials.gov under NCT00004494. Trial was registered before the first patient was enrolled.
Multicenter, Open-Label, Two-Arm, Pilot Trial for Safety Reduction of Basal Insulin Dose Combined with SGLT2 Inhibitor in Type 1 Diabetes Mellitus: Study Protocol for RISING-STAR.
Authors: Hamaguchi Masahide , Hashimoto Yoshitaka , Tanaka Toru , Hasegawa Goji , Ishii Michiyo , Okada Hiroshi , Mitsuhashi Kazuteru , Kitagawa Noriyuki , Ushigome Emi , Yamazaki Masahiro , Fukui Michiaki
Published: August 2020

Background: SGLT2 inhibitor combined with insulin therapy is a novel therapy for patients with type 1 diabetes mellitus. Without the reduction of basal insulin, hypoglycemia could occur frequently in this therapy. But diabetic ketoacidosis is an undesirable adverse effect in case with basal insulin reduction. The aim of this study is to explore whether the reduction of the basal insulin dose combined with SGLT2 inhibitor in patients with type 1 diabetes mellitus can reduce the frequency of hypoglycemia and be used safely. We hypothesized that with an adequate basal insulin dose, the frequency of hypoglycemia is higher if the basal insulin dose is not reduced when combined with SGLT2 inhibitor.Methods and Analysis: The study has a two-arm design; 60 subjects with type 1 diabetes mellitus are being recruited from 7 hospitals. The basal insulin dose before the start of the SGLT2 inhibitor combination therapy is the reference. Study subjects are stratified into two groups based on the ratio of basal insulin daily dose (Basal) to total daily insulin dose (TDD). The subjects are instructed to reduce the basal insulin dose by 10% or 0% for Basal to TDD ratio of <0.4 and > 0.4, respectively.The primary outcome is the frequency of hypoglycemia per day during the intervention period (administration of SGLT2 inhibitor) as determined by self-monitoring of blood glucose (SMBG). The secondary outcome is the frequency of ketosis before and after the intervention. Discussion: 10% basal insulin reduction could reduce hypoglycemia as well as could not increase ketosis in case that the ratio of basal insulin daily dose to total daily insulin dose is 0.4 or higher, which improve the efficacy and safety of SGLT2 inhibitor treatment patients with type 1 diabetes mellitus.Ethics and Dissemination: The study was approved by Kyoto Prefectural University of Medicine, Clinical Research Review Board (CRB5180001). The results will be disseminated through presentations at appropriate conferences and meetings, and published in peer-reviewed journals.Trial registration: Registered with Japan Registry of Clinical Trials (jRCTs051190114) on 2 March, 2020. https://rctportal.niph.go.jp/detail/jr?trial_id=jRCTs051190114)
Development of an Automated Drug Delivery System for an Ultra-Short-acting β-Blocker, Landiolol, to Stably Reduce Myocardial Oxygen Consumption without Inducing Circulatory Collapse in a Canine Heart Failure Model
Authors: Nishikawa Takuya , Uemura Kazunori , Hayama Yohsuke , Kawada Toru , Saku Keita , Sugimachi Masaru
Published: August 2020

Background: Beta-blockers are well known to reduce myocardial oxygen consumption (MVO2) and improve the prognosis of heart failure (HF) patients. Although the use of β-blockers in the acute phase of HF can be expected to be beneficial, the negative chronotropic and inotropic effects limit their use due to the risk of circulatory collapse (cardiogenic shock, and/or pulmonary congestion). A safe method to administer β-blockers in the acute phase of HF is in great need. In this study, we developed an automated drug delivery system that controls the infusion of landiolol, an ultra-short-acting β-blocker, while preventing circulatory collapse. Method: We designed a system that simultaneously regulates cardiac function and volume status to control haemodynamics. The system monitors arterial pressure (AP), left atrial pressure (PLA), right atrial pressure, and cardiac output. Using negative feedback of haemodynamics, the system controls mean AP and mean PLA by administering landiolol, dextran, and furosemide. We applied the system for 60 min to 5 mongrel dogs with rapid pacing-induced HF, and assessed haemodynamics, MVO2 and lactate.Results: In all dogs, the system successfully adjusted delivery of the drugs resulting in accurate control of mean AP and mean PLA. From 15 to 60 min after the system was activated, median of absolute performance error (index of precision of control) was small for mean AP (median [interquartile range], 2.5 [2.1 – 3.7] %) and mean PLA (4.1 [1.8 – 6.2] %). Although the system decreased mean AP compared to baseline, mean and systolic AP were maintained not lower than 70 and 100 mmHg, respectively, and lactate did not increase. Furthermore, the system significantly decreased PLA and MVO2 (3.6 [3.3 – 4.0] to 2.7 [2.5 – 3.3] ml·min-1·100 g left ventricular weight-1) compared to baseline. Consequently, the automated drug delivery system successfully reduced MVO2 without inducing circulatory collapse.Conclusion: We developed an automated landiolol delivery system that achieved safe administration of landiolol in a canine model of acute HF. The system controlled AP and PLA accurately and stably, and reduced MVO2. With further development for clinical application, the automated drug delivery system may be the key tool to improve management of patients with HF.
Echocardiographic patterns in critically ill COVID-19 patients.
Authors: Vieillard-Baron Antoine , Charron Cyril , Tran Ségolène , Godement Matthieu , Repessé Xavier , Haruel Pierre-Alexandre , Prigent Amélie , Castro Samuel , Girodias Lola , Charbit Emilie , Isnard Foucault , Saleh Mohamed , Bouferrache Koceila , Page Bernard , Jouffroy Romain , Geri Guillaume
Published: August 2020

Background: Need for catecholamines is frequent in COVID-19 patients, but the main echocardiographic patterns are unknown. The objective was to report the main echo patterns in critically-ill COVID-19 patients. Methods: Observational and descriptive study in consecutive COVID-19 patients admitted to the ICU between March 12 and May 8, 2020. Systematic critical care echocardiography (CCE) was performed and retrospectively analyzed off-line. Echo values are reported in the overall population and in patients who required catecholamine infusion during the first 2 days following admission (D1-2) or afterwards until day 7 (D3-7). Results: Of the 79 patients (78% male; median age 63 [56-71]; body mass index 29 [26-30]) included, 90% had at least 1 comorbidity. PaO2/FiO2 at admission was 85 [67-162] mmHg. 53% of patients were mechanically ventilated. ICU length of stay was 9 [5-16] days and mortality 34%. 134 echocardiographic studies were performed during the first week in 65 patients. Pulmonary artery acceleration time was decreased (77 [65-97] ms), suggesting pulmonary hypertension. All 39 patients (49%) who required catecholamine infusion underwent CCE and 25.6% had left ventricular (LV) systolic dysfunction, 28.2% acute cor pulmonale (ACP), 7.7% hypovolemia, and 38.5% vasoplegia. Modification of echo patterns was observed at D3-7, with less LV systolic dysfunction and more ACP, which was the most frequent pattern. Computed tomography pulmonary angiography in 6 patients with ACP indicated intrapulmonary thrombus in 4. Conclusion: Different echocardiographic patterns were observed during the first week following ICU admission in COVID-19 patients. ACP was frequent and often related to thrombus in the pulmonary circulation.
Markers of NETosis and DAMPs are altered in critically ill COVID-19 patients
Authors: Huckriede Joram , Anderberg Sara Bülow , Morales Albert , Vries Femke de , Hultström Michael , Bergqvist Anders , Ortiz José T. , Sels Jan Willem , Wichapong Kanin , Lipcsey Miklos , Poll Marcel van de , Larsson Anders , Luther Tomas , Reutelingsperger Chris , Frutos Pablo Garcia de , Frithiof Robert , Nicolaes Gerry A.F.
Published: August 2020

Background Coronavirus disease 19 (COVID-19) is known to present with disease severities of varying degree. In its most severe form, infection may lead to respiratory failure and multi-organ dysfunction. Here we study the levels of extracellular histone H3 (H3), neutrophil elastase (NE) and cfDNA in relation to other plasma parameters, including the immune modulators GAS6 and AXL, ICU scoring systems and mortality in patients with severe COVID-19.Methods We measured plasma H3, NE, cfDNA, GAS6 and AXL concentration in plasma of 83 COVID-19-positive and 11 COVID-19-negative patients at admission to the Intensive Care Unit (ICU) at the Uppsala University hospital, a tertiary hospital in Sweden and a total of 333 samples obtained from these patients during the ICU-stay. We determined their correlation with disease severity, organ failure, mortality and other blood parameters.Results H3, NE, cfDNA, GAS6 and AXL were increased in plasma of COVID-19 patients compared to controls. cfDNA and GAS6 decreased in time in in patients surviving to 30 days post ICU admission. Plasma H3 was a common feature of COVID-19 patients, detected in 40% of the patients at ICU admission. Although these measures were not predictive of the final outcome of the disease, they correlated well with parameters of tissue damage (H3 and cfDNA) and neutrophil counts (NE). A subset of samples displayed H3 processing, possibly due to proteolysis.Conclusions Elevated H3 and cfDNA levels in COVID-19 patients illustrate the severity of the cellular damage observed in critically ill COVID-19 patients. The increase in NE indicates the important role of neutrophil response and the process of NETosis in the disease. GAS6 appears as part of an early activated mechanism of response in Covid-19.
Construction of a Novel 3-lncRNA Risk Score System for the Prognostic Prediction of Triple-Negative Breast Cancer
Authors: Yuan Chao , Yuan Hongjun , Chen Li , Sheng Miaomiao , Tang Wenru
Published: August 2020

Background：Triple-negative breast cancer (TNBC) is an essential type of breast cancer (BC). Compared with other molecular subtypes of BC, TNBC has the features of fast tumor increase, quick recurrence and natural metastasis. It is more urgent to establish a comprehensive evaluation system containing multiple biomarkers than single parameter.Methods：We conduct a bioinformatics analysis on 13 BC expression datasets from the Gene Expression Omnibus (GEO), which covered 2950 samples. We took 3484 genes with a more significant difference between TNBC and normal-like candidate genes for weighted correlation network analysis (WGCNA). A total of 54 genes were chosen as hub genes with great connectivity with the TNBC significant module. Based on The Cancer Genome Atlas (TCGA) data, we identify the best prognostic three lncRNA. Multivariate Cox regression was used to construct a 3-lncRNA risk score model. We evaluated prognostic capacity using time-dependent subject operating characteristics (ROC) and Kaplan-Meier (KM) survival analysis. The predictive power of the model was demonstrated by the time-dependent ROC spline and Kaplan-Meier spline. At the same time, it also shows good predictive ability in the validation set. Ultimately, Functional enrichment analysis of hub genes and three lncRNAs were offered to advise the possible biological pathways. Results：The construct LNC00337, DEPCE-AS1, DDX11-AS1 multi-factor risk scoring model was meaningfully associated with the prognosis of TNBC patients. Through survival analysis, the risk score efficiently divided the patients into high-risk groups with poor overall survival. The time-dependent ROC curve revealed that the model presented robust in predicting survival over the first 3 years. The validity of the model in the validation set is also verified. Finally, functional enrichment analysis proposed some biological pathways that may be correlated to the tumor. Conclusions：In our study, we established a lncRNA-based model to prognosticate the prediction of TNBC, which might afford a strong prognosis estimate tool to help therapy policy-making in the clinic.
Analysis of prognostic factors after Surgery for Stage IA Invasive Lung Adenocarcinoma
Authors: Chen Wenshu , Ding Yun , You Peilin , Tu Pengjie , Huang Jianyuan , Pan Xiaojie
Published: August 2020

Background

Lung cancer is one of the most common malignant tumors with poor prognosis. Even for stage IA, many cases relapsed after completed resection. In the era of precision medicine, it is of great significance to determine the risk factors for postoperative recurrence or death in stage IA invasive lung adenocarcinoma.
Methods

The data of patients with pathological stage IA invasive lung adenocarcinoma underwent complete resection from June 2012 to December 2016 in Fujian Provincial Hospital were collected and retrospectively analyzed. Recurrence-free survival (RFS) was estimated by the Kaplan-Meier method and compared with the log-rank test. The Cox proportional risk model was used to analyze the factors affecting the RFS.
Results

A total of 210 patients were enrolled in the study. During the follow-up period, 14 (6.7%) patients recurred. Univariate survival analysis showed that predominant pathological subtype, micropapillary/solid pattern, stage T1b and lymphovascular invasion were correlated with RFS (P < 0.05). Cox multivariate analysis showed that the micropapillary/solid pattern was associated with RFS (P < 0.01). Patients with micropapillary/solid pattern had a worse 5-year RFS rate than those without micropapillary/solid pattern (82.3% versus 96.7%, P < 0.001).
Conclusion

Pathological subtype is a prognostic factor for patients with pathological stage IA invasive lung adenocarcinoma. Patients with micropapillary/solid pattern have a poor prognosis. Lymphovascular invasion and stage T1b are also correlated with poor RFS. These findings may serve as reliable predictive factors for long-term prognostic, and provide theory evidence for the choice of postoperative adjuvant therapy for patients with lung adenocarcinoma in stage IA.
Who is Left Behind? Altruism of Giving, Happiness and Mental Health during the Covid-19 Period in the UK
Authors: Giovanis Eleftherios , Ozdamar Oznur
Published: August 2020

The UK government has decided to implement lockdown measures in the end of March 2020 as a response to the outbreak and spread of the Covid-19 pandemic. As a consequence, households have experienced job losses and a significant drop in their finances and living standards. During these unprecedented and difficult times, people provide financial assistance to those who are in need and have to cope with falls in their living standards. In this study we are interested to investigate the subjective well-being (SWB), which is expressed by mental health and components of general happiness, of the givers rather than of receivers. We apply a difference-in-differences (DiD) framework to investigate the impact of altruism on the givers’ SWB in the UK. Altruism is denoted by transfers made to adult children, parents, siblings, and friends. Using the DiD estimator and the estimated coefficient of the household income we calculate the implicit willingness-to-pay (WTP) for altruism. We perform various regressions by gender and racial-ethnic background using data from the UK Household Longitudinal Study (UKHLS). The analysis shows that altruistic behaviours impact different domains of SWB between men and women, as well as, among people with different racial-ethnic background.
Combating Osteoporosis and Obesity With Green Tea Polyphenols: Molecular Switching of Osteogenesis Versus Adipogenesis During Early Differentiation of Human Adipose Tissue-Derived Stem Cells
Authors: Lao Weiguo , Tan Yi , Johnson Michael , Li Yan , Lin Yiguang , Xiao Linda , Qu Xianqin
Published: August 2020

Background: Osteoporosis is a metabolic disease affecting the bone mineral density associated with increased adiposity in the aging population with obesity. The nutrients to control osteoblast and adipocyte differentiation from a common precursor, the pluripotent mesenchymal stem cell (MSC), may be a promising therapy for osteoporosis. Previously, we have shown that green tea polyphenols (GTP) exert anti-adipogenic effects on preadipocyte proliferation. In the present study, we investigated regulatory effects of GTP on osteogenesis and adipogenesis during early differentiation of human adipose tissue-derived stem cells (hADSCs). Methods: GTP at concentrations of 1 and 10 µg/ml was incubated with primary hADSCs in presence or absence of pioglitazone (100 µmol) during hADSCs differentiation. Adipogenesis of hADSCs was determined by Oil Red O staining and measurement of the cellular triglyceride synthesis in mature adipocyte. Alkaline phosphatase (ALP) assay and the measurement of intracellular calcium were utilized to determine osteoporosis of hADSCs. Immunofluorescence staining and qRT-PCR were employed to detect PPARγ-CEBPA regulated adipogenic pathway and the RUNX2-BMP2 mediated osteogenic pathway. Results: GTP treatment significantly decreased lipid accumulation and the cellular triglyceride synthesis in mature adipocytes and attenuated pioglitazone-induced adipogenesis in a dose-dependent manner. GTP downregulated protein and mRNA expression of Pparγ and attenuated pioglitazone-stimulated Cebpa expression in mature adipocytes. Concurrently, measurements of calcium content and ALP activity showed that GTP treatment significantly enhanced hADSCs differentiation into osteocytes compared with the control and pioglitazone-treated cells. Meanwhile, GTP upregulated protein and mRNA expression of RunX2 and Bmp2 compared to the control and GTP at 10 µg/mL significantly attenuated the decreased mRNA expression of Runx2 and Bmp2 by pioglitazone. Conclusions: The present study demonstrated that GTP possess a greater ability to facilitate osteogenesis and simultaneously inhibit hADSCs differentiation into the adipogenic lineage through upregulating the RUNX2-BMP2 mediated osteogenic pathway and suppressing PPARγ-induced signaling of adipogenesis. The findings of this study highlight that GTP may be a therapeutic intervention to combat osteoporosis associated obesity.
Roquin1 Suppresses Breast Cancer Growth by Inducing Cell Cycle Arrest via Selectively Destabilizing Cell Cycle–Promoting Gene mRNAs
Authors: Lu Wenbao , Zhou Meicen , Wang Bing , Liu Xueting , Li Bingwei
Published: August 2020

Background: Dysregulation of cell cycle progression is one of the common features of human cancer cells, however, its mechanism remains unclear. This study aims to clarify the role and the underlying mechanisms of Roquin1 in cell cycle arrest induction in breast cancer.Methods: Public cancer databases were analyzed to identify the expression pattern of Roquin1 in human breast cancers and the significant association with patient survival. Quantitative real-time PCR and western blots were performed to detect the expression of Roquin1 in breast cancer samples and cell lines. Cell counting, MTT assay, flow cytometry, and in vivo study were conducted to investigate the effects of Roquin1 on cell proliferation, cell cycle progression and tumor progression. RNA-sequencing was applied to identify the differential genes and pathways regulated by Roquin1. RNA immunoprecipitation assay, luciferase reporter assay, mRNA half-life detection, RNA affinity binding assay, and RIP-ChIP were used to explore the molecular mechanisms of Roquin1.Results: We showed that Roquin1 expression in breast cancer tissues and cell lines was inhibited, and the reduction in Roquin1 expression was associated with poor overall survival and relapse free survival of patients with breast cancer. Roquin1 overexpression inhibited breast cancer cell proliferation and induced G1/S cell cycle arrest without causing significant apoptosis. In contrast, knockdown of Roquin1 promoted breast cancer cell growth and cycle progression. Moreover, in vivo induction of Roquin1 by adenovirus significantly suppressed breast tumor growth and metastasis. Mechanistically, Roquin1 selectively destabilizing cell cycle–promoting genes, including Cyclin D1, Cyclin E1, cyclin dependent kinase 6 (CDK6) and minichromosome maintenance 2 (MCM2) through targeting the stem–loop structure in the 3’untranslated region (3’UTR) of mRNAs via its ROQ domain, leading to the downregulation of cell cycle–promoting mRNAs.Conclusions: Our findings demonstrated that Roquin1 was a novel breast tumor suppressor and could induce G1/S cell cycle arrest by selectively downregulating the expression of cell cycle–promoting genes, which might as a potential molecular target for breast cancer treatment.
A Urine-Based Liquid Biopsy Method for Detection of Upper Tract Urinary Carcinoma
Authors: Xu Yansheng , Ma Xin , Ai Xing , Gao Jiangping , Liang Yiming , Zhang Qin , Ma Tonghui , Mao Kaisheng , Zheng Qiaosong , Wang Sizhen , Jiao Yuchen , Zhang Xu , Li Hongzhao
Published: August 2020

Background: Conventional clinical detection methods such as CT, urine cytology, and ureteroscopy display low sensitivity and/or are invasive in the diagnosis of upper tract urinary carcinoma (UTUC), a factor precluding their use. Previous studies on urine biopsy have not shown satisfactory sensitivity and specificity in the application of both gene mutation or gene methylation panels. Therefore, these unfavorable factors call for an urgent need for a sensitive and non-invasive method for the diagnosis of UTUC.Methods: In this study, a total of 161 hematuria patients were enrolled with (n=69) or without (n=92) UTUC. High-throughput sequencing of 17 genes and methylation analysis for ONECUT2 CpG sites were combined as a liquid biopsy test panel. Further, a logistic regression prediction model that contained several significant features was used to evaluate the risk of UTUC in these patients.Results: In total, 86 UTUC- and 64 UTUC+ case samples were enrolled for the analysis. A logistic regression analysis of significant features including age, the mutation status of TERT promoter and ONECUT2 methylation level resulted inan optimal model with a sensitivity of 94.0%, a specificity of 93.1%, the positive predictive value of 92.2% and a negative predictive value of 94.7%. Notably, the area under the curve (AUC) was 0.957 in the training dataset while internal validation produced an AUC of 0.962. It is worth noting that during follow-up, a patient diagnosed with ureteral inflammation at the time of diagnosis exhibiting both positive mutation and methylation test results was diagnosed with ureteral carcinoma 17 months after his enrollment.Conclusion: This work utilized the epigenetic biomarker ONECUT2 for the first time in the detection of UTUC and discovered its superior performance. To improve its sensitivity, we combined the biomarker with a high-throughput sequencing of 17 genes test. It was found that the selected logistic regression model diagnosed with ureteral cancerThetcan evaluate upper tract urinary carcinoma risk of patients with hematuria and outperform other existing panels in providing clinical recommendations for the diagnosis of UTUC. Moreover, its high negative predictive value is conducive to rule to exclude patients without UTUC.
Endoscopic Resection Versus Surgical Resection for Gastric Neuroendocrine Neoplasms Without Distant Metastasis
Authors: Shi Huiying , Yao Hailing , Tian Shuxin , Jiang Chen , Zhang Qin , Lin Rong
Published: August 2020

Background: Resection is the main method for treating gastric neuroendocrine neoplasms (g-NENs). However, the threshold for tumor size needs to be removed, and the prognostic difference between the endoscopic and surgical resection groups remains unclear.

Methods: In this study, 929 g-NENs patients without distant metastasis were collected and analyzed (857 patients from the SEER database, 72 patients from Wuhan Union Hospital or the First Affiliated Hospital of Shihezi University).

Results: Overall, for g-NENs without distant metastasis, the resected group had a better prognosis than the unresected group ( p =0.0019). For tumor >2cm, the resection group had a better prognosis than the unresected group ( p =0.0002), but there was no significant difference in survival between the endoscopic and surgical resection group ( p >0.05). For tumor <1cm or 1-2cm, there was no significant difference in survival between the resected group and the unresected group, and there was no significant difference in survival between the endoscopic resection group and the surgical resection group ( p >0.05). Furthermore, for g-NENs confined to in-situ and T1, or with well-differentiated morphology or w/wo lymph node metastasis without distant metastasis, there was no significant difference in prognosis between the endoscopic resection group and the surgical resection group ( p >0.05).

Conclusions: Resection can significantly improve the prognosis of g-NENs patients without distant metastasis, and 2cm can be used as a resection threshold. For g-NENs within the size of endoscopic resection, which localized in situ and T1, or with well-differentiated morphology, or w/wo lymph node metastasis without distant metastasis, endoscopic resection is feasible.
Referrals to a Pediatric Emergency Department of a Tertiary Care Teaching Hospital Before and After Introduction of a Referral Education Module - A Quality Improvement Study
Authors: Ezhumalai Gopalakrishnan , Jayashree Muralidharan , Nallasamy Karthi , Bansal Arun , Bharti Bhavneet
Published: August 2020

Background: Provision of timely care to critically ill children is essential for good outcome. Referral from smaller peripheral hospitals to higher centers for intensive care is common. However, lack of an organized referral and feedback system compromises optimal care. We studied the quality of referral letters coming to our Emergency Department (ED) with respect to their demography, association with severity of illness and mortality before and after referral education. Methods: Our study was completed in three phases in the Pediatric ED; Pre-intervention, Intervention and Post intervention phases. Quality of referral letter was matched with a quality checklist proforma and graded as ‘good’, ‘fair’ and ‘poor’ if it scored >7, 5 –7 and < 5 points respectively. A peer reviewed referral education module was prepared using case studies, expert opinions, and lacunae observed in the first phase and administered to health care providers (HCP’s) of referring hospitals. Quality of referral letter was compared between pre and post intervention phases.Results: Most referrals belonged to the neighboring states of Punjab (48.2%) and Haryana (22.4%). Major referring hospitals were from public sector (80.9%), of which the teaching hospitals topped the list (53.6%). Government run ambulance services (85.5%) was commonest mode of transport used and need for a PICU bed and/or mechanical ventilation (50.4%) was the commonest reason for referral. The post intervention phase saw a significant decline in the proportion of poor (93.2 vs.78.2%; p=0.001) and a significant increase in the proportion of fair (6.1 vs 18%; p=0.001) and good referral letters (0.7 vs 18%; p=0.001). The proportion of children with physiological decompensation at triage had reduced significantly in the post intervention phase [513 out of 1403 (36.5%) vs. 310 out of 957 (32.3%); p= 0.001]. Conclusion: Referral education had significantly improved the quality of referral letters. Proportion of children with physiological decompensation at triage had decreased significantly after referral module. This change suggests sensitization of the peripheral hospitals towards a better referral process. Continued multifaceted approach will be required for sustained and increased benefits.
Topological holography: The example of the D2-D4 brane system
Authors: Ishtiaque Nafiz , Moosavian Seyed Faroogh , Zhou Yehao
Published: August 2020

We propose a toy model for holographic duality. The model is
constructed by embedding a stack of NN
D2-branes and KK
D4-branes (with one dimensional intersection) in a 6d topological string
theory. The world-volume theory on the D2-branes (resp. D4-branes) is 2d
BF theory (resp. 4D Chern-Simons theory) with
\mathrm{GL}_NGLN
(resp. \mathrm{GL}_KGLK)
gauge group. We propose that in the large NN
limit the BF theory on \mathbb{R}^2ℝ2
is dual to the closed string theory on \mathbb{R}^2 \times \mathbb{R}_+ \times S^3ℝ2×ℝ+×S3
with the Chern-Simons defect on \mathbb{R} \times \mathbb{R}_+ \times S^2ℝ×ℝ+×S2.
As a check for the duality we compute the operator algebra in the BF
theory, along the D2-D4 intersection – the algebra is the Yangian of
\mathfrak{gl}_K𝔤𝔩K.
We then compute the same algebra, in the guise of a scattering algebra,
using Witten diagrams in the Chern-Simons theory. Our computations of
the algebras are exact (valid at all loops). Finally, we propose a
physical string theory construction of this duality using D3-D5 brane
configuration in type IIB – using supersymmetric twist and
\OmegaΩ-deformation.
Assessment of Effects of Solvents on Cocrystallization by Computational Simulation Approach
Authors: Dhibar Manami , Chakraborty Santanu , Basak Souvik
Published: August 2020

Purpose:

The sole purpose of this study is to improve the solubility and dissolution of
telmisartan by cocrystallization technique and apply a computational simulation approach to assess the
nature of chemical interactions between telmisartan and coformer as well as the solvent contribution to
the molecules for furnishing cocrystallization.

Methods:

The effects of various concentrations of coformer i.e. oxalic acid on physicochemical parameters
and drug release were investigated.

Results:

Solubility studies suggested that cocrystallization technique with oxalic acid helps to increase
the solubility of pure telmisartan of about 7 folds and drug release study revealed that telmisartan-oxalic
acid cocrystals showed greater dissolution as compared to pure telmisartan. SEM study suggested that
prepared telmisartan cocrystals showed rhomboid-shaped crystals with sharp edges and smooth surface.
FTIR study revealed that shifting in the vibrational frequencies of C=O group of telmisartan in telmisartan-
oxalic acid cocrystal indicates the formation of supra molecular hetero synthon of the cocrystal. DSC
and XRD studies confirmed the formation of telmisartan-oxalic acid cocrystals. Computational simulation
approach revealed that telmisartan and oxalic acid can interact with each other in the presence of
methanol and water where oxalic acid can form interactions principally with the others. The interactions,
thereof, may form several associations or bondings in between the drug and carrier modifying the planarity,
bond energy, bond angles of both which subsequently lead to cocrystallization.

Conclusion:

So, the present research concluded that prepared telmisartan-oxalic acid cocrystal is a successful
application of crystal engineering approach to improve the physicochemical properties as well as
to enhance the solubility and dissolution of telmisartan.
Whole Milk and Full-Fat Dairy Products and Hypertensive Risks
Authors: Roy Stephen J. , Tanaka Hirofumi
Published: August 2020

Lifestyle modifications in the form of diet and exercise are generally the first-line approach
to reduce hypertensive risk and overall cardiovascular disease (CVD) risk. Accumulating research
evidence has revealed that consumption of non- and low-fat dairy products incorporated into
the routine diet is an effective means to reduce elevated blood pressure and improve vascular
functions. However, the idea of incorporating whole-fat or full-fat dairy products in the normal routine
diet as a strategy to reduce CVD risk has been met with controversy. The aim of this review
was to evaluate both sides of the argument surrounding saturated fat intake and CVD risk from the
standpoint of dairy intake. Throughout the review, we examined observational studies on relationships
between CVD risk and dairy consumption, dietary intervention studies using non-fat and
whole-fat dairy, and mechanistic studies investigating physiological mechanisms of saturated fat intake
that may help to explain increases in cardiovascular disease risk. Currently available data have
demonstrated that whole-fat dairy is unlikely to augment hypertensive risk when added to the normal
routine diet but may negatively impact CVD risk. In conclusion, whole-fat dairy may not be a
recommended alternative to non- or low-fat dairy products as a mean to reduce hypertensive or
overall CVD risk.
Molecular Docking, Drug-Likeness and ADMET Analysis, Application of
Density Functional Theory (DFT) and Molecular Dynamics (MD) Simulation
to the Phytochemicals from Withania Somnifera as Potential Antagonists
of Estrogen Receptor Alpha (ER- α)
Authors: Hossain Alamgir
Published: August 2020

Introduction:

Breast cancer is one of the leading causes of death of women every year. Estrogen receptor alpha (ER-α) is an important pathway that is responsible for the development of breast cancer. Tamoxifen is the most commonly used to treat breast cancer. But the main drawback of using the drug is that it increases the risk of uterine cancer, stroke,and pulmonary embolism.

Methods:

In this research, the in-silico approach was followed to get the anticancer agent from Withania somnifera as the root extract of the plant is active against breast cancer. For this, 15 bioactive molecules were subjected to molecular docking and got 9 molecules comparing the consensus binding affinity of H3B-9224.

Results:

After rescoring, drug-likeness analysis, and ADMET analysis of the molecules were done and 3 molecules remained. These 3 molecules showed good ADMET properties which arecrucial requirements in the drug discovery process. Their activity was checked by applying density functional theory (DFT) and all of them showed good reactivity. Their binding interaction was also evaluated.

Conclusion:

Finally, the stability of those molecules checked by applying molecular dynamics (MD) simulation. After this simulation, 2 molecules remained that had good stability with the protein during the simulation period.
A comparative study of BRTV and NTA Maiduguri regarding their compliance with Nigeria Broadcasting Code on religious programming
Authors: Yusuf Ibrahim Uba , Usman Musa , Ibrahim Adamkolo Mohammed
Published: August 2020

The regulation of broadcast religious programming is a critical challenge the National Broadcasting Commission (NBC) is facing in Nigeria. In Maiduguri, the capital of the north-eastern Nigerian state of Borno where religion forms a core part of the people’s culture, a great deal of Borno Radio Television (BRTV) and Nigerian Television Authority Maiduguri’s (NTA Maiduguri) airtime is allocated to Islamic preaching during the Muslim’s annual Ramadan fasting. However, there is a dearth of research on whether the airtime those broadcast stations allocate to Islamic programming complies with the NBC code on religious programming. This research gap formed the main research question of this study which was conducted during the second quarter of 2019. Primary data were collected using key informant interviews with five personnel from the two broadcast stations and the Maiduguri office of NBC, while secondary data were obtained through the review of official documents. Key findings showed that the airtime allocatedto religious programmes exceeded the 10% NBC limit, BRTV allocated more airtime to religious programmes than NTA Maiduguri and Islamic programmes were allocated more airtime than programmes of other religions. Recommendations on how to improve compliance to NBC’s regulations were offered at the end.Peraturan program siaran keagamaan merupakan tantangan bagi NationalBroadcasting Commission (NBC)/Komisi Penyiaran Nasional di Nigeria. Maiduguri, ibukota Negara bagian Borno, Nigeria Timur Laut di mana agama merupakan bagian inti dari budaya masyarakat, banyak Radio Televisi Borno (BRTV) dan Otoritas Televisi Nigeria Maiduguri (NTA Maiduguri) mengalokasikan jam tayang untuk khotbah Islam selama Ramadhan. Namun, ada kelangkaan penelitian tentang apakah jam tayang yang disiarkan oleh stasiun-stasiun siaran itu untuk program Islami. Kesenjangan penelitian ini membentuk pertanyaan penelitian utama yang dilakukan selama kuartal kedua 2019. Data penelitian ini dikumpulkan menggunakan wawancara informan kunci dengan lima personel dari keduanya stasiun siaran dan kantor Maiduguri NBC, sementara data sekunder diperoleh melalui telaah dokumen resmi. Temuan penelitian ini menunjukkan bahwa “airtime” (jam tayang) dialokasikan untuk program keagamaan yang melebihi batas 10% NBC, BRTV mengalokasikan lebih banyak “airtime” ke program keagamaan dari NTA Maiduguri dan program Islam dialokasikan lebih banyak “airtime” daripada program agama lain. Implikasi dari penelitian ini adalah perlunya kepatuhan terhadap peraturan NBC.