bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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

Abstract
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.