bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGFβ1: an Indicator for Tumor Immune Microenvironment (TIME) of Colon Cancer from a Comprehensive Analysis of TCGA
Authors: Wang Jinyan , Wang Jinqiu , Gu Quan , Yang Yan , Ma Yajun , Zhang Quan’an 
Published: September 2020

Abstract
Background: Tumor microenvironment (TME) and tumor-infiltrating immune cells (TIC) greatly participated in the genesis and development of colon cancer (CC). However, there are few researches exploring the dynamic modulation of TME. Methods: In our study, we analyzed the proportion of immune/stromal component and TIC in TME of 473 CC samples and 41 normal samples from The Cancer Genome Atlas (TCGA) database through ESTIMATE and CIBERSORT algorithm. Correlation analysis was carried out to evaluate the association between immune/stromal component in TME and clinicopathological characteristics of CC patients. The difference analysis was performed to obtain the differentially expressed genes (DEGs). These DEGs were further analyzed by gene ontology (GO), kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses, protein–protein interaction (PPI) network construction and COX regression analysis. Transforming growth factor β1 (TGFβ1) was finally overlapping from the above analysis. Furthermore, TGFβ1 was analyzed by paired analysis, Gene Set Enrichment Analysis (GSEA). The intersection between the difference analysis and correlation analysis was also conducted to learn the association between TGFβ1 and TICs.Results: Our result showed that immune component in TME was negatively related with the stages of CC. GO and KEGG enrichment analysis revealed that 1110 DEGs obtained from difference analysis were mainly enriched in immune-related activities. The intersection analysis between PPI network and COX regression analysis indicted that TGFβ1 was significantly associated with the communication of genes in PPI network and the Hazard Ratio (HR) of CC patients’ survival. In addition, TGFβ1 was up-regulated in the tumor samples and significantly related with poor prognosis of CC patients. Further GSEA suggested that genes in TGFβ1 up-regulated group were primarily enriched in immune-related activities and the function of TGFβ1 might depend on the communications with TICs, including T cells CD4 naïve and T cells regulatory (Tregs). Conclusions: The expression of TGFβ1 might be an indicator for tumor immune microenvironment (TIME) of CC and sever as a prognostic factor of CC. Drugs targeting TGFβ1 might be a potential immunotherapy for CC patients in the future.
Establishment and Assessment of a Nomogram for Predicting Blood Transfusion Risk in Posterior Lumbar Spinal Fusion
Authors: Wang Haosheng , Wang Kai , Lv Bin , Xu Haotian , Jiang Weibo , Zhao Jianwu , Dong Rongpeng , Kang Mingyang , Qu Yang 
Published: September 2020

Abstract
Background: The aim of this study was to determine the risk factors and develop a nomogram for blood transfusions after posterior lumbar spinal fusion (PSL).Methods: We conducted a retrospective, single-center study based on 885 patients receiving lumbar PSL, and data was obtained from May 2015 to September 2019. Multivariable logistic regression analysis was conducted to identified risk factors for blood transfusion, and a nomogram was constructed to individually evaluate the risk of blood transfusion. Discrimination, calibration, and clinical usefulness were validated by the receiver operating characteristics (ROC), C-index, calibration plot, and decision curve analysis, respectively. Bootstrapping validation was performed to assess the performance of the model.Results: Of 885 patients, 885 were enrolled in the final study population and 289 receive blood transfusion. Statistical analyses showed the low preoperative hemoglobin (Hb), longer time to surgery, operative time, levels of fusion>1, longer surgery duration, and higher total intraoperative blood loss (IBL) were the risk factors for transfusion. The C-index was 0.898 (95% CI: 0.847–0.949) in this dataset and 0.895 in bootstrapping validation, respectively. Calibration curve showed satisfied discrimination and calibration of the nomogram. Decision curve analysis (DCA) shown that the nomogram was clinical utility.Conclusions: In summary, we investigated the relationship between the blood transfusion requirement and predictors: levels of fusion, operative time, time to surgery, total intraoperative EBL, and preoperative Hb level. Our nomogram with a robust performance in the assessment of risk of transfusion, which can contribute clinicians making clinical decision. However, external validation is still needed in the further.
What Discontinued Trials Teach us About Trial Registration?
Authors: Vellinga Akke , Lambe Kathryn , O'Connor Paul , O'Dea Angela 
Published: September 2020

Abstract
ObjectiveTrial registries were set up to improve transparency, remove duplication, improve awareness and avoid waste. Many trials never reach the point of patient enrolment due to a myriad of reasons. The aim of this study was to investigate the reasons for and characteristics of discontinuation of trials.ResultsA total of 163 discontinued trials were identified and compared to completed trials. A Survey was designed to further explore the nature and conduct of the trial.No differences in registered and categorised information was observed between discontinued and completed trials. Most trials discontinue due to patient or participant recruitment issues, often related to funding. Substantial changes to procedures or the protocol or changes to recruitment strategy were also commonly cited reasons.Survey information was available for 21 discontinued and 28 completed trials and no obvious differences could be identified.Our findings highlight the underlying problem of lack of detail, suboptimal recording, dated information and incomplete reporting of trials within a trial registry which hampers sharing and learning. To date, important progress has been made by the implementation of standards and the requirement of trials to be registered. Our review identifies areas where further improvements can be made.
Brain Temperature Influences Intracranial Pressure and Cerebral Perfusion Pressure After Traumatic Brain Injury: A CENTER TBI Study
Authors: Birg Tatiana , Ortolano Fabrizio , Wiegers Eveline J.A. , Smielewski Peter , Savchenko Yan , Ianosi Bogdan Andrei , Helbok Raimund , Rossi Sandra , Carbonara Marco , Zoerle Tommaso , Stocchetti Nino 
Published: September 2020

Abstract
BackgroundAfter Traumatic Brain Injury (TBI) fever is frequent. Brain temperature, which is directly linked to body temperature, may influence brain physiology. Increased body and/or brain temperature may cause secondary brain damage, with deleterious effects on intracranial pressure (ICP), cerebral perfusion pressure (CPP) and outcome. MethodsCENTER-TBI, a prospective, multicenter, longitudinal study on TBI in Europe and Israel, includes a high resolution (HR) cohort of patients with data sampled at high-frequency (from 100 Hz to 500 Hz). In this study, simultaneous BT, ICP and CPP recordings were investigated. A mixed effects linear model was used to examine the association between different BT levels and ICP. We additionally focused on changes of ICP and CPP during the episodes of BT changes (delta BT ≥0.5 °C, lasting from 15 minutes to 3 hours) up or down-wards. The significance of ICP and CPP variations was estimated with the paired samples Wilcoxon test. Results Twenty-one patients with 2435 hours of simultaneous BT and ICP monitoring were studied. All patients reached a BT of 38° and experienced at least one episode of ICP above 20 mmHg. The linear mixed effects model revealed an association between BT above 37.5°C and higher ICP levels that was not confirmed for lower BT. We identified 149 episodes of BT changes. During BT elevations (n=79) ICP increased while CPP was reduced; opposite ICP and CPP variations occurred during episodes of BT reduction (n=70). All these changes were of moderate clinical relevance, even if statistically significant (p<0.0001). It has to be noted, however, that a number of therapeutic interventions against intracranial hypertension was documented during those episodes.ConclusionPatients after TBI usually develop BT> 38° soon after the injury. Brain temperature may influence brain physiology, as reflected by ICP and CPP. An association between BT exceeding 37.5°C and a higher ICP was identified. The relationship between BT, ICP and CPP become clearer during rapid temperature changes.Trial registration: The core study was registered with ClinicalTrials.gov, number NCT02210221, registered on July 29, 2014
Acceptability of Physician Associate Interns in Primary Care: Results from a Service Evaluation
Authors: Cottrell Elizabeth , Silverwood Victoria , Strivens-Joyce Alex , Minshull Lucy , Edwards John J , Lawton Sarah , Aiello Matt , Turner Sharon 
Published: September 2020

Abstract
Background: Physician associates (PA) form part of the policy-driven response to increased primary care demand and a general practitioner recruitment and retention crisis. However, they are novel to the primary care workforce, have limitations such as being unable to prescribe and order ionising radiation investigations, and there are very limited directly-relevant data to guide the integration of PAs into primary care. To address this, a novel internship scheme was established in Staffordshire to support PAs entering primary care. This evaluation was designed to establish the acceptability of Physician Associate (PA) Interns within primary care.Methods: The Staffordshire PA Internship (SPAI) scheme was introduced in Staffordshire in 2017. PAs were concurrently working in primary and secondary care posts for one year, with protected weekly education sessions to equip them for work in primary care. Within the nine primary care practices hosting 10 PA interns in the first two cohorts, the PA interns, supervising GPs and practice managers, and patients who attended an appointment with a PA intern were invited to participate in the evaluation.Results: By evaluation end, eight of the ten PAs had completed the internship. Overall PA interns were acceptable to practices and patients, however there was ambiguity about the PA role itself, and how best to communicate this, as well as how to operationalise their roles. An expectation-preparedness gap was identified for PAs working in primary care. This resulted in high levels of supervision required for PA interns early within the internship. The internship provided a platform upon which the expectation-preparedness gap could be closed and made the high supervision requirements more acceptable to practices.Conclusions: This test-of-concept SPAI has highlighted that, to ensure successful integration of new PAs into primary care and to support them to reach their full potential, commitments to longer-term, sustainable, cohesive and appropriately funded schemes, including structured and standardised education and supervision, need to be delivered. Without such investment, there is a risk that acceptability of PAs in primary care, and PAs’ views of primary care careers, will be undermined before the profession has attained its full potential.
Comprehensive Home Palliative Care Could Reduce Emergency Department Visits Due to Psychologic Dyspnea Among Cancer Patients: A Retrospective Cohort Study
Authors: Hsu Hua-Shui , Wu Tai-Hsien , Lin Chin-Yu , Lin Ching-Chun , Chen Tsung-Po , Lin Wen-Yuan 
Published: September 2020

Abstract
Objective Dyspnea symptom is a common trigger of emergency department among the terminal illness and cancer patients. The frequent emergency department (ED) visits at the end of life are the indicator of poor-quality care. We examine the emergency department visits rate due to dyspnea symptom among the palliative patients by enhanced home palliative care.MethodsIn our home palliative care team, patients are managed by palliative care specialists, residents, home care nurses, social workers, and chaplains. We enhanced the weekly home palliative care visit time from 5 days a week to 7 days a week, one to two times visit per week based on patient’s need, to devise team-based medical services and formulate standard operating procedures for dyspnea care.ResultsOur team cared for a total of 762 patients with 512 ED visits, and 178 ED visits because of dyspnea (mean ± SD age, 70.4 ± 13.0 years; 49.4% male). Dyspnea (27.8%) was the most common reason recorded for ED visit, followed by pain (19.0%), GI symptoms (15.7%), and fever (15.3%). The analysis of unexposed versus exposed groups revealed that the proportion of non-family workers (42.9% vs.19.4%) and family members (57.1% vs. 80.6%) acting as caregivers significantly changed than basic (P <0.05). Compared with ED visits of unexposed group, the risks evidently decreased 30.7% in exposed group (P <0.05). Conclusion This study proves that comprehensive home palliative care with add two days per week and formulate standard operating procedures for dyspnea could significantly reduce ED visits rate because of controllable dyspnea in the last six months of life.
Analysis of ADAM9 Regulation and Function in Vestibular Schwannoma Primary Cells
Authors: Nattmann Anja , Breun Maria , Monoranu Camelia , Matthies Cordula , Ernestus Ralf-Ingo , Löhr Mario , Hagemann Carsten 
Published: September 2020

Abstract
Objective: Recently, we described a disintegrin and metalloproteinase 9 (ADAM9) overexpression by Schwann cells of vestibular schwannoma (VS) and suggested that it might be a marker for VS tumor growth and invasiveness. This research note provides additional data utilizing a small cohort of VS primary cultures and tissue samples. We examined whether reconstitution of Merlin expression in VS cells regulates ADAM9 protein expression and performed lentiviral ADAM9 knock down to investigate possible effects on VS cells numbers. Moreover, the co-localization of ADAM9 and Integrins α6 and α2β1, respectively, was examined by immunofluorescence double staining.Results: ADAM9 expression was confirmed in VS but not regulated by Merlin. However, ADAM9 knock down led to significant 2.38 fold reduced cell numbers in VS primary cell cultures (p<0.001). While ADAM9 and Integrin α2β1 were co-localized in only 22% (2 of 9) of VS, ADAM9 and Integrin α6 were co-localized in 91% (10 of 11) of VS. Therefore, we provide first observations on possible regulatory functions of ADAM9 expression in VS.
Risk Assessment for Cardiac Arrest : A Deep Learning Approach With Channel Selection
Authors: Yılmaz Atınç 
Published: September 2020

Abstract
Background: Risk of developing cardiovascular diseases, in the world, is increasing day by day. Accordingly, the number of deaths due to heart attacks is quite remarkable. Early risk assessment and diagnosis of heart disease are vital to prevent heart attacks by providing effective treatment planning and evaluation of outcomes. When a patient with high risk of heart attack is not treated correctly, chances of survival may reduce dramatically. For this reason, artificial intelligence-assisted systems can support the decision of doctors and it can anticipate risk without fatal consequences.Methods: In this study, individuals who has heart attack risks are predicted by using a proposed CNNs method. A set of medical data from patients with heart attacks and healthy individuals are provided from the UCI database. Reinforced deep learning and ANFIS architectures are also applied to the same problem in order to compare the results and put forth the efficiency of proposed method. In addition, ROC analysis and measurements of processing times for the applied methods were performed to reveal the performance, accuracy and efficiency of the study.Results: The proposed CNNs method and other methods are tested and evaluated. The accuracy performance of the methods were 94.34% for the proposed CNNs method, 91.58% for the ANFIS, and 92.66% for the deep multilayer neural network. Highest accuracy has been obtained by using the proposed CNNs method, which is 94.34%. The reasons why the proposed CNNs method is better than other methods is the use of channel selection layer, the number of convolution and pooling layers, the filter size used in these layers, and the functions used in the loss and activation layers.Conclusions: In the study, the channel selection formula is introduced in the proposed CNNs model to select the most discriminatory feature filters. Besides, the applicability of proposed CNNs method with images obtained from numerical data has been demonstrated. With the early prediction system proposed, it is now possible to take precautionary measures against possible cardiac arrest. In this study; a new method based on CNNs is proposed for early detection of possible heart attack, which is a great risk for human life. Different from studies in the literature, the channel selection formula is presented in the proposed CNNs method to select the most selective feature filters. Besides differently, it was used in the proposed CNNs method by converting all numerical data from dataset into 2D images. Afterwards, to show whether this the proposed method is applicable or not, the dataset which is numerical form was applied to other methods and compared.
Recreational opium use as a risk factor for coronary artery disease: results from the premature coronary artery disease Milano-Iran (MIran) study
Authors: Maino Alberto , Sadeghian Saeed , Mancini Ilaria , Abbasi Seyed Hesameddin , Poorhosseini Hamidreza , Boroumand Mohammad Ali , Lotfi-Tokaldany Masoumeh , Jalali Arash , Pagliari Maria Teresa , Rosendaal Frits , Peyvandi Flora 
Published: September 2020

Abstract
The spreading of recreational opium use pose new health related concerns. In some areas of Asia its use is believed to protect from cardiovascular disorders, such as coronary artery disease (CAD). However, whether opium use has an association with CAD is unclear. We aimed to investigate the association between opium use and CAD. We set up a case-control analysis, i.e., the premature CAD Milano-Iran (MIran) study by enrolling consecutive young patients who underwent a coronary angiography at the Tehran Heart Center, between 2009 and 2012. Incident cases with CAD were contrasted with controls for recreational opium use. Relative risks were calculated in terms of odds ratios (ORs) by logistic regression models adjusted for age, sex, cigarette smoking, body mass index, hypertension, hyperlipidaemia, and diabetes. Interaction analyses were performed between opium and major cardiovascular risk factors. 1011 patients with CAD (mean age 43.6 years) and 2002 controls (mean age 54.3 years) were included in the study. Habitual opium users had a 3.8-fold increased risk of CAD (95%CI 2.4–6.2) compared with non-users. The association was strongest for men, with a fully adjusted OR of 5.5 (95%CI 3.0-9.9). No interaction was observed for the combination of opium addiction and hypertension, or diabetes, but an excess in risk was found in opium users with hyperlipidaemia (OR 16.8, 95%CI 8.9–31.7, expected OR 12.2), suggesting supra-additive interaction. In conclusion, despite common beliefs, we showed that recreational opium use is associated with an increased risk of CAD, even when other cardiovascular risk factors are taken into account.
Dose All of the Coronary Fistulas been Created by the Reopening Wire After Successful Revascularization of Chronic Total Occlusion?
Authors: Fan Rong , Tan Haipeng , Song Yanan , Yao Wang , Yang Yawei , Wu Feng , Liu Haoqi , Feng Can , Fan Min , Huang Zheyong , Ge Junbo 
Published: September 2020

Abstract
Background: Coronary fistulas may be congenital or acquired generally as consequence of coronary interventions, mainly chronic total occlusion (CTO) reopening. When the reopening wire passes through the occlusion it may microperforate the advential vascular layers, favoring the fistulous communication between coronary vessel and cardiac chambers. But some of acquired coronary fistulas (ACFs) had been already present at the CTO vessels and would been seen after revascularization. This study was designed to investigate the characteristics of ACFs, which albeit mostly benign can cause concern and unnecessary treatment post successful CTO percutaneous coronary intervention (PCI).Methods: Data, including clinical and procedural characteristics, medical history, and findings in electrocardiography, echocardiography and coronary angiography, from 2169 consecutive patients undergoing CTO PCI between January 2018 and December 2019 were analyzed retrospectively. Results: 1844 (85.0%) underwent successful CTO PCI with complete revascularization. Among them, there were 49 cases (mean age, 62.80 ± 11.24 years; 40 men) of ACFs: 24 (49%) involved the right coronary artery, 19 (38.8%) the left anterior descending artery, and 6 (12.2%) the circumflex branch; and 38 (77.6%) were coupled with multiple fistulas (>3), and 29 (59.2%) affected multiple branches of the CTO vessel (>3). The majority of patients with ACFs had a history of MI or Q-wave (n=34, 69.4%), and angina was the most common complaint (n=41, 83.7%). None of them had pericardial effusion, tamponade and Hemodynamic abnormalities before or after PCI.Conclusion: ACFs after successful CTO PCI mostly developed in patients with MI history, originated from the right coronary artery or left anterior descending artery, and involved multiple fistulas and CTO vessel branches.
The Effect of Nanosecond Pulsed Electric Field on Hepatic Veins—A Mid-Term Investigation
Authors: Dong Yeping , Lu Jiahua , Huang Zhiliang , Chen Xinhua , Ren Zhigang , Hong Liangjie , Wang Haiyu , Yang Dezhi , Xie Haiyang , Zhang Wu 
Published: September 2020

Abstract
Background: Nanosecond pulsed electric field (nsPEF) is a novel ablative technique for treating tumours of the liver, kidneys, and other organs. This study investigated the effect of nsPEF on hepatic veins of different diameters and evaluated the feasibility and safety of using nsPEF to ablate tissues in porcine livers.Methods: A total of 15 pigs were included in the study. B-mode ultrasonography was used to guide two-needle nsPEF electrodes inserted adjacent to the left, middle, and right hepatic veins. The animals were followed up at 1 hour and at 1, 3, 7, and 14 days post treatment. Results: During and after the procedure of nsPEF treatment, electrocardiographs (ECGs) detected no cardiovascular events, and B-mode ultrasonography found no hepatic venous thrombosis formation. Follow-up at 1 hour to 7 days post treatment revealed complete ablation of the perivascular tissue within the ablated area. There was no apparent structural damage to the hepatic veins of different diameters, but there appeared to be red blood cells and residual inflammatory cell infiltration in the subendothelial layer from 1 hour to 7 days post treatment. Follow-up blood biochemical tests showed transient damage to the liver and myocardial function, and immediate recovery, which is consistent with the pathological changes.Conclusion: NsPEF achieved complete liver tissue ablation while causing little damage to the hepatic veins. Thus, nsPEF could be used to ablate central tumour lesions that are located nearing the major hepatic veins, thereby avoiding some of the limitations of conventional surgical therapies and thermal ablations.