bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive analyses of immunodynamics and immunoreactivity in response to treatment in ALK-positive non-small-cell lung cancer
Authors: Pyo Kyoung-Ho , Lim Sun Min , Park Chae-Won , Jo Ha-Ni , Kim Jae Hwan , Yun Mi-Ran , Kim Dohee , Xin Chun-Feng , Lee Wongeun , Gheorghiu Bianca , Hong Min Hee , Kim Hye Ryun , Shim Hyo Sup , Jang Mi , Lee Sung Sook , Cho Byoung Chul 
Published: July 2020

BackgroundEML4-ALK is a distinct molecular entity that is highly sensitive to ALK tyrosine kinase inhibitors (TKIs). Immune checkpoint inhibitors (ICIs) have not proved efficacy in ALK-positive non-small cell lung cancer so far. In this study, we performed a mouse clinical trial using EML4-ALK transgenic mice model to comprehensively investigate immunomodulatory effects of ALK TKI and to investigate the mechanisms of resistance to ICIs.MethodsEML4-ALK transgenic mice were randomized to three treatment arms (arm A: antiprogrammed death cell protein-1 (PD-1), arm B: ceritinib, arm C: anti-PD-1 and ceritinib), and tumor response was evaluated using MRI. Progression-free survival and overall survival were measured to compare the efficacy. Flow cytometry, multispectral imaging, whole exome sequencing and RNA sequencing were performed from tumors obtained before and after drug resistance.ResultsMouse clinical trial revealed that anti-PD-1 therapy was ineffective, and the efficacy of ceritinib and anti-PD-1 combination was not more effective than ceritinib alone in the first line. Dynamic changes in immune cells and cytokines were observed following each treatment, while changes in T lymphocytes were not prominent. A closer look at the tumor immune microenvironment before and after ceritinib resistance revealed increased regulatory T cells and programmed death-ligand 1 (PD-L1)-expressing cells both in the tumor and the stroma. Despite the increase of PD-L1 expression, these findings were not accompanied by increased effector T cells which mediate antitumor immune responses.ConclusionsALK-positive tumors progressing on ceritinib is not immunogenic enough to respond to immune checkpoint inhibitors.
Radial access for neurointervention: room set-up and technique for diagnostic angiography
Authors: Chen Stephanie H , Peterson Eric C 
Published: July 2020

A number of prospective randomized trials have shown that the radial artery is a safer access site than the femoral artery for endovascular procedures.1–4 In the cardiac literature there was a 60% reduction in access site complications as well as significant decreases in all-cause mortality with the transradial approach compared with the transfemoral approach, which has led to the adoption of a radial first strategy.5–7 The neurointerventional literature has demonstrated similar safety benefits as well as improved patient preference.8–14 However, the technical aspects of how to perform neurointervention via the radial approach are still unknown to the majority of neurointerventionalists. This technical video 1 covers the details of how to perform a diagnostic angiogram via the radial approach. Initially, steps such as pre-procedure preparation, room set-up, and patient positioning are discussed. Following this, puncture techniques and sheath placement are outlined, including the snuffbox technique. The steps of a full six-vessel cerebral angiogram are then shown in detail. Finally, closure techniques are demonstrated.Video 1The image in the opening frame and at 2:24 is reused with permission from Brunetet al, Distal transradial access in the anatomical snuffbox for diagnostic cerebral angiography. J Neurointerv Surg 2019;11:710–3. Copyright 2019 BMJ Publishing Group.The other image in the opening frame is reused with permission from Chenet al, Transradial approach for flow diversion treatment of cerebral aneurysms: a multicenter study. J Neurointerv Surg, 2019;11:796-800. Copyright 2019 BMJ Publishing Group.The images at 0:38 and 8:24 are reused with permission from Snellinget al, Transradial cerebral angiography: techniques and outcomes. J Neurointerv Surg 2018;10:874–81. Copyright 2018 BMJ Publishing Group.
The four-point correlation function of the energy-momentum tensor in the free conformal field theory of a scalar field
Authors: Serino Mirko 
Published: July 2020

AbstractWe present an explicit momentum space computation of the four-point function of the energy-momentum tensor in 4 spacetime dimensions for the free and conformally invariant theory of a scalar field. The result is obtained by explicit evaluation of the Feynman diagrams by tensor reduction. We work by embedding the scalar field theory in a gravitational background consistently with conformal invariance in order to derive all the terms the correlator consists of and all the Ward identities implied by the requirements of general covariance and anomalous Weyl symmetry. We test all these identities numerically in several kinematic configurations. Mathematica notebooks detailing the step-by-step computation are made publicly available through a GitHub repository (https://github.com/mirkos86/4-EMT-correlation-function-in-a-4d-CFT.). To the best of our knowledge, this is the first explicit result for the four-point correlation function of the energy-momentum tensor in a conformal and non supersymmetric field theory which is readily numerically evaluable in any kinematic configuration.
IoT Platform Business Model for Innovative Management Systems
Authors: Mishra Shrutika , Tripathi A. R. 
Published: July 2020

Internet of Everything (IoE) in the business is a multiple and distributed interconnection of strategies and devices over the Internet. It is a group of technology which requires a set of protocols, data server storage strategy, infrastructure mechanism, integration of all technology, and communication protocols with all the connecting devices. The Internet of Things (IoT) is likely to convey accelerative, innovative, encouraging elucidations in numerous domains including business and managements. It allows devices to communicate with us very efficiently and accomplish the decisions with applications with other devices. The IoT creates transforming businesses, financial prudence and business culture. IoT platforms with greater access 5G technology are evolving as the upcoming tools and substantial support in the global IoEs setup in business ecosystem. In this paper, we examine up-to-date landscape of IoT platforms, 5G technology scope for business and management to how they work and the main aspects to consider when choosing a platform provider for cutting-edge decisions. It involves a set of approaches for business behaviors of the IoT and IoE classification, which can be defined as IoE business outlines in the cutting edge 5G technology.
The Myc and Ras Partnership in Cancer: Indistinguishable Alliance or Contextual Relationship?
Authors: Mahauad-Fernandez Wadie D. , Felsher Dean W. 
Published: July 2020

Abstract
Myc and Ras are two of the most commonly activated oncogenes in tumorigenesis. Together and independently they regulate many cancer hallmarks including proliferation, apoptosis, and self-renewal. Recently, they were shown to cooperate to regulate host tumor microenvironment programs including host immune responses. But, is their partnership always cooperative or do they have distinguishable functions? Here, we provide one perspective that Myc and Ras cooperation depends on the genetic evolution of a particular cancer. This in turn, dictates when they cooperate via overlapping and identifiably distinct cellular- and host immune–dependent mechanisms that are cancer type specific.
Regulatory Considerations for Contribution of Effect of Drugs Used in Combination Regimens: Renal Cell Cancer Case Studies
Authors: Brewer Jamie R. , Chang Elaine , Agrawal Sundeep , Singh Harpreet , Suzman Daniel L. , Xu James , Weinstock Chana , Fernandes Laura L. , Cheng Joyce , Zhang Lijun , Xie Diqiong , Goldberg Kirsten B. , Bloomquist Erik W. , Tang Shenghui , Sridhara Rajeshwari , Theoret Marc R. , Pazdur Richard , Ibrahim Amna , Beaver Julia A. 
Published: July 2020

Abstract
The development and review of combination drug regimens in oncology may present unique challenges to investigators and regulators. For regulatory approval of combination regimens, it is necessary to demonstrate the contribution of effect of each monotherapy to the overall combination. Alternative approaches to traditional designs may be needed to accelerate oncology drug development, for example, when combinations are substantially superior to available therapy, to reduce exposure to less effective therapies, and for drugs that are inactive as single agents and that in combination potentiate activity of another drug. These approaches include demonstration of activity in smaller randomized trials and/or monotherapy trials conducted in a similar disease setting. This article will discuss alternative approaches used in the development of approved drugs in combination, based on examples of recent approvals of combination regimens in renal cell carcinoma.
Human Cardiac Mesenchymal Stem Cells Remodel in Disease and Can Regulate Arrhythmia Substrates
Authors: Sattayaprasert Prasongchai , Vasireddi Sunil K. , Bektik Emre , Jeon Oju , Hajjiri Mohammad , Mackall Judith A. , Moravec Christine S. , Alsberg Eben , Fu Jidong , Laurita Kenneth R. 
Published: July 2020

Background:
The mesenchymal stem cell (MSC), known to remodel in disease and have an extensive secretome, has recently been isolated from the human heart. However, the effects of normal and diseased cardiac MSCs on myocyte electrophysiology remain unclear. We hypothesize that in disease the inflammatory secretome of cardiac human MSCs (hMSCs) remodels and can regulate arrhythmia substrates.

Methods:
hMSCs were isolated from patients with or without heart failure from tissue attached to extracted device leads and from samples taken from explanted/donor hearts. Failing hMSCs or nonfailing hMSCs were cocultured with normal human cardiac myocytes derived from induced pluripotent stem cells. Using fluorescent indicators, action potential duration, Ca2+ alternans, and spontaneous calcium release (SCR) incidence were determined.

Results:

Failing and nonfailing hMSCs from both sources exhibited similar trilineage differentiation potential and cell surface marker expression as bone marrow hMSCs. Compared with nonfailing hMSCs, failing hMSCs prolonged action potential duration by 24% (
P
<0.001, n=15), increased Ca2+ alternans by 300% (
P
<0.001, n=18), and promoted spontaneous calcium release activity (n=14,
P
<0.013) in human cardiac myocytes derived from induced pluripotent stem cells. Failing hMSCs exhibited increased secretion of inflammatory cytokines IL (interleukin)-1β (98%,
P
<0.0001) and IL-6 (460%,
P
<0.02) compared with nonfailing hMSCs. IL-1β or IL-6 in the absence of hMSCs prolonged action potential duration but only IL-6 increased Ca2+ alternans and promoted spontaneous calcium release activity in human cardiac myocytes derived from induced pluripotent stem cells, replicating the effects of failing hMSCs. In contrast, nonfailing hMSCs prevented Ca2+ alternans in human cardiac myocytes derived from induced pluripotent stem cells during oxidative stress. Finally, nonfailing hMSCs exhibited >25× higher secretion of IGF (insulin-like growth factor)-1 compared with failing hMSCs. Importantly, IGF-1 supplementation or anti–IL-6 treatment rescued the arrhythmia substrates induced by failing hMSCs.

Conclusions:
We identified device leads as a novel source of cardiac hMSCs. Our findings show that cardiac hMSCs can regulate arrhythmia substrates by remodeling their secretome in disease. Importantly, therapy inhibiting (anti–IL-6) or mimicking (IGF-1) the cardiac hMSC secretome can rescue arrhythmia substrates.
High-Resolution Transcriptomic Profiling of the Heart During Chronic Stress Reveals Cellular Drivers of Cardiac Fibrosis and Hypertrophy
Authors: McLellan Micheal A. , Skelly Daniel A. , Dona Malathi S.I. , Squiers Galen T. , Farrugia Gabriella E. , Gaynor Taylah L. , Cohen Charles D. , Pandey Raghav , Diep Henry , Vinh Antony , Rosenthal Nadia A. , Pinto Alexander R. 
Published: July 2020

Background:
Cardiac fibrosis is a key antecedent to many types of cardiac dysfunction including heart failure. Physiological factors leading to cardiac fibrosis have been recognized for decades. However, the specific cellular and molecular mediators that drive cardiac fibrosis, and the relative effect of disparate cell populations on cardiac fibrosis, remain unclear.

Methods:
We developed a novel cardiac single-cell transcriptomic strategy to characterize the cardiac cellulome, the network of cells that forms the heart. This method was used to profile the cardiac cellular ecosystem in response to 2 weeks of continuous administration of angiotensin II, a profibrotic stimulus that drives pathological cardiac remodeling.

Results:

Our analysis provides a comprehensive map of the cardiac cellular landscape uncovering multiple cell populations that contribute to pathological remodeling of the extracellular matrix of the heart. Two phenotypically distinct fibroblast populations, Fibroblast-
Cilp
and Fibroblast-
Thbs4
, emerged after induction of tissue stress to promote fibrosis in the absence of smooth muscle actin–expressing myofibroblasts, a key profibrotic cell population. After angiotensin II treatment, Fibroblast-
Cilp
develops as the most abundant fibroblast subpopulation and the predominant fibrogenic cell type. Mapping intercellular communication networks within the heart, we identified key intercellular trophic relationships and shifts in cellular communication after angiotensin II treatment that promote the development of a profibrotic cellular microenvironment. Furthermore, the cellular responses to angiotensin II and the relative abundance of fibrogenic cells were sexually dimorphic.

Conclusions:
These results offer a valuable resource for exploring the cardiac cellular landscape in health and after chronic cardiovascular stress. These data provide insights into the cellular and molecular mechanisms that promote pathological remodeling of the mammalian heart, highlighting early transcriptional changes that precede chronic cardiac fibrosis.
Elevated Heart Rate and Survival in Children With Dilated Cardiomyopathy: A Multicenter Study From the Pediatric Cardiomyopathy Registry
Authors: Rossano Joseph W. , Kantor Paul F. , Shaddy Robert E. , Shi Ling , Wilkinson James D. , Jefferies John L. , Czachor Jason D. , Razoky Hiedy , Wirtz Heidi S. , Depre Christophe , Lipshultz Steven E. 
Published: July 2020

Background
In adults with heart failure, elevated heart rate is associated with lower survival. We determined whether an elevated heart rate was associated with an increased risk of death or heart transplant in children with dilated cardiomyopathy.

Methods and Results

The study is an analysis of the Pediatric Cardiomyopathy Registry and includes baseline data, annual follow‐up, and censoring events (transplant or death) in 557 children (51% male, median age 1.8 years) with dilated cardiomyopathy diagnosed between 1994 and 2011. An elevated heart rate was defined as 2 or more SDs above the mean heart rate of children, adjusted for age. The primary outcomes were heart transplant and death. Heart rate was elevated in 192 children (34%), who were older (median age, 2.3 versus 0.9 years;
P
<0.001), more likely to have heart failure symptoms (83% versus 67%;
P
<0.001), had worse ventricular function (median fractional shortening
z
score, −9.7 versus −9.1;
P
=0.02), and were more often receiving anticongestive therapies (96% versus 86%;
P
<0.001) than were children with a normal heart rate. Controlling for age, ventricular function, and cardiac medications, an elevated heart rate was independently associated with death (adjusted hazard ratio [HR] 2.6;
P
<0.001) and with death or transplant (adjusted HR 1.5;
P
=0.01).

Conclusions
In children with dilated cardiomyopathy, elevated heart rate was associated with an increased risk of death and cardiac transplant. Further study is warranted into the association of elevated heart rate and disease severity in children with dilated cardiomyopathy and as a potential target of therapy.
Does Human Amnion Membrane Prevent Postoperative Abdominal Adhesions?
Authors: Nemec Hannah M. , Atalah Hany , Kling Melissa , Nichols Larry , Powers Bowen , Montgomery Anne , Ashley Dennis W. 
Published: July 2020

Background Adhesions are bands of tissue that form postoperatively after intra-abdominal surgery. Adhesions cause significant morbidity and despite ongoing research no agent or method has been shown to completely prevent adhesions. Human amnion-derived matrix is a complex tissue matrix derived from human placenta and has been used in other areas of surgery to promote healing and decrease scar tissue formation. Our hypothesis was that aerosolized human amnion-derived matrix particulate solution (HAMPS) applied during abdominal surgery would decrease adhesion formation in rats. Methods Twenty-four Sprague-Dawley rats were divided into 4 different groups. Group 1 was the control group (CG) which had cecal abrasion 20× with a surgical rasp to generate the adhesion model. Groups 2-4 were the treatment groups (TGs) and had cecal abrasion plus application of the HAMPS at concentrations of 6.25, 12.5, and 25 mg/cc, respectively. After 30 days, rats were euthanized and adhesion assessment performed. Results In all groups there were minimal adhesions noted at necropsy. Moderate inflammation was 33% in CG versus 11% in combined TGs. Average adhesion was 1.00 in CG versus 0.44 in combined TGs. This indicated an observational improvement in adhesions/inflammation in the TGs, although this did not reach statistical significance. There was a trend toward significance in the 12.5 mg/cc group alone ( P = .054). Conclusion Overall, HAMPS showed an observational decrease in adhesions in TGs although not statistically significant. There was a trend toward significance in the 12.5 mg group. Additional studies will have to be performed to further evaluate this subgroup.
Minimum Variance Unbiased Estimation of Reliability Function for a Class of Generalizations of Lindley Distribution
Authors: Bhattacharya Rahul , Sudhansu S. Maiti , Mriganka Mouli Choudhury , Mukherjee Dipangsu 
Published: July 2020

Uniformly minimum variance unbiased (UMVU) estimators of reliability function (both stress–strength and mission time) and the associated variance are derived for a class of generalization of Lindley distribution. The application of the results is further validated by a real data study. AMS 2020 subject classification: 62N05 62F10
Is it safe to move away from a full sternotomy for aortic valve replacement?
Authors: Kenawy Ayman , Abdelbar Abdelrahman , Tennyson Charlene , Taylor Rebecca , Zacharias Joseph 
Published: July 2020

Background Minimally invasive surgical approaches have gained popularity among patients and surgeons. The aim of this project was to assess the safety of initiating aortic valve replacement via an anterior right thoracotomy program. Methods Between May 2015 and May 2019, data of all isolated primary aortic valve replacements were extracted retrospectively from our prospectively collected database and categorized into conventional median sternotomy, hemisternotomy, and anterior right thoracotomy cases. In total, 661 patients underwent isolated primary aortic valve replacement, of whom 429 (65%) had a median sternotomy, 126 (19%) had a hemisternotomy, and 106 (16%) had an anterior right thoracotomy. Preoperative characteristics were similar in each of the three groups. Statistical testing of the surgical groups was undertaken using the chi-square test for categorical variables and one-way analysis of variance with Tukey post-hoc pairwise tests (where appropriate) for continuous variables, to identify differences between pairs of data. Results Cardiopulmonary bypass and crossclamp times were significantly longer in the anterior right thoracotomy group compared to the hemisternotomy and median sternotomy groups ( p < 0.001). Blood loss was significantly less and hospital stay significantly shorter in the hemisternotomy group compared to median sternotomy group but not the anterior right thoracotomy group. Mortality, stroke, renal, gastrointestinal and respiratory complications showed no statistical differences. Conclusion Surgical aortic valve replacement had a very low mortality and morbidity in our experience, and it is safe to start a minimal access program for aortic valve replacement.
Identifying emotional Facial Expressions in Practice: A Study on Medical Students
Authors: Bandyopadhyay Alapan , Sarkar Sarbari , Mukherjee Abhijit , Bhattacherjee Sharmistha , Basu Soumya 
Published: July 2020

Background: Successful identification of emotional expression in patients is of considerable importance in the diagnosis of diseases and while developing rapport between physicians and patients. Despite the importance of such skills, this aspect remains grossly overlooked in conventional medical training in India. This study aims to explore the extent to which medical students can identify emotions by observing photographs of male and female subjects expressing different facial expressions. Methods: A total of 106 medical students aged 18–25, without any diagnosed mental illnesses, were shown images of the six universal facial expressions (anger, sadness, fear, happiness, disgust, and surprise) at 100% intensity with an exposure time of 2 seconds for each image. The participants marked their responses after each image was shown. Collected data were analyzed using Statistical Package for the Social Sciences. Results: Participants could identify 76.54% of the emotions on average, with higher accuracy for positive emotions (95.6% for happiness) and lower for negative emotions (46% for fear). There were no significant variations in identification with respect to sex of the observers. However, it was seen that participants could identify emotions better from male faces than those from female faces, a finding that was statistically significant. Negative emotions were identified more accurately from male faces, while positive emotions were identified better from female ones. Conclusions: Male participants identified emotions better from male faces, while females identified positive emotions better from female faces and negative ones from male faces.