bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of the angiotensin-receptor-neprilysin inhibitor in heart failure patients with left ventricular ejection fraction higher than 40%: Retracted
Authors: Zhao Mingyue , Xin Yanguo , Li Junli , Cao Xiaofan , Liu Xiaojing 
Published: September 2019

Abstract
The angiotensin-receptor-neprilysin inhibitor (ARNI) reduced cardiovascular deaths and heart failure hospitalization in patients with heart failure of reduced ejection fraction (HFrEF). Its role in non-HFrEF patients was not clear. This study aims to answer this question.
In this retrospective study, we enrolled 928 patients diagnosed with non-HFrEF, 492 of them received angiotensin converting enzyme inhibitor (ACEI) and the rest 436 received angiotensin-receptor-neprilysin inhibitor. Outcomes were compared by Kaplan-Meier survival analysis and various clinical parameters were investigated using Cox multivariable analysis, followed by interaction analysis. Minnesota living with heart failure Questionnaire (MLHFQ) was employed as one of the criteria to assess heart failure outcome.
The cardiovascular (CV) death or HF hospitalization at 24 months occurred in 49 patients in ACEI group compared with 31 in ARNI group (Hazard Ratio (HR): 1.231, 95% confidence Interval (CI): 1.080–2.460, P = .031). And ARNI showed better prognosis of HF hospitalization (HR: 1.283, 95%CI: 1.065–1.360, P = .038). Cumulative Kaplan-Meier estimates of endpoints, ARNI could reduce the incidence of CV death or HF hospitalization (P = .042) and HF hospitalization (P = .035). The stratified analysis revealed that participants with age less than 70 years old had a lower incidence of CV death or HF hospitalization (HR: 1.194, 95%CI: 1.011–1992, P = .031) after treated with ARNI. Patients received diuretics could benefit from ARNI (HR: 1.383, 95%CI: 1.082–1.471, P = .019). Similar results were also observed in patients with heart rate lower than 90 bpm (HR: 1.556, 95%CI: 1.045–2.386, P = .003) and patients with atrial fibrillation history (HR: 1.873, 95%CI: 1.420–2.809, P = .011). ARNI could improve the quality of life both from the total, emotional and physical aspects.
ARNI is an efficacy treatment strategy to improve the outcome and quality of life in patients with non-HFrEF.
Effect of intraoperative position in single-level transforaminal lumbar interbody fusion at the L4/5 level on segmental and overall lumbar lordosis in patients with lumbar degenerative disease
Authors: Miyazaki Masashi , Ishihara Toshinobu , Abe Tetsutaro , Kanezaki Shozo , Notani Naoki , Kataoka Masashi , Tsumura Hiroshi 
Published: September 2019

Abstract
The purpose of this study was to investigate the effect of intraoperative positions in single-level (L4–5) transforaminal lumbar interbody fusion (TLIF) on segmental and overall lumbar lordosis (LL) in patients with lumbar degenerative disease. Thirty-eight consecutive patients who had undergone single-segment (L4–5) TLIF with 0° polyetheretherketone (PEEK) cage and pedicle screw fixation were evaluated. Twenty patients underwent surgery on the four-poster type frame with hip flexion at 30° (Group I) and 18 patients were operated on a Jackson spinal table to adjust their hip flexion to 0° (Group II). Preoperative standing, intraoperative prone, and postoperative standing lateral radiographs were obtained in each patient. The overall and segmental LL were analyzed according to the position in which the patients were placed for their operation and results compared between Groups I and II. Intraoperative intervertebral segmental LL at L4–5 and L5–S1 was increased in Group II than in Group I, whereas postoperative intervertebral segmental LL at L4–5 (fused level) was increased LL. In Group I intraoperative intervertebral segmental LL at L4–5 did not achieve sufficient lordosis, whereas postoperative intervertebral segmental LL at L3–4 was increased. The overall spinal alignment was unaffected by the decreased segmental LL in the fused level owing to the compensation of the upper adjacent segments. The more the hip was extended intraoperatively, the more the segmental lordosis increased in the lower lumbar spine. Thus, selecting the appropriate surgical table and hip position are very important. Underachievement of segmental lordosis leads to the acceleration of upper adjacent segment load.
A case report of glecaprevir/pibrentasvir-induced severe hyperbilirubinemia in a patient with compensated liver cirrhosis
Authors: Yoon Jae Hyun , Kim Sun Min , Kang Gaeun , Kim Hee Joon , Jun Chung Hwan , Choi Sung Kyu 
Published: September 2019

Abstract

Rationale:
Glecaprevir/pibrentasvir, a pan-genotypic and ribavirin-free direct acting antiviral agent regimen, has shown significant efficacy and very few serious complications. However, as the drug metabolizes in the liver, it is not recommended in patients with decompensated liver cirrhosis. Herein, we report the case of a patient with compensated liver cirrhosis who developed severe jaundice after glecaprevir/pibrentasvir medication.

Patient concerns:
A 77-year-old man diagnosed with chronic hepatitis C-related compensated liver cirrhosis visited hospital due to severe jaundice after 12 weeks of glecaprevir/pibrentasvir medication.

Diagnoses:
On the laboratory work-up, the total/direct bilirubin level was markedly elevated to 21.56/11.68 from 1.81 mg/dL; the alanine aminotransferase and aspartate aminotransferase levels were within the normal range. We checked the plasma drug concentration level of glecaprevir, and 18,500 ng/mL was detected, which was more than 15 times higher than the drug concentration level verified in normal healthy adults.

Interventions:
Glecaprevir/pibrentasvir was abruptly stopped and after 6 days, the drug concentration level decreased to 35 ng/mL and the serum total/direct bilirubin decreased to 7.49/4.06 mg/dL.

Outcomes:
Three months after drug cessation, the serum total bilirubin level normalized to 1.21 mg/dL and HCV RNA was not detected.

Lessons:
We report what is likely the first known case of severe jaundice after medication with glecaprevir/pibrentasvir in a patient with compensated liver cirrhosis. Clinicians should bear potential hyperbilirubinemia in mind when treating chronic hepatitis C with this regimen and should monitor the patient closely during follow-up laboratory exams, especially in elderly cirrhotic patients.
Long-term aspirin use for cancer primary prevention
Authors: Wu Qibiao , Chen Hongwei , Yao Xiaojun , Li Ting , Xu Cong , Wang Jue , Sui Xinbing , Leung Elaine Lai-Han 
Published: September 2019

Abstract

Background:
Long-term use of aspirin for primary prevention of cancer remains inconclusive, and variation in the effects of aspirin use on cancer outcomes by cancer site, aspirin dose, follow-up duration, or different populations has never been systematically evaluated.

Methods:
Seven electronic databases (PubMed, EMBASE, ClinicalTrials.gov, etc) will be searched from inception to September 30, 2019. Randomized clinical trials (RCTs) comparing aspirin versus no aspirin in participants without pre-existing cancer and reporting cancer incidence, and/or cancer mortality outcomes will be selected and assessed for inclusion. The Cochrane's Risk of Bias Tool and the Jadad scale will be used to evaluate the risk of bias and the methodologic quality of the RCTs. Data will be screened and extracted by independent investigators. Total cancer incidence will be defined as the primary clinical endpoint, and total cancer mortality, all-cause mortality, and the risk of major bleeding will be the secondary outcomes. Subgroup analyses based on cancer site, aspirin dose, follow-up duration, or different populations will be conducted. Analyses will be performed using Review Manager 5.3, Comprehensive Meta-Analysis 2.0, and Trial Sequential Analysis (TSA) software.

Results:
This study will systematically evaluate the effects of long-term aspirin use on total cancer incidence, cancer mortality, all-cause mortality, and the risk of major bleeding. Subgroup analyses will indicate whether the effects of aspirin on cancer outcomes are associated with cancer site, daily dose of aspirin, follow-up duration, or different subgroup of participants. The results will be submitted and published in a peer-reviewed scientific journal.

Conclusions:
This systematic review will systematically evaluate the efficacy and safety of long-term use of aspirin for primary prevention of cancer and determine whether there are some potential influencing factors affecting the effects of aspirin on cancer outcomes, thus strengthening the evidence base for the clinical practice and future research of this intervention.
A simple prediction model using fluorodeoxyglucose-PET and high-resolution computed tomography for discrimination of invasive adenocarcinomas among solitary pulmonary ground-glass opacity nodules
Authors: Shao Xiaonan , Shao Xiaoliang , Niu Rong , Xing Wei , Wang Yuetao 
Published: September 2019

Objective
To analyze the FDG-PET and high-resolution computed tomography (HRCT) features of early lung adenocarcinoma manifesting as solitary ground-glass opacity nodules (GGNs), and to establish a new risk model for predicting the invasiveness of early lung adenocarcinoma.

Methods
We retrospectively analyzed the data of clinical stage IA lung adenocarcinoma patients who received preoperative PET/CT and HRCT examination. Patients were divided into invasive adenocarcinoma (IVA) group and preinvasive minimally invasive adenocarcinoma (MIA) group. The correlations between FDG-PET parameters, HRCT parameters and histopathological invasiveness, and their predictive efficacy were analyzed. A mathematical model for predicting histopathological invasiveness of early lung adenocarcinoma was established and assessed.

Results
This study enrolled 56 patients, 48 were in IVA group and 8 were in preinvasive MIA group. Compared with those in preinvasive MIA group, GGNs in IVA group showed larger diameter, higher ground-glass opacity (GGO) density and more pleural indentation signs (70.8%) on HRCT; they also showed higher maximum standardized uptake value (SUV) and SUV index on FDG-PET (P = 0.001–0.037). Logistic regression analysis found a risk model for predicting IVA of solitary GGNs that were established by CTGGO and SUV index. Receiver operating characteristic curves showed that this model had the highest area under the curve (AUC), sensitivity, specificity and accuracy (AUC, 0.948; sensitivity, 95.8%; specificity, 87.5%; accuracy, 94.6%).

Conclusion
Using HRCT combined with FDG-PET to establish the corresponding mathematical prediction model has the potential to identify IVA in early lung adenocarcinoma preoperatively.
Periosteal Reaction Possibly Induced by Pazopanib: A Case Report and Literature Review
Authors: Hosokawa Takahiro , Hara Tomoko , Arakawa Yuki , Oguma Eiji , Yamada Yoshitake 
Published: September 2019

Background:Although complications associated with pazopanib, a multitarget tyrosine kinase inhibitor, are known, periosteal reaction as a side effect has never been reported.Observation:We present a case involving a male pediatric patient with desmoid tumors treated for 6 months with pazopanib who presented with pain and periosteal reaction in the ilium and scapula. Three months after termination of pazopanib therapy, the periosteal reaction in the scapula resolved and that in the ilium improved.Conclusion:Children receiving pazopanib presenting with focal pain should be examined for the periosteal reaction; this knowledge may facilitate correct diagnosis of symptoms as a drug-associated finding.
Near Miss in Intraoperative Magnetic Resonance Imaging: A Case for In Situ Simulation
Authors: Rama Asheen , Knight Lynda J. , Berg Marc , Chen Michael , Gonzales Ralph , Delhagen Timothy , Copperman Lucas , Caruso Thomas J. 
Published: September 2019

Introduction:
Pediatric patients in intraoperative magnetic resonance imaging (iMRI) settings are at high risk for morbidity should an adverse event occur. We describe an experience in the iMRI scanner where no harm occurred, yet revealed an opportunity to improve the safety of patients utilizing the iMRI. The perioperative quality improvement team, resuscitation team, and radiology nurse leadership collaborated to understand the process better through in situ simulation.

Methods:
After a problem analysis, the team planned an in situ, high-fidelity simulation with predefined learning objectives to identify previously overlooked opportunities for improvement. The iMRI simulation had unique considerations, including the use of a magnetic resonance imaging (MRI)-compatible mannequin and ensuring participants' safety. Audiovisual equipment was placed in strategic locations to record the MRI and operating room (OR) segments of the simulation, and trained health-care simulation experts provided debriefing.

Results:
After completion of the iMRI simulation, the quality improvement team solicited feedback from participants and reviewed the video-recorded simulation. Several opportunities for improvement surrounding staff responsibilities and unique aspects of the iMRI environment were identified.

Conclusions:
iMRI in situ simulation has not been previously described. It presents unique challenges given the integration of personnel from OR and radiology environments, anesthetized patients, and risks from the high-powered MRI magnet. Other institutions utilizing hybrid ORs with iMRI may consider conducting in situ simulations using the described methods.
Management of Pediatric Mandibular Fractures Using Resorbable Plates
Authors: Chocron Yehuda , Azzi Alain J. , Davison Peter 
Published: September 2019

Introduction:
Despite there being several clinical studies reporting promising outcomes of resorbable plates for fixation of pediatric mandible fractures, the literature is devoid of large studies or comprehensive reviews assessing safety rates, complications and long-term outcomes. The purpose of the current review is to obtain a global consensus, shed light on efficacy and complications, and provide the reader with evidence-based data to help guide clinical management.

Methods:
A systematic review of clinical studies assessing outcomes for resorbable plates in pediatric mandibular fractures was carried out. The main outcomes included infection, hardware failure, hardware exposure, malocclusion, reoperation and nonunion. Overall rates were pooled and stratified by fracture and implant type.

Results:
Ten studies were included yielding 232 patients with 269 fractures. The mean age at surgery was 8.24 years with a mean follow up of 1.03 years. The overall complication rate was 5.2% (n = 12). Complications included infection (n = 4, 1.7%), hardware exposure (n = 3, 1.29%), wound dehiscence (n = 2, .86%) and intra-oral fistula formation (n = 2, .86%). One patient (0.43%) had malocclusion and none (0%) had hardware failure, nonunion or revision surgery. Patients with multiple fractures (≥ 2) had higher complication rates compared to isolated fractures (12.5% versus 1.7%).

Conclusion:
The use of resorbable plates for pediatric mandibular fractures is a viable option with similar rates of post-operative complications and outcomes compared to standard metallic counterparts. In the absence of large studies or systematic reviews, this study provides craniofacial surgeons with an evidence-based reference to guide decision making and improve informed consent.
Exploring Integrative Analysis using the BioMedical Evidence Graph
Authors: Struck Adam , Walsh Brian , Buchanan Alexander , Lee Jordan A. , Spangler Ryan , Stuart Josh , Ellrott Kyle 
Published: September 2019

AbstractThe analysis of cancer biology data involves extremely heterogeneous datasets including information from RNA sequencing, genome-wide copy number, DNA methylation data reporting on epigenomic regulation, somatic mutations from whole-exome or whole-genome analyses, pathology estimates from imaging sections or subtyping, drug response or other treatment outcomes, and various other clinical and phenotypic measurements. Bringing these different resources into a common framework, with a data model that allows for complex relationships as well as dense vectors of features, will unlock integrative analysis. We introduce a graph database and query engine for discovery and analysis of cancer biology, called the BioMedical Evidence Graph (BMEG). The BMEG is unique from other biological data graphs in that sample level molecular information is connected to reference knowledge bases. It combines gene expression and mutation data, with drug response experiments, pathway information databases and literature derived associations. The construction of the BMEG has resulted in a graph containing over 36M vertices and 29M edges. The BMEG system provides a graph query based API to enable analysis, with client code available for Python, Javascript and R, and a server online at bmeg.io. Using this system we have developed several forms of integrated analysis to demonstrate the utility of the system. The BMEG is an evolving resource dedicated to enabling integrative analysis. We have demonstrated queries on the system that illustrate mutation significance analysis, drug response machine learning, patient level knowledge base queries and pathway level analysis. We have compared the resulting graph to other available integrated graph systems, and demonstrated that it is unique in the scale of the graph and the type of data it makes available.HighlightsData resource connected extremely diverse set of cancer data setsGraph query engine that can be easily deployed and used on new datasetsEasily installed python clientServer online at bmeg.ioSummaryThe analysis of cancer biology data involves extremely heterogeneous datasets including information. Bringing these different resources into a common framework, with a data model that allows for complex relationships as well as dense vectors of features, will unlock integrative analysis. We introduce a graph database and query engine for discovery and analysis of cancer biology, called the BioMedical Evidence Graph (BMEG). The construction of the BMEG has resulted in a graph containing over 36M vertices and 29M edges. The BMEG system provides a graph query based API to enable analysis, with client code available for Python, Javascript and R, and a server online at bmeg.io. Using this system we have developed several forms of integrated analysis to demonstrate the utility of the system.
Applications of the Microphysiology Systems Database for Experimental ADME-Tox and Disease Models
Authors: Schurdak Mark , Vernetti Lawrence , Bergenthal Luke , Wolter Quinn K. , Shun Tong Ying , Karcher Sandra , Taylor D. Lansing , Gough Albert 
Published: September 2019

AbstractTo accelerate the development and application of Microphysiological Systems (MPS) in biomedical research and drug discovery/development, a centralized resource is required to provide the detailed design, application, and performance data that enables industry and research scientists to select, optimize, and/or develop new MPS solutions, as well as to harness data from MPS models. We have previously implemented an open source Microphysiology Systems Database (MPS-Db), with a simple icon driven interface, as a resource for MPS researchers and drug discovery/development scientists (https://mps.csb.pitt.edu). The MPS-Db captures and aggregates data from MPS, ranging from static microplate models to integrated, multi-organ microfluidic models, and associates those data with reference data from chemical, biochemical, pre-clinical, clinical and post-marketing sources to support the design, development, validation, application and interpretation of the models. The MPS-Db enables users to manage their multifactor, multichip studies, then upload, analyze, review, computationally model and share data. Here we discuss how the sharing of MPS study data in the MS-Db is under user control and can be kept private to the individual user, shared with a select group of collaborators, or be made accessible to the general scientific community. We also present a test case using our liver acinus MPS model (LAMPS) as an example and discuss the use of the MPS-Db in managing, designing, and analyzing MPS study data, assessing the reproducibility of MPS models, and evaluating the concordance of MPS model results with clinical findings. We introduce the Disease Portal module with links to resources for the design of MPS disease models and studies and discuss the integration of computational models for the prediction of PK/PD and disease pathways using data generated from MPS models.
LRRK2 is recruited to phagosomes and co-recruits Rab8 and Rab10 in human pluripotent stem cell-derived macrophages
Authors: Lee Heyne , Flynn Rowan , Sharma Ishta , Carling Phillippa J. , Nicholls Francesca J. , Stegmann Monika , Vowles Jane , Wade-Martins Richard , James William S. , Cowley Sally A. 
Published: September 2019

SummaryThe Parkinson’s disease-associated gene, LRRK2, is also associated with immune disorders and infectious disease, and is expressed in immune subsets. Here, we characterise a platform for interrogating the expression and function of endogenous LRRK2 in authentic human phagocytes, using human induced Pluripotent Stem Cell-derived macrophages and microglia. Endogenous LRRK2 is expressed and upregulated by interferon-γ in these cells, including a 187kD cleavage product. Using LRRK2 knockout and G2019S isogenic repair lines, we find that LRRK2 is not involved in initial phagocytic uptake of bioparticles, but is recruited to LAMP1(+)/Rab9(+) ‘maturing’ phagosomes, and LRRK2 kinase inhibition enhances its residency at the phagosome. Importantly, LRRK2 is required for Rab8a and Rab10 recruitment to phagosomes, implying that LRRK2 operates at the intersection between phagosome maturation and recycling pathways in these professional phagocytes.
GRIDSS, PURPLE, LINX: Unscrambling the tumor genome via integrated analysis of structural variation and copy number
Authors: Cameron Daniel L. , Baber Jonathan , Shale Charles , Papenfuss Anthony T. , Valle-Inclan Jose Espejo , Besselink Nicolle , Cuppen Edwin , Priestley Peter 
Published: September 2019

AbstractWe have developed a novel, integrated and comprehensive purity, ploidy, structural variant and copy number somatic analysis toolkit for whole genome sequencing data of paired tumor/normal samples. We show that the combination of using GRIDSS for somatic structural variant calling and PURPLE for somatic copy number alteration calling allows highly sensitive, precise and consistent copy number and structural variant determination, as well as providing novel insights for short structural variants and regions of complex local topology. LINX, an interpretation tool, leverages the integrated structural variant and copy number calling to cluster individual structural variants into higher order events and chains them together to predict local derivative chromosome structure. LINX classifies and extensively annotates genomic rearrangements including simple and reciprocal breaks, LINE, viral and pseudogene insertions, and complex events such as chromothripsis. LINX also comprehensively calls genic fusions including chained fusions. Finally, our toolkit provides novel visualisation methods providing insight into complex genomic rearrangements.