bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Asphyxia Arrest Duration on a Pediatric End-Tidal co 2-Guided Chest Compression Delivery Model*
Authors: Hamrick Jennifer L. , Hamrick Justin T. , O’Brien Caitlin E. , Reyes Michael , Santos Polan T. , Heitmiller Sophie E. , Kulikowicz Ewa , Lee Jennifer K. , Kudchadkar Sapna R. , Koehler Raymond C. , Hunt Elizabeth A. , Shaffner Donald H. 
Published: May 2019

Objectives:
To determine the effect of the duration of asphyxial arrest on the survival benefit previously seen with end-tidal co
2-guided chest compression delivery.

Design:
Preclinical randomized controlled study.

Setting:
University animal research laboratory.

Subjects:
Two-week-old swine.

Interventions:
After either 17 or 23 minutes of asphyxial arrest, animals were randomized to standard cardiopulmonary resuscitation or end-tidal co
2-guided chest compression delivery. Standard cardiopulmonary resuscitation was optimized by marker, monitor, and verbal feedback about compression rate, depth, and release. End-tidal co
2-guided delivery used adjustments to chest compression rate and depth to maximize end-tidal co
2 level without other feedback. Cardiopulmonary resuscitation for both groups proceeded from 10 minutes of basic life support to 10 minutes of advanced life support or return of spontaneous circulation.

Measurements and Main Results:
After 17 minutes of asphyxial arrest, mean end-tidal co
2 during 10 minutes of cardiopulmonary resuscitation was 18 ± 9 torr in the standard group and 33 ± 15 torr in the end-tidal co
2 group (p = 0.004). The rate of return of spontaneous circulation was three of 14 (21%) in the standard group rate and nine of 14 (64%) in the end-tidal co
2 group (p = 0.05). After a 23-minute asphyxial arrest, neither end-tidal co
2 values (20 vs 26) nor return of spontaneous circulation rate (3/14 vs 1/14) differed between the standard and end-tidal co
2-guided groups.

Conclusions:
Our previously observed survival benefit of end-tidal co
2-guided chest compression delivery after 20 minutes of asphyxial arrest was confirmed after 17 minutes of asphyxial arrest. The poor survival after 23 minutes of asphyxia shows that the benefit of end-tidal co
2-guided chest compression delivery is limited by severe asphyxia duration.
Spinal microglia contribute to cancer-induced pain through system xC −-mediated glutamate release
Authors: Miladinovic Tanya , Singh Gurmit 
Published: May 2019

Abstract

Introduction:
Microglial cells, the resident macrophages of the central nervous system, are a key contributor to the generation and maintenance of cancer-induced pain (CIP). In healthy organisms, activated microglia promote recovery through the release of trophic and anti-inflammatory factors to clear toxins and pathogens and support neuronal survival. Chronically activated microglia, however, release toxic substances, including excess glutamate, causing cytotoxicity. Accordingly, rising attention is given to microglia for their role in abnormal physiology and in mediating neurotoxicity.

Objectives:
To examine the nociceptive relationship between peripherally-released glutamate and microglial xCT.

Methods:
A validated murine model of 4T1 carcinoma cell–induced nociception was used to assess the effect of peripheral tumour on spinal microglial activation and xCT expression. Coculture systems were then used to investigate the direct effect of glutamate released by wildtype and xCT knockdown MDA-MB-231 carcinoma cells on microglial activation, functional system xC
− activity, and protein levels of interferon regulatory factor 8 (IRF8), a transcription factor implicated in microglia-mediated nociception.

Results:
Blockade of system xC
− with sulfasalazine (SSZ) in vivo attenuated nociception in a 4T1 murine model of CIP and attenuates tumour-induced microglial activation in the dorsal horn of the spinal cord. Furthermore, knockdown of xCT in MDA-MB-231 cells mitigated tumour cell–induced microglial activation and functional system xC
− activity in vitro.

Conclusions:
These data collectively demonstrate that the system xCT antiporter is functionally implicated in CIP and may be particularly relevant to pain progression through microglia. Upregulated xCT in chronically activated spinal microglia may be one pathway to central glutamate cytotoxicity. Microglial xCT may therefore be a valuable target for mitigating CIP.
Diffuse Peripheral Zone T2 Hypointensity: When to Worry About Prostate Cancer
Authors: Navot Benjamin , Ahmed Firas S. , Shaish Hiram 
Published: June 2019

Objective
Evaluate the accuracy of an obscured surgical capsule (OSC) for detecting diffuse prostate cancer (PCa) in the setting of diffusely T2 hypointense peripheral zones (PZs) on prostate magnetic resonance imaging.

Methods
Axial T2-weighted sequences of prostate magnetic resonance imaging performed on July 1, 2015, to August 1, 2017, were blindly assessed for diffusely T2 hypointense PZs, OSC, and focal diffusion abnormalities by 2 radiologists. Diffuse PCa was defined by the presence of bilateral PCa on at least 4 contiguous biopsy cores involving 2/3 levels. Interobserver agreement and multivariate analysis were performed.

Results
Seven (10%) of 70 patients had diffuse PCa. There was weak interreader agreement for OSC (κ coefficient = 0.58). Obscured surgical capsule was 57% sensitive and 89% specific for the presence of diffuse PCa and was associated with it (odds ratio, 17.6; P = 0.0008). Multivariate logistic regression demonstrated that OSC was the only significant predictor for the presence of diffuse PCa.

Conclusion
Obscured surgical capsule is a strong independent predictor for diffuse PCa in T2 hypointense PZs.
Parathyroid Glands Hyperplasias Mimicking Medullary Thyroid Carcinoma Metastatic Lymph Nodes on 18F-DOPA PET/CT
Authors: Terroir Marie , Grimaldi Serena , Hartl Dana , Leboulleux Sophie , Deandreis Désirée 
Published: June 2019

Abstract
A pre operatory assessment by neck US, 18F-DOPA and 18F-choline PET/CT was performed in a 43-year-old MEN 2A woman affected by hyperparathyroidism and medullary thyroid carcinoma (MTC). On 18F-DOPA, two thyroid uptakes were analyzed as multifocal MTC and two others in the central neck compartment as MTC metastatic lymph nodes. After surgery, multifocal intra thyroidal MTC and two parathyroid glands hyperplasias were proved without MTC adenopathies. We report a case of rare false positive uptake on 18F-DOPA. In case of several endocrine diseases coexistence as in MEN 2A, 18F-DOPA should be carefully analyzed.
Retroperitoneal Malignant Peripheral Nerve Sheath Tumor on 99mTc-DTPA Renal Scintigraphy
Authors: Jia Xi , Gao Rui , Liang Yiqian , Liang Hua , Yang Aimin 
Published: June 2019

Abstract
Findings of 99mTc-DTPA renal scintigraphy of a retroperitoneal malignant peripheral nerve sheath tumor are reported here. The patient was a 48-year-old woman who presented discomfort and intermittent dull pain in the left upper quadrant of the abdomen for approximately 3 weeks.
Does Kidney Transplantation Affect Sleep and Fatigue in Patients With Kidney Disease?
Authors: Tandukar Srijan , Hou Surui , Yabes Jonathan , Ran Xinhui , Fletcher Mary , Strollo Patrick , Patel Sanjay R. , Unruh Mark , Jhamb Manisha 
Published: June 2019

Background.
Sleep disorders and fatigue are highly prevalent in chronic kidney disease (CKD) and end-stage kidney disease (ESKD) patients but there is limited evidence on the effect of kidney transplant (KTx) on these.

Methods.
In a prospective cohort study of patients with advanced CKD (estimated glomerular filtration rate<30 mL/min/1.73 m2) or ESKD, polysomnography and patient-reported symptom assessments were conducted. Pre- and post-KTx changes in sleep apnea (SA) severity (measured by apnea hypopnea index [AHI]) were analyzed and compared with patients who did not receive KTx. Regression models were used to examine predictors of SA severity.

Results.
Among 77 patients (mean age 51 y, BMI 29 kg/m2, 66% males, 23% ESKD), 61% had SA at baseline. Among 39 KTx recipients, 56% had SA, with 39% having moderate-severe SA after 10 ± 5.6 months post-KTx. There was no difference in AHI in either the KTx (median 6 versus 8; P = 0.37) or no-KTx (median 15 versus 16; P = 0.61) groups after an average of 19.9 ± 8.9 months. KTx led to significant clinically meaningful improvements in fatigue and health-related quality of life (adjusted effect size 0.3–0.6). In multivariable regression, baseline AHI was the only significant predictor of SA severity (adjusted β = 3.6/5 units, 95% confidence interval 2.1, 5.2) after adjusting for KTx status, age, sex, and body mass index.

Conclusions.
More than half of the KTx recipients had SA. There was no significant change in SA severity with KTx. Clinically meaningful moderate size improvements in patient-reported fatigue and health-related quality of life may be seen with KTx.
Evaluating sepsis definitions for clinical decision support against a definition for epidemiological disease surveillance
Authors: Lin Anthony L. , Sendak Mark , Bedoya Armando D. , Clement Meredith E. , Brajer Nathan , Futoma Joseph , Bosworth Hayden B. , Heller Katherine A. , O’Brien Cara L. 
Published: May 2019

ABSTRACTEpidemiological definitions for sepsis have been used to improve disease surveillance and assist in national assessment of sepsis detection and treatment. However, epidemiological definitions are often optimized for retrospective review and alignment of epidemiological and real-time clinical decision support definitions is unknown. This 15-month retrospective observational study involving 43,046 adult patient encounters and 30,973 unique patients compared cohorts captured by the EHR-based Sepsis-1, Sepsis-3, and Duke Adult Sepsis definitions. We assessed hospital length of stay, in-hospital mortality, admission to the intensive care unit, and sensitivity and specificity of these definitions compared to the Centers for Disease Control and Prevention epidemiological ‘gold-standard’ definition. Both Duke Adult Sepsis and Sepsis-3 maintained a high specificity, but the former had higher sensitivity. By directly comparing definitions designed for clinical decision support with an epidemiological disease surveillance tool, this work provides guidance to health systems seeking to implement clinical decision support to improve sepsis management.
Loss-functions matter, on optimizing score functions for the estimation of protein models accuracy
Authors: Sidi Tomer , Keasar Chen 
Published: June 2019

AbstractMotivationMethods for protein structure prediction (PSP) generate multiple alternative structural models (aka decoys). Thus, supervised learning methods for the evaluation and ranking of these models are crucial elements of PSP. Supervised learning involves optimization of loss functions, but their influence on performance is typically overlooked. Here we put the loss functions in the spotlight, and study their effect on prediction performance.ResultsHere we report the performances of three variants of MESHI-score, a supervised learning method for the estimation of model accuracy (EMA). Each variant was trained with a different loss function and showed better performance in different aspects of the EMA problem. Most importantly, better discrimination between models of the same target, is gained by target centered loss functions.AvailabilityAll data is available at http://meshi1.cs.bgu.ac.il/SidiAndKeasar2018Data_download/. The MESHI-package (version 9.412) is available at https://github.com/meshiprot/meshi/releases).Contactchen.keasar@gmail.com
Mutually exclusive autism mutations point to the circadian clock and PI3K signaling pathways
Authors: Manning Hannah , O’Roak Brian J. , Babur Özgün 
Published: May 2019

ABSTRACTMutual exclusivity analysis of genomic mutations has proven useful for detecting driver alterations in cancer patient cohorts. Here we demonstrate, for the first time, that this pattern is also present among de novo mutations in autism spectrum disorder. We analyzed three large whole genome sequencing studies and identified mutual exclusivity patterns within the most confident set of autism-related genes, as well as in the circadian clock and PI3K/AKT signaling pathways.
Stringent Response Governs the Virulence and Oxidative Stress Resistance of Francisella tularensis
Authors: Ma Zhuo , King Kayla , Alqahtani Maha , Worden Madeline , Muthuraman Parthasarthy , Cioffi Christopher , Bakshi Chandra Shekhar , Malik Meenakshi 
Published: May 2019

AbstractFrancisella tularensis is a Gram-negative bacterium responsible for causing tularemia in the northern hemisphere. F. tularensis has long been developed as a biological weapon due to its ability to cause severe illness upon inhalation of as few as ten organisms and based on its potential to be used as a bioterror agent is now classified as a Tier 1 Category A select agent by the CDC. The stringent response facilitates bacterial survival under nutritionally challenging starvation conditions. The hallmark of stringent response is the accumulation of the effector molecules ppGpp and (p)ppGpp known as stress alarmones. The relA and spoT gene products generate alarmones in several Gram-negative bacterial pathogens. RelA is a ribosome-associated ppGpp synthetase that gets activated under amino acid starvation conditions whereas, SpoT is a bifunctional enzyme with both ppGpp synthetase and ppGpp hydrolase activities. Francisella encodes a monofunctional RelA and a bifunctional SpoT enzyme. Previous studies have demonstrated that stringent response under nutritional stresses increases expression of virulence-associated genes encoded on Francisella Pathogenicity Island. This study investigated how stringent response governs the oxidative stress response of F. tularensis. We demonstrate that RelA/SpoT-mediated ppGpp production alters global gene transcriptional profile of F. tularensis in the presence of oxidative stress. The lack of stringent response in relA/spoT gene deletion mutants of F. tularensis makes bacteria more susceptible to oxidants, attenuates survival in macrophages, and virulence in mice. Mechanistically, we provide evidence that the stringent response in Francisella contributes to oxidative stress resistance by enhancing the production of antioxidant enzymes.ImportanceThe unique intracellular life cycle of Francisella in addition to nutritional stress also exposes the bacteria to oxidative stress conditions upon its brief residence in the phagosomes, and escape into the cytosol where replication takes place. However, the contribution of the stringent response in gene regulation and management of the oxidative stress response when Francisella is experiencing oxidative stress conditions is not known. Our results provide a link between the stringent and oxidative stress responses. This study further improves our understanding of the intracellular survival mechanisms of F. tularensis.
Variant Phasing and Haplotypic Expression from Single-molecule Long-read Sequencing in Maize
Authors: Wang Bo , Tseng Elizabeth , Baybayan Primo , Eng Kevin , Regulski Michael , Jiao Yinping , Wang Liya , Olson Andrew , Chougule Kapeel , Buren Peter Van , Ware Doreen 
Published: May 2019

AbstractHaplotype phasing of genetic variants in maize is important for interpretation of the genome, population genetic analysis and functional genomic analysis of allelic activity. Accordingly, accurate methods for phasing the full-length isoforms are essential for functional genomics studies. We performed an isoform-level phasing study in maize, using two inbred lines and their reciprocal crosses, based on the single-molecule full-length cDNA sequencing. To phase and analyze the full-length transcripts between hybrids and parents, we developed a tool called IsoPhase. Using this tool, we validated the majority of SNPs called against matching short-read data and identified cases of allele-specific, gene-level and isoform-level expression. Our results revealed that maize parental lines and hybrid lines exhibit different splicing activities. After phasing 6,907 genes in two reciprocal hybrids using embryo, endosperm and root tissues, we annotated the SNPs and identified large-effect genes. In addition, based on single-molecule sequencing, we identified parent-of-origin isoforms in maize hybrids, distinct novel isoforms in maize parent and hybrid lines, and imprinted genes from different tissues. Finally, we characterized variation in cis- and trans-regulatory effects. Our study provides measures of haplotypic expression that could increase accuracy in studies of allelic expression.
GIP: A Gene network-based integrative approach for Inferring disease-associated signaling Pathways
Authors: Chen Xi 
Published: May 2019

AbstractDysregulation or crosstalk of signal transduction pathways contributes to disease development. Despite the initial success of identifying causal links between source and target proteins in simple or well-studied biological systems, it remains challenging to investigate alternative pathways specifically associated with a disease. We develop a Gene network-based integrative approach for Inferring disease-associated signaling Pathways (GIP). Specifically, we identify alternative pathways given source and target proteins. GIP was applied to human breast cancer data. Experimental results showed that GIP identified biologically meaningful pathway modules associated with antiestrogen resistance.
Production of interspecies somatic/pluripotent heterokaryons using polyethylene glycol (PEG) and selection by imaging flow cytometry for the study of nuclear reprogramming
Authors: Villafranca M. Cristina , Makris Melissa R. , Garrido Bauerle Maria Jesus , Jensen Roderick V. , Eyestone Willard H. 
Published: May 2019

ABSTRACTFusion of somatic cells to pluripotent cells such as mouse embryonic stem (ES) cells induces reprogramming of the somatic nucleus, and can be used to study the effect of trans-acting factors from the pluripotent cell on the somatic nucleus. Moreover, fusion of cells from different species permits the identification of the transcriptome of each cell, so the gene expression changes can be monitored. However, fusion only happens in a small proportion of the cells exposed to fusogenic conditions, hence the need for a protocol that produces high fusion rate with minimal cell damage, coupled with a method capable of identifying and selecting fusion events from the bulk of the cells. Polyethylene glycol (PEG) is a polymer of repeated ethylene oxide units known to induce cell fusion within a certain range of molecular weight. Here, we describe a method to induce formation of bi-species heterokaryons from adherent mammalian cells, which can then be specifically labeled and selected using live cell immunostaining and a combination of imaging and traditional flow cytometry. First, we tested several PEG-based fusion conditions to optimize a protocol to consistently produce both mouse NIH/3T3 fibroblast and primary bovine fetal fibroblast (bFF) homokaryons. Initially, we obtained 7.28% of NIH/3T3 homokaryons when using 50% PEG 1500. Addition of 10% of DMSO to the PEG solution increased the percentage of NIH/3T3 homokaryons to 11.71%. In bFFs, treatment with 50% PEG 1500 plus 10% DMSO produced 11.05% of homokaryons. We then produced interspecies heterokaryons by fusing mouse embryonic stem (mES) cells to bFFs. To identify bi-species fusion products, heterokaryons were labeled using indirect immunostaining in live cells and selected using imaging (Amnis ImageStream Mark II) and traditional (BD FACSAria I) flow cytometry. Heterokaryons selected with this method produced ES cell-like colonies when placed back in culture. The method described here can also be combined with downstream applications such as nucleic acid isolation for RT-PCR and RNA-seq, and used as a tool to study cellular processes in which the effect of trans-acting factors is relevant, such as in nuclear reprogramming.
Detection of apoptosis and matrical degeneration within the intervertebral discs of rats due to passive cigarette smoking
Authors: Nakahashi Masahiro , Esumi Mariko , Tokuhashi Yasuaki 
Published: May 2019

AbstractAlthough low-back pain is considered to be associated with cigarette smoking, the influence of cigarette smoking on the intervertebral discs (IVD) has not been confirmed. We established a rat model of passive cigarette smoking-induced IVD degeneration, and investigated the cytohistological changes in the IVD and the accompanying changes in gene expression. IVD from rats exposed to 8 weeks of passive cigarette smoking were stained with Elastica van Gieson, and exhibited marked destruction of the supportive structure of the reticular matrix in the nucleus pulposus (NP). Positive signals on safranin O, alcian blue, type II collagen and aggrecan staining were decreased in the destroyed structure. Safranin O and type II collagen signals were also decreased in the cartilage end-plate (CEP) after 4- and 8-weeks of cigarette smoking. In the CEP, the potential for apoptosis was increased significantly, as demonstrated by staining for single-strand DNA. However, there were no signs of apoptosis in the NP or annulus fibrosus cells. Based on these findings, we concluded that passive cigarette smoking-induced stress stimuli first affect the CEP through blood flow due to the histological proximity, thereby stimulating chondrocyte apoptosis and reduction of the extracellular matrix (ECM). This leads to reduction of the ECM in the NP, destroying the NP matrix, which can then progress to IVD degeneration.
Fit or not? Bringing regulatory fit into the frame on health food preferences
Authors: Kuo Kuo-Shuan , Chuang Shih-Chieh , Huang Molly Chien-jung , Wu Pei-ying 
Published: May 2019

Purpose
The purpose of this paper is to facilitate the use of public communication in the development of healthy food plans for consumers. This research aims to investigate whether the influence of “fit” to individuals’ goal pursuit strategies on the effectiveness of advertisement frames can intensify persuasion to consume healthy (virtue) foods or restrain the consumption of unhealthy (vice) foods in health promotion.

Design/methodology/approach
Two experiments were conducted to investigate how goal-framed messages for different food types affect consumer decision making by moderating regulatory focus.

Findings
The results demonstrate that the compatibility between the mere exposure to virtue (vice) food in a negative (positive) frame drives the effectiveness of a given goal framing. However, when additional regulatory focus is added, the fit in the vice/promotion and virtue/prevention condition causes the effect of framing to disappear. Moreover, the unfit in the virtue/promotion and vice/prevention condition suppresses the virtue (vice) preference in the positive (negative) frame.

Research limitations/implications
These findings suggest that under different valence framing, advertising messages provide different amounts of persuasion in virtue/vice conditions and the moderation effect of regulatory fit on framing to influence virtue/vice food preference.

Practical implications
Public policy executives and marketers can increase the likelihood that consumers will make healthy food choices by fitting goals to strengthen persuasion. The unfitted goal orientation between food and regulatory focus enhances the framing effect leading to food preference changes.

Originality/value
The framing effect disappears when additional regulatory fit the food type, but is enhanced when additional regulatory focus does not fit the food type. By bringing fit into the frame and the virtue/vice food type, this research extends the notion of regulatory fit into three pairs of given goal orientations on the persuasiveness of message framing to health-related communication. It provides a substantial explanation underlying persuasion to promote a greater understanding of virtue/vice food preferences.