bluuebunny/crossref_metadata_2025_split huggingface dataset:
New mouse model of pulmonary hypertension induced by respiratory syncytial virus bronchiolitis
Authors: Kimura Dai , Saravia Jordy , Jaligama Sridhar , McNamara Isabella , Vu Luan D. , Sullivan Ryan D. , Mancarella Salvatore , You Dahui , Cormier Stephania A. 
Published: June 2018

Pulmonary hypertension (PH) has been observed in up to 75% of infants with moderate to severe respiratory syncytial virus (RSV) bronchiolitis and is associated with significant morbidity and mortality in infants with congenital heart disease. The purpose of the present study was to establish a mouse model of PH secondary to RSV bronchiolitis that mimics the disease etiology as it occurs in infants. Neonatal mice were infected with RSV at 5 days of age and then reinfected 4 wk later. Serum-free medium was administered to age-matched mice as a control. Echocardiography and right ventricular systolic pressure (RVSP) measurements via right jugular vein catheterization were conducted 5 and 6 days after the second infection, respectively. Peripheral capillary oxygen saturation monitoring did not indicate hypoxia at 2–4 days post-RSV infection, before reinfection, and at 2–7 days after reinfection. RSV-infected mice had significantly higher RVSP than control mice. Pulsed-wave Doppler recording of the pulmonary blood flow by echocardiogram demonstrated a significantly shortened pulmonary artery acceleration time and decreased pulmonary artery acceleration time-to-ejection time ratio in RSV-infected mice. Morphometry showed that RSV-infected mice exhibited a significantly higher pulmonary artery medial wall thickness and had an increased number of muscularized pulmonary arteries compared with control mice. These findings, confirmed by RVSP measurements, demonstrate the development of PH in the lungs of mice infected with RSV as neonates. This animal model can be used to study the pathogenesis of PH secondary to RSV bronchiolitis and to assess the effect of treatment interventions. NEW & NOTEWORTHY This is the first mouse model of respiratory syncytial virus-induced pulmonary hypertension, to our knowledge. This model will allow us to decipher molecular mechanisms responsible for the pathogenesis of pulmonary hypertension secondary to respiratory syncytial virus bronchiolitis with the use of knockout and/or transgenic animals and to monitor therapeutic effects with echocardiography.
EWS/ETS-Driven Ewing Sarcoma Requires BET Bromodomain Proteins
Authors: Gollavilli Paradesi Naidu , Pawar Aishwarya , Wilder-Romans Kari , Natesan Ramakrishnan , Engelke Carl G. , Dommeti Vijaya L. , Krishnamurthy Pranathi M. , Nallasivam Archana , Apel Ingrid J. , Xu Tianlei , Qin Zhaohui S. , Feng Felix Y. , Asangani Irfan A. 
Published: June 2018

AbstractThe EWS/ETS fusion transcription factors drive Ewing sarcoma (EWS) by orchestrating an oncogenic transcription program. Therapeutic targeting of EWS/ETS has been unsuccessful; however, identifying mediators of the EWS/ETS function could offer new therapeutic options. Here, we describe the dependency of EWS/ETS-driven transcription upon chromatin reader BET bromdomain proteins and investigate the potential of BET inhibitors in treating EWS. EWS/FLI1 and EWS/ERG were found in a transcriptional complex with BRD4, and knockdown of BRD2/3/4 significantly impaired the oncogenic phenotype of EWS cells. RNA-seq analysis following BRD4 knockdown or inhibition with JQ1 revealed an attenuated EWS/ETS transcriptional signature. In contrast to previous reports, JQ1 reduced proliferation and induced apoptosis through MYC-independent mechanisms without affecting EWS/ETS protein levels; this was confirmed by depleting BET proteins using PROTAC-BET degrader (BETd). Polycomb repressive complex 2 (PRC2)-associated factor PHF19 was downregulated by JQ1/BETd or BRD4 knockdown in multiple EWS lines. EWS/FLI1 bound a distal regulatory element of PHF19, and EWS/FLI1 knockdown resulted in downregulation of PHF19 expression. Deletion of PHF19 via CRISPR-Cas9 resulted in a decreased tumorigenic phenotype, a transcriptional signature that overlapped with JQ1 treatment, and increased sensitivity to JQ1. PHF19 expression was also associated with worse prognosis in patients with EWS. In vivo, JQ1 demonstrated antitumor efficacy in multiple mouse xenograft models of EWS. Together these results indicate that EWS/ETS requires BET epigenetic reader proteins for its transcriptional program and can be mitigated by BET inhibitors. This study provides a clear rationale for the clinical utility of BET inhibitors in treating EWS.Significance:These findings reveal the dependency of EWS/ETS transcription factors on BET epigenetic reader proteins and demonstrate the potential of BET inhibitors for the treatment of EWS. Cancer Res; 78(16); 4760–73. ©2018 AACR.
Impact of Emergent Circulating Tumor DNA RAS Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer
Authors: Kim Tae Won , Peeters Marc , Thomas Anne , Gibbs Peter , Hool Kristina , Zhang Jianqi , Ang Agnes Lee , Bach Bruce Allen , Price Timothy 
Published: June 2018

Abstract
Purpose: The accumulation of emergent RAS mutations during anti-EGFR therapy is of interest as a mechanism for acquired resistance to anti-EGFR treatment. Plasma analysis of circulating tumor (ct) DNA is a minimally invasive and highly sensitive method to determine RAS mutational status.
Experimental Design: This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded RAS ctDNA mutations in panitumumab-treated patients. Plasma samples collected at baseline and posttreatment were analyzed categorically for the presence of RAS mutations by the PlasmaSelect-R 64-gene panel at 0.1% sensitivity.
Results: Among panitumumab-treated patients with evaluable plasma samples at baseline (n = 238), 188 (79%) were wild-type (WT) RAS, and 50 (21%) were mutant RAS. Of the 188 patients with baseline ctDNA WT RAS status, 164 had evaluable posttreatment results with a 32% rate of emergent RAS mutations. The median overall survival for WT and RAS mutant status by ctDNA at baseline was 13.7 (95% confidence interval, 11.5–15.4) and 7.9 months (6.4–9.6), respectively (P &lt; 0.0001). Clinical outcomes were not significantly different between patients with and without emergent ctDNA RAS mutations.
Conclusions: Although patients with baseline ctDNA RAS mutations had worse outcomes than patients who were WT RAS before initiating treatment, emergent ctDNA RAS mutations were not associated with less favorable patient outcomes in panitumumab-treated patients. Further research is needed to determine a clinically relevant threshold for baseline and emergent ctDNA RAS mutations. Clin Cancer Res; 24(22); 5602–9. ©2018 AACR.
Elective Nodal Irradiation Attenuates the Combinatorial Efficacy of Stereotactic Radiation Therapy and Immunotherapy
Authors: Marciscano Ariel E. , Ghasemzadeh Ali , Nirschl Thomas R. , Theodros Debebe , Kochel Christina M. , Francica Brian J. , Muroyama Yuki , Anders Robert A. , Sharabi Andrew B. , Velarde Esteban , Mao Wendy , Chaudhary Kunal R. , Chaimowitz Matthew G. , Wong John , Selby Mark J. , Thudium Kent B. , Korman Alan J. , Ulmert David , Thorek Daniel L.J. , DeWeese Theodore L. , Drake Charles G. 
Published: June 2018

Abstract
Purpose: In the proper context, radiotherapy can promote antitumor immunity. It is unknown if elective nodal irradiation (ENI), a strategy that irradiates tumor-associated draining lymph nodes (DLN), affects adaptive immune responses and combinatorial efficacy of radiotherapy with immune checkpoint blockade (ICB).
Experimental Design: We developed a preclinical model to compare stereotactic radiotherapy (Tumor RT) with or without ENI to examine immunologic differences between radiotherapy techniques that spare or irradiate the DLN.
Results: Tumor RT was associated with upregulation of an intratumoral T-cell chemoattractant chemokine signature (CXCR3, CCR5-related) that resulted in robust infiltration of antigen-specific CD8+ effector T cells as well as FoxP3+ regulatory T cells (Tregs). The addition of ENI attenuated chemokine expression, restrained immune infiltration, and adversely affected survival when combined with ICB, especially with anti-CLTA4 therapy. The combination of stereotactic radiotherapy and ICB led to long-term survival in a subset of mice and was associated with favorable CD8 effector-to-Treg ratios and increased intratumoral density of antigen-specific CD8+ T cells. Although radiotherapy technique (Tumor RT vs. ENI) affected initial tumor control and survival, the ability to reject tumor upon rechallenge was partially dependent upon the mechanism of action of ICB; as radiotherapy/anti-CTLA4 was superior to radiotherapy/anti-PD-1.
Conclusions: Our results highlight that irradiation of the DLN restrains adaptive immune responses through altered chemokine expression and CD8+ T-cell trafficking. These data have implications for combining radiotherapy and ICB, long-term survival, and induction of immunologic memory. Clinically, the immunomodulatory effect of the radiotherapy strategy should be considered when combining stereotactic radiotherapy with immunotherapy. Clin Cancer Res; 24(20); 5058–71. ©2018 AACR.
Causes and Predictors of Readmission in Patients With Atrial Fibrillation Undergoing Catheter Ablation: A National Population‐Based Cohort Study
Authors: Arora Shilpkumar , Lahewala Sopan , Tripathi Byomesh , Mehta Varshil , Kumar Varun , Chandramohan Divya , Lemor Alejandro , Dave Mihir , Patel Nileshkumar , Patel Nilay V. , Palamaner Subash Shantha Ghanshyam , Viles‐Gonzalez Juan , Deshmukh Abhishek 
Published: June 2018

Background

Reducing readmission after catheter ablation (
CA
) in atrial fibrillation (AF) is important.

Methods and Results

We utilized National Readmission Data (
NRD
) 2010–2014.
AF
was identified by
International Classification of Diseases, Ninth Edition, Clinical Modification (ICD‐9‐CM)
diagnostic code 427.31 in the primary field, while first
CA
of
AF
was identified via
ICD‐9
‐procedure code 37.34. Any admission within 30 or 90 days of index admission was considered a readmission. Cox proportional hazard regression was used to adjust for confounders. The primary outcomes were 30‐ and 90‐day readmissions and the secondary outcome was
AF
recurrence. In total, 1 128 372 patients with
AF
were identified from January 1, 2010 to September 30, 2014. Of which 37 360 (3.3%) underwent
CA
. Patients aged ≥65 years and female sex were less likely to receive
CA
for
AF
. Overall, 10.9% and 16.5% of
CA
patients were readmitted within 30 and 90 days post‐CA, respectively. Most common causes of readmissions were arrhythmia (
AF
, atrial flutter), heart failure, pulmonary causes (pneumonia, chronic obstructive pulmonary disease) and bleeding complications (gastrointestinal bleed, intracranial hemorrhage). Patients with diabetes mellitus, heart failure, coronary artery disease (
CAD
), chronic pulmonary and kidney disease, prior stroke/transient ischemic attack (TIA), female sex, length of stay ≥2 and disposition to the facility were prone to higher 30‐ and 90‐day readmissions post
‐CA
. Predictors of increase in
AF
recurrence post‐
CA
were female sex, diabetes mellitus, chronic pulmonary disease, and length of stay ≥2. Trends of 90‐day readmission and
AF
recurrence were found to improve over the study period.

Conclusions

We identified several demographic and clinical factors associated with the use of
CA
in
AF
, and short‐term outcomes of the same, which could potentially help in the patient selection and improve outcomes.
Linear Stability of Moist Convecting Atmospheres. Part I: From Linear Response Functions to a Simple Model and Applications to Convectively Coupled Waves
Authors: Kuang Zhiming 
Published: June 2018

Abstract
A procedure is presented to systematically construct simple models for the linear stability of moist convecting atmospheres. First, linear response functions of a cumulus ensemble constructed from cloud-system-resolving models are coupled with matrices expressing two-dimensional large-scale linear wave dynamics. For a radiative–convective equilibrium reference state, this model gives two branches of unstable modes: a propagating convectively coupled wave branch and a stationary branch related to storage of column-integrated moist static energy (MSE). The stationary branch is unstable only when radiative feedback is included, while the convectively coupled wave branch is less affected by radiative feedback. With a modular order-reduction procedure from control theory, the linear-response-function-based model is reduced to a system of six ordinary differential equations while still capturing the essential features of the unstable modes (eigenvalues and structures). The six-dimensional system is then split into a slow and a fast manifold. The slow manifold (again, reflecting column MSE storage) is essential for the stationary mode but not for the convectively coupled waves. The fast manifold is then transformed into a form similar to that of prior simple models of convectively coupled waves, thus placing those models and the insights derived from them on a firmer footing. The procedure also better quantifies the parameters of such simple models and allows the stability difference between different reference states to be better understood.
A Numerical Study on the Extreme Intensification of Hurricane Patricia (2015)
Authors: Fox K. Ryder , Judt Falko 
Published: June 2018

Abstract
In October 2015 Hurricane Patricia stormed through the eastern Pacific, taking its place as the strongest hurricane in recorded history when its intensity reached a record breaking 185 kt (1 kt = 0.51 m s−1). Operational models and the National Hurricane Center’s official forecast failed to predict Patricia’s unprecedented intensification, provoking questions as to whether such an extreme event can actually be forecast. This study reports on the successful simulation of Patricia using a state-of-the-art high-resolution numerical weather prediction model. It was found that high model resolution (Δx ≤ 1 km), vortex initialization, and the parameterization of dissipative heating were key factors in realistically simulating Patricia’s intensity evolution. The simulation was used to investigate Patricia’s environment in terms of sea surface temperature, vertical wind shear, and humidity, under the premise that a simulation able to capture Patricia’s peak intensity would also accurately represent Patricia’s environment. Compared with a climatology derived from the Statistical Hurricane Intensity Prediction Scheme dataset, sea surface temperature ranked in the 99th percentile and environmental vertical wind shear in the 83rd percentile (ordered from high to low). However, humidity ranked more moderately. Ensemble forecasts indicate that Patricia had relatively high predictability in comparison to other well-studied rapid intensification cases such as 2010’s Hurricane Earl. The results from this study imply that high-resolution models are in principle able to predict the intensity of extreme hurricanes like Patricia.
Human Performance Deterioration Due to Prolonged Wakefulness Can Be Accurately Detected Using Time-Varying Spectral Analysis of Electrodermal Activity
Authors: Posada-Quintero Hugo F. , Bolkhovsky Jeffrey B. , Qin Michael , Chon Ki H. 
Published: June 2018

Objective: The aim was to determine if indices of the autonomic nervous system (ANS), derived from the electrodermal activity (EDA) and electrocardiogram (ECG), could be used to detect deterioration in human cognitive performance on healthy participants during 24-hour sleep deprivation. Background: The ANS is highly sensitive to sleep deprivation. Methods: Twenty-five participants performed a desktop-computer-based version of the psychomotor vigilance task (PVT) every 2 hours. Simultaneously with reaction time (RT) and false starts from PVT, we measured EDA and ECG. We derived heart rate variability (HRV) measures from ECG recordings to assess dynamics of the ANS. Based on RT values, average reaction time (avRT), minor lapses (RT > 500 ms), and major lapses (RT > 1 s) were computed as indices of performance, along with the total number of false starts. Results: Performance measurement results were consistent with the literature. The skin conductance level, the power spectral index, and the high-frequency components of HRV were not significantly correlated to the indices of performance. The nonspecific skin conductance responses, the time-varying index of EDA (TVSymp), and normalized low-frequency components of HRV were significantly correlated to indices of performance ( p < 0.05). TVSymp exhibited the highest correlation to avRT (–0.92), major lapses (–0.85), and minor lapses (–0.83). Conclusion: We conclude that indices that account for high-frequency dynamics in the EDA, specifically the time-varying approach, constitute a valuable tool for understanding the changes in the autonomic nervous system. Application: This can be used to detect the adverse effects of prolonged wakefulness on human performance.
External snapping hip: a systematic review of outcomes following surgical intervention: External snapping hip systematic review
Authors: Pierce Todd P , Kurowicki Jennifer , Issa Kimona , Festa Antony , Scillia Anthony J , McInerney Vincent K 
Published: June 2018

Purpose: To evaluate the outcomes of surgical management for external snapping hip in terms of: (1) recurrence; (2) complications; and (3) return to pre-injury activities. Methods: A thorough review of 4 electronic databases- EMBASE, CINAHL Plus, PubMed, and Scopus was performed to find all relevant studies for this review that were published between January 2000 and January 2017 that addressed surgical treatment for external snapping hip. The following reports were excluded: (1) non-English manuscripts; (2) n ⩽ 5; (3) clinical reviews; (4) surgical technique notes; (5) studies only analysing diagnosis; and (6) nonoperative management studies. After cross-referencing, a total of 7 reports were included. Each of these studies was analysed for the incidence of recurrence, revision surgery, complications, and return to pre-injury activity level. Results: There was a recurrence rate of 7% ( n = 8 of 113 hips) with only 1 requiring revision surgery (1%). The cumulative complication rate was 9% ( n = 10 of 113) with all complications being residual weakness. Additionally, we found 98% ( n = 58 of 59) of the patients returned to their pre-injury level of activity. Conclusions: We found operative treatment for external snapping hip to be both safe and efficacious for returning patients to their pre-injury activities. When recurrence does occur, it often is painless and does not require revision surgery. Future studies should be larger and evaluate different surgical techniques to further elucidate the safety and efficacy of surgical treatment for external snapping hip.
Prescribed physical activity maintenance following exercise based cardiac rehabilitation: factors predicting low physical activity
Authors: Dagner Viveka , Clausson Eva K , Jakobsson Liselotte 
Published: June 2018

Background: Physical activity is important to reduce mortality, morbidity and risk factors in patients with coronary heart disease. This report evaluates to what extent patients are still physically active following an exercise-based cardiac rehabilitation programme 12–14 months post-myocardial infarction and factors predicting why not. Methods: Data from the National Quality Registry Swedeheart with post-myocardial infarction patients ( n=368) admitted from July 2012 to November 2014 were collected with outcomes of physical activity after 12–14 months. Baseline data included demographics, clinical variables, participation in exercise programmes, prescribed physical activity, health-related quality of life and self-reported health (EQ-5D-3L/EQ-VAS). A direct binary logistic regression analysis was used to identify indicators of low physical activity. Results: Physical activity frequency per week (PA/week) was low, i.e. zero to three times, in older patients over 64 years ( P=0.00) and in those having problems with pain/discomfort (138 PA/week vs. 195) ( P=0.01), problems with mobility (60 PA/week vs.273) ( P=0.04) and anxiety/depression (128 PA/week vs. 205) ( P=0.04). Conclusion: Indicators predicting low physical activity can be used targeting improved post-myocardial infarction care outlining person-centred rehabilitation programmes and specialist nursing-led programmes.
Acute and chronic pain affects local field potential of the medial prefrontal cortex in different band neural oscillations
Authors: Fu Bo , Wen Shao-nan , Wang Bin , Wang Kun , Zhang Ji-yan , Liu Shao-jun 
Published: June 2018

The medial prefrontal cortex is involved in the process of sensory discrimination. In this study, we examined the local field potential activity response to the different stages of pain in the prelimbic cortex (PrL) which is a sub-region of the medial prefrontal cortex. Recent studies revealed extensive information about neural oscillations, but there is limited information on the local field potential profiles for acute or chronic pain, particularly in freely moving animals. This study showed that acute mechanical pain increases alpha oscillation and decreases beta and gamma oscillations before spared nerve injury surgery. Delta oscillation was decreased by chronic pain and gamma oscillation varied with time. However, acute mechanical pain stimulus had no effects on local field potential in rats under mechanical allodynia. Together, our findings provide novel insights into the role of medial prefrontal cortex local field potential activity response to pain stimulus.