bluuebunny/crossref_metadata_2025_split huggingface dataset:
NRP1 regulates HMGB1 in vascular endothelial cells under high homocysteine condition
Authors: Ma Yeshuo , Zhang Zhen , Chen Runtai , Shi Rui , Zeng Pingyu , Chen Ruifang , Leng Yiping , Chen Alex F. 
Published: February 2019

Endothelial inflammation plays an important role in hyperhomocysteinemia (HHcy)-associated vascular diseases. High mobility group box 1 (HMGB1) is a pro-inflammatory danger molecule produced by endothelial cells. However, whether HMGB1 is involved in vascular endothelial inflammation of HHcy is poorly understood. Neuropilin-1 (NRP1) mediates inflammatory response and activates mitogen-activated protein kinases (MAPKs) pathway that has been reported to be involved in regulation of HMGB1. The aim of this study was to determine the alteration of HMGB1 in HHcy, and the role of NRP1 in regulation of endothelial HMGB1 under high homocysteine (Hcy) condition. In the present study, we first observed that the plasma level of HMGB1 was elevated in HHcy patients and an experimental rat model, and increased HMGB1 was also observed in the thoracic aorta of an HHcy rat model. HMGB1 was induced by Hcy accompanied with upregulated NRP1 in vascular endothelial cells. Overexpression of NRP1 promoted expression and secretion of HMGB1 and endothelial inflammation; knockdown of NRP1 inhibited HMGB1 and endothelial inflammation induced by Hcy, which partially regulated through p38 MAPK pathway. Furthermore, NRP1 inhibitor ATWLPPR reduced plasma HMGB1 level and expression of HMGB1 in the thoracic aorta of HHcy rats. In conclusion, our data suggested that Hcy requires NRP1 to regulate expression and secretion of HMGB1. The present study provides the evidence for inhibition of NRP1 and HMGB1 to be the novel therapeutic targets of vascular endothelial inflammation in HHcy in the future. NEW & NOTEWORTHY This study shows for the first time to our knowledge that the plasma level of high mobility group box 1 (HMGB1) is elevated in hyperhomocysteinemia (HHcy) patients, and homocysteine promotes expression and secretion of HMGB1 partially regulated by neuropilin-1 in endothelial cells, which is involved in endothelial inflammation. Most importantly, these new findings will provide a potential therapeutic strategy for vascular endothelial inflammation in HHcy.
(Not Giving Up) The Marathon Race of MET Targeting Therapy: Are We There Yet?
Authors: Ma Patrick C. 
Published: February 2019

Abstract
Among the various MET aberrations, MET amplification and METex14 have emerged as valid predictive biomarkers for MET inhibition. Despite challenges that have limited the development of MET inhibitors, we can learn from the latest efforts in biomarker-based therapy to better identify the patients who will benefit from treatment with these agents.
See related articles by Hong et al., p. 2403 and Van Cutsem et al., p. 2414
Chronic Atrial and Ventricular Pacing in the Mouse
Authors: Ståhlberg Marcus , Nakagawa Ryo , Bedja Djahida , Zhu Guangshuo , Lin Brian L. , Saberi Amir , Lee Dong I. , Kass David A. 
Published: February 2019

Background:
The mouse is the most widely used mammal in experimental biology. Although many clinically relevant in vivo cardiac stressors are used, one that has eluded translation is long-term cardiac pacing. Here, we present the first method to chronically simulate and simultaneously record cardiac electrical activity in conscious mobile mice. We then apply it to study right ventricular pacing induced electromechanical dyssynchrony and its reversal (resynchronization).

Methods and Results:
The method includes a custom implantable bipolar stimulation and recording lead and flexible external conduit and electrical micro-commutator linked to a pulse generator/recorder. This achieved continuous pacing for at least 1 month in 77% of implants. Mice were then subjected to cardiac ischemia/reperfusion injury to depress heart function, followed by 4 weeks pacing at the right ventricle (dyssynchrony), right atrium (synchrony), or for 2 weeks right ventricle and then 2 weeks normal sinus (resynchronization). Right ventricular pacing–induced dyssynchrony substantially reduced heart and myocyte function compared with the other groups, increased gene expression heterogeneity (>10 fold) comparing septum to lateral walls, and enhanced growth and metabolic kinase activity in the late-contracting lateral wall. This was ameliorated by restoring contractile synchronization.

Conclusions:
The new method to chronically pace conscious mice yields stable atrial and ventricular capture and a means to dissect basic mechanisms of electromechanical physiology and therapy. The data on dyssynchrony and resynchronization in ischemia/reperfusion hearts is the most comprehensive to date in ischemic heart disease, and its similarities to nonischemic canine results support the translational utility of the mouse.
Abnormal Fractional Flow Reserve in Nonobstructive Coronary Artery Disease
Authors: Imai Shunsuke , Kondo Takeshi , Stone Gregg W. , Kawase Yoshiaki , Ahmadi Amir A. , Narula Jagat , Matsuo Hitoshi 
Published: February 2019

Background:
The basis of discordance between invasive coronary angiographic (ICA) anatomic stenosis and fractional flow reserve (FFR) is not fully understood. We analyzed coronary computed tomography angiography (CTA) characteristics of ICA-verified nonobstructive lesions in the proximal or midleft anterior descending artery with FFR ≤0.8, that is, anatomy-physiology mismatch.

Methods and Results:

CTA and ICA were performed in 108 patients. FFR was measured during intravenous ATP (180 μg/[kg·min]) infusion. CTA-verified plaque characteristics between 53 consecutive ICA-FFR mismatch (ICA–quantitative coronary angiography <50%, FFR≤0.8) and 55 ICA-FFR match (ICA–quantitative coronary angiography<50%, FFR>0.8) vessels were compared. CTA-verified vessel area (20.7±6.7 versus 16.9±4.8 mm
2
;
P
=0.0007), positive area remodeling index (ARI; 1.38±0.23 versus 1.06±0.11;
P
<0.0001), %plaque area (64.7±12.7 versus 57.4±8.5%;
P
<0.0007), jeopardized myocardial mass (46.2±18.5 versus 37.1±14.3 g;
P
= 0.006), and the prevalence of low attenuation plaque (45.3% versus 9.1%;
P
<0.0001) at the minimum lumen area were significantly higher in the ICA-FFR mismatch than the match group. By receiver operation curve analysis, the areas under the curve for positive area remodeling index, %plaque area and jeopardized myocardial mass were 0.921, 0.681, and 0.641, respectively, for the diagnosis of mismatch (cutoff values 1.13, 66% and 58.7 g, respectively). The sensitivity and specificity of area remodeling index >1.13 for predicting ICA-FFR mismatch were 88.7% and 78.2%, respectively.

Conclusions:
In the absence of anatomically significant stenosis, abnormal FFR is more frequently encountered in patients with CTA-derived positive remodeling, larger plaque burden, and low attenuation plaque. These findings contribute to a better understanding of how FFR-based decision-making might translate into demonstrated superior clinical outcomes.
Developing and Testing a Personalized, Evidence-Based, Shared Decision-Making Tool for Stent Selection in Percutaneous Coronary Intervention Using a Pre-Post Study Design
Authors: Chhatriwalla Adnan K. , Decker Carole , Gialde Elizabeth , Catley Delwyn , Goggin Kathy , Jaschke Katie , Jones Philip , deBronkart Dave , Sun Tony , Spertus John A. 
Published: February 2019

Background:
Drug-eluting stents reduce the risk of restenosis in patients undergoing percutaneous coronary intervention, but their use necessitates prolonged dual antiplatelet therapy, which increases costs and bleeding risk, and which may delay elective surgeries. While >80% of patients in the United States receive drug-eluting stents, less than a third report that their physicians discussed options with them.

Methods and Results:

An individualized shared decision-making (SDM) tool for stent selection was designed and implemented at 2 US hospitals. In the postimplementation phase, all patients received the SDM tool before their procedure, with or without decision coaching from a trained nurse. All patients were interviewed with respect to their knowledge of stents, their participation in SDM, and their stent preference. Between May 2014 and December 2016, 332 patients not receiving the SDM tool, 113 receiving the SDM tool with coaching, and 136 receiving the tool without coaching were interviewed. Patients receiving the SDM tool + coaching, as compared with usual care, demonstrated higher knowledge scores (mean difference +1.8;
P
<0.001), reported more frequent participation in SDM (odds ratio=2.96;
P
<0.001), and were more likely to state a stent preference (odds ratio=2.00;
P
<0.001). No significant differences were observed between the use of the SDM tool without coaching and usual care. For patients who voiced a stent preference, concordance between stent desired and stent received was 98% for patients who preferred a drug-eluting stent and 50% for patients who preferred a bare metal stent. The SDM tool (with or without coaching) had no impact on stent selection or concordance.

Conclusions:
An SDM tool for stent selection was associated with improvements in patient knowledge and SDM only when accompanied by decision coaching. However, the SDM tool (with or without coaching) had no impact on stent selection or concordance between patients’ stent preference and stent received, suggesting that physician-level barriers to SDM may exist.

Clinical Trial Information

URL:
https://www.clinicaltrials.gov
. Unique Identifier: NCT02046902.
Sex‐Specific Treatment Effects After Primary Percutaneous Intervention: A Study on Coronary Blood Flow and Delay to Hospital Presentation
Authors: Cenko Edina , van der Schaar Mihaela , Yoon Jinsung , Kedev Sasko , Valvukis Marija , Vasiljevic Zorana , Ašanin Milika , Miličić Davor , Manfrini Olivia , Badimon Lina , Bugiardini Raffaele 
Published: February 2019

Background

We hypothesized that female sex is a treatment effect modifier of blood flow and related 30‐day mortality after primary percutaneous coronary intervention (
PCI
) for
ST
‐segment–elevation myocardial infarction and that the magnitude of the effect on outcomes differs depending on delay to hospital presentation.

Methods and Results

We identified 2596 patients enrolled in the
ISACS
‐
TC
(International Survey of Acute Coronary Syndromes in Transitional Countries) registry from 2010 to 2016. Primary outcome was the occurrence of 30‐day mortality. Key secondary outcome was the rate of suboptimal post‐
PCI
Thrombolysis in Myocardial Infarction (
TIMI
; flow grade 0–2). Multivariate logistic regression and inverse probability of treatment weighted models were adjusted for baseline clinical covariates. We characterized patient outcomes associated with a delay from symptom onset to hospital presentation of ≤120 minutes. In multivariable regression models, female sex was associated with postprocedural
TIMI
flow grade 0 to 2 (odds ratio [
OR
], 1.68; 95%
CI
, 1.15–2.44) and higher mortality (
OR,
1.72; 95%
CI
, 1.02–2.90). Using inverse probability of treatment weighting, 30‐day mortality was higher in women compared with men (4.8% versus 2.5%;
OR
, 2.00; 95%
CI
, 1.27–3.15). Likewise, we found a significant sex difference in post‐
PCI TIMI
flow grade 0 to 2 (8.8% versus 5.0%;
OR
, 1.83; 95%
CI
, 1.31–2.56). The sex gap in mortality was no longer significant for patients having hospital presentation of ≤120 minutes (
OR
, 1.28; 95%
CI
, 0.35–4.69). Sex difference in post‐
PCI TIMI
flow grade was consistent regardless of time to hospital presentation.

Conclusions

Delay to hospital presentation and suboptimal post‐
PCI TIMI
flow grade are variables independently associated with excess mortality in women, suggesting complementary mechanisms of reduced survival.

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
01218776.
The Response of the Midlatitude Jet to Regional Polar Heating in a Simple Storm-Track Model
Authors: Ruggieri Paolo , Kucharski Fred , Novak Lenka 
Published: February 2019

AbstractGiven the recent changes in the Arctic sea ice, understanding the effects of the resultant polar warming on the global climate is of great importance. However, the interaction between the Arctic and midlatitude circulation involves a complex chain of mechanisms, which leaves state-of-the-art general circulation models unable to represent this interaction unambiguously. This study uses an idealized general circulation model to provide a process-based understanding of the sensitivity of the midlatitude circulation to the location of high-latitude warming. A simplified atmosphere is simulated with a single zonally localized midlatitude storm track, which is analogous to the storm tracks in the Northern Hemisphere. It is found that even small changes in the position of the forcing relative to that storm track can lead to very different responses in the midlatitude circulation. More specifically, it is found that heating concentrated in one region may cause a substantially stronger global response compared to when the same amount of heating is distributed across all longitudes at the same latitude. Linear interference between climatological and anomalous flow is an important component of the response, but it does not explain differences between different longitudes of the forcing. Feedbacks from atmospheric transient eddies are found to be associated with this strong response. A dependence between the climatological jet latitude and the jet response to polar surface heating is found. These results can be used to design and interpret experiments with complex state-of-the-art models targeted at Arctic–midlatitude interactions.
On the Use of Geophysical Parameters for the Top-of-Atmosphere Shortwave Clear-Sky Radiance-to-Flux Conversion in EarthCARE
Authors: Tornow F. , Domenech C. , Fischer J. 
Published: February 2019

AbstractWe have investigated whether differences across Clouds and the Earth’s Radiant Energy System (CERES) top-of-atmosphere (TOA) clear-sky angular distribution models, estimated separately over regional (1° × 1° longitude–latitude) and temporal (monthly) bins above land, can be explained by geophysical parameters from Max Planck Institute Aerosol Climatology, version 1 (MAC-v1), ECMWF twentieth-century reanalysis (ERA-20C), and a MODIS bidirectional reflectance distribution function (BRDF)/albedo/nadir BRDF-adjusted reflectance (NBAR) Climate Modeling Grid (CMG) gap-filled products (MCD43GF) climatology. Our research aimed to dissolve binning and to isolate inherent properties or indicators of such properties, which govern the TOA radiance-to-flux conversion in the absence of clouds. We collocated over seven million clear-sky footprints from CERES Single Scanner Footprint (SSF), edition 4, data with above geophysical auxiliary data. Looking at data per surface type and per scattering direction—as perceived by the broadband radiometer (BBR) on board Earth Clouds, Aerosol and Radiation Explorer (EarthCARE)—we identified optimal subsets of geophysical parameters using two different methods: random forest regression followed by a permutation test and multiple linear regression combined with the genetic algorithm. Using optimal subsets, we then trained artificial neural networks (ANNs). Flux error standard deviations on unseen test data were on average 2.7–4.0 W m−2, well below the 10 W m−2 flux accuracy threshold defined for the mission, with the exception of footprints containing fresh snow. Dynamic surface types (i.e., fresh snow and sea ice) required simpler ANN input sets to guarantee mission-worthy flux estimates, especially over footprints consisting of several surface types.
Stochastic Parameterization of Subgrid-Scale Velocity Enhancement of Sea Surface Fluxes
Authors: Bessac Julie , Monahan Adam H. , Christensen Hannah M. , Weitzel Nils 
Published: February 2019

Abstract
Subgrid-scale (SGS) velocity variations result in gridscale sea surface flux enhancements that must be parameterized in weather and climate models. Traditional parameterizations are deterministic in that they assign a unique value of the SGS velocity flux enhancement to any given configuration of the resolved state. In this study, we assess the statistics of SGS velocity flux enhancement over a range of averaging scales (as a proxy for varying model resolution) through systematic coarse-graining of a convection-permitting atmospheric model simulation over the Indian Ocean and west Pacific warm pool. Conditioning the statistics of the SGS velocity flux enhancement on 1) the fluxes associated with the resolved winds and 2) the precipitation rate, we find that the lack of a separation between “resolved” and “unresolved” scales results in a distribution of flux enhancements for each configuration of the resolved state. That is, the SGS velocity flux enhancement should be represented stochastically rather than deterministically. The spatial and temporal statistics of the SGS velocity flux enhancement are investigated by using basic descriptive statistics and through a fit to an anisotropic space–time covariance structure. Potential spatial inhomogeneities of the statistics of the SGS velocity flux enhancement are investigated through regional analysis, although because of the relatively short duration of the simulation (9 days) distinguishing true inhomogeneity from sampling variability is difficult. Perspectives for the implementation of such a stochastic parameterization in weather and climate models are discussed.
Outcomes Using a Postoperative Protocol in Pediatric Single-Stage Laryngotracheal Reconstruction
Authors: Thottam Prasad John , Gilliland Taylor , Ettinger Nicholas , Baijal Rahul , Mehta Deepak 
Published: February 2019

Objectives: The aim of this study was to evaluate single-stage laryngotracheal reconstruction (ssLTR) outcomes before and after the implementation of a postoperative care protocol in pediatric patients. Methods: A case-control study with chart review was conducted at 2 tertiary academic centers from 2010 to 2016. Pediatric patients who underwent ssLTR with a postoperative care protocol were compared with those who did not receive care under this protocol. Data regarding perioperative management were collected and compared using χ2 and Wilcoxon rank tests. Planned extubation, length of intubation in the intensive care unit, and complications were examined. Results: Nineteen patients completed ssLTR after the protocol was initiated, and 26 prior patients were used as control subjects. Planned extubation failed in 9 patients (35%) in the control group compared with 1 patient (5%) in the protocol group ( P < .05). Using a structured protocol demonstrated a decrease in delayed extubation and intensive care unit stay ( P < .05). Despite more postprotocol patients’ requiring posterior graft placement, preprotocol patients were less likely to be extubated within 7 days ( P < .05). Conclusions: The authors propose an intensive care unit protocol that uses a combination of pharmacologic agents to optimally reduce the risk for adverse events that delay time to extubation and thus decannulation. Timely extubation was more likely with the use of this postoperative care protocol using a multidisciplinary approach involving otolaryngologists, pharmacists, intensivists, and anesthesiologists.
A study investigating the validity of an accelerometer in quantification of step count in adult hospital inpatients recovering from critical illness
Authors: Anderson Jayne Lesley , Yoward L Samantha , Green Angela J 
Published: February 2019

Objective: To determine the validity of the ActiGraph GT3X accelerometer in step count quantification when compared to observed step count in hospitalised adults recovering from critical illness. Setting: Large National Health Service (NHS) Hospitals Trust. Subjects: In total, 20 hospital ward-based adults (age: mean 62.3, SD 11.5) who had required greater than 48 hours of mechanical ventilation in the intensive care unit. Main measures: Participants walked self-selected distances and speeds as part of a semi-structured movement protocol not exceeding 3 hours. Two ActiGraph GT3X accelerometers were worn, one on the thigh and one on the ankle of the non-dominant leg. Accelerometer-recorded step counts were compared against observed step counts. Results: In total, 31 separate walking episodes were analysed. A mean (SD) of 45.87 (±19.72) steps was calculated for observed step count (range 15–90). Mean differences (95% limits of agreement) of −0.84 steps (−3.88 to 2.2) for the ankle placement and −17.7 steps (−40.63 to 5.25) for the thigh were calculated. Intraclass correlation coefficients (95% confidence intervals) of 0.99 (0.99 to 1.0) and 0.46 (−0.1 to 0.78) were determined for the ankle and thigh, respectively. Placement sites were well tolerated by 95% of participants. Conclusion: An ankle-mounted ActiGraph GT3X accelerometer demonstrates validity in quantification of step count in hospitalised adults recovering from critical illness. A thigh placement was not considered valid.
Trends in the Utilization of Life-Sustaining Procedures and Palliative Care Consultation Among Dying Patients With Advanced Chronic Pancreas Illnesses in US Hospitals: 2005 to 2014
Authors: Liu Xibei , Shen Jay J. , Kim Pearl , Kim Sun Jung , Ukken Johnson , Choi Younseon , Hwang In Choel , Lee Jae-Hoon , Chun Sung-Youn , Hwang Jinwook , Choi Haneul , Yeom Hyeyoung , Lee Yong-Jae , Yoo Ji Won 
Published: February 2019

Aim: Pancreas cancer continues to carry a poor prognosis. Hospitalized patients with advanced chronic pancreatic illnesses increasingly receive palliative care due to its perceived clinical benefits. Meanwhile, a growing proportion of elderly patients are reportedly receiving life-sustaining procedures. Temporal trends in the utilization of life-sustaining procedures and palliative care consultation among dying patients with advanced chronic pancreatic illnesses in US hospitals were examined. Methods and Materials: A serial, cross-sectional analysis was carried out using the National Inpatient Sample Database. Decedents 18 years and older with a principal diagnosis of pancreas cancer or other advanced chronic pancreatic illnesses from 2005 through 2014. The compound annual growth rates (CAGRs) and Cochrane-Armitage correction of χ2 statistic were used. The receipt of life-sustaining systemic procedures, intra-abdominal local procedures and surgeries, and palliative care consultation were examined. Multilevel multivariate logistic regressions were performed to examine the association of various procedures with the utilization of palliative care consultation. Results: Among 77 394 183 hospitalizations, 29 515 patients were examined. The CAGRs of systemic procedures, intra-abdominal procedures, surgeries, and palliative care were −4.19% ( P = .008), 2.17%, −1.40%, and 14.03% ( P < .001), respectively. The receipt of systemic procedures (odds ratio [OR] = 2.40, 95% confidence interval [CI], 2.08-2.74), local intra-abdominal procedures (OR = 1.46, 95% CI, 1.27-1.70), and surgeries (OR = 2.51, 95% CI, 2.07-3.05) was associated with palliative care consultation ( Ps < .001). Conclusions: Among adults with pancreatic cancer or other advanced chronic pancreatic illnesses in the US hospitals from 2005 to 2014, the utilization of life-sustaining systemic procedures decreased while the prevalence of palliative care consultation increased.