bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thymic Stromal Chemokine TSLP Acts through Th2 Cytokine Production to Induce Cutaneous T-cell Lymphoma
Authors: Takahashi Naomi , Sugaya Makoto , Suga Hiraku , Oka Tomonori , Kawaguchi Makiko , Miyagaki Tomomitsu , Fujita Hideki , Sato Shinichi 
Published: September 2016

AbstractThymic stromal lymphopoietin (TSLP) activates dendritic cells to induce Th2-mediated inflammation. Periostin, an extracellular matrix protein produced by fibroblasts, induces chronic inflammation by stimulating TSLP production. Recently, a reinforcing cycle linking Th2-type immune responses with periostin-induced keratinocyte activation has been proposed in atopic dermatitis pathogenesis. In this study, we investigated the role of TSLP and periostin in the development of cutaneous T-cell lymphoma (CTCL), where Th2 cytokines and chemokines are also dominant. TSLP and periostin mRNA expression levels were elevated in CTCL lesional skin, both of which correlated with IL4 expression levels. In vitro and ex vivo, IL4 or IL13 stimulated periostin expression by dermal fibroblasts, and fibroblasts from CTCL lesional skin expressed higher levels of periostin than those from control skin. Serum periostin levels of CTCL patients were also significantly higher than those of healthy individuals. Hut78 and MJ, CTCL cell lines, and peripheral blood mononuclear cells from leukemic CTCL patients expressed the TSLP receptor. TSLP induced production of IL4 and IL13 by Hut78 and MJ cells through the activation of STAT5. Moreover, TSLP induced proliferation of CTCL cells both in vitro and in vivo. These data suggest that periostin-mediated TSLP production by keratinocytes directly stimulates CTCL tumor cell growth in addition to inducing a Th2-dominant tumor environment in CTCL. Cancer Res; 76(21); 6241–52. ©2016 AACR.
Neoadjuvant Chemotherapy of Ovarian Cancer Results in Three Patterns of Tumor-Infiltrating Lymphocyte Response with Distinct Implications for Immunotherapy
Authors: Lo Charlotte S. , Sanii Sanaz , Kroeger David R. , Milne Katy , Talhouk Aline , Chiu Derek S. , Rahimi Kurosh , Shaw Patricia A. , Clarke Blaise A. , Nelson Brad H. 
Published: September 2016

Abstract
Purpose: Some forms of chemotherapy can enhance antitumor immunity through immunogenic cell death, resulting in increased T-cell activation and tumor infiltration. Such effects could potentially sensitize tumors to immunotherapies, including checkpoint blockade. We investigated whether platinum- and taxane-based chemotherapy for ovarian cancer induces immunologic changes consistent with this possibility.
Experimental Design: Matched pre- and post-neoadjuvant chemotherapy tumor samples from 26 high-grade serous carcinoma (HGSC) patients were analyzed by immunohistochemistry (IHC) for a large panel of immune cells and associated factors. The prognostic significance of post-chemotherapy TIL patterns was assessed in an expanded cohort (n = 90).
Results: Neoadjuvant chemotherapy was associated with increased densities of CD3+, CD8+, CD8+ TIA-1+, PD-1+ and CD20+ TIL. Other immune subsets and factors were unchanged, including CD79a+ CD138+ plasma cells, CD68+ macrophages, and MHC class I on tumor cells. Immunosuppressive cell types were also unchanged, including FoxP3+ PD-1+ cells (putative regulatory T cells), IDO-1+ cells, and PD-L1+ cells (both macrophages and tumor cells). Hierarchical clustering revealed three response patterns: (i) TILhigh tumors showed increases in multiple immune markers after chemotherapy; (ii) TILlow tumors underwent similar increases, achieving patterns indistinguishable from the first group; and (iii) TILnegative cases generally remained negative. Despite the dramatic increases seen in the first two patterns, post-chemotherapy TIL showed limited prognostic significance.
Conclusions: Chemotherapy augments pre-existing TIL responses but fails to relieve major immune-suppressive mechanisms or confer significant prognostic benefit. Our findings provide rationale for multipronged approaches to immunotherapy tailored to the baseline features of the tumor microenvironment. Clin Cancer Res; 23(4); 925–34. ©2016 AACR.
Magnetic Resonance Characterization of Cardiac Adaptation and Myocardial Fibrosis in Pulmonary Hypertension Secondary to Systemic-To-Pulmonary Shunt
Authors: Pereda Daniel , García-Lunar Inés , Sierra Federico , Sánchez-Quintana Damián , Santiago Evelyn , Ballesteros Constanza , Encalada Juan F. , Sánchez-González Javier , Fuster Valentín , Ibáñez Borja , García-Álvarez Ana 
Published: September 2016

Background—
Pulmonary hypertension (PH) and right ventricular (RV) dysfunction are strong predictors of morbidity and mortality among patients with congenital heart disease. Early detection of RV involvement may be useful in the management of these patients. We aimed to assess progressive cardiac adaptation and quantify myocardial extracellular volume in an experimental porcine model of PH because of aorto-pulmonary shunt using cardiac magnetic resonance (CMR).

Methods and Results—
To characterize serial cardiac adaptation, 12 pigs (aorto-pulmonary shunt [n=6] or sham operation [n=6]) were evaluated monthly with right heart catheterization, CMR, and computed tomography during 4 months, followed by pathology analysis. Extracellular volume by CMR in different myocardial regions was studied in 20 animals (aorto-pulmonary shunt [n=10] or sham operation [n=10]) 3 months after the intervention. All shunted animals developed PH. CMR evidenced progressive RV hypertrophy and dysfunction secondary to increased afterload and left ventricular dilatation secondary to volume overload. Shunt flow by CMR strongly correlated with PH severity, left ventricular end-diastolic pressure, and left ventricular dilatation. T1-mapping sequences demonstrated increased extracellular volume at the RV insertion points, the interventricular septum, and the left ventricular lateral wall, reproducing the pattern of fibrosis found on pathology. Extracellular volume at the RV insertion points strongly correlated with pulmonary hemodynamics and RV dysfunction.

Conclusions—
Prolonged systemic-to-pulmonary shunting in growing piglets induces PH with biventricular remodeling and myocardial fibrosis that can be detected and monitored using CMR. These results may be useful for the diagnosis and management of congenital heart disease patients with pulmonary overcirculation.
Neonatal Arterial Morphology Is Related to Body Size in Abnormal Human Fetal Growth
Authors: Olander Rasmus F.W. , Sundholm Johnny K.M. , Ojala Tiina H. , Andersson Sture , Sarkola Taisto 
Published: September 2016

Background—
Restriction in fetal growth is associated with cardiovascular disease in adulthood. It is unclear whether abnormal intrauterine growth influences arterial morphology during the fetal or neonatal stage. The objective was to study the regional arterial morphology with respect to gestational age and abnormal fetal body size.

Methods and Results—

We studied body anthropometrics and arterial morphology and physiology in 174 neonates born between 31 and 42 weeks of gestation, including neonates with birth weights appropriate, small, and large for age, with very high resolution vascular ultrasound (35–55 MHz). In simple linear regressions, parameters of body size (body weight, body surface area, and organ circumference) and gestational age were statistically significantly associated with common carotid, brachial, femoral arterial parameters (lumen diameter [LD], wall layer thickness [intima-media thickness and intima-media-adventitia thickness], and carotid artery wall stress [CAWS]). Male sex was statistically significantly associated with LD and CAWS. In multiple linear regression models, body size, gestational age, and sex explained a large proportion of the arterial variance (

R
2

range, 0.37–0.47 for LD; 0.09–0.35 for intima-media thickness; 0.21–0.41 for intima-media-adventitia thickness; and 0.23 for CAWS; all models
P
<0.001). Arterial wall layer thickness, LDs, and CAWS were independently and strongly predicted by body size, and no effect of maternal disease was observed when added to the models. Gestational age and male sex were also independently but more weakly associated with arterial LDs and CAWS (
P
<0.01), but not with arterial wall layers.

Conclusions—
These results indicate that the intrauterine growth of fetal arterial LD and wall layer thickness are primarily attributed to body growth overall. LD and CAWS show weaker association with gestational age and sex.
Insights Into Timing, Risk Factors, and Outcomes of Stroke and Transient Ischemic Attack After Transcatheter Aortic Valve Replacement in the PARTNER Trial (Placement of Aortic Transcatheter Valves)
Authors: Kapadia Samir , Agarwal Shikhar , Miller D. Craig , Webb John G. , Mack Michael , Ellis Stephen , Herrmann Howard C. , Pichard Augusto D. , Tuzcu E. Murat , Svensson Lars G. , Smith Craig R. , Rajeswaran Jeevanantham , Ehrlinger John , Kodali Susheel , Makkar Raj , Thourani Vinod H. , Blackstone Eugene H. , Leon Martin B. 
Published: September 2016

Background—
Prior studies of stroke and transient ischemic attack (TIA) after transcatheter aortic valve replacement (TAVR) are limited by reporting and follow-up variability. This is a comprehensive analysis of time-related incidence, risk factors, and outcomes of these events.

Methods and Results—

From April 2007 to February 2012, 2621 patients, aged 84±7.2 years, underwent transfemoral (TF; 1521) or transapical (TA; 1100) TAVR in the PARTNER trial (Placement of Aortic Transcatheter Valves; as-treated), including the continued access registry. Stroke and TIA were identified by protocol and adjudicated by a Clinical Events Committee. Within 30 days of TAVR, 87 (3.3%) patients experienced a stroke (TF 58 [3.8%]; TA 29 [2.7%];
P
=0.09), 85% within 1 week. Instantaneous stroke risk peaked on day 2, then fell to a low prolonged risk of 0.8% by 1 to 2 weeks. Within 30 days, 13 (0.50%) patients experienced a TIA (TF 10 [0.67%]; TA 3 [0.27%];
P
>0.17). Stroke and TIA were associated with lower 1-year survival than expected (TF 47% after stroke versus 82%, and 64% after TIA versus 83%; TA 53% after stroke versus 80%, and 64% after TIA versus 83%). Risk factors for early stroke after TA-TAVR included more postdilatations, pure aortic stenosis without regurgitation, and possibly more pacing runs, earlier date of procedure, and no dual antiplatelet therapy; high pre-TAVR aortic peak gradient was a risk factor for stroke early after TF-TAVR.

Conclusions—
Risk of stroke or TIA is highest early after TAVR and is associated with increased 1-year mortality. Modifications of TAVR, emboli-prevention devices, and better intraprocedural pharmacological protection may mitigate this risk.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00530894.
Differences in Short- and Long-Term Outcomes Among Older Patients With ST-Elevation Versus Non–ST-Elevation Myocardial Infarction With Angiographically Proven Coronary Artery Disease
Authors: Vora Amit N. , Wang Tracy Y. , Hellkamp Anne S. , Thomas Laine , Henry Timothy D. , Goyal Abhinav , Roe Matthew T. 
Published: September 2016

Background—
Among older patients with acute myocardial infarction (MI), it remains uncertain whether there is a time-dependent difference in the risk of recurrent mortality and nonfatal cardiovascular and cerebrovascular events for those with ST-segment–elevation MI (STEMI) compared with those with non–ST-segment–elevation MI.

Methods and Results—

Older patients ≥65 years with acute MI and significant coronary artery disease identified with coronary angiography from the ACTION Registry-GWTG (Get With the Guidelines) were linked to Medicare claims data from 2007 to 2010. We examined the unadjusted cumulative incidence of each outcome studied from hospital discharge through 2 years with log-rank tests and then performed a piece-wise proportional hazards modeling with 2 time periods: discharge to 90 days and 90 days to 2 years. Among the 46 199 patients linked with Medicare data, 17 287 (37.4%) presented with STEMI. Through 2 years, the unadjusted cumulative incidence of all-cause mortality (16.0% versus 19.8%;
P
<0.001) and the composite outcome (21.9% versus 27.9%;
P
<0.001) was lower for STEMI patients. Within the first 90 days, unadjusted rates of mortality (5.5% versus 5.3%) and the composite outcome (7.9% versus 8.1%) were similar but diverged from 90 days to 2 years (mortality, 11.1% versus 15.4%;
P
<0.001; composite outcome, 15.2% versus 21.5%;
P
<0.001). After multivariable adjustment, the adjusted risks of mortality and the composite outcome through 90 days were higher for STEMI patients, whereas risks of mortality and the composite outcome were attenuated from 90 days through 2 years.

Conclusions—
Among older acute MI patients with angiographically confirmed coronary artery disease discharged alive, STEMI patients (compared with non–ST-segment–elevation MI patients) were found to have a lower frequency of unadjusted postdischarge mortality and composite cardiovascular and cerebrovascular outcomes through 2 years after hospital discharge. This analysis provides unique insight into differential short- and long-term risks of ischemic cardiovascular and cerebrovascular outcomes by MI classification among older MI patients with confirmed coronary artery disease surviving to hospital discharge.
Influence of Device Choice on the Effect of Intra-Arterial Treatment for Acute Ischemic Stroke in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands)
Authors: Dippel Diederik W. , Majoie Charles B. , Roos Yvo B. , van der Lugt Aad , van Oostenbrugge Robert J. , van Zwam Wim H. , Lingsma Hester F. , Koudstaal Peter J. , Treurniet Kilian M. , van den Berg Lucie A. , Beumer Debbie , Fransen Puck S. , Berkhemer Olvert A. ,   for the MR CLEAN Investigators
Published: September 2016

Background and Purpose—
Intra-arterial treatment by means of retrievable stents has been proven safe and effective. In MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands), the choice of the type of thrombectomy device was left to the discretion of the interventionist. The aim of this study was to explore the differences in functional outcome, neurological recovery, reperfusion, extent of infarction, and adverse events according to stent type and make.

Methods—
The primary outcome was functional outcome at 90 days, assessed with the modified Rankin Scale (mRS). Neuroimaging outcomes included occlusion on computed tomographic angiography at 24 hours, infarct volume at 5 to 7 days, and modified thrombolysis in cerebral infarction scores. Safety outcomes included death within 90 days and any symptomatic intracerebral hemorrhage. We analyzed possible interactions between stent type and treatment with multiple regression models. Treatment effects were adjusted for patient age, stroke severity, and collateral score.

Results—
Of the 500 patients included in the trial, 233 were allocated to intervention. Of these, 124 (53%) were first treated with Trevo (adjusted common odds ratio for shift on the mRS [acOR, 1.98; 95% confidence interval, 1.30–2.92]), 31 (13%) with Solitaire (acOR, 1.90; 95% confidence interval, 0.97–3.73), 40 (17%) with other retrievable stents or mechanical devices (acOR, 0.96; 95% confidence interval, 0.51–3.93], and 38 (16%) could not be treated. There was no interaction between device and treatment effect on functional outcome and all other secondary and safety outcomes.

Conclusions—
We found no evidence for a differential effect of thrombectomy for acute ischemic stroke by type of stent.

Clinical Trial Registration—

URL:
http://www.isrctn.com
. Unique identifier: ISRCTN10888758.
Toward Reduced Representation of Mixing State for Simulating Aerosol Effects on Climate
Authors: Riemer Nicole , Bond Tami C. 
Published: September 2016

AbstractAtmospheric aerosols affect Earth’s energy budget, and hence its climate, by scattering and absorbing solar radiation and by altering the radiative properties and the lifetime of clouds. These two major aerosol effects depend on the optical properties and the cloud-nucleating ability of individual particles, which, in turn, depend on the distribution of components among individual particles, termed the “aerosol mixing state.” Global models have moved toward including aerosol schemes to represent the evolution of particle characteristics, but individual particle properties cannot be resolved in global-scale simulations. Instead, models approximate the aerosol mixing state. The errors in climate-relevant aerosol properties introduced by such approximations may be large but have not yet been well quantified. This paper quantitatively addresses the question of to what extent the aerosol mixing state must be resolved to adequately represent the optical properties and cloud-nucleating properties of particle populations. Using a detailed benchmarking model to simulate gas condensation and particle coagulation, we show that, after the particles evolve in the atmosphere, simple mixing-state representations are sufficient for modeling cloud condensation nuclei concentrations, and we quantify the mixing time scale that characterizes this transformation. In contrast, a detailed representation of the mixing state is required to model aerosol light absorption, even for populations that are fully mixed with respect to their hygroscopic properties.
Radiation Fluxes in a Business District of Shanghai, China
Authors: Ao Xiangyu , Grimmond C. S. B. , Liu Dongwei , Han Zhihui , Hu Ping , Wang Yadong , Zhen Xinrong , Tan Jianguo 
Published: September 2016

AbstractRadiative fluxes are key drivers of surface–atmosphere heat exchanges in cities. Here the first yearlong (December 2012–November 2013) measurements of the full radiation balance for a dense urban site in Shanghai, China, are presented, collected with a CNR4 net radiometer mounted 80 m above ground. Clear-sky incoming shortwave radiation K↓ (median daytime maxima) ranges from 575 W m−2 in winter to 875 W m−2 in spring, with cloud cover reducing the daily maxima by about 160 W m−2. The median incoming longwave radiation daytime maxima are 305 and 468 W m−2 in winter and summer, respectively, with increases of 30 and 15 W m−2 for cloudy conditions. The effect of air quality is evident: haze conditions decrease hourly median K↓ by 11.3%. The midday (1100–1300 LST) clear-sky surface albedo α is 0.128, 0.141, 0.143, and 0.129 for winter, spring, summer, and autumn, respectively. The value of α varies with solar elevation and azimuth angle because of the heterogeneity of the urban surface. In winter, shadows play an important role in decreasing α in the late afternoon. For the site, the bulk α is 0.14. The Net All-Wave Radiation Parameterization Scheme/Surface Urban Energy and Water Balance Scheme (NARP/SUEWS) land surface model reproduces the radiation components at this site well, which is a promising result for applications elsewhere. These observations help to fill the gap of long-term radiation measurements in East Asian and low-latitude cities, quantifying the effects of season, cloud cover, and air quality.
Projected Changes in Precipitation Extremes for Western Canada based on High-Resolution Regional Climate Simulations
Authors: Erler Andre R. , Peltier W. Richard 
Published: September 2016

Abstract
An analysis of changes in precipitation extremes in western Canada is presented, based upon an ensemble of high-resolution regional climate projections. The ensemble is composed of four independent, identically configured Community Earth System Model (CESM) integrations that were dynamically downscaled to 10-km resolution, using the WRF Model in two different configurations. Only the representative concentration pathway 8.5 (RCP8.5) scenario is considered. Changes in extremes are found to generally follow changes in the (seasonal) mean, but changes in mean and extreme precipitation differ strongly between seasons and regions (where extremes are defined as the seasonal maximum of daily precipitation). At the end of the twenty-first century, the highest projected increase in precipitation extremes is approximately 30% in winter away from the coast and in fall at the coast. Changes in winter are consistent between models; however, changes in summer are not: CESM is characterized by a decrease in summer precipitation (and extremes), while one WRF configuration shows a significant increase and another no statistically significant change. Nevertheless, the fraction of convective precipitation (extremes) in summer increases by 20%–30% in all models. There is also evidence that the climate change signal in summer is sensitive to the choice of the convection scheme. A comparison of CESM and WRF shows that higher resolution clearly improves the representation of winter precipitation (extremes), while summer precipitation does not appear to be sensitive to resolution (convection is parameterized in both models). To increase the statistical power of the extreme value analysis that has been performed, a novel method for combining data from climatologically similar stations was employed.
Processes Governing Water Vapor Isotope Composition in the Indo-Pacific Region: Convection and Water Vapor Transport
Authors: Cai Zhongyin , Tian Lide 
Published: September 2016

AbstractIn an effort to understand the mechanisms controlling water vapor isotope composition in the Indo-Pacific region, encompassing southeastern Asia, this study investigates the spatial and interannual patterns in summer [June–September (JJAS)] water vapor isotopologues retrieved from the Tropospheric Emission Spectrometer (TES), especially those patterns associated with convection and water vapor transport. Both precipitation and water vapor isotope values exhibit a V-shaped longitudinal pattern in their spatial variations, reflecting the gradual rainout and increase in convective intensity along water vapor transport routes. On the temporal scale, compared with the 2006–10 JJAS mean conditions, TES water vapor δD over the eastern Indian Ocean and southeastern Asia (R_W120; 10°S–30°N, 80°–120°E) is higher in the 2009 JJAS El Niño event when convective activity is reduced and lower in the 2010 JJAS La Niña event when convective activity is enhanced. This is consistent with the direct response of water vapor δD to deep convection. In contrast, TES water vapor δD over the western Pacific (R_WP; 10°S–30°N, 120°–140°E) is higher in the La Niña year than in the El Niño year, although convective activity in R_WP varies in the same manner as in R_W120. A comparison of water vapor δD values with convection and water vapor transport suggests that the westward transport of water vapor–isotopic anomalies and changes in the flux of water vapor transported from the central to the western Pacific lead to such an opposite response in the R_WP. These findings help interpret what causes the interannual variations recorded by Indo-Pacific water isotopologues.