bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monosialoganglioside‐Containing Nanoliposomes Restore Endothelial Function Impaired by AL Amyloidosis Light Chain Proteins
Authors: Franco Daniel A. , Truran Seth , Weissig Volkmar , Guzman‐Villanueva Diana , Karamanova Nina , Senapati Subhadip , Burciu Camelia , Ramirez‐Alvarado Marina , Blancas‐Mejia Luis M. , Lindsay Stuart , Hari Parameswaran , Migrino Raymond Q. 
Published: June 2016

Background

Light chain amyloidosis (AL) is associated with high mortality, especially in patients with advanced cardiovascular involvement. It is caused by toxicity of misfolded light chain proteins (
LC
) in vascular, cardiac, and other tissues. There is no treatment to reverse
LC
tissue toxicity. We tested the hypothesis that nanoliposomes composed of monosialoganglioside, phosphatidylcholine, and cholesterol (GM1 ganglioside–containing nanoliposomes [
NLGM
1]) can protect against
LC
‐induced human microvascular dysfunction and assess mechanisms behind the protective effect.

Methods and Results

The dilator responses of ex vivo abdominal adipose arterioles from human participants without AL to acetylcholine and papaverine were measured before and after exposure to
LC
(20 μg/mL) with or without
NLGM
1 (1:10 ratio for
LC
:
NLGM
1 mass). Human umbilical vein endothelial cells were exposed for 18 to 20 hours to vehicle, LC with or without
NLGM
1, or
NLGM
1 and compared for oxidative and nitrative stress response and cellular viability. LC impaired arteriole dilator response to acetylcholine, which was restored by co‐treatment with
NLGM
1.
LC
decreased endothelial cell nitric oxide production and cell viability while increasing superoxide and peroxynitrite; these adverse effects were reversed by
NLGM
1.
NLGM
1 increased endothelial cell protein expression of antioxidant enzymes heme oxygenase 1 and
NAD
(P)H quinone dehydrogenase 1 and increased nuclear factor, erythroid 2 like 2 (Nrf‐2) protein. Nrf‐2 gene knockdown reduced antioxidant stress response and reversed the protective effects of
NLGM
1.

Conclusions

NLGM1 protects against
LC
‐induced human microvascular endothelial dysfunction through increased nitric oxide bioavailability and reduced oxidative and nitrative stress mediated by Nrf‐2–dependent antioxidant stress response. These findings point to a potential novel therapeutic approach for light chain amyloidosis.
No Decline in the Risk of Stroke Following Incident Atrial Fibrillation Since 2000 in the Community: A Concerning Trend
Authors: Chamberlain Alanna M. , Brown Robert D. , Alonso Alvaro , Gersh Bernard J. , Killian Jill M. , Weston Susan A. , Roger Véronique L. 
Published: June 2016

Background
While atrial fibrillation is a recognized risk factor for stroke, contemporary data on trends in stroke incidence after the diagnosis of atrial fibrillation are scarce.

Methods and Results

Olmsted County,
MN
residents with incident atrial fibrillation or atrial flutter (collectively referred to as
AF
) from 2000 to 2010 were identified. Cox regression determined associations of year of
AF
diagnosis with ischemic stroke and transient ischemic attack (
TIA
) occurring through 2013. Among 3247
AF
patients, 321 (10%) had an ischemic stroke/
TIA
over a mean of 4.6 years (incidence rate [95%
CI
] per 100 person‐years: 2.14 [1.91–2.38]). Two hundred thirty‐nine (7%) of 3265
AF
patients experienced an ischemic stroke (incidence rate: 1.54 [1.35–1.75]). The risk of both outcomes remained unchanged over time after adjusting for demographics and comorbidities (hazard ratio [95%
CI
] per year of
AF
diagnosis: 1.00 [0.96–1.04] for ischemic stroke/
TIA
; 1.01 [0.96–1.06] for ischemic stroke only). In analyses restricted to patients with prescription information, the rates of anticoagulation use did not change over time, reaching 50.8% at 1 year after
AF
diagnosis. Further adjustment for anticoagulation use did not alter the temporal trends in stroke incidence (hazard ratio [95%
CI
] per year of
AF
diagnosis: 1.06 [0.97–1.15] for ischemic stroke/
TIA
; 1.08 [0.98–1.20] for ischemic stroke only).

Conclusions

Strokes/
TIA
s are frequent after
AF
, occurring in 10% of patients after 5 years of follow‐up. The occurrence of stroke/
TIA
did not decline over the last decade, which may be influenced by a leveling off of anticoagulation use. This concerning trend has major public health implications.
ECG Criteria to Differentiate Between Takotsubo (Stress) Cardiomyopathy and Myocardial Infarction
Authors: Frangieh Antonio H. , Obeid Slayman , Ghadri Jelena‐Rima , Imori Yoichi , D'Ascenzo Fabrizio , Kovac Marc , Ruschitzka Frank , Lüscher Thomas F. , Duru Firat , Templin Christian ,   the InterTAK Collaborators, Diekmann Johanna , Cammann Victoria L. , Jaguszewski Milosz , Dichtl Wolfgang , Franz Wolfgang M. , Fijalkowski Marcin , Opolski Grzegorz , Franke Jennifer , Katus Hugo A. , Michels Guido , Pfister Roman , Cuculi Florim 
Published: June 2016

Background
ECG criteria differentiating Takotsubo cardiomyopathy (TTC) from mainly anterior myocardial infarction (MI) have been suggested; however, this was in small patient populations.

Methods and Results

Twelve‐lead admission ECGs of consecutive 200 TTC and 200 MI patients were compared in dichotomized groups based on the presence or absence of ST‐elevation MI (STEMI versus STE‐TTC and non‐ST elevation MI versus non ST‐elevation‐TTC). When comparing STEMI and STE‐TTC, ST‐elevation in –aVR was characteristic of STE‐TTC with a sensitivity/specificity of 43% and 95%, positive predictive value (PPV) 91%, and a negative predictive value (NPV) 62% (
P
<0.001); when ST‐elevation in –aVR is accompanied by ST‐elevation in inferior leads, sensitivity/specificity were 14% and 98% (PPV was 89% and NPV 52%) (
P
=0.001), and 12% and 100% when associated with ST‐elevation in anteroseptal leads (PPV 100%, NPV 52%) (
P
<0.001). On the other hand, STEMI was characterized by ST‐elevation in aVR (sensitivity/specificity of 31% and 95%
P
<0.001, PPV 85% and NPV 59%) and ST‐depression in V2‐V3‐V4 (sensitivity/specificity of 24% and 100%
P
<0.001, PPV 100% and NPV 76%). When comparing non‐ST elevation MI and non ST‐elevation‐TTC, T‐inversion in leads I‐aVL‐V5‐V6 had a sensitivity/specificity of 17% and 97% for non ST‐elevation‐TTC (PPV 83% and NPV 55%) (
P
<0.001), and ST‐elevation in –aVR with T‐inversion in any lead was also specific for non ST‐elevation‐TTC (sensitivity/specificity of 8% and 100%, PPV 100% and NPV 53%) (
P
=0.006). In non‐ST elevation MI patients, the presence of ST‐depression in V2‐V3 was specific (sensitivity/specificity of 11% and 99%, PPV 91% and NPV 51%) (
P
=0.01).

Conclusions
ECG on admission can differentiate between TTC and acute MI, with high specificity and positive predictive value.

Clinical Trial Registration

URL:
https://www.clinicaltrials.gov/
. Unique identifier:
NCT01947621
.
Effectiveness and Safety of Dabigatran, Rivaroxaban, and Apixaban Versus Warfarin in Nonvalvular Atrial Fibrillation
Authors: Yao Xiaoxi , Abraham Neena S. , Sangaralingham Lindsey R. , Bellolio M. Fernanda , McBane Robert D. , Shah Nilay D. , Noseworthy Peter A. 
Published: June 2016

Background
The introduction of non–vitamin K antagonist oral anticoagulants has been a major advance for stroke prevention in atrial fibrillation; however, outcomes achieved in clinical trials may not translate to routine practice. We aimed to evaluate the effectiveness and safety of dabigatran, rivaroxaban, and apixaban by comparing each agent with warfarin.

Methods and Results

Using a large US insurance database, we identified privately insured and Medicare Advantage patients with nonvalvular atrial fibrillation who were users of apixaban, dabigatran, rivaroxaban, or warfarin between October 1, 2010, and June 30, 2015. We created 3 matched cohorts using 1:1 propensity score matching: apixaban versus warfarin (n=15 390), dabigatran versus warfarin (n=28 614), and rivaroxaban versus warfarin (n=32 350). Using Cox proportional hazards regression, we found that for stroke or systemic embolism, apixaban was associated with lower risk (hazard ratio [
HR
] 0.67, 95% CI 0.46–0.98,
P
=0.04), but dabigatran and rivaroxaban were associated with a similar risk (dabigatran:
HR
0.98, 95% CI 0.76–1.26,
P
=0.98; rivaroxaban:
HR
0.93, 95% CI 0.72–1.19,
P
=0.56). For major bleeding, apixaban and dabigatran were associated with lower risk (apixaban:
HR
0.45, 95% CI 0.34–0.59,
P
<0.001; dabigatran:
HR
0.79, 95% CI 0.67–0.94,
P
<0.01), and rivaroxaban was associated with a similar risk (
HR
1.04, 95% CI 0.90–1.20],
P
=0.60). All non–vitamin K antagonist oral anticoagulants were associated with a lower risk of intracranial bleeding.

Conclusions
In patients with nonvalvular atrial fibrillation, apixaban was associated with lower risks of both stroke and major bleeding, dabigatran was associated with similar risk of stroke but lower risk of major bleeding, and rivaroxaban was associated with similar risks of both stroke and major bleeding in comparison to warfarin.
NP COORDINATION IN MEDIEVAL CHINESE: A DISCOURSE APPROACH
Authors: Hongyin Tao 
Published: June 2016

This paper deals with the historical development, from a discourse perspective, of nominal (NP) coordination from Early Medieval Chinese, as reflected in Shishuo Xinyu 世说新语 to Late Medieval Chinese, as reflected in Dunhuang Bianwen 敦煌变文
It is shown that simple juxtaposition (or zero form) is the basic device used throughout Medieval Chinese. Conjunctions are found to appear with conjuncts that are either non-specific, or specific but sub-dividable in terms of discourse context and conception. The distinction between coordination and comitatives is maintained through a comparison of a cluster of discourse properties such as anaphora, topicality and empathy, as exhibited in the NPs of the two constructions. We show that the most prominent development from Early Medieval Chinese to Late Medieval Chinese is the grammaticization of sub-dividability. Based on the observation that unitary NPs tend to be expressed with simple juxtaposition and distant NPs overt conjunction, we propose the iconicity principle to account for the grammar of NP coordination in Medieval Chinese.
Sensitivity of the Middle East–North African Tropical Rainbelt to Dust Shortwave Absorption: A High-Resolution AGCM Experiment
Authors: Bangalath Hamza Kunhu , Stenchikov Georgiy 
Published: June 2016

Abstract
Shortwave absorption is one of the most important, but the most uncertain, components of direct radiative effect by mineral dust. It has a broad range of estimates from different observational and modeling studies and there is no consensus on the strength of absorption. To elucidate the sensitivity of the Middle East–North African (MENA) tropical summer rainbelt to a plausible range of uncertainty in dust shortwave absorption, AMIP-style global high-resolution (25 km) simulations are conducted with and without dust, using the High-Resolution Atmospheric Model (HiRAM). Simulations with dust comprise three different cases by assuming dust as a very efficient, as a standard, and as an inefficient absorber. Intercomparison of these simulations shows that the response of the MENA tropical rainbelt is extremely sensitive to the strength of shortwave absorption. Further analyses reveal that the sensitivity of the rainbelt stems from the sensitivity of the multiscale circulations that define the rainbelt. The maximum response and sensitivity are predicted over the northern edge of the rainbelt, geographically over the Sahel. The sensitivity of the responses over the Sahel, especially that of precipitation, is comparable to the mean state. Locally, the response in precipitation reaches up to 50% of the mean, while dust is assumed to be a very efficient absorber. Taking into account that the Sahel has a very high climate variability and is extremely vulnerable to changes in precipitation, the present study suggests the importance of reducing uncertainty in dust shortwave absorption for a better simulation and interpretation of the Sahel climate.
The Multibudget Soil, Vegetation, and Snow (SVS) Scheme for Land Surface Parameterization: Offline Warm Season Evaluation
Authors: Husain Syed Zahid , Alavi Nasim , Bélair Stéphane , Carrera Marco , Zhang Shunli , Fortin Vincent , Abrahamowicz Maria , Gauthier Nathalie 
Published: June 2016

Abstract
A new land surface parameterization scheme, named the Soil, Vegetation, and Snow (SVS) scheme, was recently developed at Environment and Climate Change Canada to replace the operationally used Interactions between Soil, Biosphere, and Atmosphere (ISBA) scheme. The new scheme is designed to address a number of weaknesses and limitations of ISBA that have been identified over the last decade. Unlike ISBA, which calculates a single energy budget for the different land surface components, SVS introduces a new tiling approach that includes separate energy budgets for bare ground, vegetation, and two different snowpacks (over bare ground and low vegetation and under high vegetation). The inclusion of a photosynthesis module as an option to determine the surface stomatal resistance is another significant addition in SVS. The representation of vertical water transport through soil has also been substantially improved in SVS with the introduction of multiple soil layers. Overall, offline simulations conducted in the present study demonstrated clear improvements in warm season meteorological predictions with SVS compared to the ISBA scheme. The results also revealed considerable reduction of standard error in the SVS-predicted L-band brightness temperature. This demonstrates the scheme’s ability for better hydrological prediction and its potential for providing more accurate soil moisture analysis. The impact of the photosynthesis module within the current implementation of SVS is, however, found to be negligible on near-surface meteorological prediction and slightly negative for brightness temperature.
Warming and Weakening of the Abyssal Flow through Samoan Passage
Authors: Voet Gunnar , Alford Matthew H. , Girton James B. , Carter Glenn S. , Mickett John B. , Klymak Jody M. 
Published: June 2016

AbstractThe abyssal flow of water through the Samoan Passage accounts for the majority of the bottom water renewal in the North Pacific, thereby making it an important element of the meridional overturning circulation. Here the authors report recent measurements of the flow of dense waters of Antarctic and North Atlantic origin through the Samoan Passage. A 15-month long moored time series of velocity and temperature of the abyssal flow was recorded between 2012 and 2013. This allows for an update of the only prior volume transport time series from the Samoan Passage from WOCE moored measurements between 1992 and 1994. While highly variable on multiple time scales, the overall pattern of the abyssal flow through the Samoan Passage was remarkably steady. The time-mean northward volume transport of about 5.4 Sv (1 Sv ≡ 106 m3 s−1) in 2012/13 was reduced compared to 6.0 Sv measured between 1992 and 1994. This volume transport reduction is significant within 68% confidence limits (±0.4 Sv) but not at 95% confidence limits (±0.6 Sv). In agreement with recent studies of the abyssal Pacific, the bottom flow through the Samoan Passage warmed significantly on average by 1 × 10−3°C yr−1 over the past two decades, as observed both in moored and shipboard hydrographic observations. While the warming reflects the recently observed increasing role of the deep oceans for heat uptake, decreasing flow through Samoan Passage may indicate a future weakening of this trend for the abyssal North Pacific.
Personal Care Participation Assessment and Resource Tool: Clinical utility for inpatient rehabilitation
Authors: Darzins Susan W. , Imms Christine , Stefano Marilyn Di , Radia-George Camilla A. 
Published: June 2016

Background. Evidence supports validity of the Personal Care Participation Assessment and Resource Tool (PC-PART), but clinical utility remains unverified. Purpose. This study aimed to investigate occupational therapists’ perceptions about the PC-PART’s clinical utility for inpatient rehabilitation. Method. Using mixed methods, occupational therapists who had used the PC-PART as part of a research study in an inpatient rehabilitation setting completed a questionnaire ( n = 9) and participated in a focus group ( n = 6) to explore their perspectives about its clinical utility. Quantitative data were summarized and qualitative data analyzed using inductive thematic analysis. Findings. Quantitative data highlighted both positive and negative aspects of the PC-PART’s clinical utility. Five themes emerged from the qualitative data: nature of information gathered; familiarity with the instrument; perceived time and effort; item phrasing, interpretation, and presentation; and external influences on clinical use. Implications. The PC-PART was perceived to support gathering of clinically useful information, helpful to intervention and discharge planning. Recommendations for improving some item phrasing, operational definitions, and instructions were identified. Although standardized assessments were valued, use in routine practice was challenging, requiring a knowledge translation strategy.
Survey on the Current State of Endotracheal Intubation Among the Critically Ill
Authors: Seisa Mohamed O. , Gondhi Venkatesh , Demirci Onur , Diedrich Daniel A. , Kashyap Rahul , Smischney Nathan J. 
Published: June 2016

Objectives: In the last decade, the practice of intubation in the intensive care unit (ICU) has evolved. To further examine the current intubation practice in the ICU, we administered a survey to critical care physicians. Design: Cross-sectional survey study design. Setting: Thirty-two academic/nonacademic centers nationally and internationally. Measurements and Main Results: The survey was developed among a core group of physicians with the assistance of the Survey Research Center at Mayo Clinic, Rochester, Minnesota. The survey was pilot tested for functionality and reliability. The response rate was 82 (51%) of 160 among the 32 centers. Although propofol was the induction drug of choice, there was a significant difference with actual ketamine use and those who indicated a preference for it (ketamine: 52% vs 61%; P < .001). The most common airway device used for intubation was direct laryngoscopy (Miller laryngoscope blade) at 56 (68%) followed by video laryngoscopy at 26 (32%). Most (>90%) indicated that they have a difficult airway cart, but only 55 (67%) indicated they have a documented plan to handle a difficult airway with even lower results for documented review of adverse events (49%). Conclusion: Although propofol was the induction drug of choice, ketamine was a medication that many preferred to use, possibly relating to the fact that the most common complication postintubation is hypotension. Direct laryngoscopy remains the primary airway device for endotracheal intubation. Finally, although the majority stated they had a difficult airway cart available, most did not have a documented plan in place when encountering a difficult airway or a documented process to review adverse events surrounding intubation.
Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial
Authors: Alvarnas Joseph C. , Le Rademacher Jennifer , Wang Yanli , Little Richard F. , Akpek Gorgun , Ayala Ernesto , Devine Steven , Baiocchi Robert , Lozanski Gerard , Kaplan Lawrence , Noy Ariela , Popat Uday , Hsu Jack , Morris Lawrence E. , Thompson Jason , Horowitz Mary M. , Mendizabal Adam , Levine Alexandra , Krishnan Amrita , Forman Stephen J. , Navarro Willis H. , Ambinder Richard 
Published: June 2016

Key PointsAutologous hematopoietic cell transplantation is safe and effective in patients with HIV-related lymphoma who meet standard transplant criteria. Patients with HIV-related lymphomas should not be precluded from participating in AHCT clinical trials.
Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma
Authors: Boddicker Rebecca L. , Razidlo Gina L. , Dasari Surendra , Zeng Yu , Hu Guangzhen , Knudson Ryan A. , Greipp Patricia T. , Davila Jaime I. , Johnson Sarah H. , Porcher Julie C. , Smadbeck James B. , Eckloff Bruce W. , Billadeau Daniel D. , Kurtin Paul J. , McNiven Mark A. , Link Brian K. , Ansell Stephen M. , Cerhan James R. , Asmann Yan W. , Vasmatzis George , Feldman Andrew L. 
Published: June 2016

Abstract
Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of T-cell malignancies that generally demonstrate aggressive clinical behavior, often are refractory to standard therapy, and remain significantly understudied. The most common World Health Organization subtype is PTCL, not otherwise specified (NOS), essentially a “wastebasket” category because of inadequate understanding to assign cases to a more specific diagnostic entity. Identification of novel fusion genes has contributed significantly to improving the classification, biologic understanding, and therapeutic targeting of PTCLs. Here, we integrated mate-pair DNA and RNA next-generation sequencing to identify chromosomal rearrangements encoding expressed fusion transcripts in PTCL, NOS. Two of 11 cases had novel fusions involving VAV1, encoding a truncated form of the VAV1 guanine nucleotide exchange factor important in T-cell receptor signaling. Fluorescence in situ hybridization studies identified VAV1 rearrangements in 10 of 148 PTCLs (7%). These were observed exclusively in PTCL, NOS (11%) and anaplastic large cell lymphoma (11%). In vitro, ectopic expression of a VAV1 fusion promoted cell growth and migration in a RAC1-dependent manner. This growth was inhibited by azathioprine, a clinically available RAC1 inhibitor. We also identified novel kinase gene fusions, ITK-FER and IKZF2-ERBB4, as candidate therapeutic targets that show similarities to known recurrent oncogenic ITK-SYK fusions and ERBB4 transcript variants in PTCLs, respectively. Additional novel and potentially clinically relevant fusions also were discovered. Together, these findings identify VAV1 fusions as recurrent and targetable events in PTCLs and highlight the potential for clinical sequencing to guide individualized therapy approaches for this group of aggressive malignancies.