bluuebunny/crossref_metadata_2025_split huggingface dataset:
‘All that glitters is not gold’: when hyperammonaemia is not from hepatic aetiology
Authors: Hassan Abubaker A.I. , Ibrahim Walid , Subahi Ahmed , Mohamed Abdelaziz 
Published: May 2017

Hyperammonaemia is often caused by decompensated liver disease. However, non-hepatic causes can sometimes result in hyperammonaemia, severe enough to cause symptoms.We report a case of a 65-year-old man with a history of hypertension and bilateral peripelvic renal cyst who presented with acute confusion. Laboratory investigations revealed hyperammonaemia and normal liver function test. The abdominal ultrasound did not reveal any finding of liver disease or portal-systemic shunting but demonstrated bilateral peripelvic cysts with no hydronephrosis.Hyperammonaemia was attributed to urinary tract infection with a urea-splittingEscherichia colibacterium.Antibiotic therapy and lactulose were administered. His neurological status rapidly normalised over the next 48 hours, concomitantly with a decrease in ammonia level. Clinician awareness of non-hepatic causes of hyperammonaemic encephalopathy like urinary tract infection can contribute to early diagnosis and timely initiation of appropriate and potentially life-saving treatment including antimicrobial therapy, alleviating urinary obstruction, if present, and lactulose.
Giant cell myocarditis presenting with acute heart failure
Authors: Kasouridis Ioannis , Majo Joaquim , MacGowan Guy , Clark Andrew L. 
Published: May 2017

Idiopathic giant cell myocarditis (GCM) is a rare and rapidly progressing form of myocarditis predominantly affecting younger people. We report a case of a 23-year-old athletic patient who presented with features of acute heart failure due to GCM and discuss his management that included a left ventricular assist device as a bridge to transplant. He died immediately following the transplant.We also review the literature on this rare disease, highlighting the advances in the management of the disease including immunosuppressive therapy, ventricular assist devices and heart transplantation.
Deformed space–time transformations in Mercury
Authors: Cardone F. , Albertini G. , Bassani D. , Cherubini G. , Guerriero E. , Mignani R. , Monti M. , Petrucci A. , Ridolfi F. , Rosada A. , Rosetto F. , Sala V. , Santoro E. , Spera G. 
Published: May 2017

A mole of Mercury was suitably treated by ultrasound in order to generate in it the same conditions of local Lorentz invariance violation that were generated in a sonicated cylindrical bar of AISI 304 steel and that are the cause of neutron emission during the sonication. After 3 min, part of the mercury turned into a solid material which turned out to contain isotopes having a different mass (higher and lower) with respect to the isotopes already present in the initial material (mercury). These transformations in the atomic weight without gamma production above the background are brought about during Deformed Space–Time reactions. We present the results of the analyses performed on samples taken from the transformation product. The analyses have been done in two groups, the first one using five different analytical techniques: ICP-OES, XRF, ESEM-EDS, ICP-MS, INAA. In the second group of analyses, we used only two techniques: INAA and ICP-MS. The second group of analyses confirmed the occurring of the transformations in mercury.
Akt Signaling Is Sustained by a CD44 Splice Isoform–Mediated Positive Feedback Loop
Authors: Liu Sali , Cheng Chonghui 
Published: May 2017

AbstractTumor cells nearly invariably evolve sustained PI3K/Akt signaling as an effective means to circumvent apoptosis and maintain survival. However, for those tumor cells that do not acquire PI3K/Akt mutations to achieve this end, the underlying mechanisms have remained obscure. Here, we describe the discovery of a splice isoform–dependent positive feedback loop that is essential to sustain PI3K/Akt signaling in breast cancer. Splice isoform CD44s promoted expression of the hyaluronan synthase HAS2 by activating the Akt signaling cascade. The HAS2 product hyaluronan further stimulated CD44s-mediated Akt signaling, creating a feed-forward signaling circuit that promoted tumor cell survival. Mechanistically, we identified FOXO1 as a bona fide transcriptional repressor of HAS2. Akt-mediated phosphorylation of FOXO1 relieved its suppression of HAS2 transcription, with FOXO1 phosphorylation status maintained by operation of the positive feedback loop. In clinical specimens of breast cancer, we established that the expression of CD44s and HAS2 was positively correlated. Our results establish a positive feedback mechanism that sustains PI3K/Akt signaling in tumor cells, further illuminating the nearly universal role of this pathway in cancer cell survival. Cancer Res; 77(14); 3791–801. ©2017 AACR.
MONARCH 1, A Phase II Study of Abemaciclib, a CDK4 and CDK6 Inhibitor, as a Single Agent, in Patients with Refractory HR+/HER2− Metastatic Breast Cancer
Authors: Dickler Maura N. , Tolaney Sara M. , Rugo Hope S. , Cortés Javier , Diéras Véronique , Patt Debra , Wildiers Hans , Hudis Clifford A. , O'Shaughnessy Joyce , Zamora Esther , Yardley Denise A. , Frenzel Martin , Koustenis Andrew , Baselga José 
Published: May 2017

Abstract
Purpose: The phase II MONARCH 1 study was designed to evaluate the single-agent activity and adverse event (AE) profile of abemaciclib, a selective inhibitor of CDK4 and CDK6, in women with refractory hormone receptor–positive (HR+), HER2− metastatic breast cancer (MBC).
Experimental Design: MONARCH 1 was a phase II single-arm open-label study. Women with HR+/HER2− MBC who had progressed on or after prior endocrine therapy and had 1 or 2 chemotherapy regimens in the metastatic setting were eligible. Abemaciclib 200 mg was administered orally on a continuous schedule every 12 hours until disease progression or unacceptable toxicity. The primary objective of MONARCH 1 was investigator-assessed objective response rate (ORR). Other endpoints included clinical benefit rate, progression-free survival (PFS), and overall survival (OS).
Results: Patients (n = 132) had a median of 3 (range, 1–8) lines of prior systemic therapy in the metastatic setting, 90.2% had visceral disease, and 50.8% had ≥3 metastatic sites. At the 12-month final analysis, the primary objective of confirmed objective response rate was 19.7% (95% CI, 13.3–27.5; 15% not excluded); clinical benefit rate (CR+PR+SD≥6 months) was 42.4%, median progression-free survival was 6.0 months, and median overall survival was 17.7 months. The most common treatment-emergent AEs of any grade were diarrhea, fatigue, and nausea; discontinuations due to AEs were infrequent (7.6%).
Conclusions: In this poor-prognosis, heavily pretreated population with refractory HR+/HER2− metastatic breast cancer, continuous dosing of single-agent abemaciciclib was well tolerated and exhibited promising clinical activity. Clin Cancer Res; 23(17); 5218–24. ©2017 AACR.
Metformin Synergizes with BCL-XL/BCL-2 Inhibitor ABT-263 to Induce Apoptosis Specifically in p53-Defective Cancer Cells
Authors: Li Xinzhe , Li Bo , Ni Zhenhong , Zhou Peng , Wang Bin , He Jintao , Xiong Haojun , Yang Fan , Wu Yaran , Lyu Xilin , Zhang Yan , Zeng Yijun , Lian Jiqin , He Fengtian 
Published: May 2017

Abstract
p53 deficiency, a frequent event in multiple kinds of malignancies, decreases the sensitivity of diverse targeted chemotherapeutics including the BCL-XL/BCL-2 inhibitor ABT-263. Loss of p53 function can activate mTOR complex 1 (mTORC1), which may make it a vulnerable target. Metformin has shown anti-neoplastic efficiency partially through suppressing mTORC1. However, it remains unknown whether mTORC1 activation confers ABT-263 resistance and whether metformin can overcome it in the p53-defective contexts. In this study, we for the first time demonstrated that metformin and ABT-263 synergistically elicited remarkable apoptosis through orchestrating the proapoptotic machineries in various p53-defective cancer cells. Mechanistic studies revealed that metformin sensitized ABT-263 via attenuating mTORC1-mediated cap-dependent translation of MCL-1 and survivin and weakening internal ribosome entry site (IRES)-dependent translation of XIAP. Meanwhile, ABT-263 sensitized metformin through disrupting the BCL-XL/BIM complex. However, metformin and ABT-263 had no synergistic killing effect in p53 wild-type (p53-WT) cancer cells because the cotreatment dramatically induced the senescence-associated secretory phenotype (SASP) in the presence of wild type p53, and SASP could aberrantly activate the AKT/ERK–mTORC1–4EBP1–MCL-1/survivin signaling axis. Blocking the axis using corresponding kinase inhibitors or neutralizing antibodies against different SASP components sensitized the cotreatment effect of metformin and ABT-263 in p53-WT cancer cells. The in vivo experiments showed that metformin and ABT-263 synergistically inhibited the growth of p53-defective (but not p53-WT) cancer cells in tumor xenograft nude mice. These results suggest that the combination of metformin and ABT-263 may be a novel targeted therapeutic strategy for p53-defective cancers. Mol Cancer Ther; 16(9); 1806–18. ©2017 AACR.
Enzymatic Inactivation of Endogenous IgG by IdeS Enhances Therapeutic Antibody Efficacy
Authors: Järnum Sofia , Runström Anna , Bockermann Robert , Winstedt Lena , Crispin Max , Kjellman Christian 
Published: May 2017

Abstract
Endogenous plasma IgG sets an immunologic threshold that dictates the activity of tumor-directed therapeutic antibodies. Saturation of cellular antibody receptors by endogenous antibody limits antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Here, we show how enzymatic cleavage of IgG using the bacterial enzyme IdeS can be utilized to empty both high and low affinity Fcγ-receptors and clear the entire endogenous antibody pool. Using in vitro models, tumor animal models as well as ex vivo analysis of sera collected during a previous clinical trial with IdeS, we show how clearing of competing plasma antibody levels with IdeS unblocks cellular antibody receptors. We show that therapeutic antibodies against breast cancer (trastuzumab), colon cancer (cetuximab), and lymphomas (rituximab and alemtuzumab) can be potentiated when endogenous IgG is removed. Overall, IdeS is shown to be a potent tool to reboot the human antibody repertoire and to generate a window to preferentially load therapeutic antibodies onto effector cells and thereby create an armada of dedicated tumor-seeking immune cells. Mol Cancer Ther; 16(9); 1887–97. ©2017 AACR.
Changes in Cardiovascular Disease Risk Factors With Immediate Versus Deferred Antiretroviral Therapy Initiation Among HIV‐Positive Participants in the START (Strategic Timing of Antiretroviral Treatment) Trial
Authors: Baker Jason V. , Sharma Shweta , Achhra Amit C. , Bernardino Jose Ignacio , Bogner Johannes R. , Duprez Daniel , Emery Sean , Gazzard Brian , Gordin Jonathan , Grandits Greg , Phillips Andrew N. , Schwarze Siegfried , Soliman Elsayed Z. , Spector Stephen A. , Tambussi Giuseppe , Lundgren Jens ,   the INSIGHT (International Network for Strategic Initiatives in Global HIV Trials) START (Strategic Timing of Antiretroviral Treatment) Study Group
Published: May 2017

Introduction

HIV
infection and certain antiretroviral therapy (
ART
) medications increase atherosclerotic cardiovascular disease risk, mediated, in part, through traditional cardiovascular disease risk factors.

Methods and Results

We studied cardiovascular disease risk factor changes in the START (Strategic Timing of Antiretroviral Treatment) trial, a randomized study of immediate versus deferred
ART
initiation among HIV‐positive persons with
CD
4
+
cell counts >500 cells/mm
3
. Mean change from baseline in risk factors and the incidence of comorbid conditions were compared between groups. The characteristics among 4685
HIV
‐positive
START
trial participants include a median age of 36 years, a CD4 cell count of 651 cells/mm
3
, an HIV viral load of 12 759 copies/mL, a current smoking status of 32%, a median systolic/diastolic blood pressure of 120/76 mm Hg, and median levels of total cholesterol of 168 mg/dL, low‐density lipoprotein cholesterol of 102 mg/dL, and high‐density lipoprotein cholesterol of 41 mg/dL. Mean follow‐up was 3.0 years. The immediate and deferred
ART
groups spent 94% and 28% of follow‐up time taking
ART
, respectively. Compared with patients in the deferral group, patients in the immediate
ART
group had increased total cholesterol and low‐density lipoprotein cholesterol and higher use of lipid‐lowering therapy (1.2%; 95%
CI
, 0.1–2.2). Concurrent increases in high‐density lipoprotein cholesterol with immediate
ART
resulted in a 0.1 lower total cholesterol to high‐density lipoprotein cholesterol ratio (95%
CI
, 0.1–0.2). Immediate
ART
resulted in 2.3% less
BP
‐lowering therapy use (95%
CI
, 0.9–3.6), but there were no differences in new‐onset hypertension or diabetes mellitus.

Conclusions

Among HIV‐positive persons with preserved immunity, immediate
ART
led to increases in total cholesterol and low‐density lipoprotein cholesterol but also concurrent increases in high‐density lipoprotein cholesterol and decreased use of blood pressure medications. These opposing effects suggest that, in the short term, the net effect of early
ART
on traditional cardiovascular disease risk factors may be clinically insignificant."

Clinical Trial Registration

URL
:
http://www.clinicaltrials.gov
. Unique identifier:
NCT
00867048.
The Place of Subjectivity in the Academic Study of Religion: A Response to Craig Martin
Authors: Schilbrack Kevin 
Published: May 2017

AbstractThis paper responds to post-structuralist criticisms of my book,Philosophy and the Study of Religions: A Manifesto, made by Craig Martin. In particular, it defends my realist accounts of human beliefs and of religions as structures that operate, respectively, in human subjectivity and in history, even when they are not named.
Reconstruction, Critical Accommodation or Business as Usual? Challenges of Criticisms of the World Religions Paradigm to the Design of Teaching Programmes in the Study of Religions
Authors: Alberts Wanda 
Published: May 2017

AbstractThis article discusses the challenge of criticisms of the world religions paradigm to the design of teaching programmes in the academic Study of Religions, in general and with a particular focus on didactics-related courses as part of teacher training programmes. It uses the design of a particular Bachelor programme at a German university as an example for the general challenge of teaching about religion in an emancipatory framework that critically reflects its own presuppositions, both at university and school levels. Taking seriously recent criticisms of the world religions paradigm, it is argued, involves a shift of focus from the communication of supposedly given knowledge about religions to the communication of critical competences in analysing different types of discourse about religion, religions or “world religions.”
Two new species of Nemouridae (Plecoptera) from Vietnam
Authors: FOCHETTI ROMOLO , CECI MASSIMO 
Published: May 2017

Two new species belonging to the family Nemouridae, Nemoura kontumensis sp. nov. and Amphinemura konplongensis sp. nov. are described from the Central Highlands of Vietnam. Remarks on the affinities with related species are given.
Key Issues for Seamless Integrated Chemistry–Meteorology Modeling
Authors: Baklanov Alexander , Brunner Dominik , Carmichael Gregory , Flemming Johannes , Freitas Saulo , Gauss Michael , Hov Øystein , Mathur Rohit , Schlünzen K. Heinke , Seigneur Christian , Vogel Bernhard 
Published: May 2017

AbstractOnline coupled meteorology–atmospheric chemistry models have greatly evolved in recent years. Although mainly developed by the air quality modeling community, these integrated models are also of interest for numerical weather prediction and climate modeling, as they can consider both the effects of meteorology on air quality and the potentially important effects of atmospheric composition on weather. This paper summarizes the main conclusions from the “Symposium on Coupled Chemistry–Meteorology/Climate Modelling: Status and Relevance for Numerical Weather Prediction, Air Quality and Climate Research,” which was initiated by the European COST Action ES1004 “European Framework for Online Integrated Air Quality and Meteorology Modelling (EuMetChem).” It offers a brief review of the current status of online coupled meteorology and atmospheric chemistry modeling and a survey of processes relevant to the interactions between atmospheric physics, dynamics, and composition. In addition, it highlights scientific issues and emerging challenges that require proper consideration to improve the reliability and usability of these models for three main application areas: air quality, meteorology (including weather prediction), and climate modeling. It presents a synthesis of scientific progress in the form of answers to nine key questions, and provides recommendations for future research directions and priorities in the development, application, and evaluation of online coupled models.
Relative Role of Turbulent and Radiative Flux on the Near-Surface Temperature in a Single-Layer Urban Canopy Model over Houston
Authors: Brownlee James , Ray Pallav , Tewari Mukul , Tan Haochen 
Published: May 2017

AbstractNumerical simulations without hydrological processes tend to overestimate the near-surface temperatures over urban areas. This is presumably due to underestimation of surface latent heat flux. To test this hypothesis, the existing single-layer urban canopy model (SLUCM) within the Weather Research and Forecasting Model is evaluated over Houston, Texas. Three simulations were conducted during 24–26 August 2000. The simulations include the use of the default “BULK” urban scheme, the SLUCM without hydrological processes, and the SLUCM with hydrological processes. The results show that the BULK scheme was least accurate, and it overestimated the near-surface temperatures and winds over the urban regions. In the presence of urban hydrological processes, the SLUCM underestimates these parameters. An analysis of the surface heat fluxes suggests that the error in the BULK scheme is due to a lack of moisture at the urban surface, whereas the error in the SLUCM with hydrological processes is due to increases in moisture at the urban surface. These results confirm earlier studies in which changes in near-surface temperature were primarily due to the changes in the turbulent (latent and sensible heat) fluxes in the presence of hydrological processes. The contribution from radiative flux was about one-third of that from turbulent flux. In the absence of hydrological processes, however, the results indicate that the changes in radiative flux contribute more to the near-surface temperature changes than the turbulent heat flux. The implications of these results are discussed.
Twenty-First-Century Climate in CMIP5 Simulations: Implications for Snow and Water Yield across the Contiguous United States
Authors: Mahat Vinod , Ramírez Jorge A. , Brown Thomas C. 
Published: May 2017

Abstract
For 14 alternative climate futures, water yield and snow water equivalent (SWE) throughout the contiguous United States (CONUS) were projected over the twenty-first century using the Variable Infiltration Capacity model (VIC). The futures correspond to climate projections from seven CMIP5 models each forced by two representative concentration pathways for greenhouse gases (RCP4.5 and RCP8.5). With both RCPs, decreases in water yields are projected for roughly two-thirds of the CONUS, and in 60% of that area—mainly at more northern latitudes, where the greatest temperature increases are expected—this occurs despite projected increases in precipitation. The greatest relative decreases in yield are projected for the southern Great Plains and the Southwest, where temperature and precipitation changes combine to decrease yield. Snow accumulation is projected to decrease almost everywhere by the latter half of the century, with the time of peak SWE in some basins projected to occur up to 2 months earlier than it now does. These changes, should they come to pass, will challenge the adaptation capacity of future water management.
Surface Wave Effects on the Translation of Wind Stress across the Air–Sea Interface in a Fetch-Limited, Coastal Embayment
Authors: Fisher Alexander W. , Sanford Lawrence P. , Scully Malcolm E. , Suttles Steven E. 
Published: May 2017

AbstractThe role of surface gravity waves in structuring the air–sea momentum flux is examined in the middle reaches of Chesapeake Bay. Observed wave spectra showed that wave direction in Chesapeake Bay is strongly correlated with basin geometry. Waves preferentially developed in the direction of maximum fetch, suggesting that dominant wave frequencies may be commonly and persistently misaligned with local wind forcing. Direct observations from an ultrasonic anemometer and vertical array of ADVs show that the magnitude and direction of stress changed across the air–sea interface, suggesting that a stress divergence occurred at or near the water surface. Using a numerical wave model in combination with direct flux measurements, the air–sea momentum flux was partitioned between the surface wave field and the mean flow. Results indicate that the surface wave field can store or release a significant fraction of the total momentum flux depending on the direction of the wind. When wind blew across dominant fetch axes, the generation of short gravity waves stored as much as 40% of the total wind stress. Accounting for the storage of momentum in the surface wave field closed the air–sea momentum budget. Agreement between the direction of Lagrangian shear and the direction of the stress vector in the mixed surface layer suggests that the observed directional difference was due to the combined effect of breaking waves producing downward sweeps of momentum in the direction of wave propagation and the straining of that vorticity field in a manner similar to Langmuir turbulence.
Aryl hydrocarbon receptor inhibition promotes hematolymphoid development from human pluripotent stem cells
Authors: Angelos Mathew G. , Ruh Paige N. , Webber Beau R. , Blum Robert H. , Ryan Caitlin D. , Bendzick Laura , Shim Seonhui , Yingst Ashley M. , Tufa Dejene M. , Verneris Michael R. , Kaufman Dan S. 
Published: May 2017

Key PointsSmall-molecule inhibition and CRISPR/Cas9 deletion of AHR promote early hematoendothelial cell differentiation from hESCs. AHR inhibition enhances the differentiation of cNK cells from hESCs whereas AHR hyperactivation supports development of ILC3s.
Mutations of MAP2K1 are frequent in pediatric-type follicular lymphoma and result in ERK pathway activation
Authors: Schmidt Janine , Ramis-Zaldivar Joan Enric , Nadeu Ferran , Gonzalez-Farre Blanca , Navarro Alba , Egan Caoimhe , Montes-Mojarro Ivonne Aidee , Marafioti Teresa , Cabeçadas Jose , van der Walt Jon , Dojcinov Stefan , Rosenwald Andreas , Ott German , Bonzheim Irina , Fend Falko , Campo Elias , Jaffe Elaine S. , Salaverria Itziar , Quintanilla-Martinez Leticia 
Published: May 2017

Key PointsTNFRSF14 and MAP2K1 mutations are frequent in PTFL but do not occur together in the majority of cases. MAP2K1 mutations lead to activation of the downstream target phosphorylated extracellular signal-regulated kinase.
SOX11 promotes tumor protective microenvironment interactions through CXCR4 and FAK regulation in mantle cell lymphoma
Authors: Balsas Patricia , Palomero Jara , Eguileor Álvaro , Rodríguez Marta Leonor , Vegliante Maria Carmela , Planas-Rigol Ester , Sureda-Gómez Marta , Cid Maria C. , Campo Elias , Amador Virginia 
Published: May 2017

Key PointsSOX11 regulates MCL homing and invasion via direct regulation of CXCR4 and FAK expression and PI3K/AKT and ERK1/2 signaling activation. SOX11 expression increases CAM-DR, contributing to a more aggressive MCL phenotype.