bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Genetic Platform to Model Sarcomagenesis from Primary Adult Mesenchymal Stem Cells
Authors: Guarnerio Jlenia , Riccardi Luisa , Taulli Riccardo , Maeda Takahiro , Wang Guocan , Hobbs Robin M. , Song Min Sup , Sportoletti Paolo , Bernardi Rosa , Bronson Roderick T. , Castillo-Martin Mireia , Cordon-Cardo Carlos , Lunardi Andrea , Pandolfi Pier Paolo 
Published: January 2015

Abstract
The regulatory factors governing adult mesenchymal stem cell (MSC) physiology and their tumorigenic potential are still largely unknown, which substantially delays the identification of effective therapeutic approaches for the treatment of aggressive and lethal forms of MSC-derived mesenchymal tumors, such as undifferentiated sarcomas. Here, we have developed a novel platform to screen and quickly identify genes and pathways responsible for adult MSC transformation, modeled undifferentiated sarcoma in vivo, and, ultimately, tested the efficacy of targeting the identified oncopathways. Importantly, by taking advantage of this new platform, we demonstrate the key role of an aberrant LRF–DLK1–SOX9 pathway in the pathogenesis of undifferentiated sarcoma, with important therapeutic implications.
Significance: The paucity of therapeutic options for the treatment of sarcoma calls for a rapid and effective preclinical assessment of new therapeutic modalities. We have here developed a new platform to deconstruct the molecular genetics underlying the pathogenesis of sarcoma and to evaluatein vivo the efficacy of novel targeted therapies. Cancer Discov; 5(4); 396–409. ©2015 AACR.
This article is highlighted in the In This Issue feature, p. 333
Antibody Blockade of Semaphorin 4D Promotes Immune Infiltration into Tumor and Enhances Response to Other Immunomodulatory Therapies
Authors: Evans Elizabeth E. , Jonason Alan S. , Bussler Holm , Torno Sebold , Veeraraghavan Janaki , Reilly Christine , Doherty Michael A. , Seils Jennifer , Winter Laurie A. , Mallow Crystal , Kirk Renee , Howell Alan , Giralico Susan , Scrivens Maria , Klimatcheva Katya , Fisher Terrence L. , Bowers William J. , Paris Mark , Smith Ernest S. , Zauderer Maurice 
Published: January 2015

Abstract
Semaphorin 4D (SEMA4D, CD100) and its receptor plexin-B1 (PLXNB1) are broadly expressed in murine and human tumors, and their expression has been shown to correlate with invasive disease in several human tumors. SEMA4D normally functions to regulate the motility and differentiation of multiple cell types, including those of the immune, vascular, and nervous systems. In the setting of cancer, SEMA4D–PLXNB1 interactions have been reported to affect vascular stabilization and transactivation of ERBB2, but effects on immune-cell trafficking in the tumor microenvironment (TME) have not been investigated. We describe a novel immunomodulatory function of SEMA4D, whereby strong expression of SEMA4D at the invasive margins of actively growing tumors influences the infiltration and distribution of leukocytes in the TME. Antibody neutralization of SEMA4D disrupts this gradient of expression, enhances recruitment of activated monocytes and lymphocytes into the tumor, and shifts the balance of cells and cytokines toward a proinflammatory and antitumor milieu within the TME. This orchestrated change in the tumor architecture was associated with durable tumor rejection in murine Colon26 and ERBB2+ mammary carcinoma models. The immunomodulatory activity of anti-SEMA4D antibody can be enhanced by combination with other immunotherapies, including immune checkpoint inhibition and chemotherapy. Strikingly, the combination of anti-SEMA4D antibody with antibody to CTLA-4 acts synergistically to promote complete tumor rejection and survival. Inhibition of SEMA4D represents a novel mechanism and therapeutic strategy to promote functional immune infiltration into the TME and inhibit tumor progression. Cancer Immunol Res; 3(6); 689–701. ©2015 AACR.
Fibrin, γ′-Fibrinogen, and Transclot Pressure Gradient Control Hemostatic Clot Growth During Human Blood Flow Over a Collagen/Tissue Factor Wound
Authors: Muthard Ryan W. , Welsh John D. , Brass Lawrence F. , Diamond Scott L. 
Published: January 2015

Objective—

Biological and physical factors interact to modulate blood response in a wounded vessel, resulting in a hemostatic clot or an occlusive thrombus. Flow and pressure differential (Δ
P
) across the wound from the lumen to the extravascular compartment may impact hemostasis and the observed core/shell architecture. We examined physical and biological factors responsible for regulating thrombin-mediated clot growth.

Approach and Results—

Using factor XIIa-inhibited human whole blood perfused in a microfluidic device over collagen/tissue factor at controlled wall shear rate and Δ
P
, we found thrombin to be highly localized in the P-selectin
+
core of hemostatic clots. Increasing Δ
P
from 9 to 29 mm Hg (wall shear rate=400 s
−1
) reduced P-selectin
+
core size and total clot size because of enhanced extravasation of thrombin. Blockade of fibrin polymerization with 5 mmol/L Gly-Pro-Arg-Pro dysregulated hemostasis by enhancing both P-selectin
+
core size and clot size at 400 s
−1
(20 mm Hg). For whole-blood flow (no Gly-Pro-Arg-Pro), the thickness of the P-selectin-negative shell was reduced under arterial conditions (2000 s
−1
, 20 mm Hg). Consistent with the antithrombin-1 activity of fibrin implicated with Gly-Pro-Arg-Pro, anti-γ′-fibrinogen antibody enhanced core-localized thrombin, core size, and overall clot size, especially at venous (100 s
−1
) but not arterial wall shear rates (2000 s
−1
). Pathological shear (15 000 s
−1
) and Gly-Pro-Arg-Pro synergized to exacerbate clot growth.

Conclusions—
Hemostatic clotting was dependent on core-localized thrombin that (1) triggered platelet P-selectin display and (2) was highly regulated by fibrin and the transclot ΔP. Also, γ′-fibrinogen had a role in venous but not arterial conditions.
GATA-Binding Factor 6 Contributes to Atrioventricular Node Development and Function
Authors: Liu Fang , Lu Min Min , Patel Neil N. , Schillinger Kurt J. , Wang Tao , Patel Vickas V. 
Published: January 2015

Background—
Several transcription factors regulate cardiac conduction system (CCS) development and function but the role of each in specifying distinct CCS components remains unclear. GATA-binding factor 6 (GATA6) is a zinc-finger transcription factor that is critical for patterning the cardiovascular system. However, the role of GATA6 in the embryonic heart and CCS has never been shown.

Methods and Results—

We report that
Gata6
is expressed abundantly in the proximal CCS during midgestation in mice. Myocardial-specific deletion of the carboxyl zinc-finger of
Gata6
induces loss of hyperpolarizing cyclic nucleotide–gated channel, subtype 4 staining in the compact atrioventricular node with some retention of hyperpolarizing cyclic nucleotide–gated channel, subtype 4 staining in the atrioventricular bundle, but has no significant effect on the connexin-40–positive bundle branches. Furthermore, myocardial-specific deletion of the carboxyl zinc-finger of
Gata6
alters atrioventricular conduction in postnatal life as assessed by surface and invasive electrophysiological evaluation, as well as decreasing the number of ventricular myocytes and inducing compensatory myocyte hypertrophy. Myocardial-specific deletion of the carboxyl zinc-finger of
Gata6
is also associated with downregulation of the transcriptional repressor ID2 and the cardiac sodium–calcium exchanger NCX1 in the proximal CCS, where GATA6 transactivates both of these factors. Finally, carboxyl zinc-finger deletion of
Gata6
reduces cell-cycle exit of TBX3+ myocytes in the developing atrioventricular bundle during the period of atrioventricular node specification, which results in fewer TBX3+ cells in the proximal CCS of mature mutant mice.

Conclusions—
GATA6 contributes to the development and postnatal function of the murine atrioventricular node by promoting cell-cycle exit of specified cardiomyocytes toward a conduction system lineage.
Genetic Overlap Between Diagnostic Subtypes of Ischemic Stroke
Authors: Holliday Elizabeth G. , Traylor Matthew , Malik Rainer , Bevan Steve , Falcone Guido , Hopewell Jemma C. , Cheng Yu-Ching , Cotlarciuc Ioana , Bis Joshua C. , Boerwinkle Eric , Boncoraglio Giorgio B. , Clarke Robert , Cole John W. , Fornage Myriam , Furie Karen L. , Ikram M. Arfan , Jannes Jim , Kittner Steven J. , Lincz Lisa F. , Maguire Jane M. , Meschia James F. , Mosley Thomas H. , Nalls Mike A. , Oldmeadow Christopher , Parati Eugenio A. , Psaty Bruce M. , Rothwell Peter M. , Seshadri Sudha , Scott Rodney J. , Sharma Pankaj , Sudlow Cathie , Wiggins Kerri L. , Worrall Bradford B. , Rosand Jonathan , Mitchell Braxton D. , Dichgans Martin , Markus Hugh S. , Levi Christopher , Attia John , Wray Naomi R. 
Published: January 2015

Background and Purpose—
Despite moderate heritability, the phenotypic heterogeneity of ischemic stroke has hampered gene discovery, motivating analyses of diagnostic subtypes with reduced sample sizes. We assessed evidence for a shared genetic basis among the 3 major subtypes: large artery atherosclerosis (LAA), cardioembolism, and small vessel disease (SVD), to inform potential cross-subtype analyses.

Methods—
Analyses used genome-wide summary data for 12 389 ischemic stroke cases (including 2167 LAA, 2405 cardioembolism, and 1854 SVD) and 62 004 controls from the Metastroke consortium. For 4561 cases and 7094 controls, individual-level genotype data were also available. Genetic correlations between subtypes were estimated using linear mixed models and polygenic profile scores. Meta-analysis of a combined LAA–SVD phenotype (4021 cases and 51 976 controls) was performed to identify shared risk alleles.

Results—

High genetic correlation was identified between LAA and SVD using linear mixed models (
r
g
=0.96, SE=0.47,
P
=9×10
−4
) and profile scores (
r
g
=0.72; 95% confidence interval, 0.52–0.93). Between LAA and cardioembolism and SVD and cardioembolism, correlation was moderate using linear mixed models but not significantly different from zero for profile scoring. Joint meta-analysis of LAA and SVD identified strong association (
P
=1×10
−7
) for single nucleotide polymorphisms near the opioid receptor μ1 (
OPRM1
) gene.

Conclusions—
Our results suggest that LAA and SVD, which have been hitherto treated as genetically distinct, may share a substantial genetic component. Combined analyses of LAA and SVD may increase power to identify small-effect alleles influencing shared pathophysiological processes.
An Old Language with a New Status. Some Aspects of the Kvens’ Identity in the Borderland
Authors: Petryk Marta 
Published: January 2015

An Old Language with a New Status. Some Aspects of the Kvens’ Identity in the BorderlandKvens are one of the groups which are recognized as minorities in Norway. In this article I will address the issue of language as an important identity creating factor. After I have given the most important informations about the hardly known minority group I will present a short description of the Kven language’s classification and status in Norway – both earlier and nowadays. Then I want to present how the Kven language is used while creating the Kven identity. Stary język o nowym statusie. Kilka aspektów tożsamości Kvenów na PograniczuKvenowie są jedną z kilku grup uznawanych w Norwegii za mniejszości. Zarówno definicja jak i etnonim „Kven” budzą wiele kontrowersji. W myśl najpowszechniejszej definicji Kvenowie to potomkowie fińskich imigrantów w Norwegii. Jednakże trzeba pamiętać, że posługując się słowem „imigranci” możemy natrafić na sprzeciw, ponieważ w przypadku Kvenów mówimy często o migracjach na obszarze północnej Skandynawii wcześniejszych od ustanowienia dzisiejszych granic państwowych. Podobnie termin Finowie nie jest powszechnie akceptowany. Wątpliwości budzi on zwłaszcza wśród badaczy oraz tych członków grupy, którzy podkreślają zróżnicowanie etniczne dzisiejszej Finlandii. Mimo to wielu członków grupy nazywanej Kvenami uważa, że „Kven” i „Fin” oznaczają to samo. Protestują przy tym przeciwko nazywaniu ich Kvenami, ponieważ to niegdyś używane przez norweską większość słowo miało pejoratywny wydźwięk. Wśród współczesnych definicji kategorii „Kven” często pojawia się następująca: „Kvenowie to fińskojęzyczny lud przybyły do Norwegii przed rokiem 1900 oraz jego potomkowie” (Skarstein 2002: 85). Również i ta definicja może napotkać opór, ponieważ kveński uważany jest w Norwegii za odrębny język od roku 2005, a różnicę między kveńskim a fińskim bardzo wielu badaczy i użytkowników języka uważa za istotną. W niniejszym artykule zajmę się kwestią języka jako znaczącego czynnika tworzącego tożsamość. Przedstawię najważniejsze wiadomości o mało znanej mniejszości, a następnie omówię krótko klasyfikację i status języka kveńskiego w Norwegii, dawniej i dzisiaj. W końcu zajmę się kwestią wykorzystywania języka w procesie tworzenia tożsamości Kvenów.
How to Escape? The Trap of the Transition in the Recent Cinema of Bosnia and Herzegovina (2000-2012)
Authors: Rawski Tomasz , Roman Katarzyna 
Published: January 2015

How to Escape? The Trap of the Transition in the Recent Cinema of Bosnia and Herzegovina (2000-2012)The paper concerns the latest cinema of Bosnia and Herzegovina (2000-2012). Focusing on the cinema of social criticism (represented by movies which try to rethink the new socio-political order gradually emerging in BiH after the war of 1992-95), the authors recognize the Bosnian society as a community captured in the trap of an unfinished system transition. The story of the Bosnian society, simultaneously stuck in a dysfunctional and oppressive state and completely devoid of any prospects for the improvement of this situation, seems to be dominated by several escape strategies into an alternative reality: the nostalgic past, the imagined present or the utopian future. In that sense, the Bosnian cinema of social criticism turns out to be a cinema of social escapism. Jak uciec? Pułapka transformacji w najnowszym kinie Bośni i Hercegowiny (2000-2012)Tekst dotyczy najnowszej kinematografii Bośni i Hercegowiny (2000-2012). Skupienie na nurcie kina krytycznego (do którego zaliczone zostały filmy, które próbują interpretować nowy porządek społeczno-polityczny powoli wyłaniający się w Bośni i Hercegowinie po wojnie z lat 1992-95) pozwala ukazać społeczeństwo Bośni i Hercegowiny jako znajdujące się w pułapce wciąż niedokończonej transformacji systemowej. Opowieść o społeczeństwie z jednej strony uwięzionym w dysfunkcjonalnym i opresyjnym państwie, a z drugiej całkowicie pozbawionym perspektyw i nadziei na poprawę sytuacji, zdominowana jest przez rozmaite strategie ucieczki w alternatywną rzeczywistość: nostalgiczną przeszłość, wyobrażoną teraźniejszość lub utopijną przyszłość. W tym sensie, bośniackie kino krytyczne jawi się jako kino eskapizmu społecznego.
Direct Radiative Effect by Multicomponent Aerosol over China*
Authors: Huang Xin , Song Yu , Zhao Chun , Cai Xuhui , Zhang Hongsheng , Zhu Tong 
Published: January 2015

AbstractThe direct radiative effect (DRE) of multiple aerosol species [sulfate, nitrate, ammonium, black carbon (BC), organic carbon (OC), and mineral aerosol] and their spatiotemporal variations over China were investigated using a fully coupled meteorology–chemistry model [Weather Research and Forecasting (WRF) Model coupled with Chemistry (WRF-Chem)] for the entire year of 2006. This study made modifications to improve the model performance, including updating land surface parameters, improving the calculation of transition-metal-catalyzed oxidation of SO2, and adding heterogeneous reactions between mineral dust aerosol and acid gases. The modified model generally reproduced the magnitude, seasonal pattern, and spatial distribution of the measured meteorological conditions, concentrations of PM10 and its components, and aerosol optical depth (AOD), although some low biases existed in modeled aerosol concentrations. A diagnostic iteration method was used to estimate the overall DRE of aerosols and contributions from different components. At the land surface, the incident net radiation flux was reduced by 10.2 W m−2 over China. Aerosols significantly warmed the atmosphere with the national mean DRE of +10.8 W m−2. BC was the leading radiative heating component (+8.7 W m−2), followed by mineral aerosol (+1.1 W m−2). At the top of the atmosphere (TOA), BC introduced the largest radiative perturbation (+4.5 W m−2), followed by sulfate (−1.4 W m−2). The overall perturbation of aerosols on radiation transfer is quite small over China, demonstrating the counterbalancing effect between scattering and adsorbing aerosols. Aerosol DRE at the TOA had distinct seasonality, generally with a summer maximum and winter minimum, mainly determined by mass loadings, hygroscopic growth, and incident radiation flux.
Oral immunotherapy with type V collagen in idiopathic pulmonary fibrosis
Authors: Wilkes David S. , Chew Terrence , Flaherty Kevin R. , Frye Sarah , Gibson Kevin F. , Kaminski Naftali , Klemsz Michael J. , Lange Wade , Noth Imre , Rothhaar Katia 
Published: January 2015

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with poor prognosis. IPF appears to be heterogeneous in pathobiology with ∼40% of IPF patients found to have elevated levels of circulating antibodies to the autoantigen type V collagen (col(V)).Following a targeted, precision medicine approach, we conducted a phase 1 study to test the safety and explore potential efficacy of IW001, a col(V) oral immunotherapeutic developed to treat antibody-positive IPF patients. We divided 30 antibody-positive IPF patients into three cohorts for daily dosing over a 24-week period.All patients completed treatment without serious adverse events, acute exacerbations or IPF-related hospitalisations. A decline in lung function occurred in the lowest-dose cohort that was comparable to that reported in placebo arms of published IPF trials. In contrast, the highest-dose cohort showed a trend toward stabilisation of forced vital capacity and matrix metalloproteinase 7, and a reduction in binding of C1q to anti-col(V) antibodies.IW001 may modulate the immune response to col(V) and may represent a new therapeutic for col(V)- reactive IPF patients.
Complicated grief after death of a relative in the intensive care unit
Authors: Kentish-Barnes Nancy , Chaize Marine , Seegers Valérie , Legriel Stéphane , Cariou Alain , Jaber Samir , Lefrant Jean-Yves , Floccard Bernard , Renault Anne , Vinatier Isabelle , Mathonnet Armelle , Reuter Danielle , Guisset Olivier , Cohen-Solal Zoé , Cracco Christophe , Seguin Amélie , Durand-Gasselin Jacques , Éon Béatrice , Thirion Marina , Rigaud Jean-Philippe , Philippon-Jouve Bénédicte , Argaud Laurent , Chouquer Renaud , Adda Mélanie , Dedrie Céline , Georges Hugues , Lebas Eddy , Rolin Nathalie , Bollaert Pierre-Edouard , Lecuyer Lucien , Viquesnel Gérard , Léone Marc , Chalumeau-Lemoine Ludivine , Garrouste Maïté , Schlemmer Benoit , Chevret Sylvie , Falissard Bruno , Azoulay Élie 
Published: January 2015

An increased proportion of deaths occur in the intensive care unit (ICU).We performed this prospective study in 41 ICUs to determine the prevalence and determinants of complicated grief after death of a loved one in the ICU. Relatives of 475 adult patients were followed up. Complicated grief was assessed at 6 and 12 months using the Inventory of Complicated Grief (cut-off score >25). Relatives also completed the Hospital Anxiety and Depression Scale at 3 months, and the Revised Impact of Event Scale for post-traumatic stress disorder symptoms at 3, 6 and 12 months. We used a mixed multivariate logistic regression model to identify determinants of complicated grief after 6 months.Among the 475 patients, 282 (59.4%) had a relative evaluated at 6 months. Complicated grief symptoms were identified in 147 (52%) relatives. Independent determinants of complicated grief symptoms were either not amenable to changes (relative of female sex, relative living alone and intensivist board certification before 2009) or potential targets for improvements (refusal of treatment by the patient, patient died while intubated, relatives present at the time of death, relatives did not say goodbye to the patient, and poor communication between physicians and relatives).End-of-life practices, communication and loneliness in bereaved relatives may be amenable to improvements.
Common fixed points of Caristi’s type mappings via w-distance
Authors: Sitthikul Kittipong , Saejung Satit 
Published: January 2015

AbstractMotivated by fixed point theorems of Obama and Kuroiwa (Sci. Math. Jpn. 72(1), 41-48, 2010), we discuss their results with another, weaker assumption and obtain some estimating expressions. Furthermore, we also discuss the results with the lower semicontinuities of the dominated functions in place of the original orbital continuities of the mappings.
Factors affecting viability of Bifidobacterium bifidum during spray drying
Authors: Shokri Zahra , Fazeli Mohammad Reza , Ardjmand Mehdi , Mousavi Seyyed Mohammad , Gilani Kambiz 
Published: January 2015

Abstract

Background
There is substantial clinical data supporting the role of Bifidobacterium bifidum in human health particularly in benefiting the immune system and suppressing intestinal infections. Compared to the traditional lyophilization, spray-drying is an economical process for preparing large quantities of viable microorganisms. The technique offers high production rates and low operating costs but is not usually used for drying of substances prone to high temperature. The aim of this study was to establish the optimized environmental factors in spray drying of cultured bifidobacteria to obtain a viable and stable powder.

Methods
The experiments were designed to test variables such as inlet air temperature, air pressure and also maltodextrin content. The combined effect of these variables on survival rateand moisture content of bacterial powder was studied using a central composite design (CCD). Sub-lethal heat-adaptation of a B. bifidum strain which was previously adapted to acid-bile-NaCl led to much more resistance to high outlet temperature during spray drying. The resistant B. bifidum was supplemented with cost friendly permeate, sucrose, yeast extract and different amount of maltodextrin before it was fed into a Buchi B-191 mini spray-dryer.

Results
Second-order polynomials were established to identify the relationship between the responses andthe three variables. Results of verification experiments and predicted values from fitted correlations were in close agreement at 95% confidence interval. The optimal values of the variables for maximum survival and minimum moisture content of B. bifidum powder were as follows: inlet air temperature of 111.15°C, air pressure of 4.5 bar and maltodextrin concentration of 6%. Under optimum conditions, the maximum survival of 28.38% was achieved while moisture was maintained at 4.05%.

Conclusion
Viable and cost effective spray drying of Bifidobacterium bifidum could be achieved by cultivating heat and acid adapted strain into the culture media containing nutritional protective agents.