bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of and risk factors for chronic arthralgia and rheumatoid-like polyarthritis more than 2 years after infection with chikungunya virus
Authors: Essackjee Khadijah , Goorah Smita , Ramchurn Satish Kumar , Cheeneebash Jayrani , Walker-Bone Karen 
Published: May 2013

Abstract

Objectives
Chikungunya virus (CHIKV), transmitted to humans from infected mosquitoes, causes acute fever, arthralgia and rash. There is increasing evidence that it also causes longer-term rheumatic symptoms. In a circumscribed part of Mauritius where infectivity was high, a cohort of inhabitants was surveyed with the objectives of assessing the prevalence of and risk factors for chronic musculoskeletal symptoms and for a rheumatoid arthritis-like condition at 27.5 months after initial infection.

Methods
Participants were recruited May–November 2008 and invited to complete a questionnaire. CHIKV was diagnosed clinically. The primary outcomes for the analyses were (a) self-reported ongoing musculoskeletal symptoms and (b) fulfilment of modified diagnostic criteria for rheumatoid arthritis. Risk factors for these outcomes were explored in univariate analyses using logistic regression. Subsequently, multivariate logistic regression was used to identify factors that were independently associated with the outcomes.

Results
173 individuals were identified with CHIKV, of whom 136 (78.6%) reported persisting musculoskeletal symptoms 27.5 months after infection. Persistent symptoms were associated with older age at time of infection, female gender and baseline symmetrical distribution of joint symptoms. We found that 5% of those infected with CHIKV fulfilled a modified version of the American College of Rheumatology criteria for rheumatoid arthritis 27.5 months after infection.

Conclusions
CHIKV is associated with a high prevalence of persistent rheumatic symptoms. Physicians need to be aware of CHIKV as a cause of acute and chronic rheumatic symptoms.
Efficacy and Mechanism-of-Action of a Novel Superagonist Interleukin-15: Interleukin-15 Receptor αSu/Fc Fusion Complex in Syngeneic Murine Models of Multiple Myeloma
Authors: Xu Wenxin , Jones Monica , Liu Bai , Zhu Xiaoyun , Johnson Christopher B. , Edwards Ana C. , Kong Lin , Jeng Emily K. , Han Kaiping , Marcus Warren D. , Rubinstein Mark P. , Rhode Peter R. , Wong Hing C. 
Published: May 2013

Abstract
ALT-803, a complex of an interleukin (IL)-15 superagonist mutant and a dimeric IL-15 receptor αSu/Fc fusion protein, was found to exhibit significantly stronger in vivo biologic activity on NK and T cells than IL-15. In this study, we show that a single dose of ALT-803, but not IL-15 alone, eliminated well-established 5T33P and MOPC-315P myeloma cells in the bone marrow of tumor-bearing mice. ALT-803 treatment also significantly prolonged survival of myeloma-bearing mice and provided resistance to rechallenge with the same tumor cells through a CD8+ T-cell–dependent mechanism. ALT-803 treatment stimulated CD8+ T cells to secrete large amounts of IFN-γ and promoted rapid expansion of CD8+CD44high memory T cells in vivo. These memory CD8+ T cells exhibited ALT-803–mediated upregulation of NKG2D (KLRK1) but not PD-1 (PDCD1) or CD25 (IL2RA) on their cell surfaces. ALT-803–activated CD8+ memory T cells also exhibited nonspecific cytotoxicity against myeloma and other tumor cells in vitro, whereas IFN-γ had no direct effect on myeloma cell growth. ALT-803 lost its antimyeloma activity in tumor-bearing IFN-γ knockout mice but retained the ability to promote CD8+CD44high memory T-cell proliferation, indicating that ALT-803–mediated stimulation of CD8+CD44high memory T cells is IFN-γ–independent. Thus, besides well-known IL-15 biologic functions in host immunity, this study shows that IL-15–based ALT-803 could activate CD8+CD44high memory T cells to acquire a unique innate-like phenotype and secrete IFN-γ for nonspecific tumor cell killing. This unique immunomodulatory property of ALT-803 strongly supports its clinical development as a novel immunotherapeutic agent against cancer and viral infections. Cancer Res; 73(10); 3075–86. ©2013 AACR.
CIP4 Controls CCL19-Driven Cell Steering and Chemotaxis in Chronic Lymphocytic Leukemia
Authors: Malet-Engra Gema , Viaud Julien , Ysebaert Loïc , Farcé Manon , Lafouresse Fanny , Laurent Guy , Gaits-Iacovoni Frédérique , Scita Giorgio , Dupré Loïc 
Published: May 2013

Abstract
Solid tumor dissemination relies on the reprogramming of molecular pathways controlling chemotaxis. Whether the motility of nonsolid tumors such as leukemia depends on the deregulated expression of molecules decoding chemotactic signals remains an open question. We identify here the membrane remodeling F-BAR adapter protein Cdc42-interacting protein 4 (CIP4) as a key regulator of chemotaxis in chronic lymphocytic leukemia (CLL). CIP4 is expressed at abnormally high levels in CLL cells, where it is required for CCL19-induced chemotaxis. Upon CCL19 stimulation of CLL cells, CIP4 associates with GTP-bound Cdc42 and is recruited to the rear of the lamellipodium and along microspikes radiating through the lamellipodium. Consistent with its cellular distribution, CIP4 removal impairs both the assembly of the polarized lamellipodium and directional migration along a diffusible CCL19 gradient. Furthermore, CIP4 depletion results in decreased activation of WASP, but increased activation of PAK1 and p38 mitogen-activated protein kinase (MAPK). Notably, p38 MAPK inhibition results in impaired lamellipodium assembly and loss of directional migration. This suggests that CIP4 modulates both the WASP and p38 MAPK pathways to promote lamellipodium assembly and chemotaxis. Overall, our study reveals a critical role of CIP4 in mediating chemotaxis of CLL cells by controlling the dynamics of microspike-containing protrusions and cell steering. Cancer Res; 73(11); 3412–24. ©2013 AACR.
KDM4/JMJD2 Histone Demethylases: Epigenetic Regulators in Cancer Cells
Authors: Berry William L. , Janknecht Ralf 
Published: May 2013

Abstract
Lysine methylation is one of the most prominent histone posttranslational modifications that regulate chromatin structure. Changes in histone lysine methylation status have been observed during cancer formation, which is thought to be a consequence of the dysregulation of histone lysine methyltransferases or the opposing demethylases. KDM4/JMJD2 proteins are demethylases that target histone H3 on lysines 9 and 36 and histone H1.4 on lysine 26. This protein family consists of three ∼130-kDa proteins (KDM4A-C) and KDM4D/JMJD2D, which is half the size, lacks the double PHD and Tudor domains that are epigenome readers and present in the other KDM4 proteins, and has a different substrate specificity. Various studies have shown that KDM4A/JMJD2A, KDM4B/JMJD2B, and/or KDM4C/JMJD2C are overexpressed in breast, colorectal, lung, prostate, and other tumors and are required for efficient cancer cell growth. In part, this may be due to their ability to modulate transcription factors such as the androgen and estrogen receptor. Thus, KDM4 proteins present themselves as novel potential drug targets. Accordingly, multiple attempts are under way to develop KDM4 inhibitors, which could complement the existing arsenal of epigenetic drugs that are currently limited to DNA methyltransferases and histone deacetylases. Cancer Res; 73(10); 2936–42. ©2013 AACR.
β1 Integrin Targeting Potentiates Antiangiogenic Therapy and Inhibits the Growth of Bevacizumab-Resistant Glioblastoma
Authors: Carbonell W. Shawn , DeLay Michael , Jahangiri Arman , Park Catherine C. , Aghi Manish K. 
Published: May 2013

Abstract
Antiangiogenic therapies like bevacizumab offer promise for cancer treatment, but acquired resistance, which often includes an aggressive mesenchymal phenotype, can limit the use of these agents. Upregulation of β1 integrin (ITGB1) occurs in some bevacizumab-resistant glioblastomas (BRG) whereby, mediating tumor–microenvironment interactions, we hypothesized that it may mediate a mesenchymal-type resistance to antiangiogenic therapy. Immunostaining analyses of β1 integrin and its downstream effector kinase FAK revealed upregulation in 75% and 86% of BRGs, respectively, compared with pretreatment paired specimens. Furthermore, flow cytometry revealed eight-fold more β1 integrin in primary BRG cells compared with cells from bevacizumab-naïve glioblastomas (BNG). Fluorescence recovery after photobleaching of cells engineered to express a β1-GFP fusion protein indicated that the mobile β1 integrin fraction was doubled, and half-life of β1 integrin turnover in focal adhesions was reduced markedly in BRG cells compared with bevacizumab-responsive glioblastoma multiforme cells. Hypoxia, which was increased with acquisition of bevacizumab resistance, was associated with increased β1 integrin expression in cultured BNG cells. BRGs displayed an aggressive mesenchymal-like phenotype in vitro. We found that growth of BRG xenograft tumors was attenuated by the β1 antibody, OS2966, allowing a 20-fold dose reduction of bevacizumab per cycle in this model. Intracranial delivery of OS2966 through osmotic pumps over 28 days increased tumor cell apoptosis, decreased tumor cell invasiveness, and blunted the mesenchymal morphology of tumor cells. We concluded that β1 integrin upregulation in BRGs likely reflects an onset of hypoxia caused by antiangiogenic therapy, and that β1 inhibition is well tolerated in vivo as a tractable strategy to disrupt resistance to this therapy. Cancer Res; 73(10); 3145–54. ©2013 AACR.
Multivalent Scaffold Proteins as Superagonists of TRAIL Receptor 2–Induced Apoptosis
Authors: Swers Jeffery S. , Grinberg Luba , Wang Lin , Feng Hui , Lekstrom Kristen , Carrasco Rosa , Xiao Zhan , Inigo Ivan , Leow Ching Ching , Wu Herren , Tice David A. , Baca Manuel 
Published: May 2013

AbstractActivation of TNF-related apoptosis-inducing ligand receptor 2 (TRAILR2) can induce apoptosis in a variety of human cancer cell lines and xenografts, while lacking toxicity in normal cells. The natural ligand and agonistic antibodies show antitumor activity in preclinical models of cancer, and this had led to significant excitement in the clinical potential of these agents. Unfortunately, this optimism has been tempered by trial data that, thus far, are not showing clear signs of efficacy in cancer patients. The reasons for discrepant preclinical and clinical observations are not understood, but one possibility is that the current TRAILR2 agonists lack sufficient potency to achieve a meaningful response in patients. Toward addressing that possibility, we have developed multivalent forms of a new binding scaffold (Tn3) that are superagonists of TRAILR2 and can induce apoptosis in tumor cell lines at subpicomolar concentrations. The monomer Tn3 unit was a fibronectin type III domain engineered for high-affinity TRAILR2 binding. Multivalent presentation of this basic unit induced cell death in TRAILR2-expressing cell lines. Optimization of binding affinity, molecular format, and valency contributed to cumulative enhancements of agonistic activity. An optimized multivalent agonist consisting of 8 tandem Tn3 repeats was highly potent in triggering cell death in TRAIL-sensitive cell lines and was 1 to 2 orders of magnitude more potent than TRAIL. Enhanced potency was also observed in vivo in a tumor xenograft setting. The TRAILR2 superagonists described here have the potential for superior clinical activity in settings insensitive to the current therapeutic agonists that target this pathway. Mol Cancer Ther; 12(7); 1235–44. ©2013 AACR.
Aerosol Administration of Phospho-Sulindac Inhibits Lung Tumorigenesis
Authors: Cheng Ka Wing , Wong Chi C. , Alston Ninche , Mackenzie Gerardo G. , Huang Liqun , Ouyang Nengtai , Xie Gang , Wiedmann Timothy , Rigas Basil 
Published: May 2013

Abstract
Phospho-sulindac is a sulindac derivative with promising anticancer activity in lung cancer, but its limited metabolic stability presents a major challenge for systemic therapy. We reasoned that inhalation delivery of phospho-sulindac might overcome first-pass metabolism and produce high levels of intact drug in lung tumors. Here, we developed a system for aerosolization of phospho-sulindac and evaluated the antitumor efficacy of inhaled phospho-sulindac in an orthotopic model of human non–small cell lung cancer (A549 cells). We found that administration by inhalation delivered high levels of phospho-sulindac to the lungs and minimized its hydrolysis to less active metabolites. Consequently, inhaled phospho-sulindac (6.5 mg/kg) was highly effective in inhibiting lung tumorigenesis (75%; P &lt; 0.01) and significantly improved the survival of mice bearing orthotopic A549 xenografts. Mechanistically, phospho-sulindac suppressed lung tumorigenesis by (i) inhibiting EGF receptor (EGFR) activation, leading to profound inhibition of Raf/MEK/ERK and PI3K/AKT/mTOR survival cascades; (ii) inducing oxidative stress, which provokes the collapse of mitochondrial membrane potential and mitochondria-dependent cell death; and (iii) inducing autophagic cell death. Our data establish that inhalation delivery of phospho-sulindac is an efficacious approach to the control of lung cancer, which merits further evaluation. Mol Cancer Ther; 12(8); 1417–28. ©2013 AACR.
Antiproliferative Effects of Continued Mitogen-Activated Protein Kinase Pathway Inhibition following Acquired Resistance to BRAF and/or MEK Inhibition in Melanoma
Authors: Carlino Matteo S. , Gowrishankar Kavitha , Saunders Catherine A.B. , Pupo Gulietta M. , Snoyman Stephanie , Zhang Xu Dong , Saw Robyn , Becker Therese M. , Kefford Richard F. , Long Georgina V. , Rizos Helen 
Published: May 2013

Abstract
Inhibitors of the mitogen-activated protein kinases (MAPK), BRAF, and MAP–ERK kinase (MEK) induce tumor regression in the majority of patients with BRAF-mutant metastatic melanoma. The clinical benefit of MAPK inhibitors is restricted by the development of acquired resistance with half of those who benefit having progressed by 6 to 7 months and long-term responders uncommon. There remains no agreed treatment strategy on disease progression in these patients. Without published evidence, fears of accelerated disease progression on inhibitor withdrawal have led to the continuation of drugs beyond formal disease progression. We now show that treatment with MAPK inhibitors beyond disease progression can provide significant clinical benefit, and the withdrawal of these inhibitors led to a marked increase in the rate of disease progression in two patients. We also show that MAPK inhibitors retain partial activity in acquired resistant melanoma by examining drug-resistant clones generated to dabrafenib, trametinib, or the combination of these drugs. All resistant sublines displayed a markedly slower rate of proliferation when exposed to MAPK inhibitors, and this coincided with a reduction in MAPK signaling, decrease in bromodeoxyuridine incorporation, and S-phase inhibition. This cytostatic effect was also associated with diminished levels of cyclin D1 and p-pRb. Two short-term melanoma cultures generated from resistant tumor biopsies also responded to MAPK inhibition, with comparable inhibitory changes in proliferation and MAPK signaling. These data provide a rationale for the continuation of BRAF and MEK inhibitors after disease progression and support the development of clinical trials to examine this strategy. Mol Cancer Ther; 12(7); 1332–42. ©2013 AACR.
A Supplementary Source for the Study of Mamluk Social History: The Taqārīẓ*
Authors: Levanoni Amalia 
Published: May 2013

Abstract
The taqārīẓ were part of an established system of academic recognition and the ʿulamāʾ patronage networks and at times, they could also be a powerful satirical weapon used by the learned elite members to denigrate and exclude a colleague. The large collection of the satire taqārīẓ written for the panegyric Biography composed in 819/1416 by Šams al-Dīn Muḥammad b. Nāhiḍ for the Mamluk sultan al-Muʾayyad Šayḫ is explored in this article as a supplementary source to the historical narratives for the study of the ʿulamāʾ milieu during the strained period of the transition from Turkish to Circassian sultanate (784/1382). Placing these taqārīẓ in the context of the increasing social insecurity entailed by the political reshuffles, reveals the growing anxiety of the incumbent learned elites over their positions and status in the administration of justice, the academe (madāris) and the waqf institution—the spheres where they exercised their hegemony of knowledge and religious power—and the strategies they adopted for their social survival.
Polemics in the Koran: The Koran’s Negative Argumentation over its Own Origin1
Authors: Boisliveau Anne-Sylvie 
Published: May 2013

Abstract
In this article I propose that the polemical passages in the Koran should not be addressed as if they were aiming at narrating a portion of Muḥammad’s life but as parts of the koranic argumentation about its own origin and status. The first part of this paper shows how these polemics convey a religious debate by addressing the question of the sacred origin of the koranic text and the authenticity of Muḥammad’s prophetic role, in parallel. The second part provides an analysis of how the Koran argues about its own religious authority through these polemical passages: by meeting expectations which are described as Jewish and Christian, by refusing any attitude of denial, and by accusing the opponents of forgery. Hypotheses on the type of audiences of these passages are then exposed.
Un cas de dérivation « pivot » en arabe
Authors: Larcher Pierre 
Published: May 2013

Résumé
Maʿīn, transcrit en caractères latins Maïn, est une marque d’eau minérale de Tunisie. C’est peut-être un jeu de mots avec l’arabe dialectal mā ʿīn « eau de source » (cl. māʾ ʿayn). Mais c’est aussi une réminiscence coranique. Le mot maʿīn apparaît quatre fois dans le Coran, qualifiant deux fois l’eau, une fois implicitement et une fois explicitement, et deux fois, métaphoriquement, la boisson des élus au Paradis. Les sources arabes anciennes se demandent si maʿīn doit être lu comme un maf ʿūl, lié à la famille lexicale de ʿayn (« source », cf. le verbe ʿāna-yaʿīnu « arriver à une source ») ou un faʿīl, lié à la famille lexicale de maʿn (« couler », en parlant de l’eau). Cette discussion montre que maʿīn est le mot qui a permis le passage d’une famille lexicale à une autre. Il illustre les conditions formelles et sémantiques de ce type de dérivation, qu’on appellera « dérivation pivot ».
One Sky: The Palestinian Writer Liyāna Badr between Two Periods
Authors: Gottesfeld Dorit 
Published: May 2013

Abstract
The present article illustrates how the change in the geographic location of Liyāna Badr, one of the prominent Palestinian women writers, influenced her writing in thematic and stylistic terms. It shows how Badr’s writing shifts from descriptions of isolation and loneliness, alienation and yearning for the past, to describing feelings of rage and frustration with the reality of Israeli occupation, and how from an innovative and vague writing style she shifts to a realistic, simple, and direct style that reflects the themes of her stories and the messages she wishes to convey. In this way Badr reinforces the connection of her work with Palestinian existence and the reality of occupation, and does not let the contemporary writing directions adopted by the young women authors influence the degree of Palestinian-ness of her texts.
Among Kings and Sages: Greek and Indian Wisdom in an Arabic Mirror for Princes
Authors: Marlow Louise 
Published: May 2013

Abstract
The mirror for princes known as the Naṣīḥat al-mulūk of al-Māwardī, probably a tenth-century text, is replete with references to sources identified by the author as “Indian”. A large number of these texts also appear in the so-called Waṣiyyat Arisṭāṭālīs li-l-Iskandar; some examples find parallels in Kalīla wa-Dimna and Bilawhar wa-Būḏāsaf. These coincidences raise several possibilities: first, that the author’s “Indian” source represents a work of Indic background, translated from Sanskrit or another Indian language into Arabic, probably at the time when the Barmakids were sponsoring such translations in significant numbers; secondly, that it was rendered from an Indian language into Middle Persian in the Sasanian period and from that language into Arabic in the early centuries of the Islamic era; thirdly, that the text was composed in a non-Indian language, probably Middle Persian, and acquired a “forged” Indian genealogy in a parallel to the numerous spurious Greek attributions (a category that would subsequently include the pseudo-Aristotelian testament). The article addresses these three possibilities, and, on the basis of textual and contextual considerations, suggests that at the present stage of research, it is the second that seems most likely.
Ğāḥiẓiana. Addition à l’essai d’inventaire de l’œuvre ǧāḥiẓienne : le Kitāb al-Fityān retrouvé ?1
Authors: Regourd Anne 
Published: May 2013

Résumé
Parmi les documents de la Geniza conservés à l’Académie hongroise des Sciences (Budapest), figure un feuillet dont une face porte le titre d’une œuvre attribuée à Ğāḥiẓ, le Kitāb al-Fityān, et dont l’autre comporte le début du texte associé à ce titre. L’objet de cet article est de tenter d’identifier l’œuvre et son sujet, de dater sa composition, de dater et situer la copie, en s’appuyant pour beaucoup sur des arguments philologiques. Une édition complète du texte figure en annexe. Enfin, le feuillet ayant été mis à jour dans la Geniza du Caire, l’article attire l’attention sur son statut de document. L’original a malheureusement disparu de la Bibliothèque de l’Académie des Sciences de Budapest, il n’en demeure qu’une copie argentique, reproduite ici.
Outside the Ghetto: Jews and Christians in the Duchy of Modena
Authors: Aron-Beller Katherine 
Published: May 2013

Abstract
Historians have in the past concentrated their studies of early modern Jewish life on the main city-states of Northern Italy where the largest Jewish communities existed. These areas have been categorized as territories which absorbed Jewish immigrants, enclosed them in ghettos, and monitored their actions with the creation of specific agencies. My essay turns to Jewish existence in the smaller towns and rural areas of the duchy of Modena in the seventeenth century, and attempts to question how this alienated minority was able to fare in areas which housed no ghettos. Here the political and religious decentralization, particularly in the early seventeenth century, generated retaliatory hostility as well as intimacy between Jews and Christians. Sources for this study will be Inquisitorial documents that concerned professing Jews. These sources, once decoded, provide extraordinarily rich images of daily life and provide a unique picture of social relations between the two religionists.
Abortion for Foetal Abnormalities in Ireland; The Limited Scope of the Irish Government’s Response to the A, B and C Judgment
Authors: Donoghue Stephen , Smyth Claire-Michelle 
Published: May 2013

Abstract
Abortion has been a controversial topic in Irish law and one which the Government has been forced to address following the decision of the European Court of Human Rights in A, B and C v. Ireland. The Working Group established to make recommendations have specifically been instructed to deal only with the issues raised in the A, B and C judgment and legislate on the basic of the ‘X case’. This restricted approach calls for legalisation of abortion only where the life of the mother is at risk, a position unique only to Ireland and Andorra within Europe. The vast majority of member states to the European Convention on Human Rights allow for legal abortion on the basis of foetal abnormality and with this emerging consensus the margin of appreciation hitherto afforded by the European Court to member states is diminishing. The advancement and availability of non-invasive genetic tests that can determine foetal abnormalities together with the ruling in R. R. v. Poland leaves Ireland in a precarious position for omitting any reference to foetal abnormalities in any proposed legislation.