bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silent cerebral infarcts: a review on a prevalent and progressive cause of neurologic injury in sickle cell anemia
Authors: DeBaun Michael R. , Armstrong F. Daniel , McKinstry Robert C. , Ware Russell E. , Vichinsky Elliot , Kirkham Fenella J. 
Published: February 2012

AbstractSilent cerebral infarct (SCI) is the most common form of neurologic disease in children with sickle cell anemia (SCA). SCI is defined as abnormal magnetic resonance imaging (MRI) of the brain in the setting of a normal neurologic examination without a history or physical findings associated with an overt stroke. SCI occurs in 27% of this population before their sixth, and 37% by their 14th birthdays. In adults with SCA, the clinical history of SCI is poorly defined, although recent evidence suggests that they too may have ongoing risk of progressive injury. Risk factors for SCI include male sex, lower baseline hemoglobin concentration, higher baseline systolic blood pressure, and previous seizures. Specific morbidity associated with SCI includes a decrement in general intellectual abilities, poor academic achievement, progression to overt stroke, and progressive SCI. In addition, children with previous stroke continue to have both overt strokes and new SCI despite receiving regular blood transfusion therapy for secondary stroke prevention. Studies that only include overt stroke as a measure of CNS injury significantly underestimate the total cerebral injury burden in this population. In this review, we describe the epidemiology, natural history, morbidity, medical management, and potential therapeutic options for SCI in SCA.
Redefining interferon-producing killer dendritic cells as a novel intermediate in NK-cell differentiation
Authors: Guimont-Desrochers Fanny , Boucher Geneviève , Dong Zhongjun , Dupuis Martine , Veillette André , Lesage Sylvie 
Published: February 2012

Abstract
The cell lineage origin of IFN-producing killer dendritic cells (IKDCs), which exhibit prominent antitumoral activity, has been subject to debate. Although IKDCs were first described as a cell type exhibiting both plasmacytoid DC and natural killer (NK) cell properties, the current view reflects that IKDCs merely represent activated NK cells expressing B220, which were thus renamed B220+ NK cells. Herein, we further investigate the lineage relation of B220+ NK cells with regard to other NK-cell subsets. We surprisingly find that, after adoptive transfer, B220− NK cells did not acquire B220 expression, even in the presence of potent activating stimuli. These findings strongly argue against the concept that B220+ NK cells are activated NK cells. Moreover, we unequivocally show that B220+ NK cells are highly proliferative and differentiate into mature NK cells after in vivo adoptive transfer. Additional phenotypic, functional, and transcriptional characterizations further define B220+ NK cells as immediate precursors to mature NK cells. The characterization of these novel attributes to B220+ NK cells will guide the identification of their ortholog in humans, contributing to the design of potent cancer immunotherapies.
Tumor-targeted T cells modified to secrete IL-12 eradicate systemic tumors without need for prior conditioning
Authors: Pegram Hollie J. , Lee James C. , Hayman Erik G. , Imperato Gavin H. , Tedder Thomas F. , Sadelain Michel , Brentjens Renier J. 
Published: February 2012

Abstract
Adoptive cell therapy with tumor-targeted T cells is a promising approach to cancer therapy. Enhanced clinical outcome using this approach requires conditioning regimens with total body irradiation, lymphodepleting chemotherapy, and/or additional cytokine support. However, the need for prior conditioning precludes optimal application of this approach to a significant number of cancer patients intolerant to these regimens. Herein, we present preclinical studies demonstrating that treatment with CD19-specific, chimeric antigen receptor (CAR)–modified T cells that are further modified to constitutively secrete IL-12 are able to safely eradicate established disease in the absence of prior conditioning. We demonstrate in a novel syngeneic tumor model that tumor elimination requires both CD4+ and CD8+ T-cell subsets, autocrine IL-12 stimulation, and subsequent IFNγ secretion by the CAR+ T cells. Importantly, IL-12–secreting, tumor-targeted T cells acquire intrinsic resistance to T regulatory cell–mediated inhibition. Based on these preclinical data, we anticipate that adoptive therapy using CAR-targeted T cells modified to secrete IL-12 will obviate or reduce the need for potentially hazardous conditioning regimens to achieve optimal antitumor responses in cancer patients.
Interaction of HmC1q with leech microglial cells: involvement of C1qBP-related molecule in the induction of cell chemotaxis
Authors: Tahtouh Muriel , Garçon-Bocquet Annelise , Croq Françoise , Vizioli Jacopo , Sautière Pierre-Eric , Van Camp Christelle , Salzet Michel , Nagnan-le Meillour Patricia , Pestel Joël , Lefebvre Christophe 
Published: February 2012

Abstract

Background
In invertebrates, the medicinal leech is considered to be an interesting and appropriate model to study neuroimmune mechanisms. Indeed, this non-vertebrate animal can restore normal function of its central nervous system (CNS) after injury. Microglia accumulation at the damage site has been shown to be required for axon sprouting and for efficient regeneration. We characterized HmC1q as a novel chemotactic factor for leech microglial cell recruitment. In mammals, a C1q-binding protein (C1qBP alias gC1qR), which interacts with the globular head of C1q, has been reported to participate in C1q-mediated chemotaxis of blood immune cells. In this study, we evaluated the chemotactic activities of a recombinant form of HmC1q and its interaction with a newly characterized leech C1qBP that acts as its potential ligand.

Methods
Recombinant HmC1q (rHmC1q) was produced in the yeast Pichia pastoris. Chemotaxis assays were performed to investigate rHmC1q-dependent microglia migration. The involvement of a C1qBP-related molecule in this chemotaxis mechanism was assessed by flow cytometry and with affinity purification experiments. The cellular localization of C1qBP mRNA and protein in leech was investigated using immunohistochemistry and in situ hybridization techniques.

Results
rHmC1q-stimulated microglia migrate in a dose-dependent manner. This rHmC1q-induced chemotaxis was reduced when cells were preincubated with either anti-HmC1q or anti-human C1qBP antibodies. A C1qBP-related molecule was characterized in leech microglia.

Conclusions
A previous study showed that recruitment of microglia is observed after HmC1q release at the cut end of axons. Here, we demonstrate that rHmC1q-dependent chemotaxis might be driven via a HmC1q-binding protein located on the microglial cell surface. Taken together, these results highlight the importance of the interaction between C1q and C1qBP in microglial activation leading to nerve repair in the medicinal leech.
Involvement of PPAR-γ in the neuroprotective and anti-inflammatory effects of angiotensin type 1 receptor inhibition: effects of the receptor antagonist telmisartan and receptor deletion in a mouse MPTP model of Parkinson's disease
Authors: Garrido-Gil Pablo , Joglar Belen , Rodriguez-Perez Ana I , Guerra Maria J , Labandeira-Garcia Jose L 
Published: February 2012

AbstractBackgroundSeveral recent studies have shown that angiotensin type 1 receptor (AT1) antagonists such as candesartan inhibit the microglial inflammatory response and dopaminergic cell loss in animal models of Parkinson's disease. However, the mechanisms involved in the neuroprotective and anti-inflammatory effects of AT1 blockers in the brain have not been clarified. A number of studies have reported that AT1 blockers activate peroxisome proliferator-activated receptor gamma (PPAR γ). PPAR-γ activation inhibits inflammation, and may be responsible for neuroprotective effects, independently of AT1 blocking actions.MethodsWe have investigated whether oral treatment with telmisartan (the most potent PPAR-γ activator among AT1 blockers) provides neuroprotection against dopaminergic cell death and neuroinflammation, and the possible role of PPAR-γ activation in any such neuroprotection. We used a mouse model of parkinsonism induced by the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and co-administration of the PPAR-γ antagonist GW9662 to study the role of PPAR-γ activation. In addition, we used AT1a-null mice lesioned with MPTP to study whether deletion of AT1 in the absence of any pharmacological effect of AT1 blockers provides neuroprotection, and investigated whether PPAR-γ activation may also be involved in any such effect of AT1 deletion by co-administration of the PPAR-γ antagonist GW9662.ResultsWe observed that telmisartan protects mouse dopaminergic neurons and inhibits the microglial response induced by administration of MPTP. The protective effects of telmisartan on dopaminergic cell death and microglial activation were inhibited by co-administration of GW9662. Dopaminergic cell death and microglial activation were significantly lower in AT1a-null mice treated with MPTP than in mice not subjected to AT1a deletion. Interestingly, the protective effects of AT1 deletion were also inhibited by co-administration of GW9662.ConclusionThe results suggest that telmisartan provides effective neuroprotection against dopaminergic cell death and that the neuroprotective effect is mediated by PPAR-γ activation. However, the results in AT1-deficient mice show that blockage of AT1, unrelated to the pharmacological properties of AT1 blockers, also protects against dopaminergic cell death and neuroinflammation. Furthermore, the results show that PPAR-γ activation is involved in the anti-inflammatory and neuroprotective effects of AT1 deletion.
Adherence to Stage-Specific Treatment Guidelines for Patients With Colon Cancer
Authors: Chagpar Ryaz , Xing Yan , Chiang Yi-Ju , Feig Barry W. , Chang George J. , You Y. Nancy , Cormier Janice N. 
Published: February 2012

Purpose Adherence to evidence-based treatment guidelines has been proposed as a measure of cancer care quality. We sought to determine rates of and factors associated with adherence to the National Comprehensive Cancer Network (NCCN) treatment guidelines for colon cancer. Patients and Methods Patients within the National Cancer Data Base treated for colon adenocarcinoma (2003 to 2007) were identified. Adherence to stage-specific NCCN guidelines was determined based on disease stage. Hierarchical regression analyses were performed to identify factors predictive of adherence, overtreatment, and undertreatment. Results A total of 173,243 patients were included in the final cohort, 123,953 (71%) of whom were treated according to NCCN guidelines. Patients with stage I disease were more likely to receive guideline-based treatment (96%) than patients with stage II (low risk, 66%; high risk, 36%), III (71%), or IV (73%) disease (P < .001). Adherence to consensus-based guidelines increased over time. Factors associated with adherence across all stages included age, Charlson-Deyo comorbidity index score, later year of diagnosis, and insurance status. Among patients with high-risk stage II or stage III disease, older patients with pre-existing comorbidities and patients with lower socioeconomic status were less likely to be offered adjuvant chemotherapy. Among patients with stage I and II disease, young, healthy patients were more likely to be recommended chemotherapy, in discordance with NCCN guidelines. Conclusion Significant variation exists in the treatment of colon cancer, particularly in treatment of high-risk stage II and stage III disease. The impact of nonadherence to guidelines on patient outcomes needs to be further elucidated.
Integrating dynamic energy budget (DEB) theory with traditional bioenergetic models
Authors: Nisbet Roger M. , Jusup Marko , Klanjscek Tin , Pecquerie Laure 
Published: February 2012

SummaryDynamic energy budget (DEB) theory offers a systematic, though abstract, way to describe how an organism acquires and uses energy and essential elements for physiological processes, in addition to how physiological performance is influenced by environmental variables such as food density and temperature. A ‘standard’ DEB model describes the performance (growth, development, reproduction, respiration, etc.) of all life stages of an animal (embryo to adult), and predicts both intraspecific and interspecific variation in physiological rates. This approach contrasts with a long tradition of more phenomenological and parameter-rich bioenergetic models that are used to make predictions from species-specific rate measurements. These less abstract models are widely used in fisheries studies; they are more readily interpretable than DEB models, but lack the generality of DEB models. We review the interconnections between the two approaches and present formulae relating the state variables and fluxes in the standard DEB model to measured bioenergetic rate processes. We illustrate this synthesis for two large fishes: Pacific bluefin tuna (Thunnus orientalis) and Pacific salmon (Oncorhynchus spp.). For each, we have a parameter-sparse, full-life-cycle DEB model that requires adding only a few species-specific features to the standard model. Both models allow powerful integration of knowledge derived from data restricted to certain life stages, processes and environments.
Use of Cilostazol for Secondary Stroke Prevention: An Old Dog with New Tricks?
Authors: Ansara Alexander J , Shiltz Dane L , Slavens Jennifer B 
Published: February 2012

Objective: To evaluate the safety and efficacy of cilostazol for secondary prevention of non-cardioembolic ischemic stroke. Data Sources: PubMed and MEDLINE searches were performed (January 1970-September 2011) using the key words cilostazol, antiplatelet, aspirin, acetylsalicylic acid, secondary stroke prevention, ischemic stroke, intracerebral hemorrhage, intracranial, cerebrovascular accident, and transient ischemic attack. Additionally, reference citations from publications identified were reviewed. Study Selection and Data Extraction: Articles published in English and relevant primary literature evaluating the efficacy and safety of cilostazol in the secondary prevention of atherosclerotic ischemic stroke were included. Data Synthesis: Antiplatelet therapy plays a vital role in the multifaceted approach to secondary stroke prevention. Current American Heart Association/American Stroke Association clinical guidelines for secondary stroke prevention support the use of aspirin, Clopidogrel, and combination aspirin/extended-release dipyridamole. The antiplatelet, antithrombotic, and vasoditatory effects of cilostazol make it a potential alternative agent for atherosclerotic stroke prevention. Recent literature has demonstrated superior efficacy of cilostazol 100 mg twice daily for secondary stroke prevention compared to placebo and aspirin. Three clinical trials were reviewed (1 placebo-controlled, 2 aspirin-controlled), all of which were conducted in Japan or China. Cilostazol reduced the primary outcome of recurrence of stroke, with significantly fewer major bleeding events when compared to aspirin. Conclusions: Available literature suggests that cilostazol may be safer and more effective than aspirin in the secondary prevention of stroke in Asian patients. Further large-scale studies in more heterogeneous study populations are warranted to determine whether cilostazol is a viable therapeutic option for patients with a history of non-cardioembolic ischemic stroke.
Informal Economies and Urban Governance in Nigeria: Popular Empowerment or Political Exclusion?
Authors: Meagher Kate 
Published: February 2012

Abstract:This article examines how popular organizational strategies and coping mechanisms affect broader trajectories of urban governance in contemporary Africa. Does the proliferation of informal livelihood networks and associations foster economic empowerment and popular political participation, or do these informal processes breed poverty and organizational chaos? This article explores the link between popular organizational strategies and structural outcomes, focusing on how institutional process and power relations shape the access of the poor to resources and decision-making structures in decentralizing urban environments. Case studies from Nigeria trace how liberalization has fragmented informal organizational strategies into networks of accumulation and survival that tend to marginalize the interests of the poor within informal enterprise associations. Distinctive political strategies of informal enterprise associations are analyzed to show why dynamic informal organization is unable to break through the barriers of social and legal marginalization that trap the urban poor in cliental forms of political incorporation. This suggests that “social capital” within the informal economy may fail to improve popular political representation and governance outcomes even in contexts of decentralization.
Update on the Women's Movement in Botswana: Have Women Stopped Talking?
Authors: Bauer Gretchen 
Published: February 2012

Abstract:Across Africa in the early twenty-first century, autonomous women's movements have transformed the political landscape. With their support, African women are lobbying for constitutional reforms, entering political office in unprecedented numbers, and initiating legislation to expand women's rights. African women's movements have been emboldened by changes in international and regional norms concerning women's rights and representation, a new availability of resources to enhance women's status, and in many places, an end to conflict. In Botswana, the 1980s and 1990s were a period of heightened women's mobilization. Led by the women's organization Emang Basadi, the women's movement accomplished many significant victories, including winning a landmark citizenship case, prompting a comprehensive review of laws to identify instances of gender discrimination, issuing the first women's manifesto in Africa, and organizing workshops for political parties and women candidates. Some scholars have suggested that Emang Basadi's work was responsible not just for increasing women's representation in parliament, but also for broadening democracy in Botswana. Since 2010, however, a once vibrant women's movement has gone quiet. This article seeks to understand this development and to explore how the movement might be revitalized. The article concludes by drawing comparisons with other women's movements in the region and suggesting that the women's movement in Botswana, like others in the region, may be, in the words of one scholar, “in abeyance.”
Imaginability, Possibility, and the Puzzle of Imaginative Resistance
Authors: Levin Janet 
Published: February 2012

IntroductionIt is standard practice in philosophical inquiry to test a general thesis (of the form ‘F iff G’ or ‘F only if G’) by attempting to construct a counterexample to it. If we canimagineorconceive ofan F that isn't a G, then we have evidence that therecould bean F that isn't a G — and thus evidence against the thesis in question; if not, then the thesis is (at least temporarily) secure. Or so it is standardly claimed.But there is increasing skepticism about how seriously to take what we can imagine or conceive as evidence for (or against)a prioriphilosophical theses, given the many historical examples of now-questionable theses that once seemed impossible to doubt — and also the recent experimental research suggesting that our verdicts on Gettier cases, trolley cases, and the scenarios depicted in other familiar thought-experiments may be affected by cultural, situational, and other adventitious factors.
CMOS Compatible Growth of Carbon Nanotubes and Their Application in Field-Effect Transistors
Authors: Uchino T. , Ayre G. N. , Smith D. C. , Hutchison J. L. , de Groot C. H. , Ashburn P. 
Published: February 2012

ABSTRACTThe metal-catalyst-free growth of carbon nanotubes (CNTs) using chemical vapor deposition and the application in field-effect transistors (FETs) is presented. The CNT growth process used a 3-nm-thick Ge layer on SiO2 that was subsequently annealed to produce Ge nanoparticles. Raman measurements show the presence of radial breathing mode (RBM) peaks and the absence of the disorder induced D-band, indicating single walled CNTs (SWNTs) with a low defect density. The synthesized CNTs are used to fabricate CNTFETs and the best device has a state-of-the-art on/off current ratio of 3×108 and a steep sub-threshold slope of 110 mV/decade.
Palliative Care Consultation Service and Palliative Care Unit: Why Do We Need Both?
Authors: Gaertner Jan , Frechen Sebastian , Sladek Markus , Ostgathe Christoph , Voltz Raymond 
Published: February 2012

Abstract

Background.
Palliative care (PC) infrastructure has developed differently around the globe. Whereas some institutions consider the palliative care unit (PCU) a valuable component, others report that the sole provision of a state-of-the art palliative care consultation service (PCCS) suffices to adequately care for the severely ill and dying.

Objective.
To aid institutional planning, this study aimed at gathering patient data to distinguish assignments of a concomitantly run PCU and PCCS at a large hospital and academic medical center.

Methods.
Demographics, Eastern Cooperative Oncology Group performance status, symptom/problem burden, discharge modality, and team satisfaction with care for all 601 PCU and 851 PCCS patients treated in 2009 and 2010 were retrospectively analyzed.

Results.
Patients admitted to the PCU versus those consulted by the PCCS: (a) had a significantly worse performance status (odds ratio [OR], 1.48); (b) were significantly more likely to suffer from severe symptoms and psychosocial problems (OR, 2.05), in particular concerning physical suffering and complexity of care; and (c) were significantly much more likely to die during hospital stay (OR, 11.03). For patients who were dying or in other challenging clinical situations (suffering from various severe symptoms), self-rated team satisfaction was significantly higher for the PCU than the PCCS.

Conclusion.
This study presents a direct comparison between patients in a PCU and a PCCS. Results strongly support the hypothesis that the coexistence of both institutions in one hospital contributes to the goal of ensuring optimal high-quality PC for patients in complex and challenging clinical situations.
Odontoid Fracture Following a Fall in an Elderly Man
Authors: Pagnez Maria Alice Mainenti , Elliott James M. 
Published: February 2012

The patient was a 79-year-old man with a chief complaint of neck pain after a fall. Three days following the fall, the patient was seen in the emergency department, where computed tomography imaging of the head and radiographs of the cervical spine were completed. The patient was subsequently referred to a physical therapist. Due to concern for a possible undetected cervical spine fracture, the patient was immediately referred to his physician. Magnetic resonance imaging demonstrated a type II fracture of the odontoid. J Orthop Sports Phys Ther 2011;41(12):981. doi:10.2519/jospt.2011.0424