bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gingival Overgrowth Among Patients Medicated With Cyclosporin A and Tacrolimus Undergoing Renal Transplantation: A Prospective Study
Authors: Paixão Caroline G. , Sekiguchi Ricardo T. , Saraiva Luciana , Pannuti Cláudio M. , Silva Hélio T. , Medina‐Pestana José O. , Romito Giuseppe A. 
Published: August 2010

Background:The aim of this study is to make a longitudinal evaluation of the incidence and severity of gingival overgrowth (GO) induced by immunosuppressive agents, such as tacrolimus (Tcr) and cyclosporin A (CsA), in the absence of calcium channel blockers in patients undergoing renal transplantation (RT).Methods:This longitudinal study is conducted in 49 patients with RT who were divided into a CsA group (n = 25) and Tcr group (n = 24). The individuals were assessed at four time intervals: before transplant and 30, 90, and 180 days after RTs. Demographic data and periodontal clinical parameters (plaque index, cemento‐enamel junction to the gingival margin, probing depth, clinical attachment level, bleeding on probing [BOP], and GO) were collected at all time intervals.Results:The mean GO index was significantly lower in the Tcr group compared to the CsA group after 30 (P= 0.03), 90 (P= 0.004), and 180 (P= 0.01) days of immunosuppressive therapy. One hundred eighty days after RTs, a clinically significant GO was observed in 20.0% of individuals in the CsA group and 8.3% of individuals in the Tcr group. However, this difference was not statistically significant (P= 0.41). There was a reduction in periodontal clinical parameters regarding the time of immunosuppressive therapy for PI and BOP (P<0.001) in both groups.Conclusion:Although there was no statistical difference in the incidences of clinically significant GO after 180 days of immunosuppressive therapy, it was observed that GO occurred later in the Tcr group, and the severity of GO in this group was lower than in patients who used CsA.
Smoking-Related Health Risks Among Persons With HIV in the Strategies for Management of Antiretroviral Therapy Clinical Trial
Authors: Lifson Alan R. , Neuhaus Jacqueline , Arribas Jose Ramon , van den Berg-Wolf Mary , Labriola Ann M. , Read Timothy R.H. ,   for the INSIGHT SMART Study Group
Published: August 2010

Objectives. We sought to determine smoking-related hazard ratios (HRs) and population-attributable risk percentage (PAR%) for serious clinical events and death among HIV-positive persons, whose smoking prevalence is higher than in the general population. Methods. For 5472 HIV-infected persons enrolled from 33 countries in the Strategies for Management of Antiretroviral Therapy clinical trial, we evaluated the relationship between baseline smoking status and development of AIDS-related or serious non-AIDS events and overall mortality. Results. Among all participants, 40.5% were current smokers and 24.8% were former smokers. Adjusted HRs were higher for current than for never smokers for overall mortality (2.4; P < .001), major cardiovascular disease (2.0; P = .002), non-AIDS cancer (1.8; P = .008), and bacterial pneumonia (2.3; P < .001). Adjusted HRs also were significantly higher for these outcomes among current than among former smokers. The PAR% for current versus former and never smokers combined was 24.3% for overall mortality, 25.3% for major cardiovascular disease, 30.6% for non-AIDS cancer, and 25.4% for bacterial pneumonia. Conclusions. Smoking contributes to substantial morbidity and mortality in this HIV-infected population. Providers should routinely integrate smoking cessation programs into HIV health care.
The Application of Net Neutrality to Wireless Networks Based on Network Architecture
Authors: Jordan Scott 
Published: August 2010

AbstractThere is considerable debate over whether and how net neutrality should apply to wireless networks. We address here whether differences between wired and wireless network technology merit different treatment with respect to net neutrality. The primary focus is on applications and traffic management, rather than device attachment. We first review the pertinent aspects of network architecture and discuss the main differences between wired and wireless networks, and find that wireless networks differ substantially from wired networks at the network layer and below. We then turn more specifically to how wired and wireless networks differ with respect to traffic management, and conclude that wireless networks require some different types of traffic management than wired networks. Finally, we turn to the question of how the differences in traffic management affect net neutrality, and find that despite the differences in traffic management, similar net neutrality concerns apply. Furthermore, we argue that since the differences lie in lower layers, net neutrality in both wired and wireless networks can be effectively accomplished by requiring an open interface between network and transport layers. We argue that this is a more streamlined and more effective solution that carving out a set of managed services.
The Essential Internet: Digital Exclusion in Low‐Income American Communities
Authors: Powell Alison , Bryne Amelia , Dailey Dharma 
Published: August 2010

AbstractAs the Internet, and broadband in particular, becomes a platform for social and political engagement, researchers investigate more carefully both the factors that drive broadband adoption and the barriers that constrain it. This paper reports on one of the only large‐scale qualitative studies of the barriers to broadband adoption in the United States, where 30% of the population lack broadband access. The primary research question asks: how can we qualitatively understand barriers to broadband adoption among low‐income communities? The study's community‐based approach, undertaken in four regions of the country, reveals the complex equilibrium of broadband adoption. Drawing from 170 interviews with broadband non‐adopters as well as community access providers and other intermediaries, this study finds that price is only one factor shaping home broadband adoption, and that libraries and other community organizations fill the gap between low home adoption and high demand for broadband. These intermediaries compensate for shortages in digital skills that also constitute barriers to adoption in a context where broadband is essential for gaining access to jobs, education, and e‐government. These three main findings suggest that low‐income people like our research participants are playing roles as actors in an ecology of broadband access games (Dutton et al. 2004). In particular, they are overcoming barriers to being online in order to participate in accessing services and gaining education. This is part of the process of defining broadband as an infrastructure for e‐democracy. The paper recommends a renewed focus on factors that sustain home access rather than drive demand, as well as support for community intermediaries in provisioning public broadband access within a context of skill shortages. It recommends further qualitative research to better understand the role of diverse populations in framing the value of broadband access.
Project RedCar: Cardiovascular Disease Risk Communication for People With Type 2 Diabetes Combining the Power of Electronic Health Records and Computer-Based Multimedia Technology
Authors: Roach Paris , Klindukhova Olena , Saha Chandan , Hudson Brenda , Cantrell Melissa , Marrero David 
Published: August 2010

In Brief
Although cardiovascular disease (CVD) is the major cause of mortality in people with type 2 diabetes, CVD risk factors are undertreated in this population. The communication of individualized CVD risk to patients before clinical encounters may facilitate the discussion of CVD risk between patients and health care providers and lead to more timely therapeutic intensification. This article presents a CVD risk communication intervention designed for an urban primary care population, utilizing an electronic health record system. Preliminary analyses indicate that the intervention increases the likelihood of patients discussing CVD risk with their physicians and makes it easier for them to participate in these discussions.
Redesign of a Diabetes System of Care Using an All-or-None Diabetes Bundle to Build Teamwork and Improve Intermediate Outcomes
Authors: Bloom Frederick J. , Graf Thomas , Anderer Tammy , Stewart Walter F. 
Published: August 2010

In Brief
Providing diabetes patients all of the care recommended by current guidelines is a clinical challenge. Geisinger Health System has designed a provider-led, team-based system of care to more consistently and reliably meet this challenge. This system of care uses an all-or-none bundle of diabetes measures and electronic health record tools to improve both process measures and intermediate diabetes outcomes.
Proximal Events in 7,12-Dimethylbenz[a]anthracene-Induced, Stromal Cell-Dependent Bone Marrow B Cell Apoptosis: Stromal Cell–B Cell Communication and Apoptosis Signaling
Authors: Teague Jessica E. , Ryu Heui-Young , Kirber Michael , Sherr David H. , Schlezinger Jennifer J. 
Published: August 2010

AbstractIntercellular communication is an essential process in stimulating lymphocyte development and in activating and shaping an immune response. B cell development requires cell-to-cell contact with and cytokine production by bone marrow stromal cells. However, this intimate relationship also may be responsible for the transfer of death-inducing molecules to the B cells. 7,12-Dimethylbenz[a]anthracene (DMBA), a prototypical polycyclic aromatic hydrocarbon, activates caspase-3 in pro/pre-B cells in a bone marrow stromal cell-dependent manner, resulting in apoptosis. These studies were designed to examine the hypothesis that an intrinsic apoptotic pathway is activated by DMBA and that the ultimate death signal is a DMBA metabolite generated by the stromal cells and transferred to the B cells. Although a loss of mitochondrial membrane potential did not occur in the DMBA/stromal cell-induced pathway, cytochrome c release was stimulated in B cells. Caspase-9 was activated, and formation of the apoptosome was required to support apoptosis, as demonstrated by the suppression of death in Apaf-1fog mutant pro-B cells. Investigation of signaling upstream of the mitochondria demonstrated an essential role for p53. Furthermore, DMBA-3,4-dihydrodiol-1,2-epoxide, a DNA-reactive metabolite of DMBA, was sufficient to upregulate p53, induce caspase-9 cleavage, and initiate B cell apoptosis in the absence of stromal cells, suggesting that production of this metabolite by the stromal cells and transfer to the B cells are proximal events in triggering apoptosis. Indeed, we provide evidence that metabolite transfer from bone marrow stromal cells occurs through membrane exchange, which may represent a novel communication mechanism between developing B cells and stromal cells.
IFN Regulatory Factor 3 Contributes to the Host Response during Pseudomonas aeruginosa Lung Infection in Mice
Authors: Carrigan Svetlana O. , Junkins Robert , Yang Yong Jun , MacNeil Adam , Richardson Christopher , Johnston Brent , Lin Tong-Jun 
Published: August 2010

Abstract
Pseudomonas aeruginosa is a major opportunistic pathogen. However, host defense mechanisms involved in P. aeruginosa lung infection remain incompletely defined. The transcription factor IFN regulatory factor 3 (IRF3) is primarily associated with host defense against viral infections, and a role of IRF3 in P. aeruginosa infection has not been reported previously. In this study, we showed that IRF3 deficiency led to impaired clearance of P. aeruginosa from the lungs of infected mice. P. aeruginosa infection induced IRF3 translocation to the nucleus, activation of IFN-stimulated response elements (ISRE), and production of IFN-β, suggesting that P. aeruginosa activates the IRF3–ISRE–IFN pathway. In vitro, macrophages from IRF3-deficient mice showed complete inhibition of CCL5 (RANTES) and CXCL10 (IP-10) production, partial inhibition of TNF, but no effect on CXCL2 (MIP-2) or CXCL1 (keratinocyte-derived chemokine) in response to P. aeruginosa stimulation. In vivo, IRF3-deficient mice showed complete inhibition of CCL5 production and partial or no effects on production of other cytokines and chemokines in the bronchoalveolar lavage fluids and lung tissues. Profiling of immune cells in the airways revealed that neutrophil and macrophage recruitment into the airspace was reduced, whereas B cell, T cell, NK cell, and NKT cell infiltration was unaffected in IRF3-deficient mice following P. aeruginosa lung infection. These data suggest that IRF3 regulates a distinct profile of cytokines and chemokines and selectively modulates neutrophil and macrophage recruitment during P. aeruginosa infection. Thus, IRF3 is an integral component in the host defense against P. aeruginosa lung infection.
P2Y2 Receptor Regulates VCAM-1 Membrane and Soluble Forms and Eosinophil Accumulation during Lung Inflammation
Authors: Vanderstocken Gilles , Bondue Benjamin , Horckmans Michael , Di Pietrantonio Larissa , Robaye Bernard , Boeynaems Jean-Marie , Communi Didier 
Published: August 2010

Abstract
ATP has been defined as a key mediator of asthma. In this study, we evaluated lung inflammation in mice deficient for the P2Y2 purinergic receptor. We observed that eosinophil accumulation, a distinctive feature of lung allergic inflammation, was defective in OVA-treated P2Y2-deficient mice compared with OVA-treated wild type animals. Interestingly, the upregulation of VCAM-1 was lower on lung endothelial cells of OVA-treated P2Y2−/− mice compared with OVA-treated wild type animals. Adhesion assays demonstrated that the action of UTP on leukocyte adhesion through the regulation of endothelial VCAM-1 was abolished in P2Y2-deficient lung endothelial cells. Additionally, the level of soluble VCAM-1, reported as an inducer of eosinophil chemotaxis, was strongly reduced in the bronchoalveolar lavage fluid (BALF) of P2Y2-deficient mice. In contrast, we observed comparable infiltration of macrophages and neutrophils in the BALF of LPS-aerosolized P2Y2+/+ and P2Y2−/− mice. This difference could be related to the much lower level of ATP in the BALF of LPS-treated mice compared with OVA-treated mice. Our data define P2Y2 as a regulator of membrane and soluble forms of VCAM-1 and eosinophil accumulation during lung inflammation.
Complement-Dependent Transport of Antigen into B Cell Follicles
Authors: Gonzalez Santiago F. , Lukacs-Kornek Veronika , Kuligowski Michael P. , Pitcher Lisa A. , Degn Søren E. , Turley Shannon J. , Carroll Michael C. 
Published: August 2010

AbstractSince the original proposal by Fearon and Locksley (Fearon and Locksley. 1996. Science 272: 50–53) that the complement system linked innate and adaptive immunity, there has been a rapid expansion of studies on this topic. With the advance of intravital imaging, a number of recent papers revealed an additional novel pathway in which complement C3 and its receptors enhance humoral immunity through delivery of Ag to the B cell compartment. In this review, we discuss this pathway and highlight several novel exceptions recently found with a model influenza vaccine, such as mannose-binding lectin opsonization of influenza and uptake by macrophages, and the capture of virus by dendritic cells residing in the medullary compartment of peripheral lymph nodes.
Inflammatory Effects of Ex Vivo Human Th17 Cells Are Suppressed by Regulatory T Cells
Authors: Crome Sarah Q. , Clive Breanna , Wang Adele Y. , Kang Christine Y. , Chow Vickie , Yu Jie , Lai Amy , Ghahary Aziz , Broady Raewyn , Levings Megan K. 
Published: August 2010

Abstract
Th17 cells are proinflammatory cells associated with many immune-mediated diseases. Major factors limiting the study of human Th17 cells are the lack of an accepted method for their in vitro differentiation or for isolation of a homogenous population of Th17 cells that do not cosecrete IFN-γ. To overcome these hurdles, we established a novel method to isolate in vivo differentiated Th17 cells from peripheral blood by sorting CD161+CCR4+CCR6+CXCR3−CD4+ T cells. The resulting cells produce high levels of IL-17 but not IFN-γ, express high levels of retinoic acid-related orphan receptor variant 2, and maintain this phenotype upon expansion. Ex vivo Th17 cells exhibit a low cytotoxic potential and are hyporesponsive to polyclonal anti-CD3/anti-CD28 stimulation. Importantly, ex vivo Th17 cells were susceptible to suppression by both naive and memory regulatory T cells (Tregs), which inhibited production of IL-17, IL-22, and CXCL8. Moreover, Tregs suppressed the antifibrotic effects of Th17 cells in a wound-healing model. These findings provide new tools for the study of normal and pathological functions of bona fide Th17 cells in humans. They also provide new insight into the cross-talk between Th17 cells and immune and nonimmune cells, and they establish the paradigm that adoptive Treg-based therapies may effectively limit Th17-mediated inflammation.
Mucosal Anti-CD3 Monoclonal Antibody Attenuates Collagen-Induced Arthritis That Is Associated with Induction of LAP+ Regulatory T Cells and Is Enhanced by Administration of an Emulsome-Based Th2-Skewing Adjuvant
Authors: Wu Henry Yim , Maron Ruth , Tukpah Ann-Marcia , Weiner Howard L. 
Published: August 2010

Abstract
Mucosal (nasal or oral) administration of anti-CD3 mAb is effective in ameliorating animal models of autoimmunity (experimental autoimmune encephalomyelitis, diabetes, and lupus) by inducing LAP+ regulatory T cells. We tested this approach in an arthritis model using type II collagen. We found that nasal anti-CD3 was more effective than oral anti-CD3 in attenuating the development of arthritis. Nasal anti-CD3 induced a LAP+ regulatory T cell that secreted high levels of IL-10 and suppressed collagen-specific T cell proliferation and anti-collagen Ab production. However, neither nasal nor oral anti-CD3 attenuated disease when given to animals with ongoing arthritis, and this was associated with a lack of induction of LAP+ regulatory T cells. We found, however, that coadministration of a novel emulsome adjuvant, which enhances Th2 responses, resulted in the induction of LAP+ regulatory T cells and suppression of ongoing arthritis by both nasal and oral anti-CD3. Suppression of arthritis by mucosal anti-CD3 was associated with less joint damage, a decrease of TNF-α and IFN-γ mRNA expression in joints, and a reduction in anti-collagen Abs. These results demonstrate that mucosal anti-CD3 therapy may serve as a therapeutic approach in arthritis and that the biologic effect is enhanced by an emulsome-based adjuvant.
Pronounced Virus-Dependent Activation Drives Exhaustion but Sustains IFN-γ Transcript Levels
Authors: Mackerness Kathryn J. , Cox Maureen A. , Lilly Lauren M. , Weaver Casey T. , Harrington Laurie E. , Zajac Allan J. 
Published: August 2010

Abstract
During many chronic infections, the responding CD8 T cells become exhausted as they progressively lose their ability to elaborate key effector functions. Unlike prototypic memory CD8 cells, which rapidly synthesize IFN-γ following activation, severely exhausted T cells fail to produce this effector molecule. Nevertheless, the ontogeny of exhausted CD8 T cells, as well as the underlying mechanisms that account for their functional inactivation, remains ill defined. We have used cytokine reporter mice, which mark the transcription of IFN-γ mRNA by the expression of Thy1.1, to decipher how activation events during the early stages of a chronic infection dictate the development of exhaustion. We show that virus-specific CD8 T cells clearly respond during the early stages of chronic lymphocytic choriomeningitis virus infection, and that this early T cell response is more pronounced than that initially observed in acutely infected hosts. Thus, exhausted CD8 T cells appear to emerge from populations of potently activated precursors. Unlike acute infections, which result in massive expansion of the responding T cells, there is a rapid attenuation of further expansion during chronic infections. The exhausted T cells that subsequently emerge in chronically infected hosts are incapable of producing the IFN-γ protein. Surprisingly, high levels of the IFN-γ transcript are still present in exhausted cells, demonstrating that ablation of IFN-γ production by exhausted cells is not due to transcriptional silencing. Thus, posttranscription regulatory mechanisms likely disable this effector module.
Immune-Mediated Mechanisms of Parasite Tissue Sequestration during Experimental Cerebral Malaria
Authors: Amante Fiona H. , Haque Ashraful , Stanley Amanda C. , Rivera Fabian de Labastida , Randall Louise M. , Wilson Yana A. , Yeo Gladys , Pieper Christian , Crabb Brendan S. , de Koning-Ward Tania F. , Lundie Rachel J. , Good Michael F. , Pinzon-Charry Alberto , Pearson Mark S. , Duke Mary G. , McManus Donald P. , Loukas Alex , Hill Geoff R. , Engwerda Christian R. 
Published: August 2010

Abstract
Cerebral malaria is a severe complication of malaria. Sequestration of parasitized RBCs in brain microvasculature is associated with disease pathogenesis, but our understanding of this process is incomplete. In this study, we examined parasite tissue sequestration in an experimental model of cerebral malaria (ECM). We show that a rapid increase in parasite biomass is strongly associated with the induction of ECM, mediated by IFN-γ and lymphotoxin α, whereas TNF and IL-10 limit this process. Crucially, we discovered that host CD4+ and CD8+ T cells promote parasite accumulation in vital organs, including the brain. Modulation of CD4+ T cell responses by helminth coinfection amplified CD4+ T cell-mediated parasite sequestration, whereas vaccination could generate CD4+ T cells that reduced parasite biomass and prevented ECM. These findings provide novel insights into immune-mediated mechanisms of ECM pathogenesis and highlight the potential of T cells to both prevent and promote infectious diseases.
CCR6 Marks Regulatory T Cells as a Colon-Tropic, IL-10–Producing Phenotype
Authors: Kitamura Kazuya , Farber Joshua M. , Kelsall Brian L. 
Published: August 2010

Abstract
Expression of CCR6 and its ligand, CCL20, are increased in the colon of humans with inflammatory bowel diseases and mice with experimental colitis; however, their role in disease pathogenesis remains obscure. In this study, we demonstrate a role for CCR6 on regulatory T (Treg) cells in the T cell-transfer model of colitis. Rag2−/− mice given Ccr6−/−CD4+CD45RBhigh T cells had more severe colitis with increased IFN-γ–producing T cells, compared with the mice given wild-type cells. Although an equivalent frequency of induced/acquired Treg (iTreg) cells was observed in mesenteric lymph nodes and colon from both groups, the suppressive capacity of Ccr6−/− iTreg cells was impaired. Cotransfer studies of wild-type or Ccr6−/− Treg cells with CD4+CD45RBhigh T cells also showed a defect in suppression by Ccr6−/− Treg cells. CCR6+ Treg cells were characterized as Ag-activated and IL-10–producing in the steady-state and preferentially migrated to the colon during inflammation. Thus, we conclude that CCR6 expression on Treg cells was required for the full function of Treg cell-mediated suppression in the T cell-transfer model of colitis. CCR6 may contribute to the regulation of colitis by directing its function in Ag-specific, IL-10–producing iTreg cells to the inflamed colon.