bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cathepsin B Controls the Persistence of Memory CD8+ T Lymphocytes
Authors: Byrne Susan M. , Aucher Anne , Alyahya Syarifah , Elder Matthew , Olson Steven T. , Davis Daniel M. , Ashton-Rickardt Philip G. 
Published: June 2012

Abstract
The persistence of memory T lymphocytes confers lifelong protection from pathogens. Memory T cells survive and undergo homeostatic proliferation (HSP) in the absence of Ag, although the cell-intrinsic mechanisms by which cytokines drive the HSP of memory T cells are not well understood. In this study we report that lysosome stability limits the long-term maintenance of memory CD8+ T cell populations. Serine protease inhibitor (Spi) 2A, an anti-apoptotic cytosolic cathepsin inhibitor, is induced by both IL-15 and IL-7. Mice deficient in Spi2A developed fewer memory phenotype CD44hiCD8+ T cells with age, which underwent reduced HSP in the bone marrow. Spi2A was also required for the maintenance of central memory CD8+ T cell populations after acute infection with lymphocytic choriomeningitis virus. Spi2A-deficient Ag-specific CD8+ T cell populations declined more than wild-type competitors after viral infection, and they were eroded further after successive infections. Spi2A protected memory cells from lysosomal breakdown by inhibiting cathepsin B. The impaired maintenance of Spi2A-deficient memory CD8+ T cells was rescued by concomitant cathepsin B deficiency, demonstrating that cathepsin B was a physiological target of Spi2A in memory CD8+ T cell survival. Our findings support a model in which protection from lysosomal rupture through cytokine-induced expression of Spi2A determines the long-term persistence of memory CD8+ T cells.
Diet-Induced Obesity Alters Dendritic Cell Function in the Presence and Absence of Tumor Growth
Authors: James Britnie R. , Tomanek-Chalkley Ann , Askeland Eric J. , Kucaba Tamara , Griffith Thomas S. , Norian Lyse A. 
Published: June 2012

Abstract
Obesity is a mounting health concern in the United States and is associated with an increased risk for developing several cancers, including renal cell carcinoma (RCC). Despite this, little is known regarding the impact of obesity on antitumor immunity. Because dendritic cells (DC) are critical regulators of antitumor immunity, we examined the combined effects of obesity and tumor outgrowth on DC function. Using a diet-induced obesity (DIO) model, DC function was evaluated in mice bearing orthotopic RCC and in tumor-free controls. Tumor-free DIO mice had profoundly altered serum cytokine and chemokine profiles, with upregulation of 15 proteins, including IL-1α, IL-17, and LIF. Tumor-free DIO mice had elevated percentages of conventional splenic DC that were impaired in their ability to stimulate naive T cell expansion, although they were phenotypically similar to normal weight (NW) controls. In DIO mice, intrarenal RCC tumor challenge in the absence of therapy led to increased local infiltration by T cell-suppressive DC and accelerated early tumor outgrowth. Following administration of a DC-dependent immunotherapy, established RCC tumors regressed in normal weight mice. The same immunotherapy was ineffective in DIO mice and was characterized by an accumulation of regulatory DC in tumor-bearing kidneys, decreased local infiltration by IFN-γ–producing CD8 T cells, and progressive tumor outgrowth. Our results suggest that the presence of obesity as a comorbidity can impair the efficacy of DC-dependent antitumor immunotherapies.
Retinal Laser Burn-Induced Neuropathy Leads to Substance P-Dependent Loss of Ocular Immune Privilege
Authors: Lucas Kenyatta , Karamichos Dimitris , Mathew Rose , Zieske James D. , Stein-Streilein Joan 
Published: June 2012

Abstract
Inflammation in the eye is tightly regulated by multiple mechanisms that together contribute to ocular immune privilege. Many studies have shown that it is very difficult to abrogate the immune privileged mechanism called anterior chamber-associated immune deviation (ACAID). Previously, we showed that retinal laser burn (RLB) to one eye abrogated immune privilege (ACAID) bilaterally for an extended period of time. In an effort to explain the inflammation in the nonburned eye, we postulated that neuronal signals initiated inflammation in the contralateral eye. In this study, we test the role of substance P, a neuroinflamatory peptide, in RLB-induced loss of ACAID. Histological examination of the retina with and without RLB revealed an increase of the substance P-inducible neurokinin 1 receptor (NK1-R) in the retina of first, the burned eye, and then the contralateral eye. Specific antagonists for NK1-R, given locally with Ag within 24 h, but not 3, 5, or 7 d post-RLB treatment, prevented the bilateral loss of ACAID. Substance P knockout (KO) mice retained their ability to develop ACAID post-RLB. These data support the postulate that substance P transmits early inflammatory signals from the RLB eye to the contralateral eye to induce changes to ocular immune privilege and has a central role in the bilateral loss of ACAID. The possibility is raised that blocking of the substance P pathway with NK1-R antagonists postocular trauma may prevent unwanted and perhaps extended consequences of trauma-induced inflammation in the eye.
Human Bocavirus NP1 Inhibits IFN-β Production by Blocking Association of IFN Regulatory Factor 3 with IFNB Promoter
Authors: Zhang Zhenfeng , Zheng Zhenhua , Luo Huanle , Meng Jin , Li Hongxia , Li Qian , Zhang Xiaowei , Ke Xianliang , Bai Bingke , Mao Panyong , Hu Qinxue , Wang Hanzhong 
Published: June 2012

Abstract
Human bocavirus (HBoV) mainly infects young children. Although many infected children suffer from respiratory or gastroenteric tract diseases, an association between HBoV and these diseases is not definite. Because modulation of type I IFN is crucial for viruses to establish efficient replication, in this study, we tested whether HBoV modulates type I IFN production. We observed that a nearly full-length HBoV clone significantly reduced both Sendai virus (SeV)- and poly(deoxyadenylic-thymidylic) acid-induced IFN-β production. Further study showed that NP1 blocked IFN-β activation in response to SeV, poly(deoxyadenylic-thymidylic) acid, and IFN-β pathway inducers, including retinoic acid-inducible protein I, mitochondrial antiviral signaling protein, inhibitor of κB kinase ε, and TANK-binding kinase 1. In addition, NP1 interfered with IRF-3–responsive PRD(III-I) promoter activated by SeV and a constitutively active mutant of IRF-3 (IRF-3/5D). Although NP1 suppressed the IRF-3 pathway, it did not affect IRF-3 activation processes, including phosphorylation, dimerization, and nuclear translocation. Coimmunoprecipitation assays confirmed the interaction between NP1 and IRF-3. Additional deletion mutagenesis and coimmunoprecipitation assays revealed that NP1 bound to the DNA-binding domain of IRF-3, resulting in the interruption of an association between IRF-3 and IFNB promoter. Altogether, our results indicate that HBoV NP1 blocks IFN production through a unique mechanism. To our knowledge, this is the first study to investigate the modulation of innate immunity by HBoV. Our findings suggest a potential immune-evasion mechanism used by HBoV and provide a basis for better understanding HBoV pathogenesis.
Multieffector-Functional Immune Responses of HMBPP-Specific Vγ2Vδ2 T Cells in Nonhuman Primates Inoculated with Listeria monocytogenes ΔactA prfA
*
Authors: Ryan-Payseur Bridgett , Frencher James , Shen Ling , Chen Crystal Y. , Huang Dan , Chen Zheng W. 
Published: June 2012

Abstract
Although Listeria monocytogenes can induce systemic infection causing spontaneous abortion, septicemia, and meningitis, studies have not been performed to investigate human anti-L. monocytogenes immune responses, including those of Ag-specific Vγ2Vδ2 T cells, a dominant human γδ T cell subset. L. monocytogenes is the only pathogen known to possess both the mevalonate and non-mevalonate isoprenoid biosynthesis pathways that produce metabolic phosphates or phosphoantigens activating human Vγ2Vδ2 T cells, making it interesting to explore in vivo anti-L. monocytogenes immune responses of Vγ2Vδ2 T cells. In this study, we demonstrated that subclinical systemic L. monocytogenes infection of rhesus macaques via parenteral inoculation or vaccination with an attenuated Listeria strain induced multieffector-functional immune responses of phosphoantigen-specific Vγ2Vδ2 T cells. Subclinical systemic infection and reinfection with attenuated L. monocytogenes uncovered the ability of Vγ2Vδ2 T cells to mount expansion and adaptive or recall-like expansion. Expanded Vγ2Vδ2 T cells could traffic to and accumulate in the pulmonary compartment and intestinal mucosa. Expanded Vγ2Vδ2 T cells could evolve into effector cells producing IFN-γ, TNF-α, IL-4, IL-17, or perforin after L. monocytogenes infection, and some effector Vγ2Vδ2 T cells could coproduce IL-17 and IFN-γ, IL-4 and IFN-γ, or TNF-α and perforin. Surprisingly, in vivo-expanded Vγ2Vδ2 T effector cells in subclinical L. monocytogenes infection could directly lyse L. monocytogenes-infected target cells and inhibit intracellular L. monocytogenes bacteria. Thus, we present the first demonstration, to our knowledge, of multieffector-functional Vγ2Vδ2 T cell responses against L. monocytogenes.
Validating the Use of the Evaluation Tool of Children’s Handwriting–Manuscript to Identify Handwriting Difficulties and Detect Change in School-Age Children
Authors: Brossard-Racine Marie , Mazer Barbara , Julien Marilyse , Majnemer Annette 
Published: June 2012

Abstract
In this study we sought to validate the discriminant ability of the Evaluation Tool of Children’s Handwriting–Manuscript in identifying children in Grades 2–3 with handwriting difficulties and to determine the percentage of change in handwriting scores that is consistently detected by occupational therapists. Thirty-four therapists judged and compared 35 pairs of handwriting samples. Receiver operating characteristic (ROC) analyses were performed to determine (1) the optimal cutoff values for word and letter legibility scores that identify children with handwriting difficulties who should be seen in rehabilitation and (2) the minimal clinically important difference (MCID) in handwriting scores. Cutoff scores of 75.0% for total word legibility and 76.0% for total letter legibility were found to provide excellent levels of accuracy. A difference of 10.0%–12.5% for total word legibility and 6.0%–7.0% for total letter legibility were found as the MCID. Study findings enable therapists to quantitatively support clinical judgment when evaluating handwriting.
Effect of a Coteaching Handwriting Program for First Graders: One-Group Pretest–Posttest Design
Authors: Case-Smith Jane , Holland Terri , Lane Alison , White Susan 
Published: June 2012

Abstract
We examined the effects of a cotaught handwriting and writing program on first-grade students grouped by low, average, and high baseline legibility. The program’s aim was to increase legibility, handwriting speed, writing fluency, and written expression in students with diverse learning needs. Thirty-six first-grade students in two classrooms participated in a 12-wk handwriting and writing program cotaught by teachers and an occupational therapist. Students were assessed at pretest, posttest, and 6-mo follow-up using the Evaluation Tool of Children’s Handwriting–Manuscript (ETCH–M) and the Woodcock–Johnson Writing Fluency and Writing Samples tests. Students made large gains in ETCH–M legibility (η2 = .74), speed (η2s = .52–.65), Writing Fluency (η2 = .58), and Writing Samples (η2 = .59). Students with initially low legibility improved most in legibility; progress on the other tests was similar across low-, average-, and high-performing groups. This program appeared to benefit first-grade students with diverse learning needs and to increase handwriting legibility and speed and writing fluency.
Effect of a Group Adherence Intervention for Mexican-American Older Adults With Type 2 Diabetes
Authors: Haltiwanger Emily Piven 
Published: June 2012

Abstract
OBJECTIVE. I evaluated the effect of a culturally tailored, peer-led support group intervention on improvement in adherence behaviors of Mexican-American older adults with type 2 diabetes mellitus and obtained feedback on the cultural relevance of the manual that structured the intervention.
METHOD. The one-group pretest–posttest design used five self-report questionnaires and blood testing to measure change among 4 men and 12 women, ages 60–85.
RESULTS. Empowerment, self-efficacy, and attitude were highly significant at 2-, 4-, and 6-mo posttests. Glycosylated hemoglobin test results were significant at p &lt; .05 between pretest and 2-mo posttest with a stabilizing effect on the 6-mo posttest.
CONCLUSION. Mexican-American older adults’ adherence may improve with a culturally sensitive, structured peer-led program with indirect consultation from an occupational therapist.
New Single-Subject and Small-n Design in Occupational Therapy: Application to Weight Loss in Obesity
Authors: Weissman-Miller Deborah , Shotwell Mary P. , Miller Rosalie J. 
Published: June 2012

Abstract
Ottenbacher (1986) showed the usefulness of single-subject design (SSD) in occupational therapy. However, SSD methodology is not regarded by the wider research community as providing statistically reliable and valid evidence of effectiveness of treatment partly because of its observational nature. Although statistical estimations can also be made from least squares regression or by a trend line, a new methodology has great potential to influence research in occupational therapy. The new model enables the use of initial client data from the beginning of treatment (for single subjects or small groups) to determine a point in the linear regression at which predictions can be made for the number of treatments needed for stability or improvement. This model is invaluable for third-party payment as well as for client motivation. The purpose of this article is to present this new methodology, the semiparametric ratio estimator (SPRE), illustrated by case application to treatment of obesity.
Flexion following Hip Resurfacing and Factors that Influence It
Authors: Grammatopoulos George , Philpott Andrew , Reilly Kathleen , Pandit Hemant , Barker Karen , Murray David W. , Gill Harinderjit S. 
Published: June 2012

Flexion following arthroplasty of the hip is important for activities of daily living. Studies have highlighted a possible reduction in flexion following Metal-on-Metal Hip Resurfacing Arthroplasty (MoMHRA) but failed to account for inter-subject variability and the possible etiology for this reduction. This in vivo study aims to determine whether flexion is restored following MoMHRA and identify factors that influence it. Charnley Class A patients (n=112) that underwent MoMHRA were reviewed in a dedicated clinic assessing flexion (resurfaced and contra-lateral hips) and outcome. The difference in flexion between both hips was defined as flexion deficit (δflexion). Various patient (age, gender, BMI) and surgical (component orientation, size, head-neck-ratio, offset) factors were examined in terms of their effect on δflexion. MoMHRA-hips had significantly reduced flexion as compared to the native hips. This flexion-deficit correlated with contra-lateral maximum flexion, component size, head-neck-ratio and component orientation. The findings demonstrate that flexion following MoMHRA is strongly correlated to but is reduced in comparison to the native, disease-free, hip flexion. Surgical practice can minimise flexion-deficit and optimise function.
Antiplatelet therapy – ticagrelor
Authors: Katus H. A. , Giannitsis E. 
Published: June 2012

SummaryTicagrelor, a cyclopentyltriazolopyrimidine (CPTP), is the representative of a new chemical class of P2Y12 receptor inhibitors that differ from thienopyridines (ticlopidin, clopidogrel, prasugrel) as ticagrelor is not a prodrug requiring active biotransformation by cytochromes in the liver and thus is characterized by a more rapid, more effective and more consistent platelet inhibition than ticlopidin or clopidogrel. An extensive study program for dose finding and safety for AZD6140 (DISPERSE studies) and a large-scaled phase III trial (PLATO) were undertaken on more than 18 000 patients for validation of efficacy and safety. In the PLATO trial, patients presenting with the broad spectrum of ACS, i.e. unstable angina, non-STEMI or STEMI, were randomized to ticagrelor (Brilique, Brilinta) or clopidogrel within 24 hours after onset of symptoms, regardless whether they were allocated to a planned invasive or conservative treatment. Compared to clopidogrel, ticagrelor reduced rates of the primary endpoint consisting of cardiovascular death, non-fatal MI, or stroke, without an excess of the primary safety endpoint that was PLATO-defined major bleedings. Results from the pre-specified confirmatory subgroup of patients undergoing planned invasive treatment was consistent with PLATO main trial. In addition, the primary endpoint, as well as CV death and all cause death were consistently reduced with ticagrelor in numerous exploratory subgroups including STEMI patients, those planned for non-invasive treatment, patients undergoing CABG, patients with renal failure, and those with diabetes mellitus, although patients were pretreated before coronary angiography and patients with clopidogrel pretreatment were not excluded. Conclusions: The pharmacological properties and convincing study results of the PLATO trial have stimulated a paradigm change for dual antiplatelet therapy. The new ESC guidelines on the management of ACS without ST segment elevation recommend the use of clopidogrel only when a new antiplatelet drug, e. g. ticagrelor or prasugrel is not available or contraindicated.
Crystalline Nephropathies
Authors: Herlitz Leal C. , D'Agati Vivette D. , Markowitz Glen S. 
Published: June 2012

Context.—The kidney is a favored site for crystal deposition because of the high concentration of ions and molecules reached at the level of the renal tubules in the course of filtration. This review focuses on crystalline nephropathies in 4 broad categories: (1) dysproteinemia- associated, (2) drug-induced, (3) calcium-containing, and (4) metabolic or genetic.Objective.—To provide a framework for accurate identification of the diverse types of crystals encountered in the kidney in order to formulate an appropriate differential diagnosis and guide additional testing and treatment.Data Sources.—Review of pertinent published literature along with practical experience gained in a high-volume renal pathology laboratory.Conclusions.—Accurate identification of crystals encountered in the kidney is essential in detecting conditions ranging from hematologic malignancy to drug toxicity to metabolic disorders. Detailed clinical-pathologic correlation is needed to accurately diagnose the underlying cause of most crystalline nephropathies.
Small-Bowel Allograft Biopsies in the Management of Small-Intestinal and Multivisceral Transplant Recipients: Histopathologic Review and Clinical Correlations
Authors: Remotti Helen , Subramanian Sukanya , Martinez Mercedes , Kato Tomoaki , Magid Margret S. 
Published: June 2012

Context.—Intestinal transplant has become a standard treatment option in the management of patients with irreversible intestinal failure. The histologic evaluation of small-bowel allograft biopsy specimens plays a central role in assessing the integrity of the graft. It is essential for the management of acute cellular and chronic rejection; detection of infections, particularly with respect to specific viruses (cytomegalovirus, adenovirus, Epstein-Barr virus); and immunosuppression-related lymphoproliferative disease.Objective.—To provide a comprehensive review of the literature and illustrate key histologic findings in small-bowel biopsy specimen evaluation of patients with small-bowel or multivisceral transplants.Data Sources.—Literature review using PubMed (US National Library of Medicine) and data obtained from national and international transplant registries in addition to case material at Columbia University, Presbyterian Hospital, and Mount Sinai Medical Center, New York, New York.Conclusions.—Key to the success of small-bowel transplantation and multivisceral transplantation are the close monitoring and appropriate clinical management of patients in the posttransplant period, requiring coordinated input from all members of the transplant team with the integration of clinical, laboratory, and histopathologic parameters.
The Role of Chemical Biology in Drug Discovery
Authors: Pope Andrew J. 
Published: June 2012

AbstractChemical biology methods are central to the discovery of new medicines. The development of new approaches and techniques has accompanied, and been central to, major advances in understanding of disease biology and a move from pharmacology‐driven to molecular‐medicine‐based drug discovery. This article will highlight some critical contributions from chemical biology methods in the context of a high‐level overview of drug discovery as practiced currently.
Plasma cytokines in polycythemia vera: Phenotypic correlates, prognostic relevance, and comparison with myelofibrosis
Authors: Vaidya Rakhee , Gangat Naseema , Jimma Thitina , Finke Christy M. , Lasho Terra L. , Pardanani Animesh , Tefferi Ayalew 
Published: June 2012

AbstractPlasma cytokine milieu is abnormal in primary myelofibrosis (PMF) and correlates with disease phenotype and prognosis. In this study, we show that several plasma cytokines are also abnormally expressed in polycythemia vera (PV; n = 65), compared to normal controls (n = 35), but with a significantly different pattern than that of PMF (n = 127). Direct phenotypic correlation in PV included levels of IL‐12 with hematocrit; IL‐1b, IL‐2, IL‐7, FGF‐b, and HGF with leukocytosis; and IFN‐α and IFN‐γ with thrombocytosis. In univariate analysis, levels of 13 cytokines (out of 30 analyzed) correlated with survival but only MIP‐1β remained significant on multivariable analysis that included the other cytokines as covariates. Increased level of MIP‐1β (P < 0.01), older age (P < 0.01), and leukocytosis (P = 0.03) maintained their association with shortened survival, on multivariable analysis. This study provides preliminary observations that warrant a larger scale study and suggests the value of plasma cytokines as prognostic biomarkers in PV. Am. J. Hematol., 2012. © 2012 Wiley Periodicals, Inc.
A method to estimate the historical US air travel demand
Authors: Li Tao , Baik Hojong , Trani Antonio A. 
Published: June 2012

SUMMARYThe complete historical US air travel demand is not available to the general public. In this paper, we propose a route‐based optimization model to estimate the historical US air travel demand. We show that the distribution of estimated demand follows a logit model. An iterative solution algorithm is proposed to solve the optimization model. The route utility is designed as a function of route characteristics. A feedback‐adjustment scheme is proposed to estimate the model coefficients in the route utility function. In the numerical example, we apply our method to estimate the US air travel demand in the year 1995. Copyright © 2012 John Wiley & Sons, Ltd.