bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutralization of IL-17 ameliorates uveitis but damages photoreceptors in a murine model of spondyloarthritis
Authors: Kezic Jelena M , Glant Tibor T , Rosenbaum James T , Rosenzweig Holly L 
Published: January 2012

Abstract
Introduction
Uveitis, or intraocular inflammatory disease, is a frequent extra-articular manifestation of several forms of arthritis. Despite the frequent co-occurrence of uveitis and arthritis, little is understood of the eye's predisposition to this disease. We recently described a previously unreported uveitis in a murine model of spondyloarthropathy triggered by autoimmunity to aggrecan, a prominent proteoglycan (PG) macromolecule in cartilage. In contrast to the joint and spine, wherein interferon-gamma (IFNγ) deficiency reduced disease, IFNγ deficiency worsened uveitis. Given the regulatory role of IFNγ on the Th17 response and the current focus of anti-interleukin-17 therapeutics in patients with uveitis and spondyloarthritis, we sought to determine the extent to which interleukin (IL)-17 mediates uveitis in the absence of IFNγ.

Methods
Antigen specific T cell cytokine production was measured in splenocyte cultures using multiplex-ELISA. Transgenic (Tg) mice expressing the T cell receptor (TCR) recognizing the dominant arthritogenic epitope in the G1 domain of PG (TCR-Tg), also lacking IFNγ, were immunized with PG. Mice were then systemically administered an anti-IL-17 neutralizing antibody. The onset and severity of peripheral arthritis was evaluated by clinical scoring criteria and histology. Uveitis was assessed using intravital videomicroscopy, which visualizes leukocyte trafficking within the vasculature and tissue of the iris, and by histology.

Results
TCR-Tg splenocytes stimulated in vitro with recombinant G1 peptide demonstrated exacerbated production of cytokines, such as macrophage inflammatory protein (MIP)-1α, MIP-1β, IL-1β, and most notably IL-17A as a consequence of IFNγ deficiency. In vivo, IL-17 inhibition prevented the component of PG-induced arthritis that occurs independently of IFNγ. Blockade of IL-17 ameliorated the ongoing leukocyte trafficking responses within the iris vasculature and tissue, which coincided with reduced infiltration of leukocytes within the anterior and posterior eye segments. However, the anti-IL-17 treatment resulted in unanticipated photoreceptor toxicity.

Conclusions
These data support a protective, regulatory role for IFNγ in suppression of IL-17-mediated intraocular disease and to a lesser extent, joint disease. The unanticipated photoreceptor toxicity raises some caution regarding the use of anti-IL-17 therapeutics until the mechanism of this potential effect is determined.
Dose-Intensification in Early Unfavorable Hodgkin's Lymphoma: Final Analysis of the German Hodgkin Study Group HD14 Trial
Authors: von Tresckow Bastian , Plütschow Annette , Fuchs Michael , Klimm Beate , Markova Jana , Lohri Andreas , Kral Zdenek , Greil Richard , Topp Max S. , Meissner Julia , Zijlstra Josée M. , Soekler Martin , Stein Harald , Eich Hans T. , Mueller Rolf P. , Diehl Volker , Borchmann Peter , Engert Andreas 
Published: January 2012

PurposeIn patients with early unfavorable Hodgkin's lymphoma (HL), combined modality treatment with four cycles of ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) and 30 Gy involved-field radiotherapy (IFRT) results in long-term tumor control of approximately 80%. We aimed to improve these results using more intensive chemotherapy.Patients and MethodsPatients with newly diagnosed early unfavorable HL were randomly assigned to either four cycles of ABVD or an intensified treatment consisting of two cycles of escalated BEACOPP (bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine, procarbazine, and prednisone) followed by two cycles of ABVD (2 + 2). Chemotherapy was followed by 30 Gy IFRT in both arms. The primary end point was freedom from treatment failure (FFTF); secondary end points included progression-free survival (PFS) and treatment-related toxicity.ResultsWith a total of 1,528 qualified patients included, the 2 + 2 regimen demonstrated superior FFTF compared with four cycles of ABVD (P < .001; hazard ratio, 0.44; 95% CI, 0.30 to 0.66), with a difference of 7.2% at 5 years (95% CI, 3.8 to 10.5). The difference in 5-year PFS was 6.2% (95% CI, 3.0% to 9.5%). There was more acute toxicity associated with 2 + 2 than with ABVD, but there were no overall differences in treatment-related mortality or secondary malignancies.ConclusionIntensified chemotherapy with two cycles of BEACOPP escalated followed by two cycles of ABVD followed by IFRT significantly improves tumor control in patients with early unfavorable HL.
Nodal mutant e

X

traembryonic

EN

doderm (XEN) stem cells upregulate markers for the anterior visceral endoderm and impact the timing of cardiac differentiation in mouse embryoid bodies
Authors: Liu Wenrui , Brown Kemar , Legros Stephanie , Foley Ann C. 
Published: January 2012

Summary
Interactions between the endoderm and mesoderm that mediate myocardial induction are difficult to study in vivo because of the small size of mammalian embryos at relevant stages. However, we and others have demonstrated that signals from endodermal cell lines can influence myocardial differentiation from both mouse and human embryoid bodies (EBs), and because of this, assays that utilize embryonic stem (ES) cells and endodermal cell lines provide excellent in vitro models to study early cardiac differentiation. Extraembryonic endoderm (XEN) stem cells have a particular advantage over other heart-inducing cell lines in that they can easily be derived from both wild type and mutant mouse blastocysts. Here we describe the first isolation of a Nodal mutant XEN stem cell line. Nodal−/− XEN cell lines were not isolated at expected Mendelian ratios, and those that were successfully established, showed an increase in markers for the anterior visceral endoderm (AVE). Since AVE represents the heart-inducing endoderm in the mouse, cardiac differentiation was compared in EBs treated with conditioned medium (CM) collected from wild type or Nodal−/− XEN cells. EBs treated with CM from Nodal−/− cells began beating earlier and showed early activation of myocardial genes, but this early cardiac differentiation did not cause an overall increase in cardiomyocyte yield. By comparison, CM from wild type XEN cells both delayed cardiac differentiation and caused a concomitant increase in overall cardiomyocyte formation. Detailed marker analysis suggested that early activation of cardiac differentiation by Nodal−/− XEN CM caused premature differentiation and subsequent depletion of cardiac progenitors.
Two-Step Biochemical Differential Diagnosis of Classic 21-Hydroxylase Deficiency and Cytochrome P450 Oxidoreductase Deficiency in Japanese Infants by GC-MS Measurement of Urinary Pregnanetriolone/ Tetrahydroxycortisone Ratio and 11β-Hydroxyandrosterone
Authors: Koyama Yuhei , Homma Keiko , Fukami Maki , Miwa Masayuki , Ikeda Kazushige , Ogata Tsutomu , Hasegawa Tomonobu , Murata Mitsuru 
Published: January 2012

Abstract

BACKGROUND
The clinical differential diagnosis of classic 21-hydroxylase deficiency (C21OHD) and cytochrome P450 oxidoreductase deficiency (PORD) is sometimes difficult, because both deficiencies can have similar phenotypes and high blood concentrations of 17α-hydroxyprogesterone (17OHP). The objective of this study was to identify biochemical markers for the differential diagnosis of C21OHD, PORD, and transient hyper 17α-hydroxyprogesteronemia (TH17OHP) in Japanese newborns. We established a 2-step biochemical differential diagnosis of C21OHD and PORD.

METHODS
We recruited 29 infants with C21OHD, 9 with PORD, and 67 with TH17OHP, and 1341 control infants. All were Japanese and between 0 and 180 days old; none received glucocorticoid treatment before urine sampling. We measured urinary pregnanetriolone (Ptl), the cortisol metabolites 5α- and 5β-tetrahydrocortisone (sum of these metabolites termed THEs), and metabolites of 3 steroids, namely dehydroepiandrosterone, androstenedione (AD4), and 11β-hydroxyandrostenedione (11OHAD4) by GC-MS.

RESULTS
At a cutoff of 0.020, the ratio of Ptl to THEs differentiated C21OHD and PORD from TH17OHP and controls with no overlap. Among metabolites of DHEA, AD4, and 11OHAD4, only 11β-hydroxyandrosterone (11HA), a metabolite of 11OHAD4, showed no overlap between C21OHD and PORD at a cutoff of 0.35 mg/g creatinine.

CONCLUSIONS
A specific cutoff for the ratio of Ptl to THEs can differentiate C21OHD and PORD from TH17OHP and controls. Additionally, the use of a specific cutoff of 11HA can distinguish between C21OHD and PORD.
Development of Electrochemiluminescence and Surface Plasmon Resonance based Immunosensors with Surface Accumulable Molecules.
Authors: Kurita Ryoji 
Published: January 2012

ABSTRACTThe electrochemiluminescence (ECL) and surface plasmon resonance (SPR) based immunosensors for measuring a trace level of disease markers are shown. It is well known that thiols form a self-assembled monolayer on a metal surface, and this has been widely used to modify metal surfaces. We employed this characteristic for a highly sensitive immunosensors by obtaining a surface pre-concentration of thiol molecules formed by the enzymatic reaction of labeled antibody.
Capital Gains Taxes and Expected Rates of Return
Authors: Sikes Stephanie A. , Verrecchia Robert E. 
Published: January 2012

ABSTRACT
Prior literature predicts a positive relation between firms' expected pre-tax rates of return and investor-level capital gains tax rates. We show that this relation is more nuanced than suggested by prior literature and that in three circumstances the relation can actually be negative. The first circumstance is when a firm's systematic risk is very high. The second circumstance is when the market risk premium is very high. The third circumstance is when the risk-free rate of return is very low. The circumstances arise because, in addition to reducing investors' expected after-tax cash proceeds, capital gains taxes reduce the risk that investors associate with the expected after-tax cash proceeds.
Screening for Dysglycemia in Overweight Youth Presenting for Weight Management
Authors: Morrison Katherine M. , Xu Liqin , Tarnopolsky Mark , Yusuf Zaheera , Atkinson Stephanie A. , Yusuf Salim 
Published: January 2012

OBJECTIVE
To examine the performance of current screening recommendations for detecting dysglycemia in children and adolescents with obesity.

RESEARCH DESIGN AND METHODS
In a cross-sectional study, an oral glucose tolerance test and demographic (age, sex, family history of diabetes, and ethnicity), clinical (BMI z score, waist circumference, and pubertal stage), and laboratory variables used in current pediatric screening criteria for type 2 diabetes mellitus were measured in 259 overweight or obese youth aged 5–17 years. Glycemic status was based on American Diabetes Association (ADA) thresholds. The performance (sensitivity and specificity) of current screening criteria and newly developed models to identify isolated IGT were compared.

RESULTS
Dysglycemia was present in 20.8% of the cohort. Of the 54 participants with dysglycemia, 68% had a normal fasting glucose and were identified with the 2-h glucose test. Current ADA criteria had low sensitivity (41.7% [95% CI 25.6–57.8]) and moderate specificity (69.5% [63.5–75.6]) to identify IGT. In receiver operating characteristic (ROC) analysis, the addition of hemoglobin A1c (HbA1c) or FPG did not improve the ROC area under the curve (AUC) (HbA1c: 0.64 vs. 0.63; P = 0.54; HbA1c + FPG: 0.66; P = 0.42), but adding triglyceride level did (AUC 0.72 vs. 0.63; P = 0.03). A simple model with fasting triglyceride level &gt;1.17 mmol/L improved AUC compared with ADA screening criteria (0.68 vs. 0.57; P = 0.04).

CONCLUSIONS
The prevalence of IGT is high among obese children and youth. Current screening criteria have low sensitivity to detect isolated IGT. Although adding nonfasting laboratory values to history and physical measures does not improve diagnostic accuracy, adding fasting lipid profile improves predictive value.
Application of Computational Mechanics to Tire Design—Yesterday, Today, and Tomorrow
Authors: Nakajima Y. 
Published: January 2012

Abstract
The tire technology related with the computational mechanics is reviewed from the standpoint of yesterday, today, and tomorrow.
Yesterday: A finite element method was developed in the 1950s as a tool of computational mechanics. In the tire manufacturers, finite element analysis (FEA) was started applying to a tire analysis in the beginning of 1970s and this was much earlier than the vehicle industry, electric industry, and others. The main reason was that construction and configurations of a tire were so complicated that analytical approach could not solve many problems related with tire mechanics. Since commercial software was not so popular in 1970s, in-house axisymmetric codes were developed for three kinds of application such as stress/strain, heat conduction, and modal analysis. Since FEA could make the stress/strain visible in a tire, the application area was mainly tire durability.
Today: combining FEA with optimization techniques, the tire design procedure is drastically changed in side wall shape, tire crown shape, pitch variation, tire pattern, etc. So the computational mechanics becomes an indispensable tool for tire industry. Furthermore, an insight to improve tire performance is obtained from the optimized solution and the new technologies were created from the insight. Then, FEA is applied to various areas such as hydroplaning and snow traction based on the formulation of fluid–tire interaction. Since the computational mechanics enables us to see what we could not see, new tire patterns were developed by seeing the streamline in tire contact area and shear stress in snow in traction.Tomorrow: The computational mechanics will be applied in multidisciplinary areas and nano-scale areas to create new technologies. The environmental subjects will be more important such as rolling resistance, noise and wear.
The Influence of Self-rated Health on the Development of Change in the Level of Physical Activity for Participants in Prescribed Exercise
Authors: Bredahl Thomas , Singhammer John 
Published: January 2012

The Influence of Self-rated Health on the Development of Change in the Level of Physical Activity for Participants in Prescribed Exercise
Background: Knowledge is needed concerning whether intense prescribed exercise interventions are effective in regards to long term effects on physical activity levels. A successful and lasting outcome of a behaviour-change intervention is believed to be contingent on the inclusion of psychological issues such as self-rated quality of life and self-rated health. This study extends previous research conducted on the long-term influence of prescribed exercise on psychosocial issues. Specifically, it was hypothesized that participants' level of self-rated health (good or poor) at baseline was decisive for level of physical activity in the long term. Methods: This study is based on a secondary analysis of a quasi-experimental study of the impact of counseling on level of physical activity. The study included a baseline analysis of participants in a treatment group (TG) and follow-up after 4, 10 and 16 months. The TG included individuals with lifestyle diseases who followed supervised group-based training and received motivational counselling. The TG was divided into "good" and "poor" self-rated health at baseline. Linear growth curve analyses (multilevel linear regression) were used to examine the data. Results: The results yielded a statistical significant difference of 1.71 metabolic equivalents (MET) between participants with good versus poor health at baseline. Also, a difference of MET was observed at 10 months. MET increased by 0.85 units for participants with good self-rated health (SE = 0.094) from baseline to 16 months, though the increase between subsequent points in time was small and non-significant. In contrast, considerably more variation in the development of MET over time was observed among participants with poor self-rated health. Overall, MET increased by 2.53 units across the whole time span. Results were influenced by the overall proportion of drop-out for participants with good and poor self-rated health with values of 28% and 79%, respectively. Conclusions: Exercise on Prescription (EoP) improves levels of physical activity (MET) of participants with good and poor self-rated health in the long term enough to accommodate national guidelines of levels of physical activity. Participants with poor self-rated health will improve their level of physical activity to a clinical relevant level in the long term, if they manage to stay compliant during the observation period. An assessment of good and poor self-rated health supplemented by a discussion of psychical and physical domains of self-rated health as barriers by the general practitioner (GP), could possibly enhance compliance and thereby long-term adherence to physical activity.
Fans' Reactions to their Team Victories: An Exploratory Look at the COFFING Process in Elite Sport Fandom
Authors: Bernache-Assollant Iouri , Chantal Yves 
Published: January 2012

Fans' Reactions to their Team Victories: An Exploratory Look at the COFFING Process in Elite Sport Fandom
The goal of this study was to provide preliminary data pertaining to the identity management process of COFFing (i.e, Cutting of Future Failure; Wann, Hamlet, Wilson, & Hodges, 1995) within the realm of sport fandom. When COFFing, fans who support a low or middle status team (i.e., relatively poorly ranked) tend to hold out enthusiasm about their team victories as a self-protective strategy against the likely advent of future failures. The present mixed sample was comprised of 93 highly involved rugby fans showing allegiance to either a middle status or a high status team. Results first revealed that, compared to fans of high status team, fans of middle status team were less likely to BIRG and were less optimistic about their local team future performances when controlling for team identification level. Secondly, with respect to the role of team identification in the COFFing process for fans of middle status team, a positive correlation was found between team identification, BIRGing and prediction of future performances.
Maintenance of T Cell Function in the Face of Chronic Antigen Stimulation and Repeated Reactivation for a Latent Virus Infection
Authors: Mackay Laura K. , Wakim Linda , van Vliet Catherine J. , Jones Claerwen M. , Mueller Scott N. , Bannard Oliver , Fearon Douglas T. , Heath William R. , Carbone Francis R. 
Published: January 2012

Abstract
Persisting infections are often associated with chronic T cell activation. For certain pathogens, this can lead to T cell exhaustion and survival of what is otherwise a cleared infection. In contrast, for herpesviruses, T cells never eliminate infection once it is established. Instead, effective immunity appears to maintain these pathogens in a state of latency. We used infection with HSV to examine whether effector-type T cells undergoing chronic stimulation retained functional and proliferative capacity during latency and subsequent reactivation. We found that latency-associated T cells exhibited a polyfunctional phenotype and could secrete a range of effector cytokines. These T cells were also capable of mounting a recall proliferative response on HSV reactivation and could do so repeatedly. Thus, for this latent infection, T cells subjected to chronic Ag stimulation and periodic reactivation retain the ability to respond to local virus challenge.
Seminal Fluid Induces Leukocyte Recruitment and Cytokine and Chemokine mRNA Expression in the Human Cervix after Coitus
Authors: Sharkey David J. , Tremellen Kelton P. , Jasper Melinda J. , Gemzell-Danielsson Kristina , Robertson Sarah A. 
Published: January 2012

AbstractIn mice, seminal fluid elicits an inflammation-like response in the female genital tract that activates immune adaptations to advance the likelihood of conception and pregnancy. In this study, we examined whether similar changes in leukocyte and cytokine parameters occur in the human cervix in response to the male partner’s seminal fluid. After a period of abstinence in proven-fertile women, duplicate sets of biopsies were taken from the ectocervix in the periovulatory period and again 48 h later, 12 h after unprotected vaginal coitus, vaginal coitus with use of a condom, or no coitus. A substantial influx of CD45+ cells mainly comprising CD14+ macrophages and CD1a+ dendritic cells expressing CD11a and MHC class II was evident in both the stratified epithelium and deeper stromal tissue after coitus. CD3+CD8+CD45RO+ T cells were also abundant and increased after coitus. Leukocyte recruitment did not occur without coitus or with condom-protected coitus. An accompanying increase in CSF2, IL6, IL8, and IL1A expression was detected by quantitative RT-PCR, and microarray analysis showed genes linked with inflammation, immune response, and related pathways are induced by seminal fluid in cervical tissues. We conclude that seminal fluid introduced at intercourse elicits expression of proinflammatory cytokines and chemokines, and a robust recruitment of macrophages, dendritic cells, and memory T cells. The leukocyte and cytokine environment induced in the cervix by seminal fluid appears competent to initiate adaptations in the female immune response that promote fertility. This response is also relevant to transmission of sexually transmitted pathogens and potentially, susceptibility to cervical metaplasia.
Clinical Implementation of KRAS Testing in Metastatic Colorectal Carcinoma: The Pathologist's Perspective
Authors: Ross Jeffrey S. 
Published: January 2012

Context.—Mutation status of the KRAS gene identifies a distinct disease subtype of metastatic colorectal carcinoma that does not respond to antibody therapeutics targeting the epidermal growth factor receptor. This is currently the only validated marker in metastatic colorectal carcinoma with a clear implication in treatment selection. KRAS testing is widely accepted in clinical practice to guide metastatic colorectal carcinoma therapeutic decisions, and there are many commercially available platforms to perform the test.Objective.—To evaluate the critical role of pathologists in the full implementation of KRAS testing by optimizing tumor tissue collection and fixation procedures and by choosing testing technologies and reliable Clinical Laboratory Improvement Amendments of 1988–certified laboratories to perform the tests.Data Sources.—Prospective clinical trials, retrospective studies, and quality assessment and survey reports were identified in the following databases: PubMed, American Society of Clinical Oncology Proceedings (American Society of Clinical Oncology Annual Meeting and Gastrointestinal Cancer Symposium) and European Society for Medical Oncology Proceedings (Annals of Oncology European Society for Medical Oncology Congress and Annals of Oncology World Congress on Gastrointestinal Cancers).Conclusions.—More bona fide standards are needed to address the variety of available test methods, which have different performance characteristics including speed, sensitivity to detect rare mutations, and technical requirements. Refined standards addressing timing of KRAS testing, laboratory performance and accuracy, quality assurance and control, proper tissue collection, and appropriate result reporting would also be greatly beneficial. Pathologists should be aware that the amount of information they need to manage will increase, because future trends and technological advances will enhance the predictive power of diagnostic tests or the scope of the biomarker panels tested routinely across tumor types.