bluuebunny/crossref_metadata_2025_split huggingface dataset:
Age-Associated B Cells with Proinflammatory Characteristics Are Expanded in a Proportion of Multiple Sclerosis Patients
Authors: Claes Nele , Fraussen Judith , Vanheusden Marjan , Hellings Niels , Stinissen Piet , Van Wijmeersch Bart , Hupperts Raymond , Somers Veerle 
Published: November 2016

Abstract
Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgD−CD27− (double negative, DN) and CD21−CD11c+ (CD21low) B cells were described as age-associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21low B cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21low (9/41) B cells compared with age-matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age-associated B cells in MS patients. The majority of DN B cells had an IgG+ memory phenotype, whereas CD21low B cells consisted of a mixed population of CD27− naive, CD27+ memory, IgG+, and IgM+ cells. DN B cells showed similar (MS patients) or increased (healthy donors) MHC-II expression as class-switched memory B cells and intermediate costimulatory molecule expression between naive and class-switched memory B cells, indicating their potential to induce (proinflammatory) T cell responses. Further, DN B cells produced proinflammatory and cytotoxic cytokines following ex vivo stimulation. Increased frequencies of DN and CD21low B cells were found in the cerebrospinal fluid of MS patients compared with paired peripheral blood. In conclusion, a proportion of MS patients showed increased peripheral expansions of age-associated B cells. DN and CD21low B cell frequencies were further increased in MS cerebrospinal fluid. These cells could contribute to inflammation by induction of T cell responses and the production of proinflammatory cytokines.
Dendritic Cell KLF2 Expression Regulates T Cell Activation and Proatherogenic Immune Responses
Authors: Alberts-Grill Noah , Engelbertsen Daniel , Bu Dexiu , Foks Amanda , Grabie Nir , Herter Jan M. , Kuperwaser Felicia , Chen Tao , Destefano Gina , Jarolim Petr , Lichtman Andrew H. 
Published: November 2016

Abstract
Dendritic cells (DCs) have been implicated as important regulators of innate and adaptive inflammation in many diseases, including atherosclerosis. However, the molecular mechanisms by which DCs mitigate or promote inflammatory pathogenesis are only partially understood. Previous studies have shown an important anti-inflammatory role for the transcription factor Krüppel-like factor 2 (KLF2) in regulating activation of various cell types that participate in atherosclerotic lesion development, including endothelial cells, macrophages, and T cells. We used a pan-DC, CD11c-specific cre-lox gene knockout mouse model to assess the role of KLF2 in DC activation, function, and control of inflammation in the context of hypercholesterolemia and atherosclerosis. We found that KLF2 deficiency enhanced surface expression of costimulatory molecules CD40 and CD86 in DCs and promoted increased T cell proliferation and apoptosis. Transplant of bone marrow from mice with KLF2-deficient DCs into Ldlr−/− mice aggravated atherosclerosis compared with control mice, most likely due to heightened vascular inflammation evidenced by increased DC presence within lesions, enhanced T cell activation and cytokine production, and increased cell death in atherosclerotic lesions. Taken together, these data indicate that KLF2 governs the degree of DC activation and hence the intensity of proatherogenic T cell responses.
The Analysis of CD83 Expression on Human Immune Cells Identifies a Unique CD83+-Activated T Cell Population
Authors: Ju Xinsheng , Silveira Pablo A. , Hsu Wei-Hsun , Elgundi Zehra , Alingcastre Renz , Verma Nirupama D. , Fromm Phillip D. , Hsu Jennifer L. , Bryant Christian , Li Ziduo , Kupresanin Fiona , Lo Tsun-Ho , Clarke Candice , Lee Kenneth , McGuire Helen , Fazekas de St. Groth Barbara , Larsen Stephen R. , Gibson John , Bradstock Kenneth F. , Clark Georgina J. , Hart Derek N. J. 
Published: November 2016

Abstract
CD83 is a member of the Ig gene superfamily, first identified in activated lymphocytes. Since then, CD83 has become an important marker for defining activated human dendritic cells (DC). Several potential CD83 mRNA isoforms have been described, including a soluble form detected in human serum, which may have an immunosuppressive function. To further understand the biology of CD83, we examined its expression in different human immune cell types before and after activation using a panel of mouse and human anti-human CD83 mAb. The mouse anti-human CD83 mAbs, HB15a and HB15e, and the human anti-human CD83 mAb, 3C12C, were selected to examine cytoplasmic and surface CD83 expression, based on their different binding characteristics. Glycosylation of CD83, the CD83 mRNA isoforms, and soluble CD83 released differed among blood DC, monocytes, and monocyte-derived DC, and other immune cell types. A small T cell population expressing surface CD83 was identified upon T cell stimulation and during allogeneic MLR. This subpopulation appeared specifically during viral Ag challenge. We did not observe human CD83 on unstimulated human natural regulatory T cells (Treg), in contrast to reports describing expression of CD83 on mouse Treg. CD83 expression was increased on CD4+, CD8+ T, and Treg cells in association with clinical acute graft-versus-host disease in allogeneic hematopoietic cell transplant recipients. The differential expression and function of CD83 on human immune cells reveal potential new roles for this molecule as a target of therapeutic manipulation in transplantation, inflammation, and autoimmune diseases.
Characterization and Transcriptomic Analysis of Porcine Blood Conventional and Plasmacytoid Dendritic Cells Reveals Striking Species-Specific Differences
Authors: Auray Gael , Keller Irene , Python Sylvie , Gerber Markus , Bruggmann Remy , Ruggli Nicolas , Summerfield Artur 
Published: November 2016

Abstract
Porcine dendritic cells (DCs) are relatively well characterized, but a clear-cut identification of all DC subsets combined with full transcriptional profiling was lacking, preventing an unbiased insight into the functional specializations of DC subsets. Using a large panel of Abs in multicolor flow cytometry, cell sorting, and RNA sequencing we identified and characterized the porcine equivalent of conventional DCs (cDC) 1 and cDC2 as well as plasmacytoid DCs (pDCs) in the peripheral blood of pigs. We demonstrate that cDC1 are CD135+CD14−CD172alowCADM1+wCD11R1+ cells, cDC2 are CD135+CD14−CD172a+CADM1+CD115+wCD11R1+CD1+ cells and pDCs are CD4+CD135+CD172a+CD123+CD303+ cells. As described in other species, only cDC1 express BATF3 and XCR1, cDC2 express FCER1A and FCGR2B, and only pDCs express TCF4 and NRP1. Nevertheless, despite these cross-species conserved subset-specific transcripts, porcine pDCs differed from the species described so far in many expressed genes and transcriptomic profiling clustered pDCs more distantly from cDCs than monocytes. The response of porcine DC subsets to TLR ligands revealed that pDCs are by far the most important source of TNF-α, IL-12p40, and of course IFN-α, whereas cDCs are most efficient in MHC and costimulatory molecule expression. Nevertheless, upregulation of CD40 and CD86 in cDCs was critically influenced or even dependent on the presence of pDCs, particularly for TLR 7 and 9 ligands. Our data demonstrate that extrapolation of data on DC biology from one species to another has to be done with care, and it shows how functional details have evolved differentially in different species.
Rac2 Functions in Both Neutrophils and Macrophages To Mediate Motility and Host Defense in Larval Zebrafish
Authors: Rosowski Emily E. , Deng Qing , Keller Nancy P. , Huttenlocher Anna 
Published: November 2016

Abstract
Leukocyte motility is required for host defense responses. Rac-family Rho GTPases are implicated in leukocyte function; however, the distinct roles of different Rac isoforms in host defense in vivo have remained unclear. In this study, we generated Rac2-deficient zebrafish using transcription activator–like effector nucleases to directly compare the role of Rac2 in vivo in neutrophils and macrophages in motility and the response to infection. This zebrafish larval model is highly amenable to live imaging of leukocyte behavior, and we report that in rac2−/− larvae both neutrophils and macrophages are defective in basic motility, leading to impaired responses to localized wounds or infections. rac2−/− larvae are highly susceptible to infection with Pseudomonas aeruginosa, which can be almost fully rescued by ectopic expression of either Rac2 or Rac1 specifically in neutrophils, indicating that these isoforms have partially overlapping functions in vivo. Rescue of Rac2 expression specifically in macrophages also confers resistance to Pseudomonas infection, highlighting an important role for Rac2 in this leukocyte population as well. Surprisingly, in contrast to neutrophils expressing a Rac2 dominant inhibitory human disease mutation, rac2−/− neutrophils do not have altered polarity or mobilization from hematopoietic tissue, suggesting that a different Rac isoform, such as Rac1, also contributes to these phenotypes in vivo.
Early Whole Blood Transcriptional Signatures Are Associated with Severity of Lung Inflammation in Cynomolgus Macaques with Mycobacterium tuberculosis Infection
Authors: Gideon Hannah P. , Skinner Jason A. , Baldwin Nicole , Flynn JoAnne L. , Lin Philana Ling 
Published: November 2016

Abstract
Whole blood transcriptional profiling offers great diagnostic and prognostic potential. Although studies identified signatures for pulmonary tuberculosis (TB) and transcripts that predict the risk for developing active TB in humans, the early transcriptional changes immediately following Mycobacterium tuberculosis infection have not been evaluated. We evaluated the gene expression changes in the cynomolgus macaque model of TB, which recapitulates all clinical aspects of human M. tuberculosis infection, using a human microarray and analytics platform. We performed genome-wide blood transcriptional analysis on 38 macaques at 11 postinfection time points during the first 6 mo of M. tuberculosis infection. Of 6371 differentially expressed transcripts between preinfection and postinfection, the greatest change in transcriptional activity occurred 20–56 d postinfection, during which fluctuation of innate and adaptive immune response–related transcripts was observed. Modest transcriptional differences between active TB and latent infection were observed over the time course with substantial overlap. The pattern of module activity previously published for human active TB was similar in macaques with active disease. Blood transcript activity was highly correlated with lung inflammation (lung [18F]fluorodeoxyglucose [FDG] avidity) measured by positron emission tomography and computed tomography at early time points postinfection. The differential signatures between animals with high and low lung FDG were stronger than between clinical outcomes. Analysis of preinfection signatures of macaques revealed that IFN signatures could influence eventual clinical outcomes and lung FDG avidity, even before infection. Our data support that transcriptional changes in the macaque model are translatable to human M. tuberculosis infection and offer important insights into early events of M. tuberculosis infection.
Cutting Edge: BAFF Overexpression Reduces Atherosclerosis via TACI-Dependent B Cell Activation
Authors: Jackson Shaun W. , Scharping Nicole E. , Jacobs Holly M. , Wang Shari , Chait Alan , Rawlings David J. 
Published: November 2016

Abstract
Patients with systemic lupus erythematosus exhibit accelerated atherosclerosis, a chronic inflammatory disease of the arterial wall. The impact of B cells in atherosclerosis is controversial, with both protective and pathogenic roles described. For example, natural IgM binding conserved oxidized lipid epitopes protect against atherosclerosis, whereas anti-oxidized low-density lipoprotein (oxLDL) IgG likely promotes disease. Because BAFF promotes B cell class-switch recombination and humoral autoimmunity, we hypothesized that excess BAFF would accelerate atherosclerosis. In contrast, BAFF overexpression markedly reduced hypercholesterolemia and atherosclerosis in hyperlipidemic mice. BAFF-mediated atheroprotection required B cells and was associated with increased protective anti-oxLDL IgM. Surprisingly, high–titer anti-oxLDL IgM production and reduced atherosclerosis was dependent on the BAFF family receptor transmembrane activator and CAML interactor. In summary, we identified a novel role for B cell–specific, BAFF-dependent transmembrane activator and CAML interactor signals in atherosclerosis pathogenesis, of particular relevance to the use of BAFF-targeted therapies in systemic lupus erythematosus.
Social support and diabetes self-management behavior among Caribbean, Caribbean American, and African American women: A descriptive correlation study
Authors: Harvey Idethia , Sherman Ledric , Spears Erica , Ford Chanee , Green Helena 
Published: November 2016

Abstract
Background: Type-2 diabetes (T2D) is one of the most prevalent chronic and noncommunicable conditions both domestically and globally. The objective of this descriptive study was to examine how perceived social support impacted self-care management behavior among female African American and Caribbean populations.
Materials and Methods: The cross-sectional study recruited 42 African American and Caribbean women diagnosed with T2D (M = 69.1, SD = 12.0). Univariate and bivariate analyses were conducted to explore the relationship between (1) demographic characteristics, (2) desired and received social support variables, and (3) self-management behaviors.
Results: Caribbean women residing in the United States were more likely to follow general diet (M = 5.38, SD = 1.43) and to engage in physical activity (M = 4.31, SD = 2.39), whereas African American women were more likely to follow a specific diabetes diet (M = 3.79, SD = 1.60) and to monitor their glucose (M = 5.70, SD = 1.75). Caribbean women living in the United States Virgin Islands were more likely to follow recommended foot care procedure (M = 4.65, SD = 1.36). A negative correlation occurred between female participants exercising and the desired support in exercising. Women who reported that they desired more support with physical activity exercised less (r
s= −0.34; P = 0.04). No relationship was found between foot care procedure and demographic characteristics or social support variables (i.e. desired or received).
Conclusion: This study suggests directions for future studies that would examine the dynamics of social support and T2D self-management behaviors, and this study might be relevant to other Caribbean and African American communities with T2D both in North America and the Caribbean.
The prevalence and predictors of cognitive impairment in type 2 diabetic population of Punjab, India
Authors: Khullar Shallu , Kaur Gurpreet , Dhillon Harjot , Sharma Ritu , Mehta Kanchan , Singh Monica , Singh Puneetpal 
Published: November 2016

Abstract
Background: The present cross sectional study was carried out on 516 subjects with type 2 diabetes from a tertiary health care hospital to identify the prevalence and predictors of cognitive impairment in diabetes.
Materials and Methods: Cognitive impairment was tested using Mini Mental Scale Examination (MMSE), Trail making tests-A and B (TMT-A and TMT-B). Efficiency of these tests to diagnose cognitive impairment was analysed using reliability index (Cronbach's α = 0.82), which ruled out any internal inconsistency. Of the study participants, 174 (33.73%) met the criteria for cognitive impairment and 342 (66.27%) were having normal cognition. Out of 174, 156 diabetic subjects (89.65 percent) were not diagnosed for neurocognitive impairment prior participation.
Results: Cognitive impairment was observed to be strongly associated with being a woman (P < 0.001), divorced or separated (P = 0.007), sedentary life style (P = 0.001), smoking (P < 0.001), drinking alcohol (P < 0.001), systolic blood pressure >120 mmHg (P = 0.003), triglycerides (TG) >150 mg/dl (P = 0.001), high density lipoprotein <40 mg/dl (P = 0.001), statin use (P = 0.009), waist hip ratio in both males and females (P = 0.001), glucose levels >125 mg/dl (P = 0.005) and duration of diabetes >2 years upto 10 years and more than 10 years (P = 0.001) in univariate testing. In multivariate logistic regression model, being a woman was an independent risk factor for cognitive decline, which is two fold higher (OR 2.00 95%CI 1.25-3.20, P = 0.004) than being a man. Other risk factors like glucose levels > 125 mg/dl, systolic blood pressure >120 mmHg, sedentary life style and duration of diabetes >10 years emerged as independent predictors of cognitive impairment in diabetes.
Conclusion: In conclusion, the present study revealed that higher prevalence of cognitive impairment in diabetes is evident in population of Punjab, especially in women and majority of these patients remain undiagnosed for it.
Analysis of variability of tropical Pacific sea surface temperatures
Authors: Davies Georgina , Cressie Noel 
Published: November 2016

Abstract. Sea surface temperature (SST) in the Pacific Ocean is a key component of many global climate models and the El Niño–Southern Oscillation (ENSO) phenomenon. We shall analyse SST for the period November 1981–December 2014. To study the temporal variability of the ENSO phenomenon, we have selected a subregion of the tropical Pacific Ocean, namely the Niño 3.4 region, as it is thought to be the area where SST anomalies indicate most clearly ENSO's influence on the global atmosphere. SST anomalies, obtained by subtracting the appropriate monthly averages from the data, are the focus of the majority of previous analyses of the Pacific and other oceans' SSTs. Preliminary data analysis showed that not only Niño 3.4 spatial means but also Niño 3.4 spatial variances varied with month of the year. In this article, we conduct an analysis of the raw SST data and introduce diagnostic plots (here, plots of variability vs. central tendency). These plots show strong negative dependence between the spatial standard deviation and the spatial mean. Outliers are present, so we consider robust regression to obtain intercept and slope estimates for the 12 individual months and for all-months-combined. Based on this mean–standard deviation relationship, we define a variance-stabilizing transformation. On the transformed scale, we describe the Niño 3.4 SST time series with a statistical model that is linear, heteroskedastic, and dynamical.
Evaluation of Gastroesophageal Reflux in Anesthetized Dogs with Brachycephalic Syndrome
Authors: Shaver Stephanie L. , Barbur Laura A. , Jimenez David A. , Brainard Benjamin M. , Cornell Karen K. , Radlinsky MaryAnn G. , Schmiedt Chad W. 
Published: November 2016

ABSTRACTBrachycephalic airway syndrome may predispose to gastroesophageal reflux (GER) because of the high negative intrathoracic pressures required to overcome conformational partial upper airway obstruction. To investigate this, 20 dogs presenting for elective correction of brachycephalic airway syndrome (cases) and 20 non-brachycephalic dogs (controls) undergoing other elective surgeries were prospectively enrolled. Dogs underwent a standardized anesthetic protocol, and esophageal pH was monitored. Signalment, body weight, historical gastrointestinal and respiratory disease, complete blood count, serum biochemical values, radiographic findings, and anesthetic and surgical time were compared between cases and controls, and dogs that did and did not have basic (pH &gt; 7.5), acidic (pH &lt; 4), or any GER. Controls had higher mean esophageal pH (6.3) compared to cases (5.6, P = .019), but there was no difference in % with GER (cases 60%, controls 40%, P = .34). When all dogs were evaluated, dogs with GER had increased creatinine (P = .01), % positive for esophageal fluid on radiographs (P = .05), and body weight (P = .04) compared to those without GER. GER was common in both cases and controls, and cases had lower esophageal pH; however, greater numbers are required to determine if a true difference exists in % GER.
A Distorted Mediation Landscape: Judicial Mediation in the Chinese Civil Courts
Authors: Chan Peter 
Published: November 2016

A Distorted Mediation Landscape: Judicial Mediation in the Chinese Civil Courts
Mediation plays a critical role in the development of any civil justice system. The positive effects of mediation could only manifest if the process is protected in ways that allow parties to truly be able to choose what is best in their interests and explore options free from interference from anyone else. The Chinese legal culture, coupled with a systemic distortion of the function of mediation during the period between March 2008 and March 2013, made it very difficult to develop an authentic mediation system that places party autonomy and other core principles at the heart of the process. As much as the leaders of the Supreme People’s Court today are aware of the need to strengthen the courts role in declaring legal norms and enforcing rights, it is argued that courts (especially lower courts) are likely to continue to use judicial mediation for institutional or strategic purposes.
HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma: Guideline From the College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology
Authors: Bartley Angela N. , Washington Mary Kay , Ventura Christina B. , Ismaila Nofisat , Colasacco Carol , Benson Al B. , Carrato Alfredo , Gulley Margaret L. , Jain Dhanpat , Kakar Sanjay , Mackay Helen J. , Streutker Catherine , Tang Laura , Troxell Megan , Ajani Jaffer A. 
Published: November 2016

Context.—ERBB2 (erb-b2 receptor tyrosine kinase 2 or HER2) is currently the only biomarker established for selection of a specific therapy for patients with advanced gastroesophageal adenocarcinoma (GEA). However, there are no comprehensive guidelines for the assessment of HER2 in patients with GEA.Objectives.—To establish an evidence-based guideline for HER2 testing in patients with GEA, to formalize the algorithms for methods to improve the accuracy of HER2 testing while addressing which patients and tumor specimens are appropriate, and to provide guidance on clinical decision making.Design.—The College of American Pathologists, American Society for Clinical Pathology, and American Society of Clinical Oncology convened an expert panel to conduct a systematic review of the literature to develop an evidence-based guideline with recommendations for optimal HER2 testing in patients with GEA.Results.—The panel is proposing 11 recommendations with strong agreement from the open-comment participants.Recommendations.—The panel recommends that tumor specimen(s) from all patients with advanced GEA, who are candidates for HER2-targeted therapy, should be assessed for HER2 status before the initiation of HER2-targeted therapy. Clinicians should offer combination chemotherapy and a HER2-targeted agent as initial therapy for all patients with HER2-positive advanced GEA. For pathologists, guidance is provided for morphologic selection of neoplastic tissue, testing algorithms, scoring methods, interpretation and reporting of results, and laboratory quality assurance.Conclusions.—This guideline provides specific recommendations for assessment of HER2 in patients with advanced GEA while addressing pertinent technical issues and clinical implications of the results.