bluuebunny/crossref_metadata_2025_split huggingface dataset:
Regulatory T cells in autoimmune neuroinflammation
Authors: Kleinewietfeld Markus , Hafler David A. 
Published: April 2014

SummaryRegulatory T cells are the central element for the maintenance of peripheral tolerance. Several subtypes of regulatory T (Treg) cells have been described, and most of them belong to the CD4+ T‐helper (Th) cell lineage. These specific subtypes can be discriminated according to phenotype and function. Forkhead box protein 3 (FoxP3)‐expressing natural Treg cells (Tregs) and IL‐10‐producing, T‐regulatory type 1 cells (Tr1) are the best‐studied types of CD4+ regulatory T cells in humans and experimental animal models. It was shown that they play a crucial role during autoimmune neuroinflammation. Both cells types seem to be particularly important for multiple sclerosis (MS). Here, we discuss the role of CD4+ regulatory T cells in autoimmune neuroinflammation with an emphasis on Tregs and Tr1 cells in MS.
Once a Treg, always a Treg?
Authors: Sawant Deepali V. , Vignali Dario A. A. 
Published: April 2014

SummaryRegulatory T cells (Tregs) prevail as a specialized cell lineage that has a central role in the dominant control of immunological tolerance and maintenance of immune homeostasis. Thymus‐derived Tregs (tTregs) and their peripherally induced counterparts (pTregs) are imprinted with unique Forkhead box protein 3 (Foxp3)‐dependent and independent transcriptional and epigenetic characteristics that bestows on them the ability to suppress disparate immunological and non‐immunological challenges. Thus, unidirectional commitment and the predominant stability of this regulatory lineage is essential for their unwavering and robust suppressor function and has clinical implications for the use of Tregs as cellular therapy for various immune pathologies. However, recent studies have revealed considerable heterogeneity or plasticity in the Treg lineage, acquisition of alternative effector or hybrid fates, and promotion rather than suppression of inflammation in extreme contexts. In addition, the absolute stability of Tregs under all circumstances has been questioned. Since these observations challenge the safety and efficacy of human Treg therapy, the issue of Treg stability versus plasticity continues to be enthusiastically debated. In this review, we assess our current understanding of the defining features of Foxp3+ Tregs, the intrinsic and extrinsic cues that guide development and commitment to the Treg lineage, and the phenotypic and functional heterogeneity that shapes the plasticity and stability of this critical regulatory population in inflammatory contexts.
B10 cell regulation of health and disease
Authors: Candando Kathleen M. , Lykken Jacquelyn M. , Tedder Thomas F. 
Published: April 2014

SummaryWhile B cells are traditionally regarded as promoters of the immune response via antibody secretion and pro‐inflammatory cytokine production, recent studies have also confirmed an important role for B‐cell‐mediated negative regulation of immunity. Tremendous advances in the characterization of the mechanisms by which regulatory B cells function has led to the identification of a novel subset of regulatory B cells known as B10 cells, which regulate immune responses through the production of the anti‐inflammatory cytokine interleukin‐10 (IL‐10). B10 cells are best defined by their functional ability to produce IL‐10, as they are not confined to any particular phenotypic subset. B10 cells function in an antigen‐specific manner that requires cognate interactions with T cells in vivo to regulate immune responses and have been demonstrated to be potent regulators of allergic and autoimmune disease, cancer, infection, and transplant rejection. Importantly, the recent discovery of human B10 cells has accelerated this field to the forefront of clinical research where the possibility of harnessing the regulatory potential of B10 cells for treatment of aberrant immune responses and diseases may become feasible.
Tachycardiomyopathy Complicated by Focal Atrial Tachycardia: Incidence, Risk Factors, and Long‐Term Outcome
Authors: JU WEIZHU , YANG BING , LI MINGFANG , ZHANG FENGXIANG , CHEN HONGWU , GU KAI , YU JINBO , CAO KEJIANG , CHEN MINGLONG 
Published: April 2014

AT‐Induced CardiomyopathyObjectiveFocal atrial tachycardias (ATs) are known to have the potential to develop tachycardiomyopathy (TCM). The aim of the study was to investigate the incidence, risk factors, and long‐term outcome of TCM patients complicated by focal ATs.Methods and ResultsA total of 237 patients undergoing electrophysiological studies were enrolled, among which 216 patients were diagnosed as focal ATs. In total, 18 patients (8.3%, 13 males) were identified to have TCM. The TCM patients were younger (29.8 ± 20.1 vs. 45.9 ± 17.3; P < 0.000) and were more frequently males (13/18 vs. 80/198; P = 0.014). The ATs were more likely to be persistent (11/18 vs. 32/198; P < 0.001). There was no difference between the 2 groups in terms of the tachycardia cycle length (392 milliseconds vs. 380 milliseconds; P = 0.56) and heart rate (144 bpm vs. 156 bpm; P = 0.15). The persistence and incidence of symptoms and prevalence of structural heart disease were comparable between the groups. In a multivariable analysis, the younger age and persistent nature were independently associated with TCM. In a 56 ± 21‐month follow‐up, all TCM patients had improved left ventricle ejection fraction after successful catheter ablation or medical therapy (43.9 ± 5.8% vs. 61.1 ± 3.5%; P ＜ 0.05). However, 1 patient suffered sudden cardiac death due to unauthorized withdrawal of the drug and progressive heart failure.ConclusionsThe incidence of TCM in focal ATs patients was 8.3%. Younger age and persistent nature were the independent risk factors of TCM. Most TCM patients had a benign outcome; however, long‐term risk of sudden death does exist.
Anatomical Classification of Left Atrial Appendages in Specimens Applicable to CT Imaging Techniques for Implantation of Amplatzer Cardiac Plug
Authors: LÓPEZ‐MÍNGUEZ JOSÉ R. , GONZÁLEZ‐FERNÁNDEZ REYES , FERNÁNDEZ‐VEGAS CONCEPCIÓN , MILLÁN‐NUÑEZ VICTORIA , FUENTES‐CAÑAMERO MARÍA E. , NOGALES‐ASENSIO JUAN M. , DONCEL‐VECINO JAVIER , ELDUAYEN‐GRAGERA JAVIER , HO SIEW Y. , SÁNCHEZ‐QUINTANA DAMIÁN 
Published: April 2014

3‐D Imaging Classification of LAABackgroundCertain anatomical characteristics of the left atrial appendage (LAA) are associated with complexity in the implantation of occluder devices.ObjectiveThe aim was to define characteristics measurable by three‐dimensional imaging that would predict complexities both in the implantation procedure and the selection of the appropriate device size.MethodsAn anatomical study was performed of 50 postmortem hearts, of which 15 had a history of atrial fibrillation, and of 30 consecutive patients undergoing LAA occlusion with the Amplatzer cardiac plug (ACP). The specimens were classified according to variables that can be visualized using computerized tomography (CT). The CT scans of 30 consecutive patients were classified according to the level of the LAA ostium, the left lateral ridge (LLR), the LAA limbus and distance from LAA to the mitral annulus before undergoing LAA occlusion, and the results were correlated.ResultsThree types of LAA orifice were defined: type I, with a usually higher, anterior LAA ostium, a short, flattened and wide LLR and almost nonexistent limbus; type II, presenting a long, pointed and narrow LLR, and a longer, more defined limbus; type III, with a lower LAA ostium, close to the left atrium floor and the mitral annulus, a marked separation from the left pulmonary vein orifices and a limbus of intermediate length.ConclusionLAA with lower ostia are more difficult to occlude. Types II and III have very prominent LLRs with longer limbi, which may increase the difficulty of inserting the guide and making measurements for selection of the right ACP size.
Frequency of Bilateral Hypertrophic Olivary Degeneration in a Large Retrospective Cohort
Authors: Carr Carrie M. , Hunt Christopher H. , Kaufmann Timothy J. , Kotsenas Amy L. , Krecke Karl N. , Wood Christopher P. 
Published: April 2014

ABSTRACTBACKGROUND AND PURPOSEHypertrophic olivary degeneration (HOD) is an uncommon type of transneuronal degeneration. Case reports and case series described in the literature provide a foundation of our current knowledge of HOD. These reports have described HOD most frequently to be unilateral and occurring in association with lesions in the dentato‐rubro‐olivary pathway. Our purpose was to evaluate the rate of bilateral versus unilateral HOD in a large case series.METHODSA retrospective review was performed to identify patients in which the phrase “hypertrophic olivary degeneration” occurred in the radiology report. A diagnosis of HOD was confirmed on imaging if there was focal hyperintensity on T2‐weighted images confined to either or both inferior olivary nuclei.RESULTSA total of 102 patients had findings consistent with HOD. Of these, 76% had findings bilaterally. In 44%, a lesion could not be identified to explain HOD. Bilateral HOD was common in both lesional and nonlesional group, though more common in the nonlesional group.CONCLUSIONThis study demonstrates that HOD is frequently bilateral. In slightly over 50% of patients with HOD, a lesion can be identified. In just under 50% patients with HOD, a lesion could not be identified and in these cases HOD was present bilaterally in the majority.
The Associations Between Park Environments and Park Use in Southern US Communities
Authors: Banda Jorge A. , Wilcox Sara , Colabianchi Natalie , Hooker Steven P. , Kaczynski Andrew T. , Hussey James 
Published: April 2014

AbstractPurposeTo document park use and park and neighborhood environment characteristics in rural communities, and to examine the relationship between park characteristics and park use.MethodsThe System for Observing Play and Recreation in Communities measured use in 42 target areas across 6 community parks in May 2010 and October 2010. Direct observation instruments were used to assess park and neighborhood environment characteristics. Logistic regression was used to determine the relationship between the condition, number of amenities, and number of incivilities in a target area with target area use.FindingsNinety‐seven people were observed across all parks during May 2010 data collection and 116 people during October 2010 data collection. Low park quality index scores and unfavorable neighborhood environment characteristics were observed. There was a significant positive association between number of incivilities in a target area and target area use (OR = 1.91; 95% CI: 1.09‐3.38; P = .03).ConclusionsThe number of people observed using the parks in this study was low, and it was considerably less than the number observed in other studies. The objective park and neighborhood environment characteristics documented in this study provide a more comprehensive understanding of parks than other studies. Further examining the complex relationship between park and neighborhood environment characteristics and park use is important, as it can inform park administrators and city planners of characteristics that are best able to attract visitors.
The present and future disease burden of hepatitis C virus (HCV) infection with today's treatment paradigm
Authors: Razavi H. , Waked I. , Sarrazin C. , Myers R. P. , Idilman R. , Calinas F. , Vogel W. , Mendes Correa M. C. , Hézode C. , Lázaro P. , Akarca U. , Aleman S. , Balık İ. , Berg T. , Bihl F. , Bilodeau M. , Blasco A. J. , Brandão Mello C. E. , Bruggmann P. , Buti M. , Calleja J. L. , Cheinquer H. , Christensen P. B. , Clausen M. , Coelho H. S. M. , Cramp M. E. , Dore G. J. , Doss W. , Duberg A. S. , El‐Sayed M. H. , Ergör G. , Esmat G. , Falconer K. , Félix J. , Ferraz M. L. G. , Ferreira P. R. , Frankova S. , García‐Samaniego J. , Gerstoft J. , Giria J. A. , Gonçales F. L. , Gower E. , Gschwantler M. , Guimarães Pessôa M. , Hindman S. J. , Hofer H. , Husa P. , Kåberg M. , Kaita K. D. E. , Kautz A. , Kaymakoglu S. , Krajden M. , Krarup H. , Laleman W. , Lavanchy D. , Marinho R. T. , Marotta P. , Mauss S. , Moreno C. , Murphy K. , Negro F. , Nemecek V. , Örmeci N. , Øvrehus A. L. H. , Parkes J. , Pasini K. , Peltekian K. M. , Ramji A. , Reis N. , Roberts S. K. , Rosenberg W. M. , Roudot‐Thoraval F. , Ryder S. D. , Sarmento‐Castro R. , Semela D. , Sherman M. , Shiha G. E. , Sievert W. , Sperl J. , Stärkel P. , Stauber R. E. , Thompson A. J. , Urbanek P. , Van Damme P. , van Thiel I. , Van Vlierberghe H. , Vandijck D. , Wedemeyer H. , Weis N. , Wiegand J. , Yosry A. , Zekry A. , Cornberg M. , Müllhaupt B. , Estes C. 
Published: April 2014

SummaryThe disease burden of hepatitis C virus (HCV) is expected to increase as the infected population ages. A modelling approach was used to estimate the total number of viremic infections, diagnosed, treated and new infections in 2013. In addition, the model was used to estimate the change in the total number of HCV infections, the disease progression and mortality in 2013–2030. Finally, expert panel consensus was used to capture current treatment practices in each country. Using today's treatment paradigm, the total number of HCV infections is projected to decline or remain flat in all countries studied. However, in the same time period, the number of individuals with late‐stage liver disease is projected to increase. This study concluded that the current treatment rate and efficacy are not sufficient to manage the disease burden of HCV. Thus, alternative strategies are required to keep the number of HCV individuals with advanced liver disease and liver‐related deaths from increasing.
Strategies to manage hepatitis C virus (HCV) disease burden
Authors: Wedemeyer H. , Duberg A. S. , Buti M. , Rosenberg W. M. , Frankova S. , Esmat G. , Örmeci N. , Van Vlierberghe H. , Gschwantler M. , Akarca U. , Aleman S. , Balık İ. , Berg T. , Bihl F. , Bilodeau M. , Blasco A. J. , Brandão Mello C. E. , Bruggmann P. , Calinas F. , Calleja J. L. , Cheinquer H. , Christensen P. B. , Clausen M. , Coelho H. S. M. , Cornberg M. , Cramp M. E. , Dore G. J. , Doss W. , El‐Sayed M. H. , Ergör G. , Estes C. , Falconer K. , Félix J. , Ferraz M. L. G. , Ferreira P. R. , García‐Samaniego J. , Gerstoft J. , Giria J. A. , Gonçales F. L. , Guimarães Pessôa M. , Hézode C. , Hindman S. J. , Hofer H. , Husa P. , Idilman R. , Kåberg M. , Kaita K. D. E. , Kautz A. , Kaymakoglu S. , Krajden M. , Krarup H. , Laleman W. , Lavanchy D. , Lázaro P. , Marinho R. T. , Marotta P. , Mauss S. , Mendes Correa M. C. , Moreno C. , Müllhaupt B. , Myers R. P. , Nemecek V. , Øvrehus A. L. H. , Parkes J. , Peltekian K. M. , Ramji A. , Razavi H. , Reis N. , Roberts S. K. , Roudot‐Thoraval F. , Ryder S. D. , Sarmento‐Castro R. , Sarrazin C. , Semela D. , Sherman M. , Shiha G. E. , Sperl J. , Stärkel P. , Stauber R. E. , Thompson A. J. , Urbanek P. , Van Damme P. , van Thiel I. , Vandijck D. , Vogel W. , Waked I. , Weis N. , Wiegand J. , Yosry A. , Zekry A. , Negro F. , Sievert W. , Gower E. 
Published: April 2014

SummaryThe number of hepatitis C virus (HCV) infections is projected to decline while those with advanced liver disease will increase. A modeling approach was used to forecast two treatment scenarios: (i) the impact of increased treatment efficacy while keeping the number of treated patients constant and (ii) increasing efficacy and treatment rate. This analysis suggests that successful diagnosis and treatment of a small proportion of patients can contribute significantly to the reduction of disease burden in the countries studied. The largest reduction in HCV‐related morbidity and mortality occurs when increased treatment is combined with higher efficacy therapies, generally in combination with increased diagnosis. With a treatment rate of approximately 10%, this analysis suggests it is possible to achieve elimination of HCV (defined as a >90% decline in total infections by 2030). However, for most countries presented, this will require a 3–5 fold increase in diagnosis and/or treatment. Thus, building the public health and clinical provider capacity for improved diagnosis and treatment will be critical.
Hepatitis C disease burden and strategies to manage the burden (Guest Editors Mark Thursz, Gregory Dore and John Ward)
Authors: Dore G. J. , Ward J. , Thursz M. 
Published: April 2014

SummaryChronic hepatitis C virus (HCV) infection leads to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). The recent Global Burden of Disease project estimated that in 2010 among 170 million people living with chronic HCV, an estimated 483 100 people died from HCV‐related liver failure or HCC. The last two decades has seen progressive improvements in treatment of HCV infection with the most recent therapies offering simple, tolerable, short‐duration therapy with extremely high efficacy. The development of public health strategies addressing emerging epidemics requires sound epidemiological data. This study covers epidemiological data collection, detailed expert opinion input and country‐specific mathematical modelling of the HCV epidemic and potential impact of improved HCV treatment strategies in 16 countries. The analysis demonstrates that the HCV epidemics vary considerably in terms of age distribution of the infected population across countries. In addition, the burden of advanced liver disease varies widely. This burden is dependent upon factors including chronic HCV prevalence, age distribution (and duration of infection) of those infected, prevalence of cofactors for disease progression (particularly heavy alcohol intake) and uptake and success of therapeutic intervention. Introduction of new therapies with assumed sustained virological response (SVR) rate of >90% will have a modest impact on projected advanced liver disease burden. A combination of enhanced treatment efficacy and improved treatment uptake will have a greater impact on population‐level disease burden. However public health advocacy and both public and private sector investment in the HCV response are required to demonstrate significant reduction in HCV disease burden.
Is There Still a Wage Penalty for Being Overeducated But Well‐matched in Skills? A Panel Data Analysis of aSwiss Graduate Cohort
Authors: Pecoraro Marco 
Published: April 2014

AbstractUsing two periods' panel data from theSwissGraduateSurvey, this study examines the incidence, persistence and wage effects of overeducation. An alternative measure of overeducation that accounts for graduate heterogeneity in perceived skills mismatch is used. This analysis differs from previous panel data studies in that two estimation methods are applied to control for unobserved ability. Results indicate that graduates who are overeducated and mismatched in skills are the most penalized in terms of earnings. This evidence is still valid when unobserved ability is accounted for, whereas the pay penalty is no more significant for graduates who are overeducated but matched in skills. This result is robust to different definitions of perceived skills mismatch and is consistent with the notion that apparent overeducation reflects a lack of unobserved attributes, such as ability.
Influence of drift and admixture on population structure of American black bears (Ursus americanus) in the Central Interior Highlands, USA, 50 years after translocation
Authors: Puckett Emily E. , Kristensen Thea V. , Wilton Clay M. , Lyda Sara B. , Noyce Karen V. , Holahan Paula M. , Leslie David M. , Beringer Jeff , Belant Jerrold L. , White Don , Eggert Lori S. 
Published: April 2014

AbstractBottlenecks, founder events, and genetic drift often result in decreased genetic diversity and increased population differentiation. These events may follow abundance declines due to natural or anthropogenic perturbations, where translocations may be an effective conservation strategy to increase population size. American black bears (Ursus americanus) were nearly extirpated from the Central Interior Highlands, USA by 1920. In an effort to restore bears, 254 individuals were translocated from Minnesota, USA, and Manitoba, Canada, into the Ouachita and Ozark Mountains from 1958 to 1968. Using 15 microsatellites and mitochondrial haplotypes, we observed contemporary genetic diversity and differentiation between the source and supplemented populations. We inferred four genetic clusters: Source, Ouachitas, Ozarks, and a cluster in Missouri where no individuals were translocated. Coalescent models using approximate Bayesian computation identified an admixture model as having the highest posterior probability (0.942) over models where the translocation was unsuccessful or acted as a founder event. Nuclear genetic diversity was highest in the source (AR = 9.11) and significantly lower in the translocated populations (AR = 7.07–7.34; P = 0.004). The Missouri cluster had the lowest genetic diversity (AR = 5.48) and served as a natural experiment showing the utility of translocations to increase genetic diversity following demographic bottlenecks. Differentiation was greater between the two admixed populations than either compared to the source, suggesting that genetic drift acted strongly over the eight generations since the translocation. The Ouachitas and Missouri were previously hypothesized to be remnant lineages. We observed a pretranslocation remnant signature in Missouri but not in the Ouachitas.
Temporospatial fate of bacteria and immune effector expression in house flies fed GFP‐Escherichia coliO157:H7
Authors: FLEMING A. , KUMAR H. V. , JOYNER C. , REYNOLDS A. , NAYDUCH D. 
Published: April 2014

AbstractThe house fly Musca domestica L. (Diptera: Muscidae) harbours and transmits a variety of human enteropathogens including Escherichia coli (Enterobacteriales: Enterobacteriaceae) O157:H7. Interactions between ingested bacteria and the fly gut directly impact bacterial persistence, survival and ultimately fly vector competence. We assessed the temporospatial fate of green fluorescent protein (GFP)‐expressing E. coli O157:H7 (GFP‐ECO157) in house flies along with fly antimicrobial responses up to 12 h post‐ingestion. In flies fed GFP‐ECO157, culture and microscopy revealed a steady decrease in bacterial load over 12 h, which is likely to be attributable to the combined effects of immobilization within the peritrophic matrix, lysis and peristaltic excretion. However, flies can putatively transmit this pathogen in excreta because intact bacteria were observed in the crop and rectum. Quantitative reverse‐transcriptase polymerase chain reaction analysis of antimicrobial peptides (AMPs) and lysozyme gene expression showed minimal upregulation in both the gut and carcass of house flies fed GFP‐ECO157. However, these genes were upregulated in fly heads and salivary glands, and effector proteins were detected in the gut in some flies. Collectively, these data indicate that house flies can serve as reservoirs of E. coli O157:H7 for up to 12 h, and factors in addition to AMPs and lysozyme may contribute to bacteria destruction in the gut.