bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allergic airway inflammation: key players beyond the Th2 cell pathway
Authors: Hirose Koichi , Iwata Arifumi , Tamachi Tomohiro , Nakajima Hiroshi 
Published: June 2017

SummaryAllergic asthma is characterized by eosinophilic airway inflammation, mucus hyperproduction, and airway hyperreactivity, causing reversible airway obstruction. Accumulating evidence indicates that antigen‐specific Th2 cells and their cytokines such as IL‐4, IL‐5, and IL‐13 orchestrate these pathognomonic features of asthma. However, over the past decade, the understanding of asthma pathogenesis has made a significant shift from a Th2 cell‐dependent, IgE‐mediated disease to a more complicated heterogeneous disease. Recent studies clearly show that not only Th2 cytokines but also other T cell‐related cytokines such as IL‐17A and IL‐22 as well as epithelial cell cytokines such as IL‐25, IL‐33, and thymic stromal lymphopoietin (TSLP) are involved in the pathogenesis of asthma. In this review, we focus on the roles of these players beyond Th2 pathways in the pathogenesis of asthma.
Mechanisms and treatments for severe, steroid‐resistant allergic airway disease and asthma
Authors: Hansbro Philip M. , Kim Richard Y. , Starkey Malcolm R. , Donovan Chantal , Dua Kamal , Mayall Jemma R. , Liu Gang , Hansbro Nicole G. , Simpson Jodie L. , Wood Lisa G. , Hirota Jeremy A. , Knight Darryl A. , Foster Paul S. , Horvat Jay C. 
Published: June 2017

SummarySevere, steroid‐resistant asthma is clinically and economically important since affected individuals do not respond to mainstay corticosteroid treatments for asthma. Patients with this disease experience more frequent exacerbations of asthma, are more likely to be hospitalized, and have a poorer quality of life. Effective therapies are urgently required, however, their development has been hampered by a lack of understanding of the pathological processes that underpin disease. A major obstacle to understanding the processes that drive severe, steroid‐resistant asthma is that the several endotypes of the disease have been described that are characterized by different inflammatory and immunological phenotypes. This heterogeneity makes pinpointing processes that drive disease difficult in humans. Clinical studies strongly associate specific respiratory infections with severe, steroid‐resistant asthma. In this review, we discuss key findings from our studies where we describe the development of representative experimental models to improve our understanding of the links between infection and severe, steroid‐resistant forms of this disease. We also discuss their use in elucidating the mechanisms, and their potential for developing effective therapeutic strategies, for severe, steroid‐resistant asthma. Finally, we highlight how the immune mechanisms and therapeutic targets we have identified may be applicable to obesity‐or pollution‐associated asthma.
The atopic march: current insights into skin barrier dysfunction and epithelial cell‐derived cytokines
Authors: Han Hongwei , Roan Florence , Ziegler Steven F. 
Published: June 2017

SummaryAtopic dermatitis often precedes the development of other atopic diseases. The atopic march describes this temporal relationship in the natural history of atopic diseases. Although the pathophysiological mechanisms that underlie this relationship are poorly understood, epidemiological and genetic data have suggested that the skin might be an important route of sensitization to allergens. Animal models have begun to elucidate how skin barrier defects can lead to systemic allergen sensitization. Emerging data now suggest that epithelial cell‐derived cytokines such as thymic stromal lymphopoietin (TSLP), IL‐33, and IL‐25 may drive the progression from atopic dermatitis to asthma and food allergy. This review focuses on current concepts of the role of skin barrier defects and epithelial cell‐derived cytokines in the initiation and maintenance of allergic inflammation and the atopic march.
Recent advances in understanding basophil‐mediated Th2 immune responses
Authors: Yamanishi Yoshinori , Miyake Kensuke , Iki Misako , Tsutsui Hidemitsu , Karasuyama Hajime 
Published: June 2017

SummaryBasophils, the least common granulocytes, represent only ~0.5% of peripheral blood leukocytes. Because of the small number and some similarity with mast cells, the functional significance of basophils remained questionable for a long time. Recent studies using newly‐developed analytical tools have revealed crucial and non‐redundant roles for basophils in various immune responses, particularly Th2 immunity including allergy and protective immunity against parasitic infections. In this review, we discuss the mechanisms how basophils mediate Th2 immune responses and the nature of basophil‐derived factors involved in them. Activated basophils release serine proteases, mouse mast cell protease 8 (mMCP‐8), and mMCP‐11, that are preferentially expressed by basophils rather than mast cells in spite of their names. These proteases elicit microvascular hyperpermeability and leukocyte infiltration in affected tissues, leading to inflammation. Basophil‐derived IL‐4 also contributes to eosinophil infiltration while it acts on tissue‐infiltrating inflammatory monocytes to promote their differentiation into M2 macrophages that in turn dampen inflammation. Although basophils produce little or no MHC class II (MHC‐II) proteins, they can acquire peptide‐MHC‐II complexes from dendritic cells via trogocytosis and present them together with IL‐4 to naive CD4 T cells, leading to Th2 cell differentiation. Thus, basophils contribute to Th2 immunity at various levels.
IL‐33: biological properties, functions, and roles in airway disease
Authors: Drake Li Yin , Kita Hirohito 
Published: June 2017

SummaryInterleukin (IL)‐33 is a key cytokine involved in type 2 immunity and allergic airway diseases. Abundantly expressed in lung epithelial cells, IL‐33 plays critical roles in both innate and adaptive immune responses in mucosal organs. In innate immunity, IL‐33 and group 2 innate lymphoid cells (ILC2s) provide an essential axis for rapid immune responses and tissue homeostasis. In adaptive immunity, IL‐33 interacts with dendritic cells, Th2 cells, follicular T cells, and regulatory T cells, where IL‐33 influences the development of chronic airway inflammation and tissue remodeling. The clinical findings that both the IL‐33 and ILC2 levels are elevated in patients with allergic airway diseases suggest that IL‐33 plays an important role in the pathogenesis of these diseases. IL‐33 and ILC2 may also serve as biomarkers for disease classification and to monitor the progression of diseases. In this article, we reviewed the current knowledge of the biology of IL‐33 and discussed the roles of the IL‐33 in regulating airway immune responses and allergic airway diseases.
Type two innate lymphoid cells: the Janus cells in health and disease
Authors: Maazi Hadi , Akbari Omid 
Published: June 2017

SummaryInnate lymphoid cells are functionally diverse subsets of immune cells including the conventional natural killer cells, lymphoid tissue inducers, type 1, 2, and 3 with significant roles in immunity and pathogenesis of inflammatory diseases. Type 2 innate lymphoid cells (ILC2s) resemble type 2 helper (Th2) cells in cytokine production and contribute to anti‐helminth immunity, maintaining mucosal tissue integrity, and adipose tissue browning. ILC2s play important roles in the pathogenesis of allergic diseases and asthma. Studying the pathways of activation and regulation of ILC2s are currently a priority for giving a better understanding of pathogenesis of diseases with immunological roots. Recently, our laboratory and others have shown several pathways of regulation of ILC2s by co‐stimulatory molecules such as ICOS, regulatory T cells and by compounds such as nicotine. In this review, we summarize the current understanding of the mechanisms of activation and regulation of ILC2s and the role of these cells in health and disease.
Innate and adaptive type 2 immunity in lung allergic inflammation
Authors: Kubo Masato 
Published: June 2017

SummaryAllergic inflammation is a type 2 immune disorder classically characterized by high levels of immunoglobulin E (IgE) and the development of Th2 cells. Asthma is a pulmonary allergic inflammatory disease resulting in bronchial hyper‐reactivity. Atopic asthma is defined by IgE antibody‐mediated mast cell degranulation, while in non‐atopic asthma there is no allergen‐specific IgE and more involvement of innate immune cells, such as basophils, group 2 innate lymphoid cells (ILC2), and eosinophils. Recently, protease allergens were shown to cause asthmatic responses in the absence of Th2 cells, suggesting that an innate cell network (IL‐33/TSLP‐basophil‐ILC2‐IL‐5/IL‐13 axis) can facilitate the sensitization phase of type 2 inflammatory responses. Recent evidence also indicates that in the chronic phase, these innate immune cells directly or indirectly contribute to the adaptive Th2 cell responses. In this review, we discuss the role of Th2 cytokines (IL‐4 and IL‐13) and innate immune cells (mast cells, basophils, ILC2s, and dendritic cells) in the cross‐talk between innate and adaptive inflammatory responses.
Epigenetic regulation of T‐helper cell differentiation, memory, and plasticity in allergic asthma
Authors: Tumes Damon J. , Papadopoulos Magdalene , Endo Yusuke , Onodera Atsushi , Hirahara Kiyoshi , Nakayama Toshinori 
Published: June 2017

SummaryAn estimated 300 million people currently suffer from asthma, which causes approximately 250 000 deaths a year. Allergen‐specific T‐helper (Th) cells produce cytokines that induce many of the hallmark features of asthma including airways hyperreactivity, eosinophilic and neutrophilic inflammation, mucus hypersecretion, and airway remodeling. Cytokine‐producing Th subsets including Th1 (IFN‐γ), Th2 (IL‐4, IL‐5, IL‐13), Th9 (IL‐9), Th17 (IL‐17), Th22 (IL‐22), and T regulatory (IL‐10) cells have all been suggested to play a role in the development of asthma. Th differentiation involves genetic regulation of gene expression through the concerted action of cytokines, transcription factors, and epigenetic regulators. We describe how Th differentiation and plasticity is regulated by epigenetic histone and DNA modifications, with a focus on the regulation of histone methylation by members of the polycomb and trithorax complexes. In addition, we outline environmental influences that could influence epigenetic regulation of Th cells and discuss the potential to regulate Th plasticity and function through drugs targeting the epigenetic machinery. It is also becoming apparent that epigenetic regulation of allergen‐specific memory Th cells may be important in the development and persistence of chronic allergies. Finally, we describe how epigenetic modifiers regulate cytokine memory in Th cells and describe recently identified hybrid, plastic, and pathogenic memory Th subsets the context of allergic asthma.
CEO's Total Wealth Characteristics and Implications on Firm Risk
Authors: Korkeamäki Timo , Liljeblom Eva , Pasternack Daniel 
Published: June 2017

AbstractWe study the connections between firm risk and the CEO's personal wealth characteristics, using a unique dataset on CEO wealth and its components. Consistent with decreasing absolute risk aversion, we find that wealthier CEOs are associated with higher risk firms. Riskier firms tend to have CEOs whose wealth is more independent of the firm. We also find that CEOs with high personal portfolio betas run firms with higher betas. CEO's tenure is negatively associated with firm risk measured either as beta, idiosynchratic risk, or volatility of accounting profitability. A possible interpretation is that risk‐averse managers are better able to imprint their risk preferences on the firm over time. Stronger corporate governance weakens the connection between CEO wealth characteristics and firm risk.
The Eastern European experience on occupational skin diseases. Make underreporting an issue?
Authors: Moldovan H.R. , Voidazan S.T. , John S.M. , Weinert P. , Moldovan G. , Vlasiu M.A. , Szasz Z.A. , Tiplica G.S. , Szasz S. , Marin A.C. , Salavastru C.M. 
Published: June 2017

AbstractBackgroundWhile legislation in most of the Eastern European countries is nowadays widely harmonized with the legal safety and health provisions of Western countries, there is still a sustained resistance to the notification of occupational skin diseases (OSD).ObjectiveThe aim of the study was to identify the main barriers in notification and recognition of OSD in 22 Eastern European countries.MethodsAn online survey was administered to key persons in the field of occupational safety and health in 22 Eastern European countries. Multiple variables of the notification system were studied, including clinical, organizational and educational issues.ResultsThe main causes of underreporting OSD are ineffective enforcement of occupational safety and health legislation, contractual relationship employer–employee, long duration of the notifying process, restrictions of the notification systems in terms of who is entitled to notify an OSD, ineffective regulations in regards to the pre‐employment and periodical medical examination, ineffective compensation schemes, restraints and hesitations, mainly from the doctors, inappropriate mentalities – fear of losing the jobs, fining of the employers by the authorities, stigmatization of the workers with OSD, additional costs for employers, stakeholders' lack of interest in notifying, lack of guidelines and protocols and lack of preventive programmes.ConclusionsThe most valuable method for a proper recognition of OSD is to increase the awareness of physicians involved in the management of OSD (occupational physicians, GPs, dermatologists), as well as employers and workers. There is an urgent need to improve national legislation, to develop and promote adequate preventive programmes, emphasizing ethical, legal, economical and psychological aspects in order to achieve an increased recognition and a real reporting of OSD, and to enforce an international action plan for Eastern Europe in order to improve the notification of OSD.
Transhumance Revisited: On Mobility and Process Between Ethnography and History
Authors: Palladino Paolo 
Published: June 2017

AbstractThis paper advances the argument that transhumance, the seasonal movement of pastoral people and their livestock, is a useful site for critical reflection on Gilles Deleuze and Félix Guattari's A Thousand Plateaus (1988) and its importance to the understanding of mobility and process. It does so by bringing into dialogue ethnographic and historical perspectives on the resonance between transhumance and Deleuzian configurations of both nomadism and relations between human and non‐human animals. It concludes that adjacent juxtaposition and syncretic ordering of diversity, rather than any ontological reconstruction, may be key to a more effective engagement with the complexities of contemporary existence.
Mid‐term outcomes of consecutive 998 cases of coronary atherectomy in contemporary clinical practice
Authors: Sareen Nishtha , Baber Usman , Aquino Melissa , Sayseng Sonny , Sweeny Joseph , Barman Nitin , Kapur Vishal , Kini Annapoorna , Sharma Samin K. 
Published: June 2017

ObjectivesTo compare clinical and safety endpoints with use of rotational (RA) and orbital (OA) atherectomy in a large patient population with moderate to severely calcified lesions undergoing percutaneous coronary intervention (PCI).BackgroundCoronary artery calcification (CAC) has been recognized as a risk factor for adverse outcomes with coronary artery disease (CAD). Though atheroablative techniques, RA and OA have been used extensively, comparison of their clinical and safety endpoints is lacking. Comparison of these two modalities formed the basis of our study.Methods and ResultsOf 12 001 patients who underwent PCI at our institution between January 2013‐December 2015, we studied 998 consecutive patients with severe calcification treated with atheroablation. We assessed clinical outcomes including death, myocardial infarction (MI) and target lesion revascularization (TLR) at 30 days and 6 months in addition to post‐procedural complications. Device perforation occurred more frequently with use of OA at high burr speed versus RA (1.9%, n = 3 vs. 0.2%, n = 2, P = 0.03). Rates of composite adverse events were similar between groups at 6 months (18.55 vs. 11.46%; P = 0.11)ConclusionIn this retrospective, single center study, we observed no significant differences in 6‐month rates of adverse events associated with use of OA vs. RA in patients with moderate to severe calcification undergoing PCI. Larger, prospective studies are needed to confirm our findings.
A pilot study of a novel smartphone application for the estimation of sleep onset
Authors: Scott Hannah , Lack Leon , Lovato Nicole 
Published: June 2017

SummaryThe aim of the study was to investigate the accuracy of Sleep On Cue: a novel iPhone application that uses behavioural responses to auditory stimuli to estimate sleep onset. Twelve young adults underwent polysomnography recording while simultaneously using Sleep On Cue. Participants completed as many sleep‐onset trials as possible within a 2‐h period following their normal bedtime. On each trial, participants were awoken by the app following behavioural sleep onset. Then, after a short break of wakefulness, commenced the next trial. There was a high degree of correspondence between polysomnography‐determined sleep onset and Sleep On Cue behavioural sleep onset, r = 0.79, P < 0.001. On average, Sleep On Cue overestimated sleep‐onset latency by 3.17 min (SD = 3.04). When polysomnography sleep onset was defined as the beginning of N2 sleep, the discrepancy was reduced considerably (M = 0.81, SD = 1.96). The discrepancy between polysomnography and Sleep On Cue varied between individuals, which was potentially due to variations in auditory stimulus intensity. Further research is required to determine whether modifications to the stimulus intensity and behavioural response could improve the accuracy of the app. Nonetheless, Sleep On Cue is a viable option for estimating sleep onset and may be used to administer Intensive Sleep Retraining or facilitate power naps in the home environment.
Effects of signal artefacts on electroencephalography spectral power during sleep: quantifying the effectiveness of automated artefact‐rejection algorithms
Authors: Liu Jianbo , Ramakrishnan Sridhar , Laxminarayan Srinivas , Neal Maxwell , Cashmere David J. , Germain Anne , Reifman Jaques 
Published: June 2017

SummaryElectroencephalography (EEG) recordings during sleep are often contaminated by muscle and ocular artefacts, which can affect the results of spectral power analyses significantly. However, the extent to which these artefacts affect EEG spectral power across different sleep states has not been quantified explicitly. Consequently, the effectiveness of automated artefact‐rejection algorithms in minimizing these effects has not been characterized fully. To address these issues, we analysed standard 10‐channel EEG recordings from 20 subjects during one night of sleep. We compared their spectral power when the recordings were contaminated by artefacts and after we removed them by visual inspection or by using automated artefact‐rejection algorithms. During both rapid eye movement (REM) and non‐REM (NREM) sleep, muscle artefacts contaminated no more than 5% of the EEG data across all channels. However, they corrupted delta, beta and gamma power levels substantially by up to 126, 171 and 938%, respectively, relative to the power level computed from artefact‐free data. Although ocular artefacts were infrequent during NREM sleep, they affected up to 16% of the frontal and temporal EEG channels during REM sleep, primarily corrupting delta power by up to 33%. For both REM and NREM sleep, the automated artefact‐rejection algorithms matched power levels to within ~10% of the artefact‐free power level for each EEG channel and frequency band. In summary, although muscle and ocular artefacts affect only a small fraction of EEG data, they affect EEG spectral power significantly. This suggests the importance of using artefact‐rejection algorithms before analysing EEG data.
Serum brain‐derived neurotrophic factor (BDNF) in sleep‐disordered patients: relation to sleep stage N3 and rapid eye movement (REM) sleep across diagnostic entities
Authors: Deuschle Michael , Schredl Michael , Wisch Christian , Schilling Claudia , Gilles Maria , Geisel Olga , Hellweg Rainer 
Published: June 2017

SummaryExperimental and clinical evidence suggests an association between neuroplasticity, brain‐derived neurotrophic factor and sleep. We aimed at testing the hypotheses that brain‐derived neurotrophic factor is associated with specific aspects of sleep architecture or sleep stages in patients with sleep disorders. We included 35 patients with primary insomnia, 31 patients with restless legs syndrome, 17 patients with idiopathic hypersomnia, 10 patients with narcolepsy and 37 healthy controls. Morning serum brain‐derived neurotrophic factor concentrations were measured in patients and controls. In patients, blood sampling was followed by polysomnographic sleep investigation. Low brain‐derived neurotrophic factor levels were associated with a low percentage of sleep stage N3 and rapid eye movement sleep across diagnostic entities. However, there was no difference in brain‐derived neurotrophic factor levels between diagnostic groups. Our data indicate that serum levels of brain‐derived neurotrophic factor, independent of a specific sleep disorder, are related to the proportion of sleep stage N3 and REM sleep. This preliminary observation is in accordance with the assumption that sleep stage N3 is involved in the regulation of neuroplasticity.