bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subcutaneous immunotherapy with purified Der p1 and 2 suppresses type 2 immunity in a murine asthma model
Authors: Hesse L. , van Ieperen N. , Habraken C. , Petersen A. H. , Korn S. , Smilda T. , Goedewaagen B. , Ruiters M. H. , van der Graaf A. C. , Nawijn M. C. 
Published: January 2018

AbstractBackgroundAllergen‐specific immunotherapy can induce long‐term suppression of allergic symptoms, reduce medication use, and prevent exacerbations of allergic rhinitis and asthma. Current treatment is based on crude allergen extracts, which contain immunostimulatory components such as β‐glucans, chitins, and endotoxin. Use of purified or recombinant allergens might therefore increase efficacy of treatment.AimsHere, we test application of purified natural group 1 and 2 allergens from Dermatophagoides pteronyssinus (Der p) for subcutaneous immunotherapy (SCIT) treatment in a house dust mite (HDM)‐driven mouse model of allergic asthma.Materials and methodsHDM‐sensitized mice received SCIT with crude HDM extract, a mixture of purified Der p1 and 2 (DerP1/2), or placebo. Upon challenges, we measured specific immunoglobulin responses, allergen‐induced ear swelling response (ESR), airway hyperresponsiveness (AHR), and inflammation in bronchoalveolar lavage fluid (BAL) and lung tissue.ResultsESR measurement shows suppression of early allergic response in HDM‐SCIT– and DerP1/2‐SCIT–treated mice. Both HDM‐SCIT and DerP1/2‐SCIT are able to suppress AHR and eosinophilic inflammation. In contrast, only DerP1/2‐SCIT is able to significantly suppress type 2 cytokines in lung tissue and BAL fluid. Moreover, DerP1/2‐SCIT treatment is uniquely able suppress CCL20 and showed a trend toward suppression of IL‐33, CCL17 and eotaxin levels in lung tissue.DiscussionTaken together, these data show that purified DerP1/2‐SCIT is able to not only suppress AHR and inflammation, but also has superior activity toward suppression of Th2 cells and HDM‐induced activation of lung structural cells including airway epithelium.ConclusionsWe postulate that treatment with purified natural major allergens derived from HDM will likely increase clinical efficacy of SCIT.
Fish oil in infancy protects against food allergy in Iceland—Results from a birth cohort study
Authors: Clausen M. , Jonasson K. , Keil T. , Beyer K. , Sigurdardottir S. T. 
Published: January 2018

AbstractBackgroundConsumption of oily fish or fish oil during pregnancy, lactation and infancy has been linked to a reduction in the development of allergic diseases in childhood.MethodsIn an observational study, Icelandic children (n = 1304) were prospectively followed from birth to 2.5 years with detailed questionnaires administered at birth and at 1 and 2 years of age, including questions about fish oil supplementation. Children with suspected food allergy were invited for physical examinations, allergic sensitization tests, and a double‐blind, placebo‐controlled food challenge if the allergy testing or clinical history indicated food allergy. The study investigated the development of sensitization to food and confirmed food allergy according to age and frequency of postnatal fish oil supplementation using proportional hazards modelling.ResultsThe incidence of diagnosed food sensitization was significantly lower in children who received regular fish oil supplementation (relative risk: 0.51, 95% confidence interval: 0.32‐0.82). The incidence of challenge‐confirmed food allergy was also reduced, although not statistically significant (0.57, 0.30‐1.12). Children who began to receive fish oil in their first half year of life were significantly more protected than those who began later (P = .045 for sensitization, P = .018 for allergy). Indicators of allergy severity decreased with increased fish oil consumption (P = .013). Adjusting for parent education and allergic family history did not change the results.ConclusionPostnatal fish oil consumption is associated with decreased food sensitization and food allergies in infants and may provide an intervention strategy for allergy prevention.
Similar localization of conformational IgE epitopes on the house dust mite allergens Der p 5 and Der p 21 despite limited IgE cross‐reactivity
Authors: Curin M. , Garmatiuk T. , Resch‐Marat Y. , Chen K. W. , Hofer G. , Fauland K. , Keller W. , Hemmer W. , Vrtala S. , Focke‐Tejkl M. , Valenta R. 
Published: January 2018

AbstractBackgroundDue to high IgE recognition frequency and high allergenic activity, Der p 5 and Der p 21 are clinically important house dust mite (HDM) allergens. The objective of this study was to characterize the immunodominant IgE epitopes of Der p 5 and Der p 21 responsible for their high allergenic activity.MethodsA panel of 12 overlapping peptides spanning the Der p 5 and Der p 21 sequence were synthesized to search for sequential IgE epitopes by direct testing for allergic patients' IgE reactivity. Peptide‐specific antibodies raised in rabbits were used in inhibition studies for localizing conformational IgE epitopes which were visualized on the surfaces of the allergen structures by molecular modelling. IgE cross‐reactivity between the allergens was investigated by IgE inhibition studies.ResultsImmunodominant IgE epitopes defined by allergic patients' IgE on Der p 5 and Der p 21 were primarily of the conformational, discontinuous type including N‐ and C‐terminal portions of the protein. They could be located on each allergen on one area with similar localization, but despite similar structure of the allergens, no relevant IgE cross‐reactivity could be detected.ConclusionOur study shows that Der p 5 and Der p 21 contain a major conformational IgE epitope‐containing area located on similar portions of their structure, but they lack relevant IgE cross‐reactivity. These data are important for the development of modern allergy vaccines based on defined molecules for allergen‐specific immunotherapy of HDM allergy.
A systematic review of outcomes in postoperative pain studies in paediatric and adolescent patients: towards development of a core outcome set
Authors: Ross A. , Young J. , Hedin R. , Aran G. , Demand A. , Stafford A. , Worley J. , Moore M. , Vassar M. 
Published: January 2018

SummarySystematic reviews of postoperative pain in children have called into question the consistency of outcomes measured by clinical triallists as well as the measurement instruments used for assessment. Core outcome set methodology may be a solution to improve standardisation. This study provides an evidence‐based foundation for the development of a core outcome set for paediatric postoperative pain studies. We searched ClinicalTrials.gov to identify relevant postoperative pain studies in children. The search yielded 300 registered trials. The following data were then extracted from each of the trials: phase of trial; study type; study design; sample size; all outcomes; whether the outcome was listed as primary, secondary, or tertiary; the measurement instrument for each reported outcome; the specific metric for each outcome; and the type of clinical procedure. Following screening, 134 studies were included in our study. Pain measurement was the most commonly reported outcome (n = 123), followed by total postoperative analgesic dosage (n = 83) and side‐effects (n = 25). Temporal trends indicated that pain assessment and unexpected events increased in use between 2000 and 2016, whereas postoperative analgesia measurement decreased. We found a lack of standardisation among outcomes and measurement instruments in paediatric postoperative pain studies. Development of a core outcome set may improve the quality of future trials and allow for more accurate study‐to‐study comparisons.
Immune checkpoint molecules in acute myeloid leukaemia: managing the double‐edged sword
Authors: Hobo Willemijn , Hutten Tim J. A. , Schaap Nicolaas P. M. , Dolstra Harry 
Published: January 2018

SummaryNew immunotherapeutic interventions have revolutionized cancer treatment. The immune responsiveness of acute myeloid leukaemia (AML) was first demonstrated by allogeneic stem cell transplantation. In addition, milder immunotherapeutic approaches are exploited. However, the long‐term efficacy of these therapies is hampered by various immune resistance and editing mechanisms. In this regard, co‐inhibitory signalling pathways have been shown to play a crucial role. Via up‐regulation of inhibitory checkpoints, tumour‐reactive T cell and Natural Killer cell responses can be strongly impeded. Accordingly, the introduction of checkpoint inhibitors targeting CTLA‐4 (CTLA4) and PD‐1 (PDCD1, CD279)/PD‐L1 (CD274, PDCD1LG1) accomplished a breakthrough in cancer treatment, with impressive clinical responses. Numerous new co‐inhibitory players and novel combination therapies are currently investigated for their potential to boost anti‐tumour immunity and improve survival of cancer patients. Although the challenge here remains to avoid severe systemic toxicity. This review addresses the involvement of co‐inhibitory signalling in AML immune evasion and discusses the opportunities for checkpoint blockers in AML treatment.
Moving on: Transitions out of care for young people with learning disabilities in England and Sweden
Authors: Roberts Helen , Ingold Anne , Liabo Kristin , Manzotti Grazia , Reeves David , Bradby Hannah 
Published: January 2018

Accessible summary

When young people with learning disabilities leave the care system, they can experience many problems.

Here we describe some of these problems and what they do (or would like us to do) to improve things.

Young people do not always want the same things that professionals or family carers want.

We do not spend enough time listening to what young people can tell us.

AbstractBackgroundYoung people with learning disabilities are frequently underrepresented in research accounts. This study describes the experiences of young people moving from the care system.MethodsWe scoped the English and Swedish literature for first‐hand accounts and interviewed four young people with learning disabilities leaving the English care system. We combined findings from both sources.Findings“Grey” and campaigning literature are more likely than academic studies to include the voices of service users, but even then, the voices tend to be those of professional or family carers. Both the literature and interviews demonstrate young peoples’ awareness and understanding of the social as well as financial benefits of work. Good foster care could be precarious, and young people in unhappy placements lacked direction. Exploitation around a young person's housing and finances could be problems. There was evidence of “threshold” difficulties in accessing services.ConclusionsDespite an NHS commitment to listening to users in the UK, and similar aspirations in Sweden, our search of the literature identified few studies reporting care leavers' with learning disabilities own words. Our data add to the voices of a group frequently silent or silenced. We found evidence of resilience and hope as well as difficulties and frustrations. The accounts in the literature and our interviews provide data on what it can be like to try to operate “the system.” The people we spoke with and those whose accounts we found in the literature were thoughtful and engaging. They provide an important source of knowledge for policy and practice.
The natural compound, formononetin, extracted from Astragalus membranaceus increases adipocyte thermogenesis by modulating PPARγ activity
Authors: Nie Tao , Zhao Shiting , Mao Liufeng , Yang Yiting , Sun Wei , Lin Xiaoliang , Liu Shuo , Li Kuai , Sun Yirong , Li Peng , Zhou Zhiguang , Lin Shaoqiang , Hui Xiaoyan , Xu Aimin , Ma Chung Wah , Xu Yong , Wang Cunchuan , Dunbar P Rod , Wu Donghai 
Published: January 2018

Background and PurposeIncreasing energy expenditure through adipocyte thermogenesis is generally accepted as a promising strategy to mitigate obesity and its related diseases. However, few clinically effective and safe agents are known to promote adipocyte thermogenesis. In this study, 20 traditional Chinese herbal medicines were screened to examine whether they induced adipocyte thermogenesis.Experimental ApproachThe effects of Chinese herbal medicines or components isolated from extracts of A. membranaceus, on adipocyte thermogenesis were analysed by assessing expression of uncoupling protein 1 (UCP1) by qPCR. Eight‐week‐old C57BL6/J male mice were fed a high‐fat diet for 8 weeks and then randomized to two groups treated with vehicle or formononetin for another 8 weeks. Glucose tolerance tests and staining of adipose tissue with haematoxylin and eosin were carried out. Whole‐body oxygen consumption was measured with an open‐circuit indirect calorimetry system.Key ResultsExtracts of A. membranaceus increased expression of Ucp1 in primary cultures of mouse adipocytes. Formononetin was the only known component of A. membranaceus extracts to increase adipocyte Ucp1 expression. Diet‐induced obese mice treated with formononetin gained less weight and showed higher energy expenditure than untreated mice. In addition, formononetin binds directly with PPARγ.Conclusions and ImplicationTaken together, our study demonstrates that the Chinese herbal medicine from A. membranaceus and its constituent formononetin have the potential to reduce obesity and associated metabolic disorders. Our results suggest that formononetin regulates adipocyte thermogenesis as a non‐classical PPARγ agonist.
Partial rescue of F508del‐cystic fibrosis transmembrane conductance regulator channel gating with modest improvement of protein processing, but not stability, by a dual‐acting small molecule
Authors: Liu Jia , Bihler Hermann , Farinha Carlos M , Awatade Nikhil T , Romão Ana M , Mercadante Dayna , Cheng Yi , Musisi Isaac , Jantarajit Walailak , Wang Yiting , Cai Zhiwei , Amaral Margarida D , Mense Martin , Sheppard David N 
Published: January 2018

Background and PurposeRescue of F508del‐cystic fibrosis (CF) transmembrane conductance regulator (CFTR), the most common CF mutation, requires small molecules that overcome protein processing, stability and channel gating defects. Here, we investigate F508del‐CFTR rescue by CFFT‐004, a small molecule designed to independently correct protein processing and channel gating defects.Experimental ApproachUsing CFTR‐expressing recombinant cells and CF patient‐derived bronchial epithelial cells, we studied CFTR expression by Western blotting and channel gating and stability with the patch‐clamp and Ussing chamber techniques.Key ResultsChronic treatment with CFFT‐004 improved modestly F508del‐CFTR processing, but not its plasma membrane stability. By contrast, CFFT‐004 rescued F508del‐CFTR channel gating better than C18, an analogue of the clinically used CFTR corrector lumacaftor. Subsequent acute addition of CFFT‐004, but not C18, potentiated F508del‐CFTR channel gating. However, CFFT‐004 was without effect on A561E‐CFTR, a CF mutation with a comparable mechanism of CFTR dysfunction as F508del‐CFTR. To investigate the mechanism of action of CFFT‐004, we used F508del‐CFTR revertant mutations. Potentiation by CFFT‐004 was unaffected by revertant mutations, but correction was abolished by the revertant mutation G550E. These data suggest that correction, but not potentiation, by CFFT‐004 might involve nucleotide‐binding domain 1 of CFTR.Conclusions and ImplicationsCFFT‐004 is a dual‐acting small molecule with independent corrector and potentiator activities that partially rescues F508del‐CFTR in recombinant cells and native airway epithelia. The limited efficacy and potency of CFFT‐004 suggests that combinations of small molecules targeting different defects in F508del‐CFTR might be a more effective therapeutic strategy than a single agent.
Driving chronicity in rheumatoid arthritis: perpetuating role of myeloid cells
Authors: Alivernini S , Tolusso B , Ferraccioli G , Gremese E , Kurowska-Stolarska M , McInnes I B 
Published: January 2018

SummaryAcute inflammation is a complex and tightly regulated homeostatic process that includes leucocyte migration from the vasculature into tissues to eliminate the pathogen/injury, followed by a pro-resolving response promoting tissue repair. However, if inflammation is uncontrolled as in chronic diseases such as rheumatoid arthritis (RA), it leads to tissue damage and disability. Synovial tissue inflammation in RA patients is maintained by sustained activation of multiple inflammatory positive-feedback regulatory pathways in a variety of cells, including myeloid cells. In this review, we will highlight recent evidence uncovering biological mechanisms contributing to the aberrant activation of myeloid cells that contributes to perpetuation of inflammation in RA, and discuss emerging data on anti-inflammatory mediators contributing to sustained remission that may inform a novel category of therapeutic targets.
Substance use among older youth transitioning from foster care: Examining the protective effects of religious and spiritual capital
Authors: Scott Lionel D. , Hodge David R. , White Tony , Munson Michelle R. 
Published: January 2018

AbstractAmong older youth transitioning from the foster care system, this longitudinal study examined the association of religious and spiritual capital to substance use in the past year at age 19. Participants consisted of African American (N = 179) and White non‐Hispanic (N = 133) older youth in foster care. Drawing from social capital theory, it was posited that religious service attendance (a proxy for religious capital) and belief in a spiritual force (a proxy for spiritual capital) would be inversely associated with substance use. Multiple logistic regression results indicated support for the first and second hypothesis for White foster youth only. Among White foster youth, more frequent religious service attendance and greater belief in a spiritual force were associated with a lower likelihood of illegal substance and polysubstance use. No association between religious or spiritual capital and substance use was found among African American foster youth. The findings underscore the importance of conducting spiritual assessments to help ensure older foster youth who have strong religious or spiritual orientations are in environments where they are accommodated and supported.
Temporally Consistent Motion Segmentation From RGB‐D Video
Authors: Bertholet P. , Ichim A.E. , Zwicker M. 
Published: January 2018

AbstractTemporally consistent motion segmentation from RGB‐D videos is challenging because of the limitations of current RGB‐D sensors. We formulate segmentation as a motion assignment problem, where a motion is a sequence of rigid transformations through all frames of the input. We capture the quality of each potential assignment by defining an appropriate energy function that accounts for occlusions and a sensor‐specific noise model. To make energy minimization tractable, we work with a discrete set instead of the continuous, high dimensional space of motions, where the discrete motion set provides an upper bound for the original energy. We repeatedly minimize our energy, and in each step extend and refine the motion set to further lower the bound. A quantitative comparison to the current state of the art demonstrates the benefits of our approach in difficult scenarios.
4,6,4′‐trimethylangelicin shows high anti‐proliferative activity on DU145 cells under both UVA and blue light
Authors: Miolo G. , Sturaro G. , Cigolini G. , Menilli L. , Tasso A. , Zago I. , Conconi M. T. 
Published: January 2018

AbstractObjectivesFurocoumarins (psoralens and angelicins) have been already used under ultraviolet A light (UVA) for the treatment of skin diseases and cutaneous T‐cell lymphoma. Besides their high anti‐proliferative activity, some severe long‐term side effects have been observed, for example genotoxicity and mutagenicity, likely strictly related to the formation of crosslinks. It has been demonstrated that blue light (BL) activation of 8‐methoxypsoralen, an FDA‐approved drug, leads to less mutagenic monoadducts in the DNA. So far, in this work the less toxic and more penetrating BL is proposed to activate 4,6,4′‐trimethylangelicin (TMA), an already known UVA photoactivatable compound.Materials and methodsPhotocleavage, crosslink formation and oxidative damage were detected in pBR322 plasmid DNA treated with 300.0 μmol/L TMA activated with various exposures of BL. Anti‐proliferative activity, reactive oxygen species (ROS) formation and activation status of some signalling pathways involved in cell growth and apoptosis were verified on DU145 cells treated with 5.0 μmol/L TMA plus 2.0 J/cm2 of BL.ResultsUnder BL‐TMA, no mutagenic crosslinks, no photocleavage and neither photooxidative lesions were detected on isolated plasmid DNA. TMA showed high anti‐proliferative activity on DU145 cells through induction of apoptosis. Besides ROS generation, the proapoptotic effect seemed to be related to activation of p38 and inhibition of p44/42 phosphorylation. Interestingly, the decrease in nuclear β‐catenin was coupled with a significant dropping of CD44‐positive cells.ConclusionOverall, our results indicate that TMA can be activated by BL and may be considered for targeted phototherapy of prostate cancer lesions.
Association of hypoglycaemia severity with clinical, patient‐reported and economic outcomes in US patients with type 2 diabetes using basal insulin
Authors: Meneghini Luigi F. , Lee Lulu K. , Gupta Shaloo , Preblick Ron 
Published: January 2018

AimsTo evaluate the clinical and patient‐reported outcomes and healthcare utilization and costs associated with patient‐reported hypoglycaemia in US adults with type 2 diabetes (T2D) treated with basal insulin.Materials and methodsThis was an observational, cross‐sectional, survey‐based study of adults with T2D on basal insulin ± oral antidiabetes drugs (OADs) or rapid‐acting/premixed insulin, who had in the past ever experienced hypoglycaemia, using US data from the National Health and Wellness Survey. Eligible patients were categorized as having no hypoglycaemia (38.7%), non‐severe hypoglycaemia (55.1%), or severe hypoglycaemia (6.2%) in the preceding 3 months. Outcomes included health‐related quality of life (HRQoL), work productivity and activity impairment, healthcare resource utilization, and estimated direct and indirect costs. Multivariable regression models were performed to control for patient characteristics.ResultsPatients who experienced severe hypoglycaemia had significantly (P < .05) lower HRQoL scores, greater overall impairment of work productivity and activity, greater healthcare resource utilization, and higher costs compared with those who experienced non‐severe or no hypoglycaemia. Patients with non‐severe hypoglycaemia also reported an impact on the number of provider visits, indirect costs, and HRQoL.ConclusionsPatients with T2D using basal insulin ± OADs or rapid‐acting/premixed insulin in the United States who experienced severe hypoglycaemia had greater impairment of activity and work productivity, utilized more healthcare resources, and incurred higher associated costs than those with non‐severe or no hypoglycaemia. The study also demonstrated the impact that non‐severe hypoglycaemic events have on economic and HRQoL outcomes. Reducing the incidence and severity of hypoglycaemia could lead to clinically meaningful improvements in HRQoL and may result in lower healthcare utilization and associated costs.