bluuebunny/crossref_metadata_2025_split huggingface dataset:
Allergen manufacturing and quality aspects for allergen immunotherapy in Europe and the United States: An analysis from the EAACI AIT Guidelines Project
Authors: Bonertz A. , Roberts G. , Slater J. E. , Bridgewater J. , Rabin R. L. , Hoefnagel M. , Timon M. , Pini C. , Pfaar O. , Sheikh A. , Ryan D. , Akdis C. , Goldstein J. , Poulsen L. K. , van Ree R. , Rhyner C. , Barber D. , Palomares O. , Pawankar R. , Hamerlijnk D. , Klimek L. , Agache I. , Angier E. , Casale T. , Fernandez‐Rivas M. , Halken S. , Jutel M. , Lau S. , Pajno G. , Sturm G. , Varga E. M. , Gerth van Wijk R. , Bonini S. , Muraro A. , Vieths S. 
Published: November 2017

AbstractAdequate quality is essential for any medicinal product to be eligible for marketing. Quality includes verification of the identity, content and purity of a medicinal product in combination with a specified production process and its control. Allergen products derived from natural sources require particular considerations to ensure adequate quality. Here, we describe key aspects of the documentation on manufacturing and quality aspects for allergen immunotherapy products in the European Union and the United States. In some key parts, requirements in these areas are harmonized while other fields are regulated separately between both regions. Essential differences are found in the use of Reference Preparations, or the requirement to apply standardized assays for potency determination. As the types of products available are different in specific regions, regulatory guidance for such products may also be available in one specific region only, such as for allergoids in the European Union. Region‐specific issues and priorities are a result of this. As allergen products derived from natural sources are inherently variable in their qualitative and quantitative composition, these products present special challenges to balance the variability and ensuring batch‐to‐batch consistency. Advancements in scientific knowledge on specific allergens and their role in allergic disease will consequentially find representation in future regulatory guidelines.
A randomized, double‐blind, placebo‐controlled, dose‐finding trial with Lolium perenne peptide immunotherapy
Authors: Mösges R. , Kasche E. M. , Raskopf E. , Singh J. , Sohlich L. , Astvatsatourov A. , Shah‐Hosseini K. , Pirotton S. , Haazen L. , Durham S. R. , Legon T. , Zadoyan G. , Shamji M. H. 
Published: November 2017

AbstractBackgroundA novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up‐dosing phase has been developed to treat grass pollen–induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety.MethodsThis prospective, double‐blind, placebo‐controlled, phase IIb, parallel, four‐arm, dose‐finding study randomized 198 grass pollen–allergic adults to receive placebo or cumulative doses of 70, 170 or 370 μg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen–specific immunoglobulins were analysed before and after treatment.ResultsConjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 μg; P = .023), 46.3% (370 μg), and 38.6% (70 μg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per‐protocol set). Also, 39% of patients in the 170‐μg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen‐binding assays revealed a highly significant (P < .001) dose‐dependent reduction in IgE allergen binding across all treatment groups (70 μg: 17.1%; 170 μg: 18.8%; 370 μg: 26.4%). Specific IgG4 levels increased to 1.6‐fold (70 μg), 3.1‐fold (170 μg) and 3.9‐fold (370 μg) (mPP).ConclusionThree‐week immunotherapy with 170 μg LPP reduced CPT reactivity significantly and increased protective specific antibodies.
Rhinitis and its impact on quality of life in swimmers
Authors: Surda P. , Putala M. , Siarnik P. , Walker A. , Bernic A. , Fokkens W. 
Published: November 2017

AbstractIntroductionLimited data suggest that swimmers might be affected by rhinitis significantly more often than the general population. This can have impact on quality of life but also on performance. The aim of this study was to determine the prevalence and impact of QOL of rhinitis in swimming compared to nonswimming athletes and controls.Materials and methodsThis was an observational case‐control, questionnaire‐based study involving elite (n = 101) and nonelite swimming athletes (n = 107), nonswimming athletes (n = 38) and sex‐ and age‐matched controls (n = 50). The survey instrument consisted of a general and the miniRQLQ. Main question used to assess the prevalence of rhinitis was from the ISAAC study.ResultsRhinitis was reported significantly more often by the elite swimmers (45%) than nonelite swimmers (31%), nonswimming athletes (32%) and controls (24%). Allergic rhinitis prevalence was similar in all groups (12%‐18%). The prevalence of nonallergic rhinitis (NAR) was significantly higher in elite swimmers (33%) and nonelite swimmers (22%) compared to nonswimming athletes and controls. Overall mean miniRQLQ score and all subdomains except the “eye” domain showed significantly reduced QOL in elite and nonelite swimmers compared to nonswimming athletes and controls. Regular nasal medication was used significantly less by elite swimmers (18%) compared to controls (67%) and nonswimming athletes (42%).ConclusionThis study revealed a high prevalence of NAR in swimmers and related impact on QoL. These findings highlight the importance to increase the awareness towards upper airway disorders in the swimming athletes and to ensure adequate management.
Poor agreement in questionnaire‐based diagnostic criteria for adult atopic dermatitis is a challenge when examining cardiovascular comorbidity
Authors: Andersen Y. M. F. , Egeberg A. , Hamann C. R. , Skov L. , Gislason G. H. , Skaaby T. , Linneberg A. , Thyssen J. P. 
Published: November 2017

AbstractBackgroundThe association between atopic dermatitis (AD) and cardio‐metabolic risk factors is not yet established. Furthermore, no validated questionnaire‐based method of identifying adults with AD is currently available.ObjectivesTo assess the cardio‐metabolic risk in adults with a history of AD using 3 different questionnaire‐based diagnostic criteria.MethodsWe utilized data from a general population study including questionnaire data and objective measurements of 9656 Danish adults. To identify adults with a history of AD, we used a question regarding physician‐diagnosed AD and 2 versions of the UK Working Party Diagnostic Criteria. Associations between AD status and cardio‐metabolic endpoints were estimated using survey weighted logistic and linear regression analysis.ResultsWe identified 462 (4.8%) adults with self‐reported physician‐diagnosed AD, whereas 903 (9.4%) and 226 (2.3%) had AD according to the UK Working Party Criteria when at least 2 and 3of 4 minor criteria were fulfilled. The populations were not comparable in terms of occurrence of cardio‐metabolic risk factors. For example, the prevalence of obesity was lower in participants with physician‐diagnosed AD but overall higher in UK 2/4 and UK 3/4.ConclusionDue to the heterogeneity in the captured study populations in terms of the studied outcomes and absence of a gold standard, no conclusions regarding the cardio‐metabolic risk in adults with AD in a general population could be made. This study serves as an example of the challenges that are often encountered in questionnaire‐based epidemiologic studies and highlights the need of better definitions for this patient group.
The effect of 6% hydroxyethyl starch (130/0.4) on acute kidney injury in paediatric cardiac surgery: a prospective, randomised trial
Authors: Oh H.‐W. , Lee J.‐H. , Kim H.‐C. , Kim E.‐H. , Song I.‐K. , Kim H.‐S. , Kim J.‐T. 
Published: November 2017

SummaryWe have evaluated the effect of a colloid solution on acute kidney injury in paediatric cardiac surgery. A total of 195 patients were ramdomly divided into an hydroxyethyl starch group and a control group. In the starch group, 6% hydroxyethyl starch 130/0.4 (Volulyte®) was used as the primary fluid for volume resuscitation but was limited to 30 ml.kg−1. In the control group, only crystalloid fluid was used during the peri‐operative period. The incidence of acute kidney injury, peri‐operative transfusion, clinical outcomes and laboratory data were compared. The incidence of acute kidney injury determined by Paediatric Risk, Injury, Failure, Loss, End‐stage renal disease (pRIFLE) and Acute Kidney Injury Network (AKIN) criteria were no different between the two groups (starch group 40.8% vs. control group 30.0%; p = 0.150 using pRIFLE; 19.6% vs. 21.1% respectively, p = 0.602 using AKIN). There were no differences in clinical outcomes such as mortality, major adverse events, intensive care unit stay or duration of mechanical ventilation. Clotting time as measured using rotational thromboelastometry (ROTEM) was prolonged, and clot firmness after 10 min and maximal clot firmness were shorter in the starch group compared with the control group after sternal closure. There was no difference in transfusion between the two groups. Patients with acute kidney injury had worse clinical courses than those without acute kidney injury. We conclude that intra‐operative use of 6% hydroxyethyl starch 130/0.4 up to 30 ml.kg−1 was not associated with postoperative acute kidney injury in paediatric cardiac patients.
Systematic review of disparities in surgical care for Māori in New Zealand
Authors: Rahiri Jamie‐Lee , Alexander Zanazir , Harwood Matire , Koea Jonathan , Hill Andrew G. 
Published: November 2017

BackgroundHealth equity for Indigenous peoples in the context of surgery has recently become topical amongst surgeons in Australasia. Health inequities are amongst the most consistent and compelling disparities between Māori and New Zealand Europeans (NZE) in New Zealand (NZ). We aimed to investigate where ethnic disparities in surgical care may occur and highlight some of the potential contributing factors, over all surgical specialties, between Māori and NZE adults in NZ.MethodsA systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) statement. A series of electronic searches were performed in Medline, Embase, PubMed and CINAHL.ResultsTen studies met the inclusion criteria. All studies employed a range of indicators for surgical care including receipt of surgery following diagnosis, delays to treatment and post‐operative morbidity and mortality. Disparities in the receipt of surgical treatment for several cancers were observed for Māori and remained after adjustment for socioeconomic variables and extent of disease. Māori were more likely to experience delays in treatment and referral to other medical specialties involved in their care.ConclusionDespite the significant variation in the types of diseases, procedures and indicators of surgical care of the included studies, consistent findings are that disparities in different aspects of surgical care exist between Māori and NZE in NZ. This review highlights the need to better quantify the important issue of health equity for Māori in surgery given the lack of studies over the majority of surgical specialties.
Randomised crossover trial showed that using breast milk or sucrose provided the same analgesic effect in preterm infants of at least 28 weeks
Authors: Collados‐Gómez L , Ferrera‐Camacho P , Fernandez‐Serrano E , Camacho‐Vicente V , Flores‐Herrero C , García‐Pozo AM , Jiménez‐García R 
Published: November 2017

AbstractAimRepeated, ongoing exposure to pain influences the growth, cognitive and motor functions, behaviour, personality and neurodevelopment of preterm infants. We compared the analgesic effects of expressed breast milk (EBM) and 24% oral sucrose on preterm neonates during venipuncture.MethodsThis multicentre randomised, noninferiority, crossover trial focused on five neonatal university units in Madrid, Spain, from October 2013 to October 2014. It comprised 66 preterm infants born at less than 37 weeks and randomly split into two groups. They received either EBM or sucrose two minutes before venepuncture, together with nonnutritive sucking and swaddling, then the opposite procedure at a later point. Pain was measured with the premature infant pain profile (PIPP) and crying was also measured.ResultsThere were no statistically significant differences between the groups. The PIPP scores were seven (4–9) with breast milk and six (4–8.25) with sucrose (p = 0.28). The 11 infants born at under 28 weeks of age showed higher median scores of nine (9–14) for breast milk and four (4–7) for sucrose (p = 0.009).ConclusionEBM and 24% sucrose had the same analgesic effect during venipuncture in most of the preterm neonates, but sucrose worked better in extremely preterm infants.
Maternal mood disorders and lithium exposure in utero were not associated with poor cognitive development during childhood
Authors: Forsberg L , Adler M , Römer Ek I , Ljungdahl M , Navér L , Gustafsson LL , Berglund G , Chotigasatien A , Hammar U , Böhm B , Wide K 
Published: November 2017

AbstractAimThis study evaluated whether maternal mood disorders (MMD), particularly bipolar disorder, and lithium treatment during pregnancy influenced the neonatal health and cognition of children born from 2006 to 2010.MethodsOur study at Karolinska University Hospital, Stockholm, Sweden, focused on women with and without mood disorders and their children. Information on pharmacotherapy, mental health, delivery and neonatal complications was retrospectively collected from electronic patient records. Children were tested in a blinded manner at four to five years of age with the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition. Maternal health, child health and social situations were evaluated.ResultsOf the 39 children, 20 were exposed to lithium and MMD during pregnancy, eight were exposed to MMD but not lithium and 11 were not exposed to MMD or lithium. The children's full scale intelligence quotient (IQ), performance IQ and verbal IQ results did not differ significantly between the groups. The processing speed quotient was significantly lower in children exposed to mood disorders, but there was a high level of missing data for this subtest.ConclusionThis small, clinical cohort showed no significant association between mothers’ prenatal exposure to lithium or mood disorders and their offspring's IQ.
Seed addition and biomass removal key to restoring native forbs in degraded temperate grassland
Authors: Johnson David P. , Catford Jane A. , Driscoll Don A. , Gibbons Philip 
Published: November 2017

AbstractQuestionsLong‐term restoration of native forb diversity can only be achieved if native forb species can recruit (colonize and establish) and reproduce. We asked whether native forbs in a temperate grassland were seed‐limited, and how the recruitment of native and exotic forbs is affected by grassland structure and resource availability.LocationAustralian Capital Territory, south‐eastern Australia.MethodsWe conducted a field experiment in a temperate grassland dominated by a native tussock grass to assess effects of: (1) addition of native forb seed, (2) thinning of native grass tussocks, (3) leaf litter removal, and (4) exotic plant removal on the recruitment of native and exotic forbs. These four actions can alter grassland structure and the availability of soil nutrients, soil moisture and light. We used GLMM to determine the importance of seed addition, grassland structure and resource availability on the richness and abundance of sown native forbs, and the abundance of exotic forb seedlings and unsown native forbs.ResultsAdding seed increased the species richness and abundance of native forbs. Tussock thinning and litter removal increased species richness and abundance of sown native forbs, and the abundance of exotic forb seedlings. Exotic plant removal also increased the abundance of sown native forbs. Abundance of unsown native forb species was unaffected by the experimental treatments. Species richness and abundance of native forbs and abundance of exotic forbs declined with increasing tussock grass cover. Leaf litter restricted the abundance of native forb species more than exotic forb species.ConclusionNative forb recruitment predominantly relied upon seed addition, suggesting that seed limitation is a major barrier to the recovery of degraded grasslands. Reducing the cover of living grass tussocks facilitated recruitment of native and exotic forbs, and removing litter disproportionally increased recruitment of native forbs compared with exotics. Combining seed addition with the reduction of both living and dead grass biomass should help restore native grassland forbs.
After Treatment with Methylene Blue is Effective against Delayed Encephalopathy after Acute Carbon Monoxide Poisoning
Authors: Zhao Ningjun , Liang Pengchong , Zhuo Xiaoying , Su Chenglei , Zong Xuemei , Guo Bingnan , Han Dong , Yan Xianliang , Hu Shuqun , Zhang Quanguang , Tie Xu 
Published: November 2017

AbstractDelayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP) is the most severe and clinically intractable complication that occurs following acute CO poisoning. Unfortunately, the mechanism of DEACMP is still vague. Growing evidence indicates that delayed cerebral damage after CO poisoning is related to oxidative stress, abnormal neuro‐inflammation, apoptosis and immune‐mediated injury. Our recent report indicated that methylene blue (MB) may be a promising therapeutic agent in the prevention of neuronal cell death and cognitive deficits after transient global cerebral ischaemia (GCI). In this study, we aimed to investigate the potential of MB therapy to ameliorate the signs and symptoms of DEACMP. Rats were exposed to 1000 ppm CO for 40 min. in the first step; CO was then increased to 3000 ppm, which was maintained for another 20 min. The rats were implanted with 7‐day release Alzet osmotic mini‐pumps subcutaneously under the back skin, which provided MB at a dose of 0.5 mg/kg/day 1 hr after CO exposure. The results showed that MB significantly suppressed oxidative damage and expression of pro‐inflammatory factors, including tumour necrosis factor‐α and interleukin (IL)‐1β. MB treatment also suitably modulated mitochondrial fission and fusion, which is helpful in the preservation of mitochondrial function. Furthermore, MB dramatically attenuated apoptosis and neuronal death. Lastly, behavioural studies revealed that MB treatment preserved spatial learning and memory in the Barnes maze test. Our findings indicated that MB may have protective effects against DEACMP.
Longitudinal pathways between mental health difficulties and academic performance during middle childhood and early adolescence
Authors: Deighton Jessica , Humphrey Neil , Belsky Jay , Boehnke Jan , Vostanis Panos , Patalay Praveetha 
Published: November 2017

There is a growing appreciation that child functioning in different domains, levels, or systems are interrelated over time. Here, we investigate links between internalizing symptoms, externalizing problems, and academic attainment during middle childhood and early adolescence, drawing on two large data sets (child: mean age 8.7 at enrolment, n = 5,878; adolescent: mean age 11.7, n = 6,388). Using a 2‐year cross‐lag design, we test three hypotheses – adjustment erosion, academic incompetence, and shared risk – while also examining the moderating influence of gender. Multilevel structural equation models provided consistent evidence of the deleterious effect of externalizing problems on later academic achievement in both cohorts, supporting the adjustment‐erosion hypothesis. Evidence supporting the academic‐incompetence hypothesis was restricted to the middle childhood cohort, revealing links between early academic failure and later internalizing symptoms. In both cohorts, inclusion of shared‐risk variables improved model fit and rendered some previously established cross‐lag pathways non‐significant. Implications of these findings are discussed, and study strengths and limitations noted.
Statement of contribution

What is already known on this subject?

Longitudinal research and in particular developmental cascades literature make the case for weaker associations between internalizing symptoms and academic performance than between externalizing problems and academic performance.

Findings vary in terms of the magnitude and inferred direction of effects. Inconsistencies may be explained by different age ranges, prevalence of small‐to‐modest sample sizes, and large time lags between measurement points.

Gender differences remain underexamined.

What does this study add?

The present study used cross‐lagged models to examine longitudinal associations in age groups (middle child and adolescence) in a large‐scale British sample.

The large sample size not only allows for improvements on previous measurement models (e.g., allowing the analysis to account for nesting, and estimation of latent variables) but also allows for examination of gender differences.

The findings clarify the role of shared‐risk factors in accounting for associations between internalizing, externalizing, and academic performance, by demonstrating that shared‐risk factors do not fully account for relationships between internalizing, externalizing, and academic achievement. Specifically, some pathways between mental health and academic attainment consistently remain, even after shared‐risk variables have been accounted for.

Findings also present consistent support for the potential impact of behavioural problems on children's academic attainment.

The negative relationship between low academic attainment and subsequent internalizing symptoms for younger children is also noteworthy.