bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potent analogues of etiprednol dicloacetate, a second generation of soft corticosteroids
Authors: Bodor Nicholas , Zubovics Zoltán , Kurucz István , Sólyom Sandor , Bodor Erik 
Published: October 2017

Abstract

Objectives
Loteprednol etabonate (LE) is the first, highly successful soft corticosteroid (SC) designed using the ‘inactive metabolite’ approach, starting with ∆1-cortienic acid (d-CA). The next generation of SCs based on d-CA was etiprednol dicloacetate (ED). The 17α-dichloroacetyl function serves both as a unique pharmacophore and as the source of the molecule's softness. Highly potent SCs were designed based on a combination of ED and LE, introducing 6, 9 and 16 substituents in the molecule.

Methods
The new 6α, 9α, 16α and β 17α-dichloroacetyl 17β-esters were synthesized from the correspondingly substituted ∆1-cortienic acids. The anti-inflammatory activity was assessed using LPS-induced TNF α-release under various conditions to determine intrinsic activity vs. systemic biological stability. In vivo anti-inflammatory activity was studied in the widely used ovalbumin-sensitized and ovalbumin-challenged Brown Norway rat model.

Key findings
The 6α or 9α-fluoro substitution produced highly potent corticosteroids, but the 17α-dichloroacetyl substituent provided ‘softness’ in all cases. Local application of these steroids will significantly reduce systemic activity, due to the facile hydrolytic deactivation of these molecules.

Conclusions
A 17α-dichloroacetyl derivative of fluticasone (FLU) is highly potent but much safer than the currently used propionate or furoate ester.
Environmental Renaissance Studies
Authors: Jones Gwilym 
Published: October 2017

AbstractRecent developments in renaissance and early modern ecocriticism, since surveys by Karen Raber and Sharon O'Dair, have made the field discursive. Some critics maintain that ecocriticism, ecostudies or environmental studies must be self‐consciously activist and presentist. Others practise a more historicist approach, which is only implicitly activist, if at all. This article considers the recent environmental criticism of renaissance literature and Shakespeare – in its place on the spectrum of presentism and historicism – and argues that the field's discursiveness is a positive development, which will lead to a growth of ecocritical work in the period. Recent relevant work in environmental history is introduced and a case made for a greater engagement with it in literary ecocriticism.
Hepatitis A outbreak in Barcelona among men who have sex with men (MSM), January‐June 2017: A hospital perspective
Authors: Rodríguez‐Tajes Sergio , Perpiñán Elena , Caballol Berta , Lens Sabela , Mariño Zoe , Costa Josep , Vilella Anna , Pérez‐del‐Pulgar Sofía , Forns Xavier , Koutsoudakis George 
Published: October 2017

AbstractBackground & AimsAcute hepatitis A is transmitted mainly via the faecal‐oral route and/or contaminated aliment. Furthermore, several outbreaks in the men who have sex with men (MSM) population classified hepatitis A as a sexually transmitted disease (STD). We aimed to clarify an ongoing hepatitis A outbreak in Barcelona with respect to patients’ characteristics and viral phylogenetic analysis.MethodsWe prospectively analyzed 46 cases of hepatitis A infection that were registered in our hospital between January and June 2017. We evaluated demographics data, risk factors, presenting symptoms, sexual orientation, comorbidities and further STD infections. The phylogenetic correlation of the current circulating viruses among them and other hepatitis A strains was assessed by sequencing of the VP1/P2A region.ResultsMost patients were male (44, 96%) with median age 33.5 years (range 28‐50). Thirty‐one (67%) were MSM and 18 (39%) required hospitalization. Molecular phylogenetic analyses revealed that all patients were infected by hepatitis A subgenotype IA strains. Moreover, current strains comprised 3 distinct clusters, previously reported in ongoing outbreaks in the United Kingdom, Berlin and the Netherlands. However, these strains were phylogenetically diverse to those previously reported in Barcelona metropolitan region.ConclusionsOngoing hepatitis A outbreak in Barcelona affects primarily the MSM community and is phylogenetically linked to current hepatitis A outbreaks described in other European countries. As a result of the high admission rate, these outbreaks may impact the admission pattern of referral liver units. Control measures, for example vaccinations programs tailored to the MSM community, must be taken to control further spreading.
Executive summary for the Micronutrient Powders Consultation: Lessons Learned for Operational Guidance
Authors: Nyhus Dhillon Christina , Sarkar Danya , Klemm Rolf DW , Neufeld Lynnette M , Rawat Rahul , Tumilowicz Alison , Namaste Sorrel ML 
Published: October 2017

AbstractIron deficiency anaemia is estimated to be the leading cause of years lived with disability among children. Young children's diets are often inadequate in iron and other micronutrients, and provision of essential vitamin and minerals has long been recommended. With the limited programmatic success of iron drop/syrup interventions, interest in micronutrient powders (MNP) has increased. MNP are a mixture of vitamins and minerals, enclosed in single‐dose sachets, which are stirred into a child's portion of food immediately before consumption. MNP are an efficacious intervention for reducing iron deficiency anaemia and filling important nutrient gaps in children 6–23 months of age. As of 2014, 50 countries have implemented MNP programmes including 9 at a national level. This paper provides an overview of a 3‐paper series, based on findings from the “Micronutrient Powders Consultation: Lessons Learned for Operational Guidance” held by the USAID‐funded Strengthening Partnerships, Results, and Innovations in Nutrition Globally (SPRING) Project. The objectives of the Consultation were to identify and summarize the most recent MNP programme experiences and lessons learned for operationalizing MNP for young children and prioritize an implementation research agenda. The Consultation was composed of 3 working groups that used the following methods: deliberations among 49 MNP programme implementers and experts, a review of published and grey literature, questionnaires, and key informant interviews, described in this overview. The following articles summarize findings in 3 broad programme areas: planning, implementation, and continual programme improvement. The papers also outline priorities for implementation research to inform improved operationalization of MNP.
Experiences and lessons learned for planning and supply of micronutrient powders interventions
Authors: Schauer Claudia , Sunley Nigel , Hubbell Melgarejo Carrie , Nyhus Dhillon Christina , Roca Claudia , Tapia Gustavo , Mathema Pragya , Walton Shelley , Situma Ruth , Zlotkin Stanley , DW Klemm Rolf 
Published: October 2017

AbstractRealistic planning for a nutrition intervention is a critical component of implementation, yet effective approaches have been poorly documented. Under the auspices of “The Micronutrient Powders Consultation: Lessons Learned for Operational Guidance,” 3 working groups were formed to summarize experiences and lessons across countries regarding micronutrient powders (MNP) interventions for young children. This paper focuses on programmatic experiences in the planning stages of an MNP intervention, encompassing assessment, enabling environment and adaptation, as well as considerations for supply. Methods included a review of published and grey literature, key informant interviews, and deliberations throughout the consultation process. We found that assessments helped justify adopting an MNP intervention, but these assessments were often limited by their narrow scope and inadequate data. Establishing coordinating bodies and integrating MNP into existing policies and programmes have helped foster an enabling environment and support programme stability. Formative research and pilots have been used to adapt MNP interventions to specific contexts, but they have been insufficient to inform scale‐up. In terms of supply, most countries have opted to procure MNP through international suppliers, but this still requires understanding and navigating the local regulatory environment at the earliest stages of an intervention. Overall, these findings indicate that although some key planning and supply activities are generally undertaken, improvements are needed to plan for effective scale‐up. Much still needs to be learned on MNP planning, and we propose a set of research questions that require further investigation.
Tournament ABC analysis of the western Palaearctic population history of an oak gall wasp, Synergus umbraculus
Authors: Stone Graham N. , White Sarah C. , Csóka György , Melika George , Mutun Serap , Pénzes Zsolt , Sadeghi S. Ebrahim , Schönrogge Karsten , Tavakoli Majid , Nicholls James A. 
Published: October 2017

AbstractApproximate Bayesian computation (ABC) is a powerful and widely used approach in inference of population history. However, the computational effort required to discriminate among alternative historical scenarios often limits the set that is compared to those considered more likely a priori. While often justifiable, this approach will fail to consider unexpected but well‐supported population histories. We used a hierarchical tournament approach, in which subsets of scenarios are compared in a first round of ABC analyses and the winners are compared in a second analysis, to reconstruct the population history of an oak gall wasp, Synergus umbraculus (Hymenoptera, Cynipidae) across the Western Palaearctic. We used 4,233 bp of sequence data across seven loci to explore the relationships between four putative Pleistocene refuge populations in Iberia, Italy, the Balkans and Western Asia. We compared support for 148 alternative scenarios in eight pools, each pool comprising all possible rearrangements of four populations over a given topology of relationships, with or without founding of one population by admixture and with or without an unsampled “ghost” population. We found very little support for the directional “out of the east” scenario previously inferred for other gall wasp community members. Instead, the best‐supported models identified Iberia as the first‐regional population to diverge from the others in the late Pleistocene, followed by divergence between the Balkans and Western Asia, and founding of the Italian population through late Pleistocene admixture from Iberia and the Balkans. We compare these results with what is known for other members of the oak gall community, and consider the strengths and weaknesses of using a tournament approach to explore phylogeographic model space.
Demographic inference from whole‐genome and RAD sequencing data suggests alternating human impacts on goose populations since the last ice age
Authors: Pujolar J. M. , Dalén L. , Hansen M. M. , Madsen J. 
Published: October 2017

AbstractWe investigated how population changes and fluctuations in the pink‐footed goose might have been affected by climatic and anthropogenic factors. First, genomic data confirmed the existence of two separate populations: western (Iceland) and eastern (Svalbard/Denmark). Second, demographic inference suggests that the species survived the last glacial period as a single ancestral population with a low population size (100–1,000 individuals) that split into the current populations at the end of the last glacial maximum with Iceland being the most plausible glacial refuge. While population changes during the last glaciation were clearly environmental, we hypothesize that more recent demographic changes are human‐related: (1) the inferred population increase in the Neolithic is due to deforestation to establish new lands for agriculture, increasing available habitat for pink‐footed geese, (2) the decline inferred during the Middle Ages is due to human persecution, and (3) improved protection explains the increasing demographic trends during the 20th century. Our results suggest both environmental (during glacial cycles) and anthropogenic effects (more recent) can be a threat to species survival.
Development and validation of a childhood self‐efficacy for functional constipation questionnaire
Authors: Santucci N. R. , Hyman P. E. , Karpinski A. , Rosenberg A. , Garguilo D. , Rein L. E. , Amado‐Feeley A. , Stoops E. , Herdes R. E. , van Tilburg M. A. L. 
Published: October 2017

AbstractBackgroundChildren with functional constipation fear painful bowel movements leading to stool withholding behavior. Self‐efficacy is the belief that an individual can accomplish a given goal. If children with constipation avoid defecation because they think that they are unable defecate comfortably, this low self‐efficacy may prevent treatment success. The aim of the current study was to develop and validate a constipation specific self‐efficacy scale.MethodsThe self‐efficacy for functional constipation questionnaire (SEFCQ) was developed by the authors and evaluated by 10 children and seven experts. Ninety‐nine healthy children and 122 children with functional constipation completed the SEFCQ and three other questionnaires measuring related constructs.Key ResultsMinor changes were made in wording based on feedback from experts and children. Factor analysis showed two scales, a 7 item Action scale (Cronbach's α = 0.88) and a 7 item Emotion scale (Cronbach α = 0.86). The SEFCQ total scale correlated positively with general self‐efficacy (r = .32, P < .001) and quality of life (r = .20; P < .01) and negatively with anxiety (r = −.15; P < .05). Scores on the SEFCQ were higher in children without functional constipation compared to those with functional constipation (53.33 + 3.38 vs 39.34 + 7.19, P < .001).Conclusions & InferencesWe developed a constipation specific self‐efficacy questionnaire with good initial internal reliability, excellent face validity and adequate content validity. A low self‐efficacy for defecation, may make the child resist their physical urge to defecate and hence, the need for further studies to assess its effect on treatment outcomes.
Pollination systems involving floral mimicry of fruit: aspects of their ecology and evolution
Authors: Goodrich Katherine R. , Jürgens Andreas 
Published: October 2017

SummaryFloral mimicry of nonfloral resources is found across many angiosperm families, with mimicry of varied models including carrion, dung, fungi, insects and fruit. These systems provide excellent models to investigate the role of visual and olfactory cues for the ecology and evolution of plant–animal interactions. Interestingly, floral mimicry of fruit is least documented in the literature, although ripe or rotting fruits play an important role as a food or brood site in many insect groups such as Diptera, Hymenoptera and Coleoptera, and frugivorous vertebrates such as bats and birds. In ecosystems where fruit represents a frequent, reliable resource (e.g. tropical forests), this form of floral mimicry could represent a common mimicry class with specialization possible along multiple axes such as fruit of different species, stages of ripeness and microbial colonization. In this review, we summarize current research on floral mimicry of fruit. We place this review in the context of floral mimicry of a broader spectrum of nonfloral resources, and we discuss conceptual frameworks of mimicry vs generalized food deception or pre‐existing sensory bias. Finally, we briefly review the specificity and complexity of fruit–insect ecological interactions, and we summarize important considerations and questions for moving forward in this field.
Selection and Exploitation of Macro‐Vertebrate Resources During the Upper Palaeolithic in Northern Spain. New Evidence from Coímbre Cave (Peñamellera Alta, Asturias)
Authors: Yravedra José , Álvarez‐Alonso David , Estaca Verónica , López‐Cisneros Pablo , Andrés‐Chaín Mirian , Arrizabalaga Álvaro , Jordá Pardo Jesús F. , Elorza Mikel , Iriarte‐Chiapusso Maria‐Jose , Sesé Carmen , Uzquiano Paloma 
Published: October 2017

SummaryThe exploitation of ungulates in the Cantabrian region during the Upper Palaeolithic is characterized by the appearance of progressively specialized hunting strategies, especially during the Magdalenian. This specialization focused on either Iberian ibex or red deer, depending on environmental or topographic features. Red deer, for instance, was hunted mostly on the plains while ibex and/or chamois was hunted in rocky and mountainous areas. Here we present new zooarchaeological and taphonomic evidence from Coímbre cave (northern Spain), a site located in the rugged region between the Picos de Europa and Sierra del Cuera (Asturias) which has evidence for specialized ibex hunting. We discuss the possible reasons for such a selective hunting pattern. While the predominance of mountain species such as Iberian ibex or chamois in the Magdalenian levels suggests prey selection based on topographic or environmental criteria, the predominance of large bovids in the Gravettian level could imply that other alternatives were available. We also provide evidence of a pattern of rabbit exploitation which is unusual by comparison with other Upper Palaeolithic sites of northern Spain, and which taphonomic evidence suggests was due to human activity.
Fields, Ritual and Religion: Holistic Approaches to the Rural Landscape in Long‐Term Perspective (c.1500 BC–AD 1086)
Authors: Ten Harkel Letty , Franconi Tyler , Gosden Chris 
Published: October 2017

SummaryThis paper discusses the relationship between agricultural activity and ritualized/religious practices in England from the middle Bronze Age to the early medieval period (c.1500 BC–AD 1086). It is written in the context of the ERC‐funded, Oxford‐based ‘English Landscapes and Identities project’ (EngLaId), which involved the compilation of an extensive spatial database of archaeological ‘monuments’, finds and other related data to chart change and continuity during this period. Drawing on this database alongside documentary and onomastic evidence, we analyze the changing relationship between fields, ritual and religion in England. We identify four moments of change, around the start of the middle Bronze Age (c.1500 BC), in the late Bronze Age (c.1150 BC), the late Iron Age (c.150 BC) and the middle/late Anglo‐Saxon period (c.800 AD). However, despite changes in both agricultural and ritual/religious practices during this extensive timeframe, a clear link between them can be observed throughout.
Lung function improvement and airways inflammation reduction in asthmatic children after a rehabilitation program at moderate altitude
Authors: Bersuch Eugen , Gräf Florian , Renner Ellen D. , Jung Andreas , Traidl‐Hoffmann Claudia , Lauener Roger , Roduit Caroline 
Published: October 2017

AbstractBackgroundRehabilitational programs at moderate altitude (1500‐2500 m) showed improvement of lung function and reduction in airways inflammation in asthmatic adults. Allergen avoidance was postulated as the major cause of these improvements.MethodsSpirometries of 344 and fractional exhaled nitric oxide measurements (FeNO) of 124 asthmatic children and adolescents, staying in a rehabilitation hospital in Davos (1590 m) with at least 14 days between admission and discharge, were analyzed in association with atopic sensitization (skin‐prick testing and/or specific IgE), level of asthma control, and inhalative corticosteroid (ICS) dose.ResultsPulmonary conditions improved significantly on average during the sojourn. Uncontrolled asthmatics benefited most with an absolute increase in predicted FEV1, MEF25, and MEF75 of 7.7%, 9.9%, and 12.7%, respectively (P < .001). FeNO decreased by 36.9 ppb for uncontrolled, by 26.9 ppb for partly controlled, and by 11.8 ppb for controlled asthmatics. In uncontrolled subjects, pulmonary improvement was comparable between patients with and without house dust mites (HDM) sensitization. Pulmonary improvements of pollen‐sensitized patients were not dependent on the season of the sojourn. For the group with constant ICS level, the absolute increase in FEV1 was 4.9% (P < .001) with a FeNO decreased by 32.7 ppb (P < .001). When the ICS dose was elevated by one GINA level, the absolute increase in FEV1 was slightly higher (6.6%, P < .001), with a FeNO decrease of 31.4 ppb (P < .001).ConclusionInpatient rehabilitation at moderate altitude improved pulmonary conditions in asthmatic children and adolescents independent of sensitization status to HDM or pollen. A positive effect was also observed in patients without change in medication.
Inflammatory bowel disease in chronic granulomatous disease: An emerging problem over a twenty years' experience
Authors: Angelino Giulia , De Angelis Paola , Faraci Simona , Rea Francesca , Romeo Erminia Francesca , Torroni Filippo , Tambucci Renato , Claps Alessia , Francalanci Paola , Chiriaco Maria , Di Matteo Gigliola , Cancrini Caterina , Palma Paolo , D'Argenio Patrizia , Dall'Oglio Luigi , Rossi Paolo , Finocchi Andrea 
Published: October 2017

AbstractBackgroundChronic granulomatous disease (CGD) is a primary immunodeficiency of phagocytes, characterized by life‐threatening infections and hyperinflammation. Due to survival improvement, inflammatory bowel disease (IBD) is becoming increasingly relevant. Here, we report our 20 year experience.MethodsWe retrospectively analyzed clinic, endoscopic, and histologic features, as well as the management of CGD‐IBD patients referred to the Bambino Gesù Children's Hospital in Rome, Italy.ResultsOf 20 patients with CGD, 9 presented with CGD‐IBD at diagnosis and/or during follow‐up. Symptoms occurred at a median age of 16 years (range 3.2‐42), with a median delay of 6 months for endoscopic confirmation. Patients mainly complained of nonspecific diarrhea (55%), with discrepancy between symptom paucity and severe endoscopic appearance, mainly represented by extensive colonic involvement (44%). Histology revealed at least 2 characteristic features (epithelioid granulomas, pigmented macrophages, and increased eosinophils) in 78% of patients. Eight of 9 patients received oral mesalamine, and 5 required systemic steroids. One patient received azathioprine due to steroid dependence. No patient required biological therapy or surgery. Clinical remission was obtained in all patients, but the majority complained of mild relapses. Two episodes of severe infection occurred early after steroid therapy.ConclusionsPenetrance of CGD‐IBD increases with age. Clinical manifestations may be subtle, and clinicians should have a low threshold to recommend endoscopy. Treatment with NSAIDs and/or steroids achieves a good response, but relapses usually occur. Infection surveillance is mandatory during treatment, to prevent opportunistic infections. A close collaboration between pediatric immunologists and gastroenterologists is pivotal, including combined follow‐up.