bluuebunny/crossref_metadata_2025_split huggingface dataset:
Therapeutic validation of an orphan G protein‐coupled receptor: The case of GPR84
Authors: Marsango Sara , Barki Natasja , Jenkins Laura , Tobin Andrew B. , Milligan Graeme 
Published: September 2020

Despite the importance of members of the GPCR superfamily as targets of a broad range of effective medicines many GPCRs remain poorly characterised. GPR84 is an example. Expression of GPR84 is strongly up regulated in immune cells in a range of pro‐inflammatory settings and clinical trials to treat idiopathic pulmonary fibrosis are currently ongoing using ligands with differing levels of selectivity and affinity as GPR84 antagonists. Although blockade of GPR84 may potentially prove effective also in diseases associated with inflammation of the lower gut there is emerging interest in defining if agonists of GPR84 might find utility in conditions in which regulation of metabolism or energy sensing is compromised. Here, we consider the physiological and pathological expression profile of GPR84 and, in the absence of direct structural information, recent developments and use of GPR84 pharmacological tool compounds to study its broader role and biology.LINKED ARTICLESThis article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
The accuracy and precision of body mass estimation in non‐avian dinosaurs
Authors: Campione Nicolás E. , Evans David C. 
Published: September 2020

ABSTRACTInferring the body mass of fossil taxa, such as non‐avian dinosaurs, provides a powerful tool for interpreting physiological and ecological properties, as well as the ability to study these traits through deep time and within a macroevolutionary context. As a result, over the past 100 years a number of studies advanced methods for estimating mass in dinosaurs and other extinct taxa. These methods can be categorized into two major approaches: volumetric‐density (VD) and extant‐scaling (ES). The former receives the most attention in non‐avian dinosaurs and advanced appreciably over the last century: from initial physical scale models to three‐dimensional (3D) virtual techniques that utilize scanned data obtained from entire skeletons. The ES approach is most commonly applied to extinct members of crown clades but some equations are proposed and utilized in non‐avian dinosaurs. Because both approaches share a common goal, they are often viewed in opposition to one another. However, current palaeobiological research problems are often approach specific and, therefore, the decision to utilize a VD or ES approach is largely question dependent. In general, biomechanical and physiological studies benefit from the full‐body reconstruction provided through a VD approach, whereas large‐scale evolutionary and ecological studies require the extensive data sets afforded by an ES approach. This study summarizes both approaches to body mass estimation in stem‐group taxa, specifically non‐avian dinosaurs, and provides a comparative quantitative framework to reciprocally illuminate and corroborate VD and ES approaches. The results indicate that mass estimates are largely consistent between approaches: 73% of VD reconstructions occur within the expected 95% prediction intervals of the ES relationship. However, almost three quarters of outliers occur below the lower 95% prediction interval, indicating that VD mass estimates are, on average, lower than would be expected given their stylopodial circumferences. Inconsistencies (high residual and per cent prediction deviation values) are recovered to a varying degree among all major dinosaurian clades along with an overall tendency for larger deviations between approaches among small‐bodied taxa. Nonetheless, our results indicate a strong corroboration between recent iterations of the VD approach based on 3D specimen scans suggesting that our current understanding of size in dinosaurs, and hence its biological correlates, has improved over time. We advance that VD and ES approaches have fundamentally (metrically) different advantages and, hence, the comparative framework used and advocated here combines the accuracy afforded by ES with the precision provided by VD and permits the rapid identification of discrepancies with the potential to open new areas of discussion.
Narrative Matters: Mental health recovery – considerations when working with youth
Authors: Khoury Emmanuelle 
Published: September 2020

BackgroundYouth mental health and well‐being is of increasing concern to practitioners and policy‐makers. Youth experiencing mental health problems face many barriers in accessing care and often have different needs to those of adults experiencing mental health problems. In order to adequately respond to the needs of young people aged 12–25, it is necessary to understand, from their perspective, their diverse needs and their different realities, using a global health approach and through participation in the development of mental health services and care. There are documented difficulties in implementing a recovery‐oriented practice approach that have led to misapplications, misunderstandings and critiques. That said, there is little research or discussion on mental health recovery by and for young people and young adults.PurposeTo help child and adolescent mental health practitioners better assess the pertinence of the mental health recovery model in their practice, a focus on the emergence of the model can be helpful in order to adapt the current conceptions of mental health recovery for work with youth.ConclusionChild and adolescent mental health professionals might want to consider the following three suggestions – consider developmental processes, focus on hope and create strong community ties.
Central hypothyroidism improves with age in very young children with Prader‐Willi syndrome
Authors: Konishi Ayako , Ida Shinobu , Shoji Yasuko , Etani Yuri , Kawai Masanobu 
Published: September 2020

AbstractObjectiveAbnormalities in the hypothalamic‐pituitary‐thyroid (HPT) axis have been implicated in Prader‐Willi syndrome (PWS); however, limited information is currently available on age‐dependent alterations in the HPT axis. We herein investigated age‐dependent differences in thyroid hormone levels in PWS children.Design/Patients/MeasurementsFree T4 (FT4), free T3 (FT3) and thyroid‐stimulating hormone (TSH) concentrations were retrospectively compared between genetically confirmed PWS children (N = 43, median age: 11.2 months) and controls (N = 85, median age: 14.5 months) matched for age, sex, body weight‐SD score (SDS), height‐SDS, body mass index‐SDS and serum albumin level, a marker of the nutritional status. Subjects were subdivided into two groups based on their age: an infant group aged between 1 and 11 months (PWS: N = 22, controls: N = 30) and a toddler group aged between 12 and 47 months (PWS: N = 21, controls: N = 55). None of the subjects had ever been treated with growth hormone or levothyroxine.ResultsAfter adjustments for confounding variables, in the infant group, FT4 levels (pmol/L) were significantly lower in PWS (11.24 in PWS vs 14.32 in controls,P = .0002), whereas no significant differences were observed in FT3 or TSH levels. In the toddler group, no significant differences were noted in FT4 (12.23 in PWS vs 15.31 in controls,P = .10), FT3 or TSH levels. The FT3/FT4 ratio was significantly increased in PWS in both groups. FT4 levels were positively correlated with age in PWS.ConclusionsInfants with PWS had lower FT4 levels, but FT3 levels were normal, indicating that the levothyroxine replacement therapy may not need to be routinely performed.
EMC10 homozygous variant identified in a family with global developmental delay, mild intellectual disability, and speech delay
Authors: Umair Muhammad , Ballow Mariam , Asiri Abdulaziz , Alyafee Yusra , al Tuwaijri Abeer , Alhamoudi Kheloud M. , Aloraini Taghrid , Abdelhakim Marwa , Althagafi Azza Thamer , Kafkas Senay , Alsubaie Lamia , Alrifai Muhammad Talal , Hoehndorf Robert , Alfares Ahmed , Alfadhel Majid 
Published: September 2020

AbstractIn recent years, several genes have been implicated in the variable disease presentation of global developmental delay (GDD) and intellectual disability (ID). The endoplasmic reticulum membrane protein complex (EMC) family is known to be involved in GDD and ID. Homozygous variants of EMC1 are associated with GDD, scoliosis, and cerebellar atrophy, indicating the relevance of this pathway for neurogenetic disorders. EMC10 is a bone marrow‐derived angiogenic growth factor that plays an important role in infarct vascularization and promoting tissue repair. However, this gene has not been previously associated with human disease. Herein, we describe a Saudi family with two individuals segregating a recessive neurodevelopmental disorder. Both of the affected individuals showed mild ID, speech delay, and GDD. Whole‐exome sequencing (WES) and Sanger sequencing were performed to identify candidate genes. Further, to elucidate the functional effects of the variant, quantitative real‐time PCR (RT‐qPCR)‐based expression analysis was performed. WES revealed a homozygous splice acceptor site variant (c.679‐1G>A) in EMC10 (chromosome 19q13.33) that segregated perfectly within the family. RT‐qPCR showed a substantial decrease in the relative EMC10 gene expression in the patients, indicating the pathogenicity of the identified variant. For the first time in the literature, the EMC10 gene variant was associated with mild ID, speech delay, and GDD. Thus, this gene plays a key role in developmental milestones, with the potential to cause neurodevelopmental disorders in humans.
Children’s perception of social boundaries: The intersectionality of age and social group affiliation in rural Pakistan
Authors: Mughal Muhammad A. Z. 
Published: September 2020

AbstractThis study explores how children perceive social boundaries in rural Pakistan. It discusses that children develop and navigate their social relationships through their perception of social boundaries, which are shaped by kinship and sociospatial organisation in rural areas. Children's perception of social boundaries is also mediated through the intersectionality of their age and social group affiliation. An ethnographic case study of a village in Southern Punjab, Pakistan, is presented here. It uses a quantifiable photo‐elicitation technique and social mapping to analyse children's everyday mobilities and intersectionality in the cultural context of rural Pakistan to illustrate their perception of social boundaries.
Risk for recurrence of disease following surgical therapy of peri‐implantitis—A prospective longitudinal study
Authors: Carcuac Olivier , Derks Jan , Abrahamsson Ingemar , Wennström Jan L. , Berglundh Tord 
Published: September 2020

AbstractObjectivesThe aim of the present prospective study was to assess the risk for disease recurrence following surgical therapy of peri‐implantitis.Material & Methods73 patients (130 implants) treated surgically for peri‐implantitis were examined at 1 and 5 years after therapy. The primary outcome was recurrence/progression of disease defined as any of the following events: (a) bone loss >1.0 mm, (b) surgical retreatment, (c) implant removal/loss after year 1. Patient‐ and implant‐related parameters as well as 1‐year outcomes were evaluated as potential predictors through multiple logistic regression analysis.Results57 implants (44%) displayed recurrence/progression of peri‐implantitis during follow‐up. Among these, 27 implants were removed. Residual deep probing pocket depth (≥6 mm; odds ratio 7.4; 95% confidence interval 2.8–19.3) and reduced marginal bone level (OR 1.4; 95%CI 1.1–1.7) at 1 year after surgery constituted risk factors for recurrence/progression of disease. Furthermore, implants with modified surfaces were at higher risk than implants with non‐modified surfaces (OR 5.1; 95%CI 1.6–16.5).ConclusionImplants with (a) residual deep probing pocket depth, (b) reduced marginal bone level, or (c) modified surfaces following surgical therapy of peri‐implantitis present with increased risk for recurrence/progression.
Biofilm formation on metal alloys, zirconia and polyetherketoneketone as implant materials in vivo
Authors: Zeller Barbara , Stöckli Simone , Zaugg Lucia K. , Astasov‐Frauenhoffer Monika , Hauser‐Gerspach Irmgard , Waltimo Tuomas , Zitzmann Nicola U. 
Published: September 2020

AbstractObjectivesThis study investigated biofilm formation on discs of metal alloys, zirconia and polyetherketoneketone in vivo.Material and MethodsSixteen healthy volunteers conducted two runs of 24 hr each wearing an intraoral splint with 15 discs representing five different materials (gold‐based [EL] and silver‐based [PA] noble metal alloys; zirconia [ZR]; polyetherketoneketone [PEKK]; titanium zirconium alloy [TiZr]). Safranin staining assays and colony‐forming unit (CFU) counts were conducted. Linear mixed‐effects models were used to compare materials, and geometric mean ratios with 95% confidence interval were calculated with the level of significance set at α = 0.05.ResultsLess biofilm mass and lower CFU counts were found on PA and EL, while ZR and PEKK developed similar levels as the reference material TiZr alloy. Compared with PA, biofilm mass was 1.5 times higher for EL (p = .004), 1.7 times higher for PEKK (p < .001), 2.2 times higher for TiZr (p < .001) and 2.4 times higher for ZR (p < .001). The culturing method confirmed these results for EL and PA with lower CFU compared to TiZr. The biomass staining technique and cell culturing correlated for EL and PA.ConclusionSilver‐based noble alloy and gold‐based high noble alloy demonstrated the least biofilm formation indicating a potential clinical use as material for implant components in the transmucosal compartment. Zirconia and Polyetherketoneketone revealed similar results as the reference material titanium zirconium alloy used in commercially available titanium dental implant.
Radiologic comparative analysis between saline and platelet‐rich fibrin filling after hydraulic transcrestal sinus lifting without adjunctive bone graft: A randomized controlled trial
Authors: Cho Yong‐Seok , Hwang Kyung‐Gyun , Jun Sang Ho , Tallarico Marco , Kwon Amy M. , Park Chang‐Joo 
Published: September 2020

AbstractObjectivesTo evaluate implant survival rate, any complications, and changes in residual alveolar bone height (RABH) using saline or platelet‐rich fibrin (PRF) filling after hydraulic transcrestal sinus lifting.MethodsDental implants were placed after hydraulic transcrestal sinus lifting and the filling of saline (20 patients) or PRF (20 patients). Outcome measurements were implant survival, any complications, and RABH changes. Cone‐beam computed tomography (CBCT) scans were taken and compared preoperatively (T0), immediately postoperatively (T1), at 3 months (T2), 6 months (T3), and 12 months postoperatively (T4), respectively.ResultsIn a total of 40 patients, 45 implants with a mean length of 10.4 ± 0.8 mm were placed in posterior maxilla of a mean RABH of 6.8 ± 1.1 mm. The increase in RABH peaked at T1, and continuous drooping of the sinus membrane was observed but stabilized at T3. Meanwhile, the gradual increase in the radiopacities was found below the lifted sinus membrane. The PRF filling induced the radiographic intrasinus bone gain of 2.6 ± 1.1 mm, which was significantly more than 1.7 ± 1.0 mm of saline filling at T4 (p < .05). All the implants were in function with no significant complications over the one‐year follow‐up period.ConclusionsIn this randomized case–control study, the feasibility of hydraulic transcrestal sinus lifting without bone graft was confirmed and PRF might be a better filler to support the elevated sinus membrane. However, adjunctive bone grafting should still be indicated for cases requiring more than 2–3 mm of intrasinus bone gain.
IL2RG‐deficient minipigs generated via CRISPR/Cas9 technology support the growth of human melanoma‐derived tumours
Authors: Ren Jilong , Yu Dawei , Fu Rui , An Peipei , Sun Renren , Wang Zhengzhu , Guo Runfa , Li Haoyun , Zhang Ying , Li Ziyi , Yang Yong‐Guang , Li Wei , Hai Tang , Hu Zheng 
Published: September 2020

AbstractObjectivesImmunodeficient mice injected with human cancer cell lines have been used for human oncology studies and anti‐cancer drug trials for several decades. However, rodents are not ideal species for modelling human cancer because rodents are physiologically dissimilar to humans. Therefore, anti‐tumour drugs tested effective in rodents have a failure rate of 90% or higher in phase III clinical trials. Pigs are similar to humans in size, anatomy, physiology and drug metabolism rate, rendering them a desirable pre‐clinical animal model for assessing anti‐cancer drugs. However, xenogeneic immune rejection is a major barrier to the use of pigs as hosts for human tumours. Interleukin (IL)‐2 receptor γ (IL2RG), a common signalling subunit for multiple immune cytokines including IL‐2, IL‐4, IL‐7, IL‐9, IL‐15 and IL‐21, is required for proper lymphoid development.Materials and MethodsIL2RG−/Y pigs were generated by CRISPR/Cas9 technology, and examined for immunodeficiency and ability to support human oncogenesis.ResultsCompared to age‐matched wild‐type pigs, IL2RG−/Y pigs exhibited a severely impaired immune system as shown by lymphopenia, lymphoid organ atrophy, poor immunoglobulin function, and T‐ and NK‐cell deficiency. Human melanoma Mel888 cells generated tumours in IL2RG−/Y pigs but not in wild‐type littermates. The human tumours grew faster in IL2RG−/Y pigs than in nude mice.ConclusionsOur results indicate that these pigs are promising hosts for modelling human cancer in vivo, which may aid in the discovery and development of anti‐cancer drugs.
Topography, more than land cover, explains genetic diversity in a Neotropical savanna tree frog
Authors: Nali Renato C. , Becker C. Guilherme , Zamudio Kelly R. , Prado Cynthia P. A. 
Published: September 2020

AbstractAimEffective conservation policies rely on information about population genetic structure and the connectivity of remnants of suitable habitats. The interaction between natural and anthropogenic discontinuities across landscapes can uncover the relative contributions of different barriers to gene flow, with direct consequences for decision‐making in conservation. We aimed to quantify the relative roles of land cover and topographic variables on the population genetic differentiation and diversity of a stream‐breeding savanna tree frog (Bokermannohyla ibitiguara) across its range.LocationSerra da Canastra mountain range, Cerrado of Minas Gerais State, Brazil.MethodsWe collected samples and extracted DNA samples from 12 populations within and outside a strictly protected park, and used 17 microsatellite markers to assess genetic structure, among‐population differentiation and within‐population diversity measures. We incorporated landscape data derived from digital models and satellite images to create connectivity matrices to correlate with genetic differentiation using Mantel tests. We used generalized linear models and path analyses to assess the roles of each landscape variable in shaping genetic diversity in this species.ResultsPopulations within and outside the park boundaries belonged to four genetic clusters. Most populations showed evidence of limited gene flow, with significant genetic differentiation, except for those within the park, which also had higher levels of allelic richness and heterozygosity. However, genetic differentiation among populations in this landscape was primarily explained by topographic complexity. Likewise, within‐population measures of genetic diversity were best explained by models including elevation and topographic complexity, and not the amount of natural habitat or gallery forests.Main conclusionsOur results underscore that topography may be a strong historical factor shaping genetic structure among amphibian populations. Therefore, effective conservation strategies for endangered amphibians should avoid focusing exclusively on habitat suitability, and incorporate topographic complexity, which seems to be a key factor for the fauna of the extremely threatened Brazilian savanna.
The effect of dopamine agonists on metabolic variables in adults with type 2 diabetes: A systematic review with meta analysis and trial sequential analysis of randomized clinical trials
Authors: Andersen Ida Brandt , Andreassen Mikkel , Krogh Jesper 
Published: September 2020

AbstractAimTo assess the metabolic effects of dopamine agonists compared with placebo in randomized controlled trials (RCTs) including adults with type 2 diabetes.Materials and methodsEligible trials were identified by searching PubMed, Embase and CENTRAL. The primary outcomes were HbA1c and serious adverse events (SAEs) assessed at longest available follow‐up. Secondary outcomes were fasting plasma glucose, adverse events, body weight, hypoglycaemia and triglycerides. We assessed risk of bias and evaluated the certainty of the evidence with the Grading of Recommendations Assessment, Development and Evaluation (GRADE).ResultsNine RCTs enrolling 3456 participants were included, six of which assessed the effect of bromocriptine, and the other three the effect of cabergoline. Dopamine agonists reduced HbA1c with 0.69 standardized mean difference (95% CI = 0.28 to 1.09; P = .0008; I2 = 80%; GRADE: low) compared with placebo. There was no difference in the effect between bromocriptine and cabergoline. Heterogeneity was partly explained by dosage and study duration, both of which were inversely associated with effect size. Only one large trial reported SAEs and no difference was reported for the risk of an SAE (RR = 0.89; 95% CI = 0.70 to 1.12; P = .32) between active intervention and placebo. Secondary outcomes suggested a decrease in fasting plasma glucose and triglycerides and no effect on the remaining outcomes.ConclusionDopamine agonists reduce HbA1c as well as fasting plasma glucose and triglycerides in patients with type 2 diabetes without causing SAEs. These data are based on moderate to low quality evidence thus our confidence in the effect estimates is limited.
Reduced phenotypic plasticity evolves in less predictable environments
Authors: Leung Christelle , Rescan Marie , Grulois Daphné , Chevin Luis‐Miguel 
Published: September 2020

AbstractPhenotypic plasticity is a prominent mechanism for coping with variable environments, and a key determinant of extinction risk. Evolutionary theory predicts that phenotypic plasticity should evolve to lower levels in environments that fluctuate less predictably, because they induce mismatches between plastic responses and selective pressures. However, this prediction is difficult to test in nature, where environmental predictability is not controlled. Here, we exposed 32 lines of the halotolerant microalga Dunaliella salina to ecologically realistic, randomly fluctuating salinity, with varying levels of predictability, for 500 generations. We found that morphological plasticity evolved to lower degrees in lines that experienced less predictable environments. Evolution of plasticity mostly concerned phases with slow population growth, rather than the exponential phase where microbes are typically phenotyped. This study underlines that long‐term experiments with complex patterns of environmental change are needed to test theories about population responses to altered environmental predictability, as currently observed under climate change.