bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enterovirus infection and type 1 diabetes: unraveling the crime scene
Authors: Rodriguez-Calvo T 
Published: October 2018

SummaryEnteroviruses (EV) have been historically associated to type 1 diabetes. Definitive proof for their implication in disease development is lacking, but growing evidence suggests that they could be involved in beta cell destruction either directly by killing beta cells or indirectly by creating an exacerbated inflammatory response in the islets, capable of attracting autoreactive T cells to the ‘scene of the crime’. Epidemiological and serological studies have been associated with the appearance of islet autoimmunity and EV RNA has been detected in prospective studies. In addition, the EV capsid protein has been detected in the islets of recent-onset type 1 diabetic donors, suggesting the existence of a low-grade EV infection that could become persistent. Increasing evidence in the field shows that a ‘viral signature’ exists in type 1 diabetes and involves interferon responses that could be sustained during prolonged periods. These include the up-regulation of markers such as protein kinase R (PKR), melanoma differentiation-associated protein 5 (MDA5), retinoic acid inducible gene I (RIG-I), myxovirus resistance protein (MxA) and human leukocyte antigen-I (HLA-I) and the release of chemokines able to attract immune cells to the islets leading to insulitis. In this scenario, the hyperexpression of HLA-I molecules would promote antigen presentation to autoreactive T cells, favoring beta cell recognition and, ultimately, destruction. In this review, an overview of the standing evidence that implicates EVs in beta cell ‘murder’ is provided, the time-line of events from EV entry in the cell to beta cell death is investigated and possible accomplices that might be involved in beta cell demise are highlighted.
IL4-10 fusion protein: a novel immunoregulatory drug combining activities of interleukin 4 and interleukin 10
Authors: Steen-Louws C , Hartgring S A Y , Popov-Celeketic J , Lopes A P , de Smet M B M , Eijkelkamp N , Lafeber F P J G , Hack C E , van Roon J A G 
Published: October 2018

Summary
The objective of this study was to test the capacity of a newly developed fusion protein of interleukin 4 (IL-4) and IL-10 [IL4-10 fusion protein (FP)] to shift multiple pro-inflammatory pathways towards immune regulation, and to inhibit pro-inflammatory activity in arthritis models. The effects of IL4-10 FP in comparison with IL-4, IL-10 and IL-4 plus IL-10 on pro- and anti-inflammatory mediators, T cells and immunoglobulin (Ig) receptors in favour of immunoregulatory activity were studied. In addition, the capacity of IL4-10 FP to inhibit pro-inflammatory activity in ex-vivo and in-vivo arthritis models was investigated. IL4-10 FP robustly inhibited pro-inflammatory cytokine [IL-1β, tumour necrosis factor (TNF)-α, IL-6 and IL-8] production in whole blood cultures, mediated by both the IL-10 and the IL-4 moiety. IL4-10 fusion protein induced IL-1 receptor antagonist (IL-1RA) production and preserved soluble TNF receptor (sTNFR) levels, strongly increasing IL-1RA/IL-1β and sTNFR/TNF-α ratios. In addition, IL4-10 FP strongly inhibited T helper (Th) type 1 and 17 cytokine secretion, while maintaining FoxP3 expression and up-regulating Th2 activity. In addition, while largely leaving expression of activating Fc gamma receptor (FcγR)I, III and Fc epsilon receptor (FcεR) unaffected, it significantly shifted the FcγRIIa/FcγRIIb ratio in favour of the inhibitory FcγRIIb. Moreover, IL4–10 FP robustly inhibited secretion of pro-inflammatory cytokines by rheumatoid arthritis synovial tissue and suppressed experimental arthritis in mice, without inducing B cell hyperactivity. IL4-10 fusion protein is a novel drug, signalling cells to induce immunoregulatory activity that overcomes limitations of IL-4 and IL-10 stand-alone therapy, and therefore has therapeutic potential for inflammatory diseases such as rheumatoid arthritis.
The use of platelet‐rich plasma to enhance the outcomes of implant therapy: A systematic review
Authors: Stähli Alexandra , Strauss Franz Josef , Gruber Reinhard 
Published: October 2018

AbstractObjectiveTo assess the effect of platelet‐rich plasma (PRP) on implant dentistry. The primary focused question was as follows: What are the clinical, histological, and radiographic outcomes of PRP administration for bone regeneration and implant therapy?MethodsA literature search was conducted involving three databases: MEDLINE, EMBASE and Cochrane database followed by a hand search of relevant scientific journals. Human studies using PRP for bone regeneration and implant therapy were considered and articles published up to December 31, 2017 were included. Eligible studies were selected based on the inclusion criteria, and quality assessments were conducted.ResultsIn total, out from the 9,497 titles meeting the original search criteria, 22 fulfilled the inclusion criteria and were chosen for data extraction. Among them were 15 randomized controlled trials (RCT) and seven controlled clinical trials (CCT). Overall, the risk of bias was moderate to high. A total of seven studies showed superior outcomes when PRP was added during sinus floor elevation and five showed no superior outcome. Three studies found a significant advantage of PRP for alveolar bone regeneration and another three studies for soft tissue healing. Three studies reported on beneficial effects of PRP directly during implant placement while another study failed to find significant differences. Due to the heterogeneity of study designs, no meta‐analysis could be performed.Summary and ConclusionsDespite the lack of consistent evidence supporting the clinical benefit of PRP in healthy patients, PRP might have a positive effect on wound healing and bone regeneration in compromised patients.
The relationship of previous dental trauma with new cases of dental trauma. A systematic review and meta‐analysis
Authors: Magno Marcela B. , Neves Aline B. , Ferreira Daniele M. , Pithon Matheus M. , Maia Lucianne C. 
Published: October 2018

AbstractBackground/AimsTraumatic dental injuries (TDI) are a public health concern with high prevalence and recurrence rate. The aim of this study was to perform a systematic review and meta‐analysis to determine whether previous dental trauma is a predictive factor for new episodes of TDI (recurrence or first episodes).Materials and MethodsElectronic searches were performed with no language or date restrictions. According to the PECOS strategy, cohort studies that investigated subjects with and without previous TDI, and its association with new TDI episodes, as primary or secondary outcomes, were included. Quality assessment and bias control were carried out according to Fowkes and Fulton guidelines. A meta‐analysis was performed by sub‐grouping studies into deciduous and permanent dentition, and the risk ratio (RR) was also calculated (P ≤ 0.05). The evidence was quality‐tested using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.ResultsAfter titles and abstracts were examined, and full texts were read, five studies were included in this systematic review. Four studies had high methodological quality, and one presented a risk of bias on confounding factors. No association and a positive association were determined between previous history of TDI and new episodes of TDI in the primary (RR 1.26 [0.99, 1.62], P = 0.06) and in the permanent dentitions (RR 2.68 [1.20, 4.19], I2 = 37%, P < 0.00001), respectively. The pooled results demonstrated a positive association (P < 0.00001) between previous dental trauma and new episodes of TDI (RR 2.17 [1.20, 3.90], P = 0.01, I2 = 83%) with moderate evidence quality level.ConclusionsIndividuals that have suffered previous TDI present a greater risk of suffering new episodes of TDI.
Latent profile analysis of psychosis liability in a community‐derived sample of adolescents: Links with mental health difficulties, suicidal ideation, bipolar‐like experiences and psychotic‐like experiences
Authors: Fonseca‐Pedrero Eduardo , Ortuño‐Sierra Javier , Muñiz José , Bobes Julio 
Published: October 2018

AimThe main goal of the present study was to explore the latent structure of schizotypy as an indicator of psychosis liability, in a community‐derived sample of adolescents. Links to mental health difficulties, prosocial behaviour, suicidal ideation, bipolar‐like experiences and psychotic‐like experiences (PLEs) (severity and distress) were compared across schizotypy latent profiles.MethodThe present research included 1588 adolescents selected by a stratified random cluster sampling. The Oviedo Schizotypy Assessment Questionnaire (ESQUIZO‐Q), The Paykel Suicide Scale (PSS), The Strengths and Difficulties Questionnaire (SDQ), The Prodromal Questionnaire‐Brief (PQ‐B), The Mood Disorder Questionnaire (MDQ), The Penn Matrix Reasoning Test (PMRT), The Family Affluence Scale‐II (FAS‐II), and The Oviedo Infrequency Scale (INF‐OV) were used.ResultsUsing latent profile analysis four latent classes (LC) were identified: “Positive schizotypy” (14.1%, n = 224), “Low schizotypy” (51.9%, n = 825), “Social Disorganization schizotypy” (27.2%, n = 432), and “High schizotypy” (6.7%, n = 107). The “High schizotypy” class scored higher on several psychometric indicators of psychopathology (ie, mental health difficulties, suicide ideation, bipolar‐like experiences and PLEs) relative to the other three LC.ConclusionFour groups of adolescents with different patterns of schizotypal traits and different clinical‐pathological meaning were found. Deficits found across schizotypy latent profiles, resembling those found in patients with psychosis and ultra‐high risk samples. The identification of homogeneous subgroups of adolescents potentially at risk for psychosis may help us in the prevention of psychotic‐spectrum disorders and mental health problems.
Strengthening Indigenous cultural competence in dentistry and oral health education: Academic perspectives
Authors: Forsyth Cathryn , Irving Michelle , Short Stephanie , Tennant Marc , Gilroy John 
Published: October 2018

AbstractIntroductionIndigenous Australians continue to experience significant oral health disparities, despite numerous closing‐the‐gap initiatives. Higher education institutions and accrediting bodies recognise the need to incorporate Indigenous culture more widely into dentistry curricula to address these inequalities. This study aimed to define and explore current Indigenous cultural competence curricula, identify enablers and barriers for integration of Indigenous cultural competence curricula and ascertain innovative strategies to aid students in becoming culturally competent upon graduation, from academics' perspectives.MethodsAcademics from the Doctor of Dental Medicine (DMD) and Bachelor of Oral Health (BOH) programmes at the University of Sydney, School of Dentistry participated in semi‐structured interviews to define and explore current and future curricula practices to enable students to become competent in Indigenous culture. Thematic analysis was conducted to synthesise academics' responses.ResultsThirteen School of Dentistry academics participated in interviews. Following analysis of the data, six key themes emerged: Theme One: Transfer of Indigenous cultural knowledge, Theme Two: Barriers to developing Indigenous cultural curriculum. Theme Three: Importance of cultural immersion, Theme Four: Resources required for Indigenous cultural education, Theme Five: Proposed Indigenous cultural content, Theme Six: Strategies to incorporate Indigenous culture into curricula.ConclusionImproving Indigenous cultural competence amongst dentistry academics and students requires an educational and philosophical shift, incorporating the social determinants of health whilst maintaining the strengths of the biomedical foundations of dental care. It requires the inclusion of an informed history of Indigenous Australians, immersion within Indigenous communities and reflection upon these experiences, to facilitate culturally appropriate ways to improve the provision of dentistry and oral health for Indigenous peoples.
Limitations on the human capital transferability of adult migrants in Spain: Incentive or barrier for a new investment in education?
Authors: Muñoz‐Comet Jacobo , Miyar‐Busto María 
Published: October 2018

AbstractMany empirical studies on immigrant integration document the benefits of an education acquired in the country of destination. In this article; we study how the degree of human capital transferability affects an immigrant's chances of studying in Spain. We used data from the Spanish Labour Force Survey (2008–2015) for a sample of adults aged 18–55 who had left the educational system. The main findings show that natives are the ethnic group with the highest likelihood of re‐enrolling in education. Amongst immigrants, those with fewer limitations on human capital transferability also invest more. These results question the predictions of the Immigrant Human Capital Investment model which expect that immigrants whose human capital depreciates upon arrival and those who can obtain a higher return on a new investment in education are therefore more likely to study. Moreover, the effect of skill transferability differs depending on the type of obstacle and the kind of education. Immigrants with less linguistic and cultural familiarity with the host country are less likely to undertake non‐formal education than formal education. However, when the transferability obstacles are related to administrative requirements and legal restrictions, the probability of investing in non‐formal education is higher. We conclude that immigrants with low skill transferability are not only less well integrated in the labour market upon arrival, but are also less able to redress that disadvantage through a new investment in education.
A randomized controlled trial of a walking training with simultaneous cognitive demand (dual‐task) in chronic stroke
Authors: Meester D. , Al‐Yahya E. , Dennis A. , Collett J. , Wade D. T. , Ovington M. , Liu F. , Meaney A. , Cockburn J. , Johansen‐Berg H. , Dawes H. 
Published: October 2018

Background and purposeThe aim was to evaluate the tolerability of, adherence to and efficacy of a community walking training programme with simultaneous cognitive demand (dual‐task) compared to a control walking training programme without cognitive distraction.MethodsAdult stroke survivors at least 6 months after stroke with a visibly obvious gait abnormality or reduced 2‐min walk distance were included in a two‐arm parallel randomized controlled trial of complex intervention with blinded assessments. Participants received a 10 week, bi‐weekly, 30 min treadmill programme at an aerobic training intensity (55%–85% heart rate maximum), either with or without simultaneous cognitive demands. Outcome was measured at 0, 11 and 22 weeks. The primary assessment involved 2‐min walk tests with and without cognitive distraction to investigate the dual‐task effect on walking and cognition; secondary results were the Short Form Health Survey 36, EuroQol‐5D‐5L, the Physical Activity Scale for the Elderly (PASE) and step activity.ResultsFifty stroke patients were included; 43 received allocated training and 45 completed all assessments. The experimental group (n = 26) increased their mean (SD) 2‐min walking distance from 90.7 (8.2) to 103.5 (8.2) m, compared with 86.7 (8.5) to 92.8 (8.6) m in the control group, and their PASE score from 74.3 (9.1) to 89.9 (9.4), compared with 94.7 (9.4) to 77.3 (9.9) in the control group. Statistically, only the change in the PASE differed between the groups (P = 0.029), with the dual‐task group improving more. There were no differences in other measures.ConclusionsWalking with specific additional cognitive distraction (dual‐task training) might increase activity more over 12 weeks, but the data are not conclusive.
A novel GABAergic dysfunction in human Dravet syndrome
Authors: Ruffolo Gabriele , Cifelli Pierangelo , Roseti Cristina , Thom Maria , van Vliet Erwin A. , Limatola Cristina , Aronica Eleonora , Palma Eleonora 
Published: October 2018

SummaryObjectiveDravet syndrome is a rare neurodevelopmental disease, characterized by general cognitive impairment and severe refractory seizures. The majority of patients carry the gene mutation SCN1A, leading to a defective sodium channel that contributes to pathogenic brain excitability. A γ‐aminobutyric acid (GABAergic) impairment, as in other neurodevelopmental diseases, has been proposed as an additional mechanism, suggesting that seizures could be alleviated by GABAergic therapies. However, up to now the physiological mechanisms underlying the GABAergic dysfunction in Dravet syndrome are still unknown due to the scarce availability of this brain tissue. Here we studied, for the first time, human GABAA‐evoked currents using cortical brain tissue from Dravet syndrome patients.MethodsWe transplanted in Xenopus oocytes cell membranes obtained from brain tissues of autopsies of Dravet syndrome patients, tuberous sclerosis complex patients as a pathological comparison, and age‐matched controls. Additionally, experiments were performed on oocytes expressing human α1β2γ2 and α1β2 GABAA receptors. GABAA currents were recorded using the two‐microelectrodes voltage‐clamp technique. Quantitative real‐time polymerase chain reaction, immunohistochemistry, and double‐labeling techniques were carried out on the same tissue samples.ResultsWe found (1) a decrease in GABA sensitivity in Dravet syndrome compared to controls, which was related to an increase in α4‐ relative to α1‐containing GABAA receptors; (2) a shift of the GABA reversal potential toward more depolarizing values in Dravet syndrome, and a parallel increase of the chloride transporters NKCC1/KCC2 expression ratio; (3) an increase of GABAA currents induced by low doses of cannabidiol both in Dravet syndrome and tuberous sclerosis complex comparable to that induced by a classical benzodiazepine, flunitrazepam, that still persists in γ‐less GABAA receptors.SignificanceOur study indicates that a dysfunction of the GABAergic system, considered as a feature of brain immaturity, together with defective sodium channels, can contribute to a general reduction of inhibitory efficacy in Dravet brain, suggesting that GABAA receptors could be a target for new therapies.
Linagliptin inhibits high glucose‐induced transdifferentiation of hypertrophic scar‐derived fibroblasts to myofibroblasts via IGF/Akt/mTOR signalling pathway
Authors: Li Yan , Zhang Julei , Zhou Qin , Wang Hongtao , Xie Songtao , Yang Xuekang , Ji Peng , Zhang Wanfu , He Ting , Liu Yang , Wang Kejia , Li Xiaoqiang , Shi Jihong , Hu Dahai 
Published: October 2018

AbstractHypertrophic scar (HS) is a fibroproliferative disease after serious burns; the underlying mechanism remains unknown. The study was performed to clarify the effect of high glucose (HG) on HS. The expression of Col1, Col3 and α‐SMA was upregulated in HS‐derived fibroblasts (HSF) exposed to HG (20 and 30 mmol/L), and HG activated the phosphorylated protein expression of IGF/Akt/mTOR signalling pathway in HSF. Dpp4, a marker targeted the treatment of diabetes mellitus, was overexpressed in HG‐induced HSF. Linagliptin, a Dpp4 inhibitor, played the antifibrotic role in HSF exposed to HG, the levels of Col1, Col3 and α‐SMA were significantly downregulated, and the cell proliferation and migration were also inhibited. Furthermore, linagliptin alleviated the phosphorylated protein expression of IGF/Akt/mTOR signalling pathway. Moreover, the mTOR inhibitor (rapamycin) mimicked the effect of linagliptin on the collagen and α‐SMA that means linagliptin may inhibit HG‐induced transdifferentiation of HSF to myofibroblasts via IGF/Akt/mTOR signalling pathway.
Small changes in timing of breeding among subarctic passerines over a 32‐year period
Authors: Ram Dafne , Nyholm NILS ERIK INGEMAR , Arlt Debora , Lindström Åke 
Published: October 2018

Many bird populations in temperate regions have advanced their timing of breeding in response to a warming climate in recent decades. However, long‐term trends in temperature differ geographically and between seasons, and so do responses of local breeding populations. Data on breeding bird phenology from subarctic and arctic passerine populations are scarce, and relatively little data has been recorded in open‐nesting species. We investigated the timing of breeding and its relationship to spring temperature of 14 mainly open‐nesting passerine species in subarctic Swedish Lapland over a period of 32 years (1984–2015). We estimated timing of breeding from the progress of post‐juvenile moult in mist‐netted birds, a new method exploring the fact that the progress of post‐juvenile moult correlates with age. Although there was a numerical tendency for earlier breeding in most species (on average −0.09 days/year), changes were statistically significant in only three species (by −0.16 to −0.23 days/year). These figures are relatively low compared with what has been found in other long‐term studies but are similar to a few other studies in subarctic areas. Generally, annual hatching dates were negatively correlated with mean temperature in May. This correlation was stronger in long‐distance than in short‐distance migrants. Although annual temperatures at high northern latitudes have increased over recent decades, there was no long‐term increase in mean temperature in May over the study period at this subarctic site. This is probably the main reason why there were only small long‐term changes in hatching dates.
Measuring and reporting obligations of social security retirement systems: Actuarial perspectives
Authors: D’Ambrogi‐Ola Barbara , Brown Robert L. 
Published: October 2018

AbstractThe article is based on the International Actuarial Association (IAA) Social Security Committee's principles‐based paper with commentary on measurement and reporting obligations of social security retirement systems (SSRSs) and proposals for appropriate disclosure requirements, for consideration by national and international organizations when developing reporting standards in respect to SSRSs. The article argues that the method of measuring and reporting obligations should be consistent with the financing basis of the SSRS. In particular, SSRSs financed on a pay‐as‐you‐go (PAYG) or partially funded basis should use an open‐group method for measuring and reporting actuarial obligations. Only SSRSs that purport to be fully funded should use a closed‐group basis, since SSRSs are not analogous to large private‐sector pension plans. For most PAYG and partially funded SSRSs, accounting for obligations on a closed‐group basis would indicate huge actuarial unfunded liabilities, which might not be understood by the general public and could inappropriately create pressure to move towards fully‐funded systems. The methodologies used for accounting and/or statistical reporting should enable the accurate assessment of the long‐term financial sustainability of any SSRS without a bias for or against a particular financing approach. The article prefers measures of sustainability of an SSRS to measures of its funding level. A system that is fully funded currently may not be sustainable while a pure PAYG SSRS may be sustainable. In the case where there is a requirement to disclose obligations on a closed‐group basis, such disclosures should be supplemented by an open‐group analysis, with appropriate reconciliations and explanations (i.e. a multiple disclosure approach).