bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cumulative incidence and relative risk of sleep problems among children and adolescents with newly diagnosed neurodevelopmental disorders: A nationwide register‐based study
Authors: Hvolby Allan , Christensen Jakob , Gasse Christiane , Dalsgaard Søren , Dreier Julie Werenberg 
Published: June 2020

AbstractWe estimated the absolute and relative risk of sleep problems in children and adolescents with newly diagnosed neurodevelopmental disorders. This was a population‐based cohort study of individuals born in Denmark in 1993–2014 and followed in nationwide registers in 2011–2016. We estimated the 5‐year cumulative incidence of sleep problems in incident cases of attention‐deficit/hyperactivity disorder (ADHD; n = 12,844), autism spectrum disorder (ASD; n = 8,073), oppositional defiant disorder/conduct disorder (ODD/CD; n = 2,234) and epilepsy (n = 3,709). Hazard ratios (HRs) for sleep problems were estimated by Cox regression. The 5‐year risk of sleep problems was highest in ADHD (29.2%; 95% CI, 28.4–30.1), ASD (24.2%; 95% CI, 23.1–25.3) and ODD/CD (27.1% 95% CI, 25.0%–29.2%) and lowest in epilepsy (11.3%; 95% CI, 10.2%–12.6%). For ADHD and ASD, sleep problems were more common in females than in males. Furthermore, sleep problems were predicted by high parental socioeconomic status and varied with the geographical region of residence, suggesting that different clinical practices exist across Denmark and that sleep problems may be more likely to go undetected in families of lower socioeconomic position. Compared with individuals without these disorders, the likelihood of sleep problems was increased in individuals with ADHD (HR, 33.81; 95% CI, 32.78–34.87), ASD (HR, 16.77; 95% CI, 16.15–17.41), ODD/CD (HR, 14.73; 95% CI, 13.88–15.64) and epilepsy (HR, 6.01; 95% CI, 5.67–6.37). After mutual adjustment for comorbidity, HRs were attenuated, especially in ASD, ODD/CD and epilepsy when adjusted for ADHD, suggesting that the increased risk of sleep problems in individuals with ASD, ODD/CD and epilepsy is driven largely by comorbid ADHD.
Stable HEV IgG seroprevalence in Belgium between 2006 and 2014
Authors: Ho Erwin , Schenk Julie , Hutse Veronik , Suin Vanessa , Litzroth Amber , Blaizot Stéphanie , Herzog Sereina A. , Verburgh Vera , Jacques Marjorie , Rahman Abbas , Michielsen Peter , Van Damme Pierre , Van Gucht Steven , Theeten Heidi , Hens Niel , Vanwolleghem Thomas 
Published: June 2020

AbstractRecent European studies suggest an emergence of hepatitis E virus (HEV) infection. We evaluated trends in birth cohort‐specific HEV seroprevalence and regional differences in Belgium. HEV IgG seroprevalence was analysed on national serum banks (1579 and 2087 samples for 2006 and 2014, respectively. Hepatitis E virus antigen was tested on positive samples. Observed data were modelled using a generalized additive model with a complementary log‐log link. No significant differences between birth cohorts or sexes were found. Modelling identified the individual's age and province as relevant factors. The probability of HEV seropositivity increases significantly with age. An estimated total of 434 819 (yearly rate of 54,352) (sero‐)infections were found between 2006 and 2014. Overall, HEV IgG seroprevalences were 4.1% (64/1579, 95% CI 3.1‐5.1) and 5.8% (121/2087, CI 4.8‐6.9) in 2006 and 2014, respectively. Observed HEV antigen seroprevalence was 0.027% (1/3666) for the entire cohort. These results show stable HEV IgG seroprevalence in Belgium.
First evidence for continuous circulation of hepatitis A virus subgenotype IIA in Central Africa
Authors: Abe Haruka , Ushijima Yuri , Bikangui Rodrigue , Ondo Georgelin N. , Zadeh Vahid R. , Pemba Christelle M. , Mpingabo Patrick I. , Igasaki Yui , de Vries Sophia G. , Grobusch Martin P. , Loembe Marguerite M. , Agnandji Selidji T. , Lell Bertrand , Yasuda Jiro 
Published: June 2020

AbstractAlthough a high seroprevalence of antibodies against hepatitis A virus (HAV) has been estimated in Central Africa, the current status of both HAV infections and seroprevalence of anti‐HAV antibodies remains unclear due to a paucity of surveillance data available. We conducted a serological survey during 2015‐2017 in Gabon, Central Africa, and confirmed a high seroprevalence of anti‐HAV antibodies in all age groups. To identify the currently circulating HAV strains and to reveal the epidemiological and genetic characteristics of the virus, we conducted molecular surveillance in a total of 1007 patients presenting febrile illness. Through HAV detection and sequencing, we identified subgenotype IIA (HAV‐IIA) infections in the country throughout the year. A significant prevalence trend emerged in the young child population, presenting several infection peaks which appeared to be unrelated to dry or rainy seasons. Whole‐genome sequencing and phylogenetic analyses revealed local HAV‐IIA evolutionary events in Central Africa, indicating the circulation of HAV‐IIA strains of a region‐specific lineage. Recombination analysis of complete genome sequences revealed potential recombination events in Gabonese HAV strains. Interestingly, Gabonese HAV‐IIA possibly acquired the 5’‐untranslated region (5’‐UTR) of the rare subgenotype HAV‐IIB in recent years, suggesting the present existence of HAV‐IIB in Central Africa. These findings indicate a currently stable HAV‐IIA circulation in Gabon, with a high risk of infections in children aged under 5 years. Our findings will enhance the understanding of the current status of HAV infections in Central Africa and provide new insight into the molecular epidemiology and evolution of HAV genotype II.
Real‐world safety and effectiveness of retreatment of Egyptian chronic hepatitis C patients not responding to NS5A inhibitor‐based therapies
Authors: Yousif Monkez M. , Ahmed Hussien , Elsadek Hany M. , shendi Ali M. , Gouda Tamer M. , Elsayed Islam A. , Gendia Mohamed A. , Magdy Mahmoud M. , lbrahim Nevin F. , Sadek Ayman M. E. M. , Zaki Ayman M. , Shafeik Hamdy , Zahran Mahmoud H. 
Published: June 2020

AbstractThe aim of this study was to assess the efficacy and safety of two protocols for retreatment of a cohort of Egyptian patients with chronic hepatitis C (CHC) who relapsed after NS5A inhibitor‐based therapy. We conducted a prospective cohort study to assess the safety and efficacy of 12 weeks’ retreatment with either combination of sofosbuvir/daclatasvir/simeprevir plus ribavirin (SOF/DCV/SMV/RBV, n = 45) or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin (SOF/OBV/PTV/r/RBV, n = 163) in patients who had previously failed NS5A inhibitors‐based regimens. The primary end point was SVR 12 weeks after the end of treatment (SVR12). Safety follow‐up data were recorded for 60 weeks after the end of treatment. Two hundred‐eight patients were included in the study. Of them, 53.4% of patients were females and 40.4% had liver cirrhosis. The most common prior drug combinations were sofosbuvir/daclatasvir (n = 94) and sofosbuvir/daclatasvir plus ribavirin (n = 109). The overall SVR12 rates were 98.1%. In SOF/DCV/SMV/RBV group, 95.6% achieved SVR12, while in SOF/OBV/PTV/r/RBV group, the SVR12 rates were 98.8%. SVR12 was higher in cirrhotic patients (84/84) than noncirrhotic (120/124), P value = .0149. Regarding the safety outcomes, anaemia and fatigue were significantly higher in SOF/OBV/PTV/r/RBV group. Hepatocellular carcinoma (HCC) was reported in eight (3.8%) patients (four in each group). Of them, death was confirmed in four patients. Retreatment of Egyptian CHC relapsed patients with either sofosbuvir/daclatasvir/simeprevir plus ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir plus ribavirin is highly effective and well‐tolerated for both noncirrhotic and compensated cirrhotic patients. Incidental de novo HCC and hepatic decompensation are comparable in the two groups.
Roe deer on ice: Selection despite limited effective population size through the Pleistocene
Authors: Alexander Alana , Dutoit Ludovic 
Published: June 2020

AbstractRoe deer (Capreolus spp.) are a little odd. They are one of only a few placental mammals—and the only genus among even‐toed ungulates—capable of putting embryonic development “on ice”, also known as embryonic diapause (Figure 1). It would seem such an unusual trait is probably the product of natural selection, but a big question is, how does selection for important traits, such as diapause, interact with the historical demography of a species? In a ‘From the Cover’ article in this issue of Molecular Ecology, de Jong et al. (2020) demonstrate that selection is acting on genes associated with reproductive biology in roe deer, despite heightened genetic drift due to reduced effective population size through the Pleistocene.
Host functional and phylogenetic composition rather than host diversity structure plant–herbivore networks
Authors: Wang Ming‐Qiang , Li Yi , Chesters Douglas , Bruelheide Helge , Ma Keping , Guo Peng‐Fei , Zhou Qing‐Song , Staab Michael , Zhu Chao‐Dong , Schuldt Andreas 
Published: June 2020

AbstractDeclining plant diversity alters ecological networks, such as plant–herbivore interactions. However, our knowledge of the potential mechanisms underlying effects of plant species loss on plant–herbivore network structure is still limited. We used DNA barcoding to identify herbivore–host plant associations along declining levels of tree diversity in a large‐scale, subtropical biodiversity experiment. We tested for effects of tree species richness, host functional and phylogenetic diversity, and host functional (leaf trait) and phylogenetic composition on species, phylogenetic and network composition of herbivore communities. We found that phylogenetic host composition and related palatability/defence traits but not tree species richness significantly affected herbivore communities and interaction network complexity at both the species and community levels. Our study indicates that evolutionary dependencies and functional traits of host plants determine the composition of higher trophic levels and corresponding interaction networks in species‐rich ecosystems. Our findings highlight that characteristics of the species lost have effects on ecosystem structure and functioning across trophic levels that cannot be predicted from mere reductions in species richness.
Chances for learning intraprofessional collaboration between residents in hospitals
Authors: Looman Natasja , Fluit Cornelia , van Wijngaarden Marielle , de Groot Esther , Dielissen Patrick , van Asselt Dieneke , de Graaf Jacqueline , Scherpbier‐de Haan Nynke 
Published: June 2020

AbstractContextIntraprofessional collaboration (intraPC) between primary care (PC) doctors and medical specialists (MSs) is becoming increasingly important. Patient safety issues are often related to intraPC. In order to equip doctors well for their task of providing good quality and continuity of care, intraPC needs explicit attention, starting in postgraduate training. Worldwide, PC residents undertake a hospital placement during their postgraduate training, where they work in proximity with MS residents. This placement offers the opportunity to learn intraPC. It is yet unknown whether and how residents learn intraPC and what barriers to and opportunities for exist in learning intraPC during hospital placements.MethodsWe performed an ethnographic non‐participatory observational study in three emergency departments and three geriatric departments of five hospitals in the Netherlands. This was followed by 42 in‐depth interviews with the observed residents and supervisors. The observations were used to feed the questions for the in‐depth interviews. We analysed the interviews iteratively following the data collection using template analysis.ResultsHospital wards are rich in opportunities for learning intraPC. These opportunities, however, are seldom exploited for various reasons: intraPC receives limited attention when formulating placement goals, so purposeful learning of intraPC hardly takes place; residents lack awareness of the learning of intraPC; MS residents are not accustomed to searching for expertise from PC residents; PC residents adapt to the MS role and they contribute very little of their PC knowledge, and power dynamics in the hospital department negatively influence the learning of intraPC. Therefore, improvements in mindset, professional identity and power dynamics are crucial to facilitate and promote intraPC.ConclusionsIntraprofessional collaboration is not learned spontaneously during hospital placements. To benefit from the abundant opportunities to learn intraPC, adjustments to the set‐up of these placements are necessary. Learning intraPC is promoted when there is a collaborative culture, hierarchy is limited, and there is dedicated time for intraPC and support from the supervisor.
Educational design research: Portraying, conducting, and enhancing productive scholarship
Authors: McKenney Susan , Reeves Thomas C. 
Published: June 2020

AbstractContextSolutionism is the all‐too‐common human propensity to jump to a solution before adequately understanding the nature of a problem. Solutionism has long been prevalent in efforts to improve education at all levels, including medical education.ThesisEducational design research (EDR) is a genre of research that features the gaining of in‐depth understanding of a problem before any prototype solution is designed and tested. It is different from other forms of scientific inquiry because it is committed to the simultaneous development of both theoretical insights and practical solutions, together with stakeholders. This approach is powerful for theory building because it privileges ecologically valid studies that embrace the complexity of investigating learning in authentic (as opposed to laboratory) settings. When conducted well, both the research process and its outcomes generate valuable contributions to practice.PreviewThis article constitutes an expository essay on EDR, comprised of three movements. First, the approach is defined, its origins are presented, and its characteristics are described. Second, a generic model for conducting EDR is offered, and illustrated with examples from the field of medical education. Third, pathways towards advancing this form of inquiry are discussed, including ways to address inherent challenges and limitations, as well as recommendations for the medical education community. Although EDR is no panacea, this article illustrates how it can serve medical education research in a wide variety of geographic and disciplinary contexts.
Why impaired wellness may be inevitable in medicine, and why that may not be a bad thing
Authors: Bynum William E. , Varpio Lara , Teunissen Pim 
Published: June 2020

AbstractContextA wellness crisis exists among physicians and medical trainees. High rates of burnout, depression, stress and other states of impaired wellness have driven a sense of urgency to create solutions, and the medical education community has mobilised impressively. However, we argue—and data suggest—that this rush to find solutions has outpaced our efforts to more fully understand the nature of impaired wellness in medicine. This, we believe, has led to the implementation of solutions informed by limited understanding of the problems we intend to solve.MethodsIn this paper, we explore three contributors to this situation: (i) shaky definitions and conceptualisations of wellness, (ii) the predominance of deductive, quantitative research informing our understanding and current solutions, and (iii) the reliance on a ‘disease‐focused’ approach to addressing impaired wellness in physicians and trainees. We discuss how these contributors have led to the current state of the science of wellness in medicine: one characterised by an expanding array of solutions built upon narrow conceptualisations of wellness and how it can be impaired.DiscussionMoving beyond the current state of the science on wellness in medicine will require three critical developments: (i) consistent use of clear definitions of wellness; (ii) expanding our methodologies to include those utilising direct interaction with participants; and (iii) moving beyond solutions informed by a disease‐model approach. We propose a different way of thinking about wellness: one based on what we view as an inherent—and potentially unavoidable—risk of experiencing impairment during a career in medicine. We argue that efforts to extinguish and eliminate all states of impaired wellness may also eliminate opportunities to develop constructive coping mechanisms and future resilience, and that wellness may best be conceptualised as healthy and authentic engagement with the inevitable adversity of a career in medicine.
Liquid platelet‐rich fibrin promotes the regenerative potential of human periodontal ligament cells
Authors: Zheng Shihang , Zhang Xiaoxin , Zhao Qin , Chai Jihua , Zhang Yufeng 
Published: June 2020

AbstractObjectiveTo compare the biological effect of PRP and liquid‐PRF on human periodontal ligament cells (hPDLCs) in vitro.MethodsThe liquid‐PRF was processed with centrifugation at 700 g for 3 min, and PRP was processed according to Curasan's protocol. Migration and proliferation assay were performed by a scratch/Transwell assay and a CCK‐8 assay, respectively. To investigate hPDLC differentiation, alkaline phosphatase (ALP) assay, Alizarin Red S staining, and gene expression level detection of Runx2, Col1a1, and OCN were conducted. Furthermore, cells cultured with lipopolysaccharide (LPS) to induce an inflammation condition were utilized to investigate the impact of liquid‐PRF on inflammatory resolution.ResultsEither PRP or liquid‐PRF can promote proliferation, migration of hPDLCs, and osteogenic differentiation of hPDLCs. It was noteworthy that liquid‐PRF demonstrated a significantly higher ability to promote the biological differentiation and mineralization of hPDLCs compared with PRP. Lastly, when hPDLCs were incubated with LPS, cells cultured with liquid‐PRF showed significantly lower mRNA expression levels of inflammatory genes.ConclusionsLiquid‐PRF notably promoted hPDLC activity and attenuated the inflammatory state induced by LPS.
Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic carcinoma and mucoepidermoid carcinoma
Authors: Wu Cong‐Cong , Li Hao , Xiao Yao , Deng Wei‐Wei , Sun Zhi‐Jun 
Published: June 2020

AbstractObjectiveAdenoid cystic carcinoma (AdCC) and mucoepidermoid carcinoma (MEC) are the most frequent malignancies in the salivary glands. The purpose of this study was to explore the roles of sine oculis homeobox homolog 1 (SIX1), malic enzyme 2 (ME2), and AP‐2 complex subunit mu (AP2M1) in AdCC and MEC, as well as the potential relationship between SIX1, ME2, AP2M1, and proliferation marker cyclin D1.Material and methodsImmunohistochemistry was performed on human salivary gland tissue microarrays that contained 76 normal salivary glands (NSGs), 14 pleomorphic adenomas (PMAs), 81 AdCCs, and 52 MECs.ResultsWe observed that the expression levels of SIX1 and ME2 were significantly elevated in AdCC and MEC when compared with NSG and PMA. In addition, we detected that AP2M1 was overexpressed in AdCC and MEC when compared with NSG. We also found that SIX1 and AP2M1 were positively associated with cyclin D1.ConclusionsThese results may prove that SIX1 and AP2M1 are involved in the proliferation of AdCC and MEC to cause tumor growth.
Primary tumor characteristics and next‐generation sequencing mutations as biomarkers for melanoma immunotherapy response
Authors: Loo Kimberly , Gauvin Gabrielle , Soliman Iman , Renzetti Madelyn , Deng Mengying , Ross Eric , Luo Biao , Wu Hong , Reddy Sanjay , Olszanski Anthony J. , Farma Jeffrey M. 
Published: June 2020

AbstractIntroductionConsiderable advances in melanoma have been realized through immunotherapy. The principal aim was to determine whether primary tumor characteristics or next‐generation sequencing (NGS) could serve as markers of immunotherapy response.Methods and ResultsThe study cohort consisted of 67 patients who received immunotherapy for recurrent or metastatic melanoma and for whom primary tumor biopsies and pathology reports were available. A subset of 59 patient tumors were profiled using an NGS panel of 50 cancer‐related genes. Objective response rate to immunotherapy was assessed using RECIST v1.1 criteria. Progression‐free survival (PFS) and overall survival (OS) were used as endpoints. Lymphovascular invasion (LVI) strongly correlated with an increased proportion of immunotherapy responders (p = .002). PFS interval (p = .003) and OS (p = .036) were significantly higher in patients with LVI. NRAS mutation was more strongly correlated with an increased proportion of immunotherapy responders (p =.050). PFS was significantly higher in patients with NRAS mutation (p = .042); no difference in OS (p = .111).DiscussionThis analysis demonstrates an association between lymphovascular invasion and immunotherapy response. Additionally, NGS mutation analysis demonstrated a potential association between NRAS mutations and immunotherapy response.
Stem cell‐derived enteroid cultures as a tool for dissecting host‐parasite interactions in the small intestinal epithelium
Authors: Hares Miriam F. , Tiffney Ellen‐Alana , Johnston Luke J. , Luu Lisa , Stewart Christopher J. , Flynn Robin J. , Coombes Janine L. 
Published: June 2020

AbstractToxoplasma gondiiandCryptosporidiumspp. can cause devastating pathological effects in humans and livestock, and in particular to young or immunocompromised individuals. The current treatment plans for these enteric parasites are limited due to long drug courses, severe side effects or simply a lack of efficacy. The study of the early interactions between the parasites and the site of infection in the small intestinal epithelium has been thwarted by the lack of accessible, physiologically relevant and species‐specific models. Increasingly, 3D stem cell‐derived enteroid models are being refined and developed into sophisticated models of infectious disease. In this review, we shall illustrate the use of enteroids to spearhead research into enteric parasitic infections, bridging the gap between cell line cultures and invivoexperiments.
Amoebic gill disease and host response in Atlantic salmon (Salmo salar L.): A review
Authors: Marcos‐López Mar , Rodger Hamish D. 
Published: June 2020

AbstractGill health is one of the main health challenges for Atlantic salmon (Salmo salar L.) mariculture worldwide, and amoebic gill disease (AGD), caused by the marine ectoprotozoan Neoparamoeba perurans, is currently one of the most significant diseases in terms of prevalence and economic impact. This review describes the host response of Atlantic salmon to the disease, focusing on the pathological changes, immune response and mechanisms underlying the prominent epithelial proliferation and mucus hypersecretion occurring in affected fish. Health management strategies and risk factors are also discussed.