bluuebunny/crossref_metadata_2025_split huggingface dataset:
“Escape the Room” – a strategy for problem-based learning and student inquiry
Authors: Pearcy Mark , Guise Eric , Heller Dana 
Published: July 2019

Purpose
Problem-based learning (PBL) has long been a regular feature in professions outside K-12 education and is growing in social studies education in recent years. PBL is built around student inquiry into an “ill-structured” or “messy” problem (Wieseman and Cadwell, 2005, p. 11). These inquiries are open ended, largely autonomous and student driven (Savin-Baden, 2014). The collaborative nature of PBL scenarios allows students to work with real-world concepts and skills to solve problems (Ferreira and Trudel, 2012). This paper aims to discuss these issues.

Design/methodology/approach
This paper describes an innovative strategy for PBL learning, an Escape the Room (ETR) activity centered on historical content knowledge – in this case, the First World War. The activity incorporates a series of ill-structured problems with the First World War as its historical context.

Findings
The paper concludes with a discussion of the utility of PBL activities like “ETR” and possible applications in the classroom for teachers.

Originality/value
There has been significant research in PBL activities but little in the specific application of “ETR” scenarios, a rising trend in commercially available activities. The potential for student inquiry and engagement is a rich field for social studies educators.
Does agricultural sector foreign direct investment promote economic growth of Pakistan? Evidence from cointegration and causality analysis
Authors: Chandio Abbas Ali , Mirani Amir Ali , Shar Rashid Usman 
Published: July 2019

PurposeThe purpose of this paper is to examine the linkage between agricultural sector foreign direct investment (FDI) and economic growth in Pakistan over the period from 1991 to 2013.Design/methodology/approachIn this study, the stationary analysis is performed by using Phillips–Perron and Dickey–Fuller generalized least squares unit root tests and Johansen cointegration technique to determine the long-run linkage among the studied variables. The robustness of long-run linkage is checked by employing autoregressive distributed lag (ARDL) approach, dynamic ordinary least squares (DOLS), fully modified ordinary least square method (FMOLS) and the canonical cointegration regression (CCR). The causal linkage between the selected variables is investigated by the VECM Granger causality test.FindingsThe results of the Johansen cointegration test confirmed a cointegrating association between the variables. In addition, the results of the ARDL, DOLS, FMOLS and CCR showed that agricultural sector FDI has a strong positive significant effect on economic growth in long run. Moreover, the findings of the present empirical study revealed that there exists bidirectional Granger causality between the agricultural sector FDI and economic growth in both short run and long run.Originality/valueThe present empirical study filled the literature gap of applying the Granger causality based on error-correction model to examine this relevant issue for Pakistan.
Examining the role of parasites in limiting unidirectional gene flow between lake and river sticklebacks
Authors: Erin Noémie I. , Benesh Daniel P. , Henrich Tina , Samonte Irene E. , Jakobsen Per J. , Kalbe Martin 
Published: July 2019

AbstractParasites are important selective agents with the potential to limit gene flow between host populations by shaping local host immunocompetence.We report on a contact zone between lake and river three‐spined sticklebacks (Gasterosteus aculeatus) that offers the ideal biogeographic setting to explore the role of parasite‐mediated selection on reproductive isolation. A waterfall acts as a natural barrier and enforces unidirectional migration from the upstream river stickleback population to the downstream river and lake populations.We assessed population genetic structure and parasite communities over four years. In a set of controlled experimental infections, we compared parasite susceptibility of upstream and downstream fish by exposing laboratory‐bred upstream river and lake fish, as well as hybrids, to two common lake parasite species: a generalist trematode parasite,Diplostomum pseudospathaceum, and a host‐specific cestode,Schistocephalus solidus.We found consistent genetic differentiation between upstream and downstream populations across four sampling years, even though the downstream river consisted of ~10% first‐generation migrants from the upstream population as detected by parentage analysis. Fish in the upstream population had lower genetic diversity and were strikingly devoid of macroparasites. Through experimental infections, we demonstrated that upstream fish and their hybrids had higher susceptibility to parasite infections than downstream fish. Despite this, naturally sampled upstream migrants were less infected than downstream residents. Thus, migrants coming from a parasite‐free environment may enjoy an initial fitness advantage, but their descendants seem likely to suffer from higher parasite loads.Our results suggest that adaptation to distinct parasite communities can influence stickleback invasion success and may represent a barrier to gene flow, even between close and connected populations.
Phase I trial of a standalone internet social anxiety treatment for adolescents who stutter: iBroadway
Authors: Gunn Anthony , Menzies Ross G. , Onslow Mark , O'Brian Sue , Packman Ann , Lowe Robyn , Helgadóttir Fjóla Dögg , Jones Mark 
Published: July 2019

AbstractBackgroundiGlebe is a fully automated internet treatment program for adults who stutter that has been shown, in some cases, to reduce anxiety and effectively manage social anxiety disorder for many participants. No such automated internet treatment program exists for adolescents who stutter.AimsThe present paper reports a Phase I trial of an adolescent version of the adult program: iBroadway.Methods & ProceduresParticipants were 29 adolescents in the age range 12–17 years who were seeking cognitive–behaviour therapy (CBT) for anxiety associated with stuttering. The design was a non‐randomized Phase I trial with outcome assessments at pre‐treatment and immediately post‐treatment after 5 months of access to the program. No contact by a clinical psychologist occurred during participant use of the program. Outcomes were a range of psychological, quality‐of‐life and stuttering severity measures.Outcomes & ResultsThe compliance rate for the seven iBroadway modules over 5 months was extremely favourable for internet CBT, at 52.4%. There was evidence of treatment effects for (1) the number of DSM‐IV mental health diagnoses with the Diagnostic Interview Schedule for Children; (2) the Unhelpful Thoughts and Beliefs About Stuttering scale; (3) the Subjective Units of Distress Scale; and (4) parent‐reported speech satisfaction.Conclusions & ImplicationsFurther development of iBroadway, the adolescent version of iGlebe, with Phase II trialling is warranted.
The price of going green: the role of greenness in green bond markets
Authors: Hyun Suk , Park Donghyun , Tian Shu 
Published: July 2019

AbstractIn this paper, we empirically investigate how greenness information is priced in the green bond market. Our comparison of liquidity‐adjusted yield premiums of green bonds versus synthetic conventional bonds indicates that, on average, there is no robust and significant yield premium or discount on green bonds. However, green bonds certified by an external reviewer enjoy a discount of about 6 bps. Furthermore, green bonds that obtain a Climate Bonds Initiative certificate show a discount of around 15 bps. The findings suggest that a universally accepted greenness measure can benefit the development of the green bond market.
Compound heterozygosity for TNXB genetic variants in a mixed‐breed dog with Ehlers‐Danlos syndrome
Authors: Bauer A. , de Lucia M. , Leuthard F. , Jagannathan V. , Leeb T. 
Published: July 2019

SummaryThe Ehlers‐Danlos syndromes (EDSs) are a heterogeneous group of inherited connective tissue disorders characterized by skin hyperextensibility, joint hypermobility and tissue fragility. Inherited disorders similar to human EDS have been reported in different mammalian species. In the present study, we investigated a female mixed‐breed dog with clinical signs of EDS. Whole‐genome sequencing of the affected dog revealed two missense variants in the TNXB gene, encoding the extracellular matrix protein tenascin XB. In humans, TNXB genetic variants cause classical‐like EDS or the milder hypermobile EDS. The affected dog was heterozygous at both identified variants. Each variant allele was transmitted from one of the case's parents, consistent with compound heterozygosity. Although one of the variant alleles, XM_003431680.3:c.2012G>A, p.(Ser671Asn), was private to the family of the affected dog and absent from whole‐genome sequencing data of 599 control dogs, the second variant allele, XM_003431680.3:c.2900G>A, p.(Gly967Asp), is present at a low frequency in the Chihuahua and Poodle population. Given that TNXB is a functional candidate gene for EDS, we suggest that compound heterozygosity for the identified TNXB variants may have caused the EDS‐like phenotype in the affected dog. Chihuahuas and Poodles should be monitored for EDS cases, which might confirm the hypothesized pathogenic effect of the segregating TNXB variant.
Does Public Support Help Democracy Survive?
Authors: Claassen Christopher 
Published: July 2019

AbstractIt is widely believed that democracy requires public support to survive. The empirical evidence for this hypothesis is weak, however, with existing tests resting on small cross‐sectional samples and producing contradictory results. The underlying problem is that survey measures of support for democracy are fragmented across time, space, and different survey questions. In response, this article uses a Bayesian latent variable model to estimate a smooth country‐year panel of democratic support for 135 countries and up to 29 years. The article then demonstrates a positive effect of support on subsequent democratic change, while adjusting for the possible confounding effects of prior levels of democracy and unobservable time‐invariant factors. Support is, moreover, more robustly linked with the endurance of democracy than its emergence in the first place. As Lipset (1959) and Easton (1965) hypothesized over 50 years ago, public support does indeed help democracy survive.
Predicting the prognosis of undifferentiated pleomorphic soft tissue sarcoma: a 20‐year experience of 266 cases
Authors: Vodanovich Domagoj A. , Spelman Tim , May Deborah , Slavin John , Choong Peter F. M. 
Published: July 2019

BackgroundUndifferentiated pleomorphic sarcoma (UPS) is a rare malignant tumour of mesenchymal origin, which was conceived following re‐classification of malignant fibrous histiocytoma (MFH). The objective of this study is to determine prognostic factors for the outcome of UPS, following multi‐modal treatment.MethodsData of UPS tumours from 1996 to 2016 were collected, totalling 266 unique UPS patients. Median follow‐up was 7.8 years. All tumours were retrospectively analysed for prognostic factors of the disease, including local recurrence (LR) and metastatic disease (MD) at diagnosis, tumour size, grade, location and depth, patient age, adjuvant therapy and surgical margin. Overall survival (OS), post‐treatment LR and metastatic‐free survival were assessed as outcomes.ResultsThe 5‐ and 10‐year OS rates for all ages were 60% and 48%, respectively, with a median survival time of 10.1 years. Multivariate analysis revealed that the adverse prognostic factors associated with decreased OS were older age (P < 0.001; hazard ratio 1.03) and MD at diagnosis (P = 0.001; 2.89), with upper extremity tumours being favourable (P = 0.043; 2.30). Poor prognosis for post‐operative LR was associated with older age (P = 0.046; 1.03) and positive surgical margins (P = 0.028; 2.68). Increased post‐treatment MD was seen in patients with large tumours (5–9 cm (P < 0.001; 4.42), ≥10 cm (P < 0.001; 6.80)) and MD at diagnosis (P < 0.001; 3.99), adjuvant therapy was favourable, shown to reduce MD (P < 0.001; 0.34).ConclusionsUPS is a high‐grade soft tissue sarcoma, for which surgery striving for negative margins, with radiotherapy, is the treatment of choice. Older age, lower extremity location, MD at presentation, large size and positive surgical margins, were unfavourable.
Meta‐analysis of unplanned readmission to hospital post‐appendectomy: an opportunity for a new benchmark
Authors: Bailey Kate , Choynowski Michelle , Kabir Syed Mohammad Umar , Lawler Jack , Badrin Adibah , Sugrue Michael 
Published: July 2019

BackgroundAppendicitis is the most common cause of acute abdominal pain requiring surgical intervention. While many studies report readmission, a meta‐analysis of readmission post‐appendectomy has not been published. This meta‐analysis was undertaken to determine rates and predictors of hospital readmission following appendectomy and to potentially provide a metric benchmark.MethodsAn ethically approved PROSPERO‐registered (ID CRD42017069040) meta‐analysis following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines, using databases PubMed and Scopus, was undertaken for studies published between January 2012 and June 2017. Articles relating to outcomes and readmissions after appendectomy were identified. Those scoring >15 for comparative studies and >10 for non‐comparative studies, using Methodological Index for Non‐Randomized Studies criteria were included in the final analysis. The odds ratios (OR) using random‐effects, Mantel–Haenszel method with 95% confidence intervals (CI), were computed for each risk factor with RevMan5.ResultsA total of 1757 articles reviewed were reduced to 45 qualifying studies for a final analysis of 836 921 appendectomies. 4.3% (range 0.0–14.4%) of patients were readmitted within 30 days. Significant preoperative patient factors for increased readmission were diabetes mellitus (OR 1.93, CI 1.63–2.28, P < 0.00001), complicated appendicitis (OR 3.6, CI 2.43–5.34, P < 0.00001) and open surgical technique (OR 1.39, CI 1.08–1.79, P < 0.00001). Increased readmission was not associated with gender, obesity or paediatric versus general surgeons or centres.ConclusionThis meta‐analysis identified that readmission is not uncommon post‐appendectomy, occurring in one in 25 cases. The mean readmission rate of 4.3% may act as a quality benchmark for improving emergency surgical care. Targeting high‐risk groups with diabetes or complicated appendicitis and increasing use of laparoscopic technique may help reduce readmission rates.
Advances in understanding the pathogenesis of red cell membrane disorders
Authors: Iolascon Achille , Andolfo Immacolata , Russo Roberta 
Published: July 2019

SummaryHereditary erythrocyte membrane disorders are caused by mutations in genes encoding various transmembrane or cytoskeletal proteins of red blood cells. The main consequences of these genetic alterations are decreased cell deformability and shortened erythrocyte survival. Red blood cell membrane defects encompass a heterogeneous group of haemolytic anaemias caused by either (i) altered membrane structural organisation (hereditary spherocytosis, hereditary elliptocytosis, hereditary pyropoikilocytosis and Southeast Asian ovalocytosis) or (ii) altered membrane transport function (overhydrated hereditary stomatocytosis, dehydrated hereditary stomatocytosis or xerocytosis, familial pseudohyperkalaemia and cryohydrocytosis). Herein we provide a comprehensive review of the recent literature on the molecular genetics of erythrocyte membrane defects and their reported clinical consequences. We also describe the effect of low‐expression genetic variants on the high inter‐ and intra‐familial phenotype variability of erythrocyte structural defects.
A non‐covalent inhibitor XMU‐MP‐3 overrides ibrutinib‐resistant BtkC481S mutation in B‐cell malignancies
Authors: Gui Fu , Jiang Jie , He Zhixiang , Li Li , Li Yunzhan , Deng Zhou , Lu Yue , Wu Xinrui , Chen Guyue , Su Jingyi , Song Siyang , Zhang Yue‐Ming , Yun Cai‐Hong , Huang Xin , Weisberg Ellen , Zhang Jianming , Deng Xianming 
Published: July 2019

Background and PurposeBruton's tyrosine kinase (BTK) plays a key role in B‐cell receptor signalling by regulating cell proliferation and survival in various B‐cell malignancies. Covalent low‐MW BTK kinase inhibitors have shown impressive clinical efficacy in B‐cell malignancies. However, the mutant BtkC481S poses a major challenge in the management of B‐cell malignancies by disrupting the formation of the covalent bond between BTK and irreversible inhibitors, such as ibrutinib. The present studies were designed to develop novel BTK inhibitors targeting ibrutinib‐resistant BtkC481S mutation.Experimental ApproachBTK‐Ba/F3, BTK(C481S)‐Ba/F3 cells, and human malignant B‐cells JeKo‐1, Ramos, and NALM‐6 were used to evaluate cellular potency of BTK inhibitors. The in vitro pharmacological efficacy and compound selectivity were assayed via cell viability, colony formation, and BTK‐mediated signalling. A tumour xenograft model with BTK‐Ba/F3, Ramos and BTK(C481S)‐Ba/F3 cells in Nu/nu BALB/c mice was used to assess in vivo efficacy of XMU‐MP‐3.Key ResultsXMU‐MP‐3 is one of a group of low MW compounds that are potent non‐covalent BTK inhibitors. XMU‐MP‐3 inhibited both BTK and the acquired mutant BTKC481S, in vitro and in vivo. Further computational modelling, site‐directed mutagenesis analysis, and structure–activity relationships studies indicated that XMU‐MP‐3 displayed a typical Type‐II inhibitor binding mode.Conclusion and ImplicationsXMU‐MP‐3 directly targets the BTK signalling pathway in B‐cell lymphoma. These findings establish XMU‐MP‐3 as a novel inhibitor of BTK, which could serve as both a tool compound and a lead for further drug development in BTK relevant B‐cell malignancies, especially those with the acquired ibrutinib‐resistant C481S mutation.
Aquaporin 4 deletion exacerbates brain impairments in a mouse model of chronic sleep disruption
Authors: Zhang Rui , Liu Yun , Chen Yan , Li Qian , Marshall Charles , Wu Ting , Hu Gang , Xiao Ming 
Published: July 2019

AbstractAimsAs a normal physiological process, sleep has recently been shown to facilitate clearance of macromolecular metabolic wastes from the brain via the glymphatic system. The aim of the present study was to investigate pathophysiological roles of astroglial aquaporin 4 (AQP4), a functional regulator of glymphatic clearance, in a mouse model of chronic sleep disruption (SD).MethodsAdult AQP4 null mice and wild‐type (WT) mice were given 7 days of SD using the improved rotating rod method, and then received behavioral, neuropathological, and neurochemical analyses.ResultsAquaporin 4 deletion resulted in an impairment of glymphatic transport and accumulation of β‐amyloid and Tau proteins in the brain following SD. AQP4 null SD mice exhibited severe activation of microglia, neuroinflammation, and synaptic protein loss in the hippocampus, as well as decreased working memory, compared with WT‐SD mice.ConclusionThese results demonstrate that AQP4‐mediated glymphatic clearance ameliorates brain impairments caused by abnormal accumulation of metabolic wastes following chronic SD, thus serving as a potential target for sleep‐related disorders.
Therapeutische Patientenschulungsprogramme und Unterstützung beim Selbstmanagement für Patienten mit Psoriasis – eine systematische Übersicht
Authors: Dressler Corinna , Lambert Jo , Grine Lynda , Galdas Paul , Paul Carle , Zidane Miriam , Nast Alexander 
Published: July 2019

ZusammenfassungPsoriasis ist eine chronisch‐entzündliche Hautkrankheit. Patientenschulungen könnten eine Möglichkeit sein, die Adhärenz und die Bewältigungsstrategien (Coping) zu verbessern. Das Ziel dieser systematischen Übersichtsarbeit ist es, Studien zu ermitteln, in denen Schulungsinterventionen für Psoriasis‐Patienten evaluiert werden. Die Übersichtsarbeit wurde im Einklang mit den von Cochrane empfohlenen Methoden erstellt. Wir durchsuchten sieben Datenbanken, ein Studienregister und drei Repositorien für graue Literatur. Die Sichtung und Extraktion der Daten wurden von zwei unabhängigen Untersuchern durchgeführt. Es wurden die Instrumente Risk of Bias 2.0, ROBINS‐I und Instrumente des NIH verwendet. Zusätzlich wurden die APEASE‐Kriterien angewendet. Sechzehn Studien wurden von uns ausgewertet. In zwei RCT (randomized clinical trials) wurden Eins‐zu‐Eins‐Interventionen (Patient/Arzt, Patient/Pflegekraft), in einer RCT wurde eine Web‐basierte Intervention, in drei RCT wurden öfter stattfindende Gruppeninterventionen und in einem RCT wurde eine einmalig stattfindende Gruppensitzung untersucht. Eine RCT stellte einen Vergleich an zwischen den beteiligten medizinischen Fachkräften. Die Bewertung des Verzerrungsrisikos (Risk of Bias; RoB) reichte von „gewisse Bedenken“ bis „hoch“. Drei RCT fanden einen Effekt. Wir schlossen vier CCT (controlled clinical trials) ein, in einer konnte ein Effekt gezeigt werden. Eine der vier Vorher‐Nachher‐Studien rechtfertigt weitere Untersuchungen. Trotz gewisser Ähnlichkeiten zwischen den Interventionen in der Art der Vermittlung waren Patientenselektion und Setting, in denen die Interventionen durchgeführt wurden, verschieden. Interventionen, die eine individuelle (Eins‐zu‐Eins) Sitzung beinhalteten, schienen erfolgreich zu sein. Nach Anwendung der APEASE‐Kriterien scheinen zwei Interventionen für eine Adaptation geeignet zu sein: das Programm zur Optimierung der topischen Therapie und die motivierende Gesprächsführung (motivational interviewing) nach einer Klimatherapie.
Inducing remission of Type 2 diabetes in the Caribbean: findings from a mixed methods feasibility study of a low‐calorie liquid diet‐based intervention in Barbados
Authors: Bynoe K. , Unwin N. , Taylor C. , Murphy M. M. , Bartholomew L. , Greenidge A. , Abed M. , Jeyaseelan S. , Cobelli C. , Dalla Man C. , Taylor R. 
Published: July 2019

AbstractAimIn a high proportion of people with recently diagnosed Type 2 diabetes, a short (2–3‐month) low‐calorie diet is able to restore normal glucose and insulin metabolism. The aim of this study was to determine the feasibility of this approach in Barbados.MethodsTwenty‐five individuals with Type 2 diabetes diagnosed within past 6 years, not on insulin, BMI ≥ 27 kg/m2 were recruited. Hypoglycaemic medication was stopped on commencement of the 8‐week liquid (760 calorie) diet. Insulin response was assessed in meal tests at baseline, 8 weeks and 8 months. Semi‐structured interviews, analysed thematically, explored participants’ experiences. ‘Responders’ were those with fasting plasma glucose (FPG) < 7 mmol/l at 8 weeks.ResultsTen men and 15 women (mean age 48, range 26–68 years) participated. Mean (sd) BMI was 34.2 kg/m2 (6.0); FPG 9.2 mmol/l (2.2). Mean weight loss at 8 weeks and 8 months was 10.1 kg [95% confidence interval (CI) 8.1, 12.0] and 8.2 kg (95% CI 5.8, 10.6); FPG was lower by 2.2 mmol/l (95% CI 1.2, 3.2) and 1.7 mmol/l (95% CI 0.8, 2.7) respectively. Nine of 11 (82%) of those who lost ≥ 10 kg were ‘responders’ compared with 6 of 14 (43%) who lost < 10 kg (P = 0.048). The 30‐min insulin increment was higher in responders at baseline and follow‐up (P ≤ 0.01). A food culture based on starchy foods and pressures to eat large amounts at social events were among the challenges identified by participants.ConclusionsThe feasibility of this approach to weight loss and diabetes remission in a predominantly black population in Barbados was demonstrated.