bluuebunny/crossref_metadata_2025_split huggingface dataset:
Editors’ Introduction: Aligning Implicit Learning and Statistical Learning: Two Approaches, One Phenomenon
Authors: Rebuschat Patrick , Monaghan Padraic 
Published: July 2019

AbstractThis editors’ introduction provides the background to the special issue. We first outline the rationale for bringing together, in a single volume, leading researchers from two distinct, yet related research strands, implicit learning and statistical learning. The aim of the special issue is to facilitate the development of a shared understanding of research questions and methodologies, to provide a platform for discussing similarities and differences between the two strands, and to encourage the formulation of joint research agendas. We then introduce the new contributions solicited for this special issue and provide our perspective on the agenda setting that results from combining these two approaches.
Canine histiocytic sarcoma cell lines with SHP2 p.Glu76Gln or p.Glu76Ala mutations are sensitive to allosteric SHP2 inhibitor SHP099
Authors: Tani Hiroyuki , Kurita Sena , Miyamoto Ryo , Ochiai Kazuhiko , Tamura Kyoichi , Bonkobara Makoto 
Published: July 2019

AbstractSome canine cases of histiocytic sarcoma (HS) carry an activating mutation in the src homology two domain‐containing phosphatase 2 (SHP2) encoded by PTPN11. SHP099 is an allosteric inhibitor of SHP2 that stabilizes SHP2 in a folded, auto‐inhibited conformation. Here, we examined the expression and mutation status of SHP2 in five canine HS cell lines and evaluated the growth inhibitory properties of SHP099 against these cell lines. All five of the canine HS cell lines expressed SHP2, with three of the lines each harbouring a distinct mutation in PTPN11/SHP2 (p.Glu76Gln, p.Glu76Ala and p.Gly503Val). In silico analysis suggested that p.Glu76Gln and p.Glu76Ala, but not p.Gly503Val, promote shifting of the SHP2 conformation from folded to open‐active state. SHP099 potently suppressed the growth of two of the mutant cell lines (harbouring SHP2 p.Glu76Gln or p.Glu76Ala) but not that of the other three cell lines. In addition, SHP099 suppressed ERK activation in the cell line harbouring the SHP2 p.Glu76Ala mutation. The SHP2 p.Glu76Gln and p.Glu76Ala mutations are considered to be activating mutations, and the signal from SHP2 p.Glu76Ala is inferred to be transduced primarily via the ERK pathway. Moreover, SHP099‐sensitive HS cells, including those with SHP2 p.Glu76Gln or p.Glu76Ala mutations, may depend on these mutations for growth. Therefore, targeting cells harbouring SHP2 p.Glu76Gln and p.Glu76Ala with SHP099 may be an approach for the treatment of canine HS.
Acremonium and trichosporon fungal keratoconjunctivitis in a Leopard Gecko (Eublepharis macularius)
Authors: Munevar Christian , Moore Bret A. , Gleeson Molly D. , Ozawa Sarah M. , Murphy Christopher J. , Paul‐Murphy Joanne R. , Leonard Brian C. 
Published: July 2019

AbstractA 6‐year‐old male leopard gecko (Eublepharis macularius) was presented with a 2‐year history of recurrent dysecdysis involving the ocular surface of both eyes. Ophthalmic examination revealed ocular surface desiccation and multifocal superficial ulcerative keratitis with patchy remnants of retained shed. Other abnormalities included stomatitis and mandibular and maxillary osteomyelitis. Topical and systemic antibiotic therapy, oral vitamin A, and improved husbandry conditions resolved the stomatitis and osteomyelitis but did not improve the ocular surface. Corneal cytology collected with a cytobrush revealed branching hyphae and budding yeast consistent with fungal keratitis. Fungal culture grew Acremonium sp. and Trichosporon sp. The addition of topical antifungal therapy improved the ocular surface health, but the patient was euthanized 7 weeks after initial presentation for persistent vomiting and dyspnea. Necropsy was declined. This case describes the first case of fungal keratitis caused by Acremonium sp. and Trichosporon sp. in a reptile.
Simultaneous Shape and Topology Optimization of Planar Linkage Mechanisms Based on the Spring-Connected Rigid Block Model
Authors: Yu Jeonghan , Han Sang Min , Kim Yoon Young 
Published: July 2019

Abstract
Using the topology optimization can be an effective means of synthesizing planar rigid-body linkage mechanisms to generate desired motion, as it does not require a baseline mechanism for a specific topology. While most earlier studies were mainly concerned with the formulation and implementation of topology optimization-based synthesis in a fixed grid, this study aims to realize the simultaneous shape and topology optimization of planar linkage mechanisms using a low-resolution spring-connected rigid block model. Here, we demonstrate the effectiveness of simultaneous optimization over a higher-resolution fixed-grid rigid block-based topology optimization process. When shape optimization to change the block shapes is combined with topology optimization to synthesize the mechanism, the use of low-resolution discretized models improves the computation efficiency considerably and helps to yield compact mechanisms with less complexity, making them more amenable to fabrication. After verifying the effectiveness of the simultaneous shape and topology optimization process with several benchmark problems, we apply the method to synthesize a mechanism which guides a planar version of a human's gait trajectory.
Comparative efficacy of once-weekly semaglutide versus SGLT-2 inhibitors in patients inadequately controlled with one to two oral antidiabetic drugs: a systematic literature review and network meta-analysis
Authors: Kanters Steve , Wilkinson Lars , Vrazic Hrvoje , Sharma Rohini , Lopes Sandra , Popoff Evan , Druyts Eric 
Published: July 2019

ObjectiveTo determine the comparative efficacy of once-weekly semaglutide relative to sodium-glucose cotransporter 2 inhibitors (SGLT-2is) licensed in Europe and North America among patients with type 2 diabetes (T2D) inadequately controlled with 1–2 oral antidiabetics (OADs), using a network meta-analysis (NMA). Design systematic review and network meta-analysis. Data Sources EMBASE, MEDLINE and CENTRAL were searched from January 1994 to August 2017.MethodsRandomised controlled trials with ≥20 weeks of treatment evaluating once-weekly semaglutide or SGLT-2is. Primary outcomes included change from baseline in: HbA1c, weight, systolic blood pressure, postprandial blood glucose and fasting plasma glucose. Fixed-effect and random-effect Bayesian NMA were used to indirectly compare treatment effects at 26 (±4) weeks. Metaregression and sensitivity analyses were conducted. Model selection was performed using the deviance information criterion and consistency was assessed by comparing indirect (edge-splitting) to direct evidence.ResultsForty-eight publications representing 21 trials were included. The mean differences (MD) in change from baseline in HbA1c of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from −0.56% for canagliflozin 300 mg (95% credible interval (CrI): −0.76 to −0.33%), to −0.95% for dapagliflozin 5 mg (95% CrI: −1.20 to −0.69%). The MD in change from baseline in weight of once-weekly semaglutide 1.0 mg versus SGLT-2is ranged from −1.35 kg for canagliflozin 300 mg to −2.48 kg for dapagliflozin 5 mg, while change from baseline in fasting plasma glucose ranged from −0.41 mmol/L for canagliflozin 300 mg to −1.37 mmol/L for dapagliflozin 5 mg. Once-weekly semaglutide was not statistically differentiable than all SGLT-2is in reducing systolic blood pressure. NMA was not feasible for postprandial blood glucose and safety outcomes.ConclusionOnce-weekly semaglutide demonstrated statistically significant and clinically meaningful reductions in HbA1c and body weight in T2D patients inadequately controlled with 1–2 OADs compared to all SGLT-2is licensed in Europe and North America.
Type and density of independent takeaway outlets: a geographical mapping study in a low socioeconomic ward, Manchester
Authors: Blow Jennifer , Gregg Rebecca , Davies Ian G , Patel Sumaiya 
Published: July 2019

ObjectivesThe socioeconomic disparity in childhood and early adult obesity prevalence has been well characterised. Takeaway outlets may cluster in lower socioeconomic areas and their proximity to schools is of concern. This study aimed to map takeaway food outlets, characterise takeaway types and their proximity to educational institutions within a low socioeconomic ward in Manchester.DesignThe Rusholme ward and a 2 km Euclidean buffer were included as the study area. Local authority Environmental Health data were used to map the takeaway outlets, using QGIS V.2.18.0 (OPENGIS.ch LLC, Einsiedeln, Switzerland). The types of takeaway outlets and major roads were included. Number of outlets within a 400 m Euclidean walking buffer of educational institutions were mapped.SettingRusholme, Manchester, UK.ResultsWithin the study area, 202 takeaway food outlets were identified and mapped as cluster points. Of these, 62.3% are located on major (A and B) roads, while the remaining outlets were located on minor roads. The majority (57.4%) of takeaway outlets sold similar items (fried chicken, burgers, pizzas, kebabs), with the remainder offering more diverse menus. Of the 53 schools, colleges and universities within the study area, 28 (52.8%) had 1–5 takeaway food outlets within 400 m, 9 (17.0%) had 6–10 outlets; 4 (7.5%) more than 11 outlets with 12 (22.6%) having zero outlets within 400 m.ConclusionWithin this low socioeconomic area, there was a high concentration of takeaway food outlets, predominantly along major roads and in easy walking distance of educational establishments with the majority offering similar foods. In addition, a high proportion of these outlets were in easy walking distance of educational establishments. Public health policy needs to consider the implications of current takeaway food outlets and not just the proliferation of these outlets with current planning laws.
Glycaemic, blood pressure and low-density lipoprotein-cholesterol control among patients with diabetes mellitus in a specialised clinic in Botswana: a cross-sectional study
Authors: Mwita Julius Chacha , Francis Joel M , Omech Bernard , Botsile Elizabeth , Oyewo Aderonke , Mokgwathi Matshidiso , Molefe-Baikai Onkabetse Julia , Godman Brian , Tshikuka Jose-Gaby 
Published: July 2019

ObjectiveControl of glycaemic, hypertension and low-density lipoprotein-cholesterol (LDL-C) among patients with type 2 diabetes mellitus (T2DM) is vital for the prevention of cardiovascular diseases. The current study was an audit of glycaemic, hypertension and LDL-C control among ambulant patients with T2DM in Botswana. Also, the study aimed at assessing factors associated with attaining optimal glycaemic, hypertension and LDL-C therapeutic goals.DesignA cross-sectional study.SettingA specialised public diabetes clinic in Gaborone, Botswana.ParticipantsPatients with T2DM who had attended the clinic for ≥3 months between August 2017 and February 2018.Primary outcome measureThe proportion of patients with optimal glycaemic (HbA1c<7%), hypertension (blood pressure <140/90 mm Hg) and LDL-C (<1.8 mmol/L) control.ResultsThe proportions of patients meeting optimal targets were 32.3% for glycaemic, 54.2% for hypertension and 20.4% for LDL-C. Age≥ 50 years was positively associated with optimal glycaemic control (adjusted OR [AOR] 5.79; 95% CI 1.08 to 31.14). On the other hand, an increase in diabetes duration was inversely associated with optimal glycemic control (AOR 0.91; 95% CI 0.85 to 0.98). Being on an ACE inhibitor was inversely associated with optimal hypertension control (AOR 0.35; 95% CI 0.14 to 0.85). Being female was inversely associated with optimal LDL-C control (AOR 0.24; 95% CI (0.09 - 0.59).ConclusionPatients with T2DM in Gaborone, Botswana, presented with suboptimal control of recommended glycaemic, hypertension and LDL-C targets. These findings call for urgent individual and health systems interventions to address key determinants of the recommended therapeutic targets among patients with diabetes in this setting.
Systematic review protocol for facilitators and barriers to integrating health services for traumatic brain injury and mental health or addictions
Authors: Chan Vincy , Toccalino Danielle , Colantonio Angela 
Published: July 2019

IntroductionIn the most populous province of Canada, one in five adults and one in six students report a lifetime history of traumatic brain injury (TBI). These individuals were also more likely to report elevated psychological distress and use illicit substances compared with those without TBI. The need for integrated health services has been recognised globally, yet efforts to develop more comprehensive and effective care for TBI and mental health and/or addictions (MHA) continue to be challenged by the siloing of the two systems. This protocol is for a systematic review that describes the current types of integrated care for TBI and MHA and identifies the barriers and facilitators to integrating healthcare for these populations.Methods and analysisThis review will systematically search MEDLINE, EMBASE, PsycINFO, CINAHL, Cochrane Central Register of Controlled Trials, Sociological Abstracts, and Dissertations & Theses Global. References of eligible articles will also be searched for additional relevant studies. The search strategy will include the use of text words and subject headings relevant to the concepts ‘TBI,’ ‘substance abuse, gambling, or mental health,’ ‘integrated healthcare,’ ‘barriers and facilitators,’ and ‘healthcare access.’ Two reviewers will independently screen all articles based on predetermined inclusion and exclusion criteria and perform quality assessment on eligible studies. A narrative synthesis will be conducted using the data abstracted by the two reviewers.Ethics and disseminationFindings from the systematic review will be published in peer-reviewed journals, presented at scientific meetings, and summarised for key stakeholders in the field of TBI and/or MHA. This protocol will form a systematic review that holds the potential to impact policy and planning in the development of integrated person-centred care for TBI and MHA and addresses a recognised gap in TBI care.Trial registration numberCRD42018108343
Fostering the physician–scientist workforce: a prospective cohort study to investigate the effect of undergraduate medical students’ motivation for research on actual research involvement
Authors: Ommering Belinda WC , van Blankenstein Floris M , Wijnen-Meijer Marjo , van Diepen Merel , Dekker Friedo W 
Published: July 2019

ObjectivesThe medical field is facing a physician–scientist shortage. Medical schools could contribute to developing physician–scientists by stimulating student involvement in research. Studies have examined motivation for research as a key parameter of success. However, previous studies did not investigate if students act on their self-reported motivation. The aim of this study is to examine if motivation for research of medical students is related to actual research involvement. Furthermore, this study distinguishes intrinsic (IM) and extrinsic motivation (EM) for research and aims to investigate if a type of motivation matters in the relation between research motivation and involvement.Design and settingProspective cohort study in which students were surveyed at the start of medical school and reported IM and EM for research, self-efficacy, perceptions of research and curiosity on a 7-point Likert scale. One year later, students involved in research were identified. Logistic regression was used to examine influences of IM and EM on research involvement.ParticipantsAll undergraduate medical students starting at one medical school in the Netherlands in 2016. In total, 315 out of 316 students participated (99.7%), of whom 55 became involved in research (17.5%).Main outcome measureResearch involvement, which was operationalised as the enrolment of students in the research-based honours programme or the involvement of students in voluntary research activities outside of the regular curriculum.ResultsStudents with higher levels of IM were more often involved in research (OR 3.4; 95% CI 2.08 to 5.61), also after adjusting for gender, age, extracurricular high school activities, self-efficacy, perceptions and curiosity (OR 2.5; 95% CI 1.35 to 4.78). Higher levels of EM increased the odds of research involvement (OR 1.4; 95% CI 0.96 to 2.11). However, the effect of EM disappeared after adjusting for the above-mentioned factors (OR 1.05; 95% CI 0.67 to 1.63). Furthermore, the effect of IM remained after adjusting for EM, whereas the effect of EM disappeared after adjusting for IM.ConclusionsOur findings suggest that the type of motivation matters and IM influences research involvement. Therefore, IM could be targeted to stimulate research involvement and could be seen as the first step towards success in fostering the physician–scientist workforce.
Psychometric properties of the Depression Stigma Scale (DSS) in Chinese cancer patients: a cross-sectional study
Authors: Zhu Lei , Yao Juntao , Wu Liyang , Wang Jun , Qiu Mengting , Zhang Chunyu , Zhang Hongmei , Xie Juan , Liu Ailan , Ranchor Adelita , Schroevers Maya 
Published: July 2019

ObjectivesThe Depression Stigma Scale (DSS) is commonly used to assess depression stigma in the general population and in people with depression. The DSS includes two 9-item subscales assumed to measure personal depression stigma (ie, personal perceptions of depression) and perceived depression stigma (ie, perceptions of how others perceive depression). The aim of the present study was to examine its psychometric properties in terms of validity and reliability in Chinese cancer patients.DesignA cross-sectional study design.Participants and settingsThis study focused on 301 Chinese cancer patients recruited from two hospitals in Xi’an, China.MethodsExploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to assess the factor structure. Internal consistency was assessed using Cronbach’s alpha. To examine concurrent validity, symptoms of depression were used as the criterion.ResultsFor each subscale of the DSS (ie, personal and perceived depression stigma), the EFA and CFA confirmed a two-factor structure: weak-not-sick (ie, perceiving that depression is not a real illness, but rather a sign of weakness) and discrimination (ie, perceiving that depressed people are discriminated against). The Cronbach’s alphas were adequate, ranging from 0.70 to 0.80. Symptoms of depression were positively but weakly correlated to personal and perceived depression stigma.ConclusionsThe DSS appeared to show satisfactory psychometric properties in our sample of cancer patients. Both personal depression stigma and perceived depression stigma subscales consisted of two underlying aspects.
Oral antidiabetic medication adherence and glycaemic control among patients with type 2 diabetes mellitus: a cross-sectional retrospective study in a tertiary hospital in Saudi Arabia
Authors: Balkhi Bander , Alwhaibi Monira , Alqahtani Nasser , Alhawassi Tariq , Alshammari Thamir M , Mahmoud Mansour , Almetwazi Mansour , Ata Sondus , Kamal Khalid M 
Published: July 2019

ObjectivesThe purpose of this study is to measure the adherence rates of oral antidiabetic drugs (OADs) in patients with type 2 diabetes mellitus (T2DM) and assess the relationship of glycaemic control and adherence to OADs after controlling for other associated factors.DesignCross-sectional retrospective study.SettingLarge tertiary hospital in the central region of Saudi Arabia.Participants5457patients aged 18 years and older diagnosed with T2DM during the period from 1 January 2016 to 31 December 2016.Primary and secondary outcome measuresThe modified medication possession ratio (mMPR) was calculated as a proxy measure for adherence of OADs. The factors associated with OADs non-adherence and medication oversupply were assessed using multinomial logistic regression models. The secondary outcomes were to measure the association between OADs adherence and glycaemic control.ResultsMajority of patients with T2DM were females (n=3400, 62.3%). The average glycated haemoglobin was 8.2±1.67. Among the study population, 48.6% had good adherence (mMPR >0.8) and 8.6% had a medication oversupply (mMPR >1.2). Good adherence was highest among those using repaglinide (71.0%) followed by pioglitazone (65.0%) and sitagliptin (59.0%). In the multivariate analysis, women with T2DM were more likely to have poor adherence (adjusted OR (AOR)=0.76, 95% CI=0.67, 0.86) compared with men. Also, medication oversupply was more likely among patients with hyperpolypharmacy (AOR=1.88, 95% CI=1.36, 2.63), comorbid osteoarthritis (AOR=1.72, 95% CI=1.20, 02.45) and non-Saudi patients (AOR=1.53, 95% CI=1.16, 2.01). However, no association was found between glycaemic control and adherence to OADs.ConclusionThe study findings support the growing concern of non-adherence to OADs among patients with T2DM in Saudi Arabia. Decision makers have to invest in behavioural interventions that will boost medication adherence rates. This is particularly important in patients with polypharmacy and high burden of comorbid conditions.
Emergence of digital biomarkers to predict and modify treatment efficacy: machine learning study
Authors: Guthrie Nicole L , Carpenter Jason , Edwards Katherine L , Appelbaum Kevin J , Dey Sourav , Eisenberg David M , Katz David L , Berman Mark A 
Published: July 2019

ObjectivesDevelopment of digital biomarkers to predict treatment response to a digital behavioural intervention.DesignMachine learning using random forest classifiers on data generated through the use of a digital therapeutic which delivers behavioural therapy to treat cardiometabolic disease. Data from 13 explanatory variables (biometric and engagement in nature) generated in the first 28 days of a 12-week intervention were used to train models. Two levels of response to treatment were predicted: (1) systolic change ≥10 mm Hg (SC model), and (2) shift down to a blood pressure category of elevated or better (ER model). Models were validated using leave-one-out cross validation and evaluated using area under the curve receiver operating characteristics (AUROC) and specificity- sensitivity. Ability to predict treatment response with a subset of nine variables, including app use and baseline blood pressure, was also tested (models SC-APP and ER-APP).SettingData generated through ad libitum use of a digital therapeutic in the USA.ParticipantsDeidentified data from 135 adults with a starting blood pressure ≥130/80, who tracked blood pressure for at least 7 weeks using the digital therapeutic.ResultsThe SC model had an AUROC of 0.82 and a sensitivity of 58% at a specificity of 90%. The ER model had an AUROC of 0.69 and a sensitivity of 32% at a specificity at 91%. Dropping explanatory variables related to blood pressure resulted in an AUROC of 0.72 with a sensitivity of 42% at a specificity of 90% for the SC-APP model and an AUROC of 0.53 for the ER-APP model.ConclusionsMachine learning was used to transform data from a digital therapeutic into digital biomarkers that predicted treatment response in individual participants. Digital biomarkers have potential to improve treatment outcomes in a digital behavioural intervention.