bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gαs signalling of the CB1 receptor and the influence of receptor number
Authors: Finlay David B , Cawston Erin E , Grimsey Natasha L , Hunter Morag R , Korde Anisha , Vemuri V Kiran , Makriyannis Alexandros , Glass Michelle 
Published: May 2017

Background and PurposeCB1 receptor signalling is canonically mediated through inhibitory Gαi proteins, but occurs through other G proteins under some circumstances, Gαs being the most characterized secondary pathway. Determinants of this signalling switch identified to date include Gαi blockade, CB1/D2 receptor co‐stimulation, CB1 agonist class and cell background. Hence, we examined the effects of receptor number and different ligands on CB1 receptor signalling.Experimental ApproachCB1 receptors were expressed in HEK cells at different levels, and signalling characterized for cAMP by real‐time BRET biosensor –CAMYEL – and for phospho‐ERK by AlphaScreen. Homogenate and whole cell radioligand binding assays were performed to characterize AM6544, a novel irreversible CB1 receptor antagonist.Key ResultsIn HEK cells expressing high levels of CB1 receptors, agonist treatment stimulated cAMP, a response not known to be mediated by receptor number. Δ9‐THC and BAY59‐3074 increased cAMP only in high‐expressing cells pretreated with pertussis toxin, and agonists demonstrated more diverse signalling profiles in the stimulatory pathway than the canonical inhibitory pathway. Pharmacological CB1 receptor knockdown and Gαi1 supplementation restored canonical Gαi signalling to high‐expressing cells. Constitutive signalling in both low‐ and high‐expressing cells was Gαi‐mediated.Conclusion and ImplicationsCB1 receptor coupling to opposing G proteins is determined by both receptor and G protein expression levels, which underpins a mechanism for non‐canonical signalling in a fashion consistent with Gαs signalling. CB1 receptors mediate opposite consequences in endpoints such as tumour viability depending on expression levels; our results may help to explain such effects at the level of G protein coupling.
Development and feasibility of smartphone application for cognitive‐behavioural case management of individuals with early psychosis
Authors: Kim Sung‐Wan , Lee Ga‐Young , Yu Hye‐Young , Jung Eun‐I , Lee Ju‐Yeon , Kim Seon‐Young , Kim Jae‐Min , Shin Il‐Seon , Yoon Jin‐Sang 
Published: May 2017

BackgroundThis article describes the development of the smartphone application for cognitive‐behavioural case management of young individuals with early psychosis and examines the acceptance and potential clinical benefits of this application through a pilot survey.MethodsGwangju Bukgu‐Community Mental Health Center developed and launched a smartphone application (Heal Your Mind [HYM]) for cognitive‐behavioural case management and symptom monitoring. The HYM application for clients includes 6 main modules including thought record, symptom record, daily life record, official notices, communication and scales. The key module is the “thought record” for self‐directed cognitive‐behavioural treatment. When the client writes and sends the self‐cognitive‐behavioural therapy sheet to the case manager, the latter receives a notification and can provide feedback in real time. We conducted a survey to investigate the acceptance and feasibility of this approach among young clients with early psychosis.ResultsA total of 24 clients with early psychosis participated in this survey. More than 80% of participants reported that it was easy to learn to use this application, and no one described this application as very complicated or reported that they needed a long time to learn how to use it. About 80% of participants were satisfied with this application, and 70% reported that they received help as a result of using this application.ConclusionsThis study suggests that this smartphone application is useful for young individuals with early psychosis and that it may contribute to the development of both young customer‐ and case manager‐friendly systems for this clinical population.
Comparison and optimization of in silico algorithms for predicting the pathogenicity of sodium channel variants in epilepsy
Authors: Holland Katherine D. , Bouley Thomas M. , Horn Paul S. 
Published: May 2017

SummaryObjectiveVariants in neuronal voltage‐gated sodium channel α‐subunits genes SCN1A, SCN2A, and SCN8A are common in early onset epileptic encephalopathies and other autosomal dominant childhood epilepsy syndromes. However, in clinical practice, missense variants are often classified as variants of uncertain significance when missense variants are identified but heritability cannot be determined. Genetic testing reports often include results of computational tests to estimate pathogenicity and the frequency of that variant in population‐based databases. The objective of this work was to enhance clinicians’ understanding of results by (1) determining how effectively computational algorithms predict epileptogenicity of sodium channel (SCN) missense variants; (2) optimizing their predictive capabilities; and (3) determining if epilepsy‐associated SCN variants are present in population‐based databases. This will help clinicians better understand the results of indeterminate SCN test results in people with epilepsy.MethodsPathogenic, likely pathogenic, and benign variants in SCNs were identified using databases of sodium channel variants. Benign variants were also identified from population‐based databases. Eight algorithms commonly used to predict pathogenicity were compared. In addition, logistic regression was used to determine if a combination of algorithms could better predict pathogenicity.ResultsBased on American College of Medical Genetic Criteria, 440 variants were classified as pathogenic or likely pathogenic and 84 were classified as benign or likely benign. Twenty‐eight variants previously associated with epilepsy were present in population‐based gene databases. The output provided by most computational algorithms had a high sensitivity but low specificity with an accuracy of 0.52–0.77. Accuracy could be improved by adjusting the threshold for pathogenicity. Using this adjustment, the Mendelian Clinically Applicable Pathogenicity (M‐CAP) algorithm had an accuracy of 0.90 and a combination of algorithms increased the accuracy to 0.92.SignificancePotentially pathogenic variants are present in population‐based sources. Most computational algorithms overestimate pathogenicity; however, a weighted combination of several algorithms increased classification accuracy to >0.90.
The Benefits of Multilingualism to the Personal and Professional Development of Residents of the US
Authors: Kroll Judith F. , Dussias Paola E. 
Published: May 2017

AbstractIn the past two decades, new research on multilingualism has changed our understanding of the consequences of learning and using two or more languages for cognition, for the brain, and for success and well‐being across the entire lifespan. Far from the stereotype that exposure to multiple languages in infancy complicates language and cognitive development, the new findings suggest that individuals benefit from that exposure, with greater openness to other languages and to new learning itself. At the other end of the lifespan, in old age, the active use of two or more languages appears to provide protection against cognitive decline. That protection is seen in healthy aging and most dramatically in compensating for the symptoms of pathology in those who develop dementia or are recovering from stroke. In this article we briefly review the most exciting of these new research developments and consider their implications.
Identifying preferred format and source of exercise information in persons with multiple sclerosis that can be delivered by health‐care providers
Authors: Learmonth Yvonne C. , Adamson Brynn C. , Balto Julia M. , Chiu Chung‐yi , Molina‐Guzman Isabel M. , Finlayson Marcia , Riskin Barry J. , Motl Robert W. 
Published: May 2017

AbstractBackgroundThere is increasing recognition of the benefits of exercise in individuals with multiple sclerosis (MS), yet the MS population does not engage in sufficient amounts of exercise to accrue health benefits. There has been little qualitative inquiry to establish the preferred format and source for receiving exercise information from health‐care providers among persons with MS.ObjectiveWe sought to identify the desired and preferred format and source of exercise information for persons with MS that can be delivered through health‐care providers.Setting and participantsParticipants were adults with MS who had mild or moderate disability and participated in a range of exercise levels. All participants lived in the Midwest of the United States.MethodsFifty semi‐structured interviews were conducted and analysed using thematic analysis.ResultsTwo themes emerged, (i) approach for receiving exercise promotion and (ii) ideal person for promoting exercise. Persons with MS want to receive exercise information through in‐person consultations with health‐care providers, print media and electronic media. Persons with MS want to receive exercise promotion from health‐care providers with expertise in MS (ie neurologists) and with expertise in exercise (eg physical therapists).ConclusionsThese data support the importance of understanding how to provide exercise information to persons with MS and identifying that health‐care providers including neurologists and physical therapists should be involved in exercise promotion.
The evolution of uncertainty in second opinions about prostate cancer treatment
Authors: Hillen Marij A. , Gutheil Caitlin M. , Smets Ellen M. A. , Hansen Moritz , Kungel Terrence M. , Strout Tania D. , Han Paul K. J. 
Published: May 2017

AbstractBackgroundPeople who have cancer increasingly seek second opinions. Yet, we know little about what motivates patients to seek them and how beneficial they are. Uncertainty—experienced by patients or communicated by physician and patient—may be crucial throughout the second opinion process.ObjectiveThis study sought to investigate (1) how uncertainty influences men with prostate cancer to seek second opinions and (2) how second opinions may affect these patients’ sense of uncertainty and subsequent experiences with their care.MethodsA qualitative study using semi‐structured interviews was performed. Men with localized or advanced prostate cancer (n=23) were interviewed by telephone about their motivations and experiences with seeking second opinions and the uncertainties they experienced. Analysis was performed using the constant comparative method.ResultsPatients sought second opinions because they were uncertain about receiving too little or biased information, experienced insufficient support in coming to a treatment decision, or because physicians expressed different levels of uncertainty than they did (“unshared uncertainty”). Uncertainty was reduced by the second opinion process for most patients, whereas for others, it increased or was sustained. This evolution depended on the way uncertainty was addressed during the second opinion consultation.ConclusionsSecond opinions may be a useful tool for some but not all patients. They should be used judiciously and not be viewed as a solution for current limitations to health‐care organization. An important yet challenging task for physicians is to focus less on information per se and more on how to assist patients manage irreducible uncertainty.
Alopecia areata – hyperactivity of the hypothalamic–pituitary–adrenal axis is a myth?
Authors: Bergler‐Czop B. , Miziołek B. , Brzezińska‐Wcisło L. 
Published: May 2017

AbstractIntroductionPsychological stress is known to cause exacerbation of different skin pathologies including alopecia areata (AA). A hyperactivity of the hypothalamic‐pituitary‐adrenal axis (the HPA axis) in patients affected by AA (AA patients) was proposed to be a neuroendocrine response to stress. Still little is known about melanocyte‐stimulating hormone (MSH) and cortisol production in AA settings.AimThe aim of the study was to compare trends in a production of MSH and cortisol in patients with AA patients and healthy controls.Material and methodsPlasma concentrations of free cortisol and MSH were measured in 43 AA patients (35.5 ± 10.6 years) and 37 healthy subjects (35.9 ± 10.5 years) selected from the Dermatology Outpatient Clinic at Medical University of Silesia in Katowice, Poland. Results were submitted to statistical analysis with Shapiro–Wilk W‐test and subsequently nonparametric (Mann–Whitney U‐test) or parametric (Student's t‐test) statistics were performed.ResultsMean plasma level of MSH was 5.39 ng/mL in AA patients and 5.71 ng/mL in healthy controls. The difference between groups was non‐significant (P = 0.435), but the control group manifested higher values of MSH (Q75 = 13.6 ng/mL vs Q75 = 5.98 ng/mL) and this tendency was especially stronger in females. AA patients had greater mean plasma level of cortisol (157.63 ± 91.16 µg/L) than healthy controls (123.32 ± 71.28 µg/L); however, the difference between them was also non‐significant (P = 0.063). No sex‐dependent tendency to a greater production of cortisol was found.ConclusionsExpectations of disturbances in production of MSH and cortisol were not fulfilled. Neither MSH nor cortisol plasma levels appear to be clearly changed in AA patients.
TEACHER CHARACTERISTICS AND THEIR EFFECTS ON STUDENT TEST SCORES: A SYSTEMATIC REVIEW
Authors: Coenen Johan , Cornelisz Ilja , Groot Wim , Maassen van den Brink Henriette , Van Klaveren Chris 
Published: May 2017

AbstractIt has become widely accepted that teachers are important in facilitating student learning. Hundreds of empirical studies have tried to explain differences in student performance by evaluating the impact of particular teacher characteristics. Yet, this topic has not been the subject of a systematic review for more than 10 years, even though most of the empirical evidence has emerged over the past decade. This study provides an up‐to‐date review, drawing on empirical findings from several countries and distinguishing between acquired and sociodemographic teacher characteristics. This review confirms the existing consensus that subject‐related degrees and knowledge, and not general teacher certifications, are positively related to student performance and particularly so for Master's degrees in math and science. A new insight is that recent findings point out that teacher experience continues to contribute to student test scores throughout a teacher's career, instead of merely the first few years. An important future research avenue would be to examine which mechanisms can explain these teacher characteristic effects.
Is oral contraceptive use associated with an increased risk of cervical cancer? An evidence‐based meta‐analysis
Authors: Peng Yunhua , Wang Xingxiu , Feng Huiqin , Yan Ge 
Published: May 2017

AbstractAimThe purpose of this meta‐analysis is to synthesize evidence‐based case–control studies to evaluate the association between oral contraceptive (OC) use and the risk of cervical cancer.MethodsTwo reviewers independently selected potentially relevant studies through PubMed, Embase, Chinese National Knowledge Infrastructure, Wanfang Data, and the Chongqing VIP databases using the core terms cervical intraepithelial neoplasia/ cervix dysplasia/ cervi* AND oral contraceptive in the article titles, abstracts, and keywords. All data were analyzed using stata 12.0. The heterogeneity was assessed by Q‐test and I2 statistic. Forest plot was used to display results graphically. Publication bias was assessed by Begg's test.ResultsIn total, 16 case–control studies, including 15 619 participants (7433 cases and 8186 controls), met the eligibility criteria. Individuals with OC use were not found to have a risk of cervical cancer (odds ratio [OR], 1.12; 95% confidence interval [CI], 0.90–1.38). In subgroup analyses, no significant associations were found for different durations of OC use (<5 years: OR, 0.84; 95%CI, 0.68–1.04; 5–10 years: OR, 1.06; 95%CI, 0.66–1.71; >10 years: OR, 1.25; 95%CI, 0.76–2.06). Additionally, using OC was not shown to increase the risk of cervical cancer among women with human papillomavirus infections (OR, 1.09; 95%CI, 0.80–1.49). However, an increased risk of cervical cancer was found in Asian populations with OC use.ConclusionThe meta‐analysis of case–control studies did not show an association between OC use and risk of cervical cancer. However, other necessary prospective cohort studies should be conducted to assess the impact of OC use on cervical cancer risk in the future.
Survived so what? Identifying priorities for research with children and families post‐paediatric intensive care unit
Authors: Manning Joseph C , Hemingway Pippa , Redsell Sarah A 
Published: May 2017

ABSTRACTThe involvement of patients and the public in the development, implementation and evaluation of health care services and research is recognized to have tangible benefits in relation to effectiveness and credibility. However, despite >96% of children and young people surviving critical illness or injury, there is a paucity of published reports demonstrating their contribution to informing the priorities for aftercare services and outcomes research. We aimed to identify the service and research priorities for Paediatric Intensive Care Unit survivors with children and young people, their families and other stakeholders. We conducted a face‐to‐face, multiple‐stakeholder consultation event, held in the Midlands (UK), to provide opportunities for experiences, views and priorities to be elicited. Data were gathered using write/draw and tell and focus group approaches. An inductive content analytical approach was used to categorize and conceptualize feedback. A total of 26 individuals attended the consultation exercise, including children and young people who were critical care survivors; their siblings; parents and carers; health professionals; academics; commissioners; and service managers. Consultation findings indicated that future services, interventions and research must be holistic and family‐centred. Children and young people advisors reported priorities that focused on longer‐term outcomes, whereas adult advisors identified priorities that mapped against the pathways of care. Specific priorities included developing and testing interventions that address unmet communication and information needs. Furthermore, initiatives to optimize the lives and longer‐term functional and psycho‐social outcomes of Paediatric Intensive Care Unit survivors were identified. This consultation exercise provides further evidence of the value of meaningful patient and public involvement in identifying the priorities for research and services for Paediatric Intensive Care Unit survivors and illuminates differences in proposed priorities between children, young people and adult advisors.
Heterogeneity of Purkinje cell simple spike–complex spike interactions: zebrin‐ and non‐zebrin‐related variations
Authors: Tang Tianyu , Xiao Jianqiang , Suh Colleen Y. , Burroughs Amelia , Cerminara Nadia L. , Jia Linjia , Marshall Sarah P. , Wise Andrew K. , Apps Richard , Sugihara Izumi , Lang Eric J. 
Published: May 2017

Key points
Cerebellar Purkinje cells (PCs) generate two types of action potentials, simple and complex spikes. Although they are generated by distinct mechanisms, interactions between the two spike types exist.
Zebrin staining produces alternating positive and negative stripes of PCs across most of the cerebellar cortex. Thus, here we compared simple spike–complex spike interactions both within and across zebrin populations.
Simple spike activity undergoes a complex modulation preceding and following a complex spike. The amplitudes of the pre‐ and post‐complex spike modulation phases were correlated across PCs. On average, the modulation was larger for PCs in zebrin positive regions.
Correlations between aspects of the complex spike waveform and simple spike activity were found, some of which varied between zebrin positive and negative PCs.
The implications of the results are discussed with regard to hypotheses that complex spikes are triggered by rises in simple spike activity for either motor learning or homeostatic functions.
AbstractPurkinje cells (PCs) generate two types of action potentials, called simple and complex spikes (SSs and CSs). We first investigated the CS‐associated modulation of SS activity and its relationship to the zebrin status of the PC. The modulation pattern consisted of a pre‐CS rise in SS activity, and then, following the CS, a pause, a rebound, and finally a late inhibition of SS activity for both zebrin positive (Z+) and negative (Z−) cells, though the amplitudes of the phases were larger in Z+ cells. Moreover, the amplitudes of the pre‐CS rise with the late inhibitory phase of the modulation were correlated across PCs. In contrast, correlations between modulation phases across CSs of individual PCs were generally weak. Next, the relationship between CS spikelets and SS activity was investigated. The number of spikelets/CS correlated with the average SS firing rate only for Z+ cells. In contrast, correlations across CSs between spikelet numbers and the amplitudes of the SS modulation phases were generally weak. Division of spikelets into likely axonally propagated and non‐propagated groups (based on their interspikelet interval) showed that the correlation of spikelet number with SS firing rate primarily reflected a relationship with non‐propagated spikelets. In sum, the results show both zebrin‐related and non‐zebrin‐related physiological heterogeneity in SS–CS interactions among PCs, which suggests that the cerebellar cortex is more functionally diverse than is assumed by standard theories of cerebellar function.
Improving Tropical Cyclone Intensity Forecasts with PRIME
Authors: Bhatia Kieran T. , Nolan David S. , Schumacher Andrea B. , DeMaria Mark 
Published: May 2017

Abstract
The Prediction of Intensity Model Error (PRIME) forecasting scheme uses various large-scale meteorological parameters as well as proxies for initial condition uncertainty and atmospheric flow stability to provide operational forecasts of tropical cyclone intensity forecast error. PRIME forecasts of bias and absolute error are developed for the Logistic Growth Equation Model (LGEM), Decay Statistical Hurricane Intensity Prediction Scheme (DSHP), Hurricane Weather Research and Forecasting Interpolated Model (HWFI), and Geophysical Fluid Dynamics Laboratory Interpolated Hurricane Model (GHMI). These forecasts are evaluated in the Atlantic and east Pacific basins for the 2011–15 hurricane seasons. PRIME is also trained with retrospective forecasts (R-PRIME) from the 2015 version of each model. PRIME error forecasts are significantly better than forecasts that use error climatology for a majority of forecast hours, which raises the question of whether PRIME could provide more than error guidance. PRIME bias forecasts for each model are used to modify intensity forecasts, and the corrected forecasts are compared with the original intensity forecasts. For almost all basins, forecast intervals, and versions of PRIME, the bias-corrected forecasts achieve significantly lower errors than the original intensity forecasts. PRIME absolute error and bias forecasts are also used to create unique ensembles of the four models. These PRIME-modified ensembles are found to frequently outperform the intensity consensus (ICON), the equally weighted ensemble of DSHP, LGEM, GHMI, and HWFI.