bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetics and pharmacogenomics of apixaban in Japanese adult patients with atrial fibrillation
Authors: Ueshima Satoshi , Hira Daiki , Kimura Yuuma , Fujii Ryo , Tomitsuka Chiho , Yamane Takuya , Tabuchi Yohei , Ozawa Tomoya , Itoh Hideki , Ohno Seiko , Horie Minoru , Terada Tomohiro , Katsura Toshiya 
Published: February 2018

AimsThis study aimed to analyse the effects of genetic polymorphisms in drug transporters and metabolizing enzymes, and clinical laboratory data on the pharmacokinetic parameters of apixaban.MethodsData were collected from 81 Japanese patients with atrial fibrillation. Pharmacogenomic data were stratified by ABCB1, ABCG2 and CYP3A5 polymorphisms. The pharmacokinetic profile of apixaban was described by a one‐compartment model with first‐order absorption. Population pharmacokinetic analysis was conducted using a nonlinear mixed effect modelling (NONMEM™) program.ResultsThe nonlinear relationship between oral clearance (CL/F) of apixaban and creatinine clearance (Ccr) was observed. The population mean of CL/F for a typical patient (Ccr value of 70 ml min−1) with the CYP3A5*1/*1 and ABCG2 421C/C or C/A genotypes was estimated to be 3.06 l h−1. When Ccr values were set to the typical value, the population mean of CL/F was 1.52 times higher in patients with the CYP3A5*1/*1 genotype compared with patients with the CYP3A5*1/*3 or *3/*3 genotype, while the population mean of CL/F was 1.49 times higher in patients with the ABCG2 421C/C or C/A genotype compared with patients with the ABCG2 421A/A genotype. However, no covariates affected the population mean of the apparent volume of distribution (Vd/F) of apixaban. The population mean of Vd/F was estimated to be 24.7 l.ConclusionThe present study suggests that the ABCG2 421A/A and CYP3A5*3 genotypes and renal function are intrinsic factors affecting apixaban pharmacokinetics. These findings may provide useful information for precision medicine using apixaban, to avoid the risk of adverse reactions.
Saudi Arabian children's reasoning about religion‐based exclusion
Authors: Alsamih Munirah , Tenenbaum Harriet R. 
Published: February 2018

This study examined how Saudi Arabian children (M = 10.50 years, SD = 1.61, Range = 8–10 years) evaluate peer exclusion based on religion when the perpetrator of exclusion was a peer or a father. Children believed that it was more acceptable for fathers than for peers to enforce exclusion and were more likely to use social conventional reasons to justify exclusion when the perpetrator was a father. The discussion focuses on how social domain theory needs to take children's cultural community into account.
Statement of contribution

What is already known on this subject?

Research suggests that children do not defer to authority in making decisions about peer exclusion.

Children tend to believe that authority figures should not order peer exclusion because it is a moral decision.

What does this study add?

Unlike children in other collectivist countries, children in Saudi Arabia support peer exclusion ordered by a father more than a peer.

Saudi children use social conventional reasoning to justify fathers' support for peer exclusion.
Addressing challenges in gaining informed consent for a research study investigating falls in people with intellectual disability
Authors: Ho Portia , Downs Jenny , Bulsara Caroline , Patman Shane , Hill Anne‐Marie 
Published: February 2018

Accessible Summary

People with intellectual disability do not often take part in research.

When people with intellectual disability are thinking about taking part in research, it is important that they are given support to participate in the decision‐making.

This study describes how an informed consent process was developed for people with intellectual disability and how it is working in a current study.

AbstractBackgroundPeople with intellectual disability encounter substantial healthcare discrepancies, yet are under‐represented in research. While people with intellectual disability can make valuable contributions to research and consequently improve their quality of life, researchers encounter multiple challenges including them in research. One challenge is to support them in making an informed decision to participate in research. Therefore, the aim of this study was to describe and reflect on a consent procedure used while gaining informed consent, when recruiting potential participants into an ongoing study.MethodsA systematic and holistic consent procedure, underpinned by ethical guidelines, was developed and used alongside recommended strategies to engage people with intellectual disability in a research study.ResultsOnly three participants (7.5%) were deemed capable of consenting independently, while 37 participants (92.5%) required the support of a proxy. Of these 37 participants, 22 participated in the consent process, while 15 depended mainly on their caregiver to make decisions for them. Adapted communication strategies were found to facilitate a person who has an intellectual disability's participation in the consent procedure. The adapted written information sheets were of secondary importance.ConclusionThe consent procedure was a respectful means of determining a person's capacity to consent and indicating where there was a need for proxy consent. Appropriate communication strategies and the inclusion of familiar caregiver(s) were critical components for facilitating the person with an intellectual disability to participate in the consent procedure.
An evaluation of the operational model when applied to quantify functional selectivity
Authors: Zhu Xiao , Finlay David B , Glass Michelle , Duffull Stephen B 
Published: February 2018

Background and PurposeFunctional selectivity describes the ability of ligands to differentially regulate multiple signalling pathways when coupled to a single receptor, and the operational model is commonly used to analyse these data. Here, we assess the mathematical properties of the operational model and evaluate the outcomes of fixing parameters on model performance.Experimental ApproachThe operational model was evaluated using both a mathematical identifiability analysis and simulation.Key ResultsMathematical analysis revealed that the parameters R0 and KE were not independently identifiable which can be solved by considering their ratio, τ. The ratio parameter, τ, was often imprecisely estimated when only functional assay data were available and generally only the transduction coefficient R (
) could be estimated precisely. The general operational model (that includes baseline and the Hill coefficient) required either the parameters Em or KA to be fixed. The normalization process largely cancelled out the mean error of the calculated Δlog (R) caused by fixing these parameters. From this analysis, it was determined that we can avoid the need for a full agonist ligand to be included in an experiment to determine Δlog (R).Conclusion and ImplicationsThis analysis has provided a ready‐to‐use understanding of current methods for quantifying functional selectivity. It showed that current methods are generally tolerant to fixing parameters. A new method was proposed that removes the need for including a high efficacy ligand in any given experiment, which allows application to large‐scale screening to identify compounds with desirable features of functional selectivity.
X‐ray‐enhanced cancer cell migration requires the linker of nucleoskeleton and cytoskeleton complex
Authors: Imaizumi Hiromasa , Sato Katsutoshi , Nishihara Asuka , Minami Kazumasa , Koizumi Masahiko , Matsuura Nariaki , Hieda Miki 
Published: February 2018

The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, including nuclear migration, mechanotransduction, chromatin tethering and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1), a component of the LINC complex, has a critical function in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown. Here, we examined the involvement of the LINC complex in radiation‐enhanced cell migration and invasion. A sublethal dose of X‐ray radiation promoted human breast cancer MDA‐MB‐231 cell migration and invasion, whereas carbon ion beam radiation suppressed these processes in a dose‐dependent manner. Depletion of SUN1 and SUN2 significantly suppressed X‐ray‐enhanced cell migration and invasion. Moreover, depletion or overexpression of each SUN1 splicing variant revealed that SUN1_888 containing 888 amino acids of SUN1 but not SUN1_916 was required for X‐ray‐enhanced migration and invasion. In addition, the results suggested that X‐ray irradiation affected the expression level of SUN1 splicing variants and a SUN protein binding partner, nesprins. Taken together, our findings supported that the LINC complex contributed to photon‐enhanced cell migration and invasion.
Dental knowledge and dental service utilization: A 2‐year follow‐up study
Authors: Amarasena Najith , Spencer Andrew John , Roberts‐Thomson Kaye F. , Brennan David S. 
Published: February 2018

AbstractObjectivesTo investigate associations of dental knowledge with dental service utilization over 2 years in South Australians aged 45‐54 years.MethodsIn 2004‐2005, a random sample of 2469 adults aged 45‐54 years from Adelaide, South Australia, who were selected from the Australian electoral roll was surveyed. The outcome variables were the numbers of visits and dental services received over 2 years. Data were analysed using log‐binomial and Poisson regression. Statistical significance was determined at P < .05.ResultsThe response rates were 43.8% in the study group (n = 879) and 50.7% in the comparison group (n = 107). Oral examinations were conducted on 709 persons (81% of study group participants). Dental services data were collected from approximately 60% of participants at the end of years 1 and 2. After adjusting for sex, education, health card status, toothbrushing and inadequate dentition, higher caries knowledge and periodontal knowledge scores were associated with higher percentages of persons making dental visits (prevalence ratio, 95% CI: 1.2, 1.1‐1.3 and 1.1, 1.0‐1.3), and lower rates of extraction (rate ratio, 95% CI: 0.2, 0.1‐0.4 and 0.4, 0.3‐0.7) and endodontic services (0.5, 0.3‐0.9 and 0.5, 0.3‐0.7). Higher caries knowledge was associated with lower rates of fillings (0.8, 0.7‐0.9) and denture services (0.1, 0.0‐0.6), while higher periodontal knowledge was associated with higher numbers of visits (1.3, 1.2‐1.5), and prophylaxis services (1.4, 1.1‐1.8) and crowns (1.7, 1.1‐2.5).ConclusionSouth Australians aged 45‐54 years with higher dental knowledge had lower rates of invasive treatment over 2 years. These findings warrant policy initiatives that highlight the importance of dental knowledge in improving oral health.
Prevalence of orofacial clefts and risks for nonsyndromic cleft lip with or without cleft palate in newborns at a university hospital from West Mexico
Authors: Corona‐Rivera Jorge Román , Bobadilla‐Morales Lucina , Corona‐Rivera Alfredo , Peña‐Padilla Christian , Olvera‐Molina Sandra , Orozco‐Martín Miriam A. , García‐Cruz Diana , Ríos‐Flores Izabel M. , Gómez‐Rodríguez Brian Gabriel , Rivas‐Soto Gemma , Pérez‐Molina J. Jesús 
Published: February 2018

ABSTRACTWe determined the overall prevalence of typical orofacial clefts and the potential risks for nonsyndromic cleft lip with or without cleft palate in a university hospital from West México. For the prevalence, 227 liveborn infants with typical orofacial clefts were included from a total of 81,193 births occurred during the period 2009–2016 at the “Dr. Juan I. Menchaca” Civil Hospital of Guadalajara (Guadalajara, Jalisco, Mexico). To evaluate potential risks, a case‐control study was conducted among 420 newborns, including only those 105 patients with nonsyndromic cleft lip with or without cleft palate (cases), and 315 infants without birth defects (controls). Data were analyzed using multivariable logistic regression analysis expressed as adjusted odds ratio with 95% confidence intervals . The overall prevalence for typical orofacial clefts was 28 per 10,000 (95% confidence interval: 24.3–31.6), or 1 per 358 live births. The mean values for the prepregnancy weight, antepartum weight, and pre‐pregnancy body mass index were statistically higher among the mothers of cases. Infants with nonsyndromic cleft lip with or without cleft palate had a significantly higher risk for previous history of any type of congenital anomaly (adjusted odds ratio: 2.7; 95% confidence interval: 1.4–5.1), history of a relative with cleft lip with or without cleft palate (adjusted odds ratio: 19.6; 95% confidence interval: 8.2–47.1), and first‐trimester exposures to progestogens (adjusted odds ratio: 6.8; 95% CI 1.8–25.3), hyperthermia (adjusted odds ratio: 3.4; 95% confidence interval: 1.1–10.6), and common cold (adjusted odds ratio: 3.6; 95% confidence interval: 1.1–11.9). These risks could have contributed to explain the high prevalence of orofacial clefts in our region of Mexico, emphasizing that except for history of relatives with cleft lip with or without cleft palate, most are susceptible of modification.
Alteration of GABAergic neurotransmission in Huntington's disease
Authors: Garret Maurice , Du Zhuowei , Chazalon Marine , Cho Yoon H. , Baufreton Jérôme 
Published: February 2018

SummaryHereditary Huntington's disease (HD) is characterized by cell dysfunction and death in the brain, leading to progressive cognitive, psychiatric, and motor impairments. Despite molecular and cellular descriptions of the effects of the HD mutation, no effective pharmacological treatment is yet available. In addition to well‐established alterations of glutamatergic and dopaminergic neurotransmitter systems, it is becoming clear that the GABAergic systems are also impaired in HD. GABA is the major inhibitory neurotransmitter in the brain, and GABAergic neurotransmission has been postulated to be modified in many neurological and psychiatric diseases. In addition, GABAergic neurotransmission is the target of many drugs that are in wide clinical use. Here, we summarize data demonstrating the occurrence of alterations of GABAergic markers in the brain of HD carriers as well as in rodent models of the disease. In particular, we pinpoint HD‐related changes in the expression of GABAA receptors (GABAARs). On the basis that a novel GABA pharmacology of GABAARs established with more selective drugs is emerging, we argue that clinical treatments acting specifically on GABAergic neurotransmission may be an appropriate strategy for improving symptoms linked to the HD mutation.
Perceptions of driving after marijuana use compared to alcohol use among rural American young adults
Authors: Greene Kaylin M. 
Published: February 2018

AbstractIntroduction and AimsSubstance use contributes to motor vehicle crashes, the leading cause of death among young adults. The current qualitative study examined perceptions of the acceptability and harms associated with driving after marijuana versus alcohol use in rural America. Illuminating rural perspectives is critical given that the motor vehicle fatality rate is twice as high in rural as in urban areas in the USA.Design and MethodsIn 2015–2016, 72 young adults aged 18–25 years (Mage = 20.2; 50.7% female) living in Montana, USA, participated in 11 focus groups. A list of descriptive codes was generated inductively and two individuals coded participant comments. Discussion, memoing and concept mapping were used to uncover broader themes and transcripts were reviewed for evidence of these themes.ResultsThere was shared consensus that, with regard to crash risk, driving after marijuana use was safer than driving after alcohol use. While alcohol was thought to impair driving ability universally, marijuana's impacts depended on individual characteristics (e.g. compensatory behaviours) and the marijuana itself (e.g. type). Participants expressed conflicting beliefs about policies surrounding marijuana use and driving but were more knowledgeable about alcohol‐related policies. Participants viewed older adults and those in frontier areas as more disapproving of driving after marijuana use.Discussion and ConclusionsMisinformation about the consequences of driving after marijuana use is common, demonstrating the need for future research and educational interventions. Developing and disseminating guidelines for driving after marijuana use would help marijuana users make informed decisions and mitigate driving‐related risks.
When a physician and a clinical ethicist collaborate for better patient care
Authors: Arawi Thalia , Charafeddine Lama 
Published: February 2018

AbstractBioethics is a relatively new addition to bedside medical care in Arab world which is characterized by a special culture that often makes blind adaptation of western ethics codes and principles; a challenge that has to be faced. To date, the American University of Beirut Medical Center is the only hospital that offers bedside ethics consultations in the Arab Region aiming towards better patient‐centered care. This article tackles the role of the bedside clinical ethics consultant as an active member of the medical team and the impact of such consultations on decision‐making and patient‐centered care. Using the case of a child with multiple medical problems and a futile medical condition, we describe how the collaboration of the medical team and the clinical ethics consultant took a comprehensive approach to accompany and lead the parents and the medical team in their decision‐making process and how the consultations allowed several salient issues to be addressed. This approach proved to be effective in the Arab cultural setting and indeed did lead to better patientcentered care.
Implications of Odera Oruka's ethics of consumerism for reducing globesity
Authors: Fayemi Ademola K. 
Published: February 2018

AbstractIn this paper, I advance Odera Oruka's insights on the ethics of consumerism in order to draw relevant implications of his thoughts on rethinking the problem of obesity. I argue that Oruka's ethics of consumerism and his right to human minimum theory entail some salient ideas that might serve as a better ethical model for reducing the global obesity prevalence. Though Oruka's African moral philosophy is yet to receive universal attention it arguably deserves, the interests of the international and ‘globesity’ community would be better served learning from the contributions of an African moral theory to contemporary bioethical discourse on obesity. Oruka's moral thoughts are by constitution, a deontological and cosmopolitan call for reducing hunger in globalized world, while also indirectly, addressing obesity of the poor. I show the limitations of his ethics of consumerism, and the shortcomings of such ethics in the context of obesity of the poor. Consequently, I develop a neo‐Orukan virtue based ethics that is worthy of attention in efforts towards addressing the obesity tide. No such perspective currently exists in the context of obesity; yet the exigent need for one is necessitated by the defects of the libertarian and harm principle approaches in Western bioethical discourse.
Development of a screening tool using electronic health records for undiagnosed Type 2 diabetes mellitus and impaired fasting glucose detection in the Slovenian population
Authors: Štiglic G. , Kocbek P. , Cilar L. , Fijačko N. , Stožer A. , Zaletel J. , Sheikh A. , Povalej Bržan P. 
Published: February 2018

AbstractAimTo develop and validate a simplified screening test for undiagnosed Type 2 diabetes mellitus and impaired fasting glucose for the Slovenian population (SloRisk) to be used in the general population.MethodsData on 11 391 people were collected from the electronic health records of comprehensive medical examinations in five Slovenian healthcare centres. Fasting plasma glucose as well as information related to the Finnish Diabetes Risk Score questionnaire, FINDRISC, were collected for 2073 people to build predictive models. Bootstrapping‐based evaluation was used to estimate the area under the receiver‐operating characteristic curve performance metric of two proposed logistic regression models as well as the Finnish Diabetes Risk Score model both at recommended and at alternative cut‐off values.ResultsThe final model contained five questions for undiagnosed Type 2 diabetes prediction and achieved an area under the receiver‐operating characteristic curve of 0.851 (95% CI 0.850–0.853). The impaired fasting glucose prediction model included six questions and achieved an area under the receiver‐operating characteristic curve of 0.840 (95% CI 0.839–0.840). There were four questions that were included in both models (age, sex, waist circumference and blood sugar history), with physical activity selected only for undiagnosed Type 2 diabetes and questions on family history and hypertension drug use selected only for the impaired fasting glucose prediction model.ConclusionsThis study proposes two simplified models based on FINDRISC questions for screening of undiagnosed Type 2 diabetes and impaired fasting glucose in the Slovenian population. A significant improvement in performance was achieved compared with the original FINDRISC questionnaire. Both models include waist circumference instead of BMI.
Investigating the longitudinal association between diabetes and anxiety: a systematic review and meta‐analysis
Authors: Smith K. J. , Deschênes S. S. , Schmitz N. 
Published: February 2018

AbstractAimPrevious research has indicated an association between diabetes and anxiety. However, no synthesis has determined the direction of this association. The aim of this study was to determine the longitudinal relationship between anxiety and diabetes.MethodsWe searched seven databases for studies examining the longitudinal relationship between anxiety and diabetes. Two independent reviewers screened studies from a population aged 16 or older that examined either anxiety as a risk factor for incident diabetes or diabetes as a risk factor for incident anxiety. Studies that met eligibility criteria were put forward for data extraction and meta‐analysis.ResultsIn total 14 studies (n = 1 760 800) that examined anxiety as a risk factor for incident diabetes and two (n = 88 109) that examined diabetes as a risk factor for incident anxiety were eligible for inclusion in the review. Only studies examining anxiety as a risk factor for incident diabetes were put forward for the meta‐analysis. The least adjusted (unadjusted or adjusted for age only) estimate indicated a significant association between baseline anxiety with incident diabetes (odds ratio 1.47, 1.23–1.75). Furthermore, most‐adjusted analyses indicated a significant association between baseline anxiety and incident diabetes. Included studies that examined diabetes to incident anxiety found no association.ConclusionsThere was an association between baseline anxiety and incident diabetes. The results also indicate the need for more research to examine the direction of association from diabetes to incident anxiety. This work adds to the growing body of evidence that poor mental health increases the risk of developing diabetes.