bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of age and gender on the serum levels of clozapine, olanzapine, risperidone, and quetiapine
Authors: Castberg I. , Westin A. A. , Skogvoll E. , Spigset O. 
Published: September 2017

ObjectiveTo investigate serum concentrations of second‐generation antipsychotics in relation to age and gender in a population ranging from 18 to 100 years.MethodResults from a routine therapeutic drug monitoring database were retrieved, and 43 079 samples from 11 968 patients were included (17 249 samples for clozapine, 16 171 samples for olanzapine, 5343 samples for risperidone, and 4316 samples for quetiapine). The dose‐adjusted concentration was used as the primary target variable. A linear mixed model was used to allow the inclusion of multiple samples from each patient.ResultsAge had a significant impact on the concentrations of all four drugs. At the age of 80, the dose‐adjusted concentrations were up to twice those of the age of 40. At the age of 90, dose‐adjusted concentrations were two‐ to three‐fold higher. Age‐related increases were largest for clozapine (+108% at 80 years; +197% at 90 years) and smallest for olanzapine (+28% at 80 years; +106% at 90 years). Females generally had dose‐adjusted concentrations 20–30% higher than males.ConclusionThe effect of age on the serum concentrations of the antipsychotics studied becomes pronounced with advanced age. The patient population aged above 70 should be subdivided according to exact age, and considerable dose reductions are recommended.
A developmental‐based motivational intervention to reduce alcohol and marijuana use among non‐treatment‐seeking young adults: a randomized controlled trial
Authors: Stein Michael D. , Caviness Celeste M. , Morse Emily F. , Grimone Kristin R. , Audet Daniel , Herman Debra S. , Moitra Ethan , Anderson Bradley J. 
Published: September 2017

AbstractAimsTo test the hypothesis that among non‐treatment‐seeking emerging adults (EA) who both use marijuana and have alcohol binges, a brief, longitudinally delivered, developmentally based motivational intervention would show greater reductions in the use of these two substances compared with a health education control condition.DesignParallel, two‐group, randomized controlled trial with follow‐up interventions conducted at 1, 3, 6 and 9 months and final assessments at 12 and 15 months.SettingHospital‐based research unit in the United States.ParticipantsCommunity‐based 18–25‐year‐olds who reported at least monthly binge drinking and at least weekly marijuana use.InterventionMotivational intervention (EA‐MI) focused primarily on themes of emerging adulthood (identity exploration, instability, self‐focus, feeling in‐between, a sense of possibilities) and the subjects' relationship to substance use (n = 110) compared with an attention‐matched health education control condition (n = 116).MeasurementsThe primary outcomes were days of binge alcohol, marijuana and dual use day as measured using the timeline follow‐back method analysing the treatment by time interaction to determine relative differences in the rate of change between intervention arms.FindingsAt baseline, the mean rate (days/30) of binge drinking was 5.23 (± 4.31) of marijuana use was 19.4 (± 10.0) and of dual (same day) use was 4.11 (± 4.13). Relative to baseline, there were reductions in the rate of binge alcohol use, marijuana use and days of combined binge alcohol and marijuana use (P < 0.001) at all follow‐up assessments. However, the treatment × time interaction was not statistically significant for alcohol (P = 0.37), for marijuana (P = 0.07) or for dual use (P = 0.55). Averaged over all follow‐ups, mean reductions in binge, marijuana and dual use days were 1.16, 1.45 and 1.08, respectively, in the health education arm, and 1.06, 1.69 and 0.96 in EA‐MI. Bayes factors were < 0.01 for frequency of binge alcohol use and frequency of dual binge alcohol and marijuana and 0.016 for marijuana use.ConclusionsA brief, longitudinally delivered, developmentally based motivational intervention for young adults did not produce reductions in binge alcohol, marijuana use or dual use days relative to a control condition.
Hen's egg allergen in house and bed dust is significantly increased after hen's egg consumption—A pilot study
Authors: Trendelenburg V. , Tschirner S. , Niggemann B. , Beyer K. 
Published: September 2017

AbstractEnvironmental exposure to food allergens may be a risk factor for cutaneous sensitization. Previous studies could detect peanut allergen in house dust. In this pilot study, we wanted to investigate whether hen's egg allergen is detectable in house dust collected from different household areas and whether levels are increased after intentional hen's egg consumption. Hen's egg protein levels of dust samples were measured using ELISA. In 8 of 8 households, hen's egg was detectable in dust samples of eating area and bed. Forty‐eight hours after intentional hen's egg consumption, hen's egg protein levels were significantly increased in both. Still, further research is necessary to investigate whether hen's egg allergen in house and bed dust plays a role in sensitization via skin.
Evaluation of the pharmacokinetic drug interaction potential of tivantinib (ARQ 197) using cocktail probes in patients with advanced solid tumours
Authors: Tachibana Masaya , Papadopoulos Kyriakos P. , Strickler John H. , Puzanov Igor , Gajee Roohi , Wang Yibin , Zahir Hamim 
Published: September 2017

AimsThis phase 1, open‐label, crossover study sought to evaluate drug–drug interactions between tivantinib and cytochrome P450 (CYP) substrates and tivantinib and P‐glycoprotein.MethodsThe effect of tivantinib doses on the pharmacokinetics of the probe drugs for CYP1A2 (caffeine), CYP2C9 (S‐warfarin), CYP2C19 (omeprazole), and CYP3A4 (midazolam), and for P‐glycoprotein (digoxin) was investigated in 28 patients with advanced cancer using a cocktail probe approach. Patients received single doses of probe drugs alone and, after 5 days of treatment, with tivantinib 360 mg twice daily.ResultsThe ratios of geometric least squares mean (90% confidence interval) for the area under the concentration–time curve from time zero to the last quantifiable concentration in the presence/absence of tivantinib were 0.97 (0.89–1.05) for caffeine, 0.88 (0.76–1.02) for S‐warfarin, 0.89 (0.60–1.31) for omeprazole, 0.83 (0.67–1.02) for midazolam, and 0.69 (0.51–0.94) for digoxin. Similar effects were observed for maximum plasma concentrations; the ratio for digoxin in the presence/absence of tivantinib was 0.75 (0.60–0.95).ConclusionsThe data suggest that tivantinib 360 mg twice daily has either a minimal or no effect on the pharmacokinetics of probe drugs for CYP1A2, CYP2C9, CYP2C19 and CYP3A4 substrates, and decreases the systemic exposure of P‐glycoprotein substrates when administered with tivantinib.
Differential regulation of PD‐1 and its ligands in allergic asthma
Authors: Bratke K. , Fritz L. , Nokodian F. , Geißler K. , Garbe K. , Lommatzsch M. , Virchow J. C. 
Published: September 2017

SummaryBackgroundTargeting PD‐1/PD‐1 ligand signalling is an established treatment option for cancer. The role of these molecules in allergic asthma has been investigated in several mouse studies yielding conflicting results. However, human studies investigating the expression and regulation of PD‐1 and its ligands in allergic inflammation are lacking.ObjectiveTo analyse the expression and regulation of PD‐1 and its ligands in human allergic asthma.MethodsThe well‐established human asthma model of segmental allergen challenge (SAC) was used to analyse the regulation of PD‐1 and its ligands PD‐L1 and PD‐L2 on T lymphocytes and dendritic cells by flow cytometry. The impact of immunoglobulin E (IgE)‐mediated signalling on PD‐L1 expression was analysed on isolated plasmacytoid dendritic cells (pDCs).ResultsPD‐1 expression by blood CD4+ T cells was negatively associated with total and specific (against the allergen used for provocation) IgE serum concentrations. Twenty‐four hours after SAC, a small decrease in endobronchial PD‐1+CD4+ T cells was accompanied by an increase in PD‐L1 expression on endobronchial myeloid dendritic cells (mDCs) and pDCs. The PD‐L1 up‐regulation on pDCs was not induced by IgE‐mediated mechanisms. In contrast, PD‐L2 was only detected on endobronchial mDCs and was significantly down‐regulated 24 hours after SAC.Conclusion and clinical relevanceThis study shows, for the first time, an association of a low PD‐1 expression by circulating CD4+ T cells with high total and specific (against the allergen used for provocation) IgE concentrations in allergic asthma. In addition, we demonstrate a differential regulation of PD‐1 ligands on endobronchial DCs after allergen challenge which may favour Th2 inflammation. Therefore, modulating PD‐1 ligand‐mediated pathways might be a promising target in allergic asthma.
Adverse effects produced by different drugs used in the treatment of Parkinson's disease: A mixed treatment comparison
Authors: Li Bao‐Dong , Bi Zhen‐Yun , Liu Jing‐Feng , Si Wei‐Jun , Shi Qian‐Qian , Xue Li‐Peng , Bai Jing 
Published: September 2017

SummaryObjectiveThis mixed treatment comparison is used to compare the adverse effects of eleven different drugs used to treat Parkinson's disease (PD). The drugs that we compare include the following: ropinirole, rasagiline, rotigotine, entacapone, apomorphine, pramipexole, sumanirole, bromocriptine, piribedil, pergolide, and levodopa.MethodsPubMed, EMBASE, and Cochrane Library were searched from the inception to December 2015. Our analysis combines the evidences of direct comparison and indirect comparison between various literatures. We evaluated the merging odds ratios (OR) value and surface under the cumulative ranking curves (SUCRA) of each of the drugs and used this as a mode of comparison.ResultsTwenty‐four randomized controlled trials (RCTs) were included in this study. Our results demonstrated that the incidence of adverse reactions of ropinirole, rotigotine, entacapone, and sumanirole were obviously higher in terms of nausea compared to the placebo. Ropinirole produced the highest incidence rates of dyskinesia side effects, whereas pramipexole was significantly higher in terms of patients’ hallucination. In addition, the SUCRA values of all the drugs showed that the incidence of adverse reaction of pergolide was relatively high (nausea: 83.5%; hallucination: 79.8%); for dyskinesia and somnolence, the incidence of ropinirole was higher (dyskinesia: 80.5%; somnolence: 69.4%); the incidence of adverse reaction of piribedil was higher on PD in terms of dizziness (67.0%); and the incidence of bromocriptine was relatively high in terms of constipation (62.3%).ConclusionsThis mixed treatment comparison showed that the drugs ropinirole, bromocriptine, and piribedil produced the highest incidence rates of nausea, dyskinesia, hallucination, dizziness, constipation, and somnolence symptoms. Thus, we conclude that as these three drugs produced the most frequent symptoms, they are not recommended for the treatment of patients with Parkinson's disease.
What does Brunei teach us about using Human Development Index rankings as a policy tool?
Authors: Michael Bryane 
Published: September 2017

AbstractThe Bruneian Government has set an ambitious target to achieve a top 10 ranking on the United Nations Development Programme's (UNDP) Human Development Index (HDI) by 2035. To achieve its objective (described in a national strategy document called the Wawasan 2035), Brunei's economy needs to grow by 6% to 7%. Is setting an HDI target a good way to govern Brunei's policy‐making? Is it a good way to govern any country's policy‐making? In this article, we look at the role of HDI‐rank targets in economic and fiscal policy. We show that such a headline target (much like a profit target in a private company) automatically sets targets for growth in various economic sectors and fiscal policy targets. As such, HDI‐rank targeting may provide a useful mechanism for co‐ordinating development policies and for monitoring progress against a wide range of development goals using only one number.
‘Collar propagation’ as an alternative propagation method for rhizomatous miscanthus
Authors: Mangold Anja , Lewandowski Iris , Xue Shuai , Kiesel Andreas 
Published: September 2017

AbstractThe demand for perennial nonfood crops, such as miscanthus, is increasing steadily, as fossil resources are replaced by biomass. However, as the establishment of miscanthus is very expensive, its cultivation area in Europe is still small. The most common propagation method for miscanthus is via rhizomes, the harvesting of which is very labour‐intensive. Seed propagation is promising, but not suitable for sterile genotypes. In this study, a new vegetative propagation method, ‘collar propagation’, was tested in field and controlled environment studies. Collars are built at the junction between rhizome and stem. They can be harvested in a less destructive way than rhizomes by pulling out the stems from winter‐dormant miscanthus plants. One genotype of each of the species M. sacchariflorus, M. × giganteus, M. sinensis in combination with three fragment types (collars, rhizomes, collars + rhizomes) were tested for establishment success and plant performance. The performance (e.g. dry matter yield) of collar‐propagated plants was either better than or not significantly different from rhizome‐propagated plants. Pregrown plantlets transplanted into the field showed no significant differences in establishment success between the fragments within a genotype. When directly planted into the field however, the fragment ‘rhizome+collar’ had a significantly better establishment success than the other two. The winter survival rate of the fragment ‘rhizome+collar’ was 70% for M. sacchariflorus and 75% for M. × giganteus. Emergence success from collar‐derived plants was not affected by harvest date (harvested monthly from November to February). This study showed that miscanthus propagation via collars is feasible and a promising alternative to rhizome propagation, as the multiplication rate of collars is comparable to that of rhizome propagation. Collar propagation is the more suitable method for the tested genotypes of the species M. sachariflorus and M. × giganteus, but not for M. sinensis genotypes, which may be better propagated by seeds.
Cumulative incidence and risk factors for the development of hepatocellular carcinoma in patients with chronic hepatitis B who achieved sustained disappearance of viremia by nucleos(t)ide analog treatment
Authors: Ando Yusuke , Ishigami Masatoshi , Ishizu Yoji , Kuzuya Teiji , Honda Takashi , Hayashi Kazuhiko , Ishikawa Tetsuya , Nakano Isao , Hirooka Yoshiki , Goto Hidemi 
Published: September 2017

AimNucleos(t)ide analog (NA) therapy has been reported to reduce the risk of hepatocellular carcinoma (HCC). However, some patients who achieve hepatitis B virus (HBV)‐DNA disappearance from serum by NA develop HCC. In this study, we investigated the cumulative incidence and risk factors for HCC in patients with chronic hepatitis B (CHB) who achieved sustained disappearance of viremia by NA treatment.MethodsA total of 133 CHB patients (median age, 51 years; 79 men [59%]; 28 with cirrhosis [21%]) who received NA therapy and achieved HBV‐DNA disappearance from serum were analyzed retrospectively. We evaluated the cumulative incidence of HCC and risk factors associated with HCC based on data collected at the time of HBV‐DNA disappearance.ResultsThirteen patients developed HCC during the follow‐up period. The 1‐, 3‐, and 5‐year cumulative incidence of HCC was 0.0%, 7.8%, and 11.1%, respectively. In multivariate analysis, advanced age (hazard ratio [HR], 4.601; 95% confidence interval [CI], 1.220–17.351; P = 0.024), liver cirrhosis (HR, 5.563; 95% CI, 1.438–21.519; P = 0.013), and higher HBV core‐related antigen (HBcrAg) levels (HR, 13.532; 95% CI, 1.683–108.815; P = 0.014) at the time of HBV‐DNA disappearance were significantly associated with the development of HCC.ConclusionOur findings indicate the importance of continuous HCC surveillance especially in patients with advanced age, cirrhosis, and/or higher serum levels of HBcrAg, even if they achieve HBV‐DNA disappearance.
The effect of photodamage on the female Caucasian facial stratum corneum corneome using mass spectrometry‐based proteomics
Authors: Voegeli R. , Monneuse J.‐M. , Schoop R. , Summers B. , Rawlings A.V. 
Published: September 2017

AbstractBackgroundThe effect of photodamage on facial stratum corneum (SC) is still poorly understood.ObjectiveTo describe the SC proteome from tape strippings of Caucasian SC from photoexposed cheek and photoprotected post‐auricular (PA) site, a global analysis of photodamage on the skin will be developed leading to a better understanding of keratinocyte signalling pathways and identification of new molecular targets for the treatment of photoaged skin.MethodsFemale Caucasian subjects had nine consecutive tape strippings taken from their cheeks and PA site. Proteins were extracted and the trypsin‐digested peptides were analysed by nanochromatography coupled to a high‐resolution mass spectrometer. Data‐dependent acquisition allowed protein identification that was processed by Paragon algorithm of Protein Pilot software.ResultsChanges in the levels of epidermal differentiation proteins were apparent indicating poor epidermal differentiation and SC maturation (keratins, cornified envelope (CE) proteins) on photoexposed cheeks. Differences in protease–anti‐protease balance were observed for corneodesmolysis (favouring desquamation) and filaggrinolysis (favouring reduced filaggrin processing). 12R‐LOX, a CE maturation enzyme, was reduced in photodamaged skin but not transglutaminases. Changes in signal keratinocyte transduction pathway markers were demonstrated especially by reduced levels of downstream signalling markers such as calreticulin (unfolded protein response; UPR) and increased level of stratifin (target of rapamycin; mTOR). Evidence for impaired proteostasis was apparent by reduced levels of a key proteasomal subunit (subunit beta type‐6). Finally, key antioxidant proteins were upregulated except catalase.ConclusionClear examples of poor keratinocyte differentiation and associated metabolic and signalling pathways together with reduced SC maturation were identified in photodamaged facial SC. Corneocyte immaturity was evident with changes in CE proteins. Particularly, the reduction in 12R‐LOX is a novel finding in photodamaged skin and supports the lack of SC maturation. Moreover, filaggrinolysis was reduced, whereas corneodesmolysis was enhanced. From our results, we propose that there is a poor cross‐talk between the keratinocyte endoplasmic reticulum UPR, proteasome network and autophagy machinery that possibly leads to impaired keratinocyte proteostasis. Superimposed on these aberrations is an apparently enhanced mTOR pathway that also contributes to reduced SC formation and maturation. Our results clearly indicate a corneocyte scaffold disorder in photodamaged cheek SC.
Multimodular assessment of a calcified extraradicular deposit on the root surfaces of a mandibular molar
Authors: Petitjean E. , Mavridou A. , Li X. , Hauben E. , Cotti E. , Lambrechts P. 
Published: September 2017

AbstractAimTo achieve a better understanding of a calcified extraradicular deposit on the apical root surfaces of a mandibular first molar associated with a radicular cyst and a sinus tract. A multimodular approach was applied using a combination of multiple investigation methods.SummaryThis case report presents a mandibular first molar with a calcified extraradicular deposit on the apical root surfaces of both roots. An apical periodontitis lesion was present and a sinus tract served as the only communication with the oral cavity. Diagnosis and treatment planning were based on clinical, radiographic (two‐ and three‐dimensional) and ultrasound examination. The tooth was further analysed after extraction using microscopic imaging, nano‐computed tomography (nano‐CT), hard‐ and soft tissue histology and electron probe microanalysis. This multimodular approach revealed the calculus‐like appearance and mineral composition of the extraradicular deposit. Multiple hypotheses about its aetiology are discussed.Key learning points

Calcified extraradicular deposits can develop on the apical root surfaces of teeth with apical periodontitis in association with a radicular cyst and sinus tract.

A sinus tract can serve as the only communication between the apical lesion and the oral cavity whilst no periodontal defects are present.

The interplay of intra‐oral radiography, high resolution CBCT, nano‐CT, hard tissue histology and EPMA can reveal the calculus‐like appearance and composition of the extraradicular deposit.

Calcified extraradicular deposits appear hyperechoic on ultrasound imaging and can lead to the occurrence of twinkling artefacts due to their rough mineralized surface.
The diffusion coefficient controlling crystal growth in a silicate glass‐former
Authors: Cassar Daniel Roberto , Rodrigues Alisson Mendes , Nascimento Marcio Luis Ferreira , Zanotto Edgar Dutra 
Published: September 2017

AbstractOne of the most relevant open issues in glass science refers to our ignorance concerning the nature of the diffusing entities that control crystal nucleation and growth in non‐crystalline materials. This information is very relevant because all the existing nucleation and growth equations account for the diffusion coefficient (DU) of these unknown entities. In this article, we measured the shear viscosity (η) and the crystal growth rates of a supercooled diopside liquid (CaMgSi2O6) in a wide temperature range. The well‐known decoupling of viscosity and crystal growth rates at deep supercoolings was detected. We tested and analyzed 4 different approaches to compute DU, three existing and one proposed here. As expected, the classical approach (DU ~ η−1) and the fractional viscosity approach (DU ~ η−ε) were not able to describe the crystal growth rates near the glass transition temperature. However, our proposed expression to calculate DU—gradually changing from a viscosity‐controlled to an Arrhenian‐controlled process—was able to describe the available data in the whole temperature range and yielded the lowest uncertainty for the adjustable parameters. Our results suggest that viscous flow ceases to control the crystal growth process below the so‐called decoupling temperature, corroborating some previous studies.
Becoming a Design Thinker: Assessing the Learning Process of Students in a Secondary Level Design Thinking Course
Authors: Aflatoony Leila , Wakkary Ron , Neustaedter Carman 
Published: September 2017

AbstractDesign thinking is a collaborative problem solving and human‐centric approach that fosters innovation by elevating participants’ creative thinking abilities. Design thinking techniques and practices have been implemented into different curricula in secondary and post‐secondary education to address the need for new skills to be learned for the twenty‐first century. However, little work has been conducted to clarify how to evaluate the students’ design thinking skills gained in these courses. This study reports on a successful evaluation of an interaction design thinking curriculum in secondary level education. Several types of data sources, including participant observation, open‐ended questions and document analysis were employed to gather extensive data on students’ skills gained during the course. The results of the study inform design thinking researchers about how to evaluate design thinking skills of students in a secondary level design thinking course.