bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of alopecia universalis with topical Janus kinase inhibitors – a double blind, placebo, and active controlled pilot study
Authors: Bokhari Laita , Sinclair Rodney 
Published: August 2018

AbstractBackgroundOral Janus kinase (JAK) inhibitors are currently being investigated in phase II and phase III clinical trials for several inflammatory skin diseases including alopecia areata (AA). Topical JAK inhibitors have been investigated in atopic dermatitis, psoriasis, and AA. While a number of case series using topical JAK inhibitors in AA have been published, to date there have been no randomized controlled clinical trials.MethodsWe conducted a phase I, 28 week prospective, placebo‐controlled, double‐blind study in patients with alopecia universalis investigating hair regrowth with two topical JAK inhibitors, 2% tofacitinib and 1% ruxolitinib. Topical clobetasol dipropionate 0.005% was the active comparator while vehicle was used as the placebo control. Sixteen patients were recruited for the study.ResultsSix patients demonstrated partial hair regrowth in areas treated with 2% tofacitinib ointment applied twice daily. Five patients demonstrated partial hair regrowth in the areas treated with 1% ruxolitinib ointment. Ten patients demonstrated partial hair regrowth in the areas treated with clobetasol dipropionate 0.05% ointment. No regrowth was observed in the placebo treated area. Interestingly, generalized hair regrowth was observed in two patients. One patient had 100% regrowth over his entire scalp and eyebrows by week 24 but relapsed after 12 weeks. A second patient also experienced generalized scalp regrowth and significant eyebrow growth and continued to maintain growth 14 weeks later.ConclusionOur findings suggest that topical JAK inhibitors could be developed as a potential new treatment for AA and alternative to clobetasol dipropionate 0.05% ointment.
A novel approach to the classification of epidermodysplasia verruciformis
Authors: Huang Simo , Wu Julie H. , Lewis Daniel J. , Rady Peter L. , Tyring Stephen K. 
Published: August 2018

AbstractBackgroundEpidermodysplasia verruciformis (EV) is a rare genodermatosis that causes disseminated eruptions of hypo‐ or hyperpigmented macules and wart‐like papules that can coalesce and scale. It is uniquely characterized by an increased susceptibility to specific human papillomavirus (HPV) genotypes. Classically, EV is associated with mutations of the EVER1/TMC6 and EVER2/TMC8 genes. The term “acquired” epidermodysplasia verruciformis was coined to describe an EV‐like syndrome that can develop in patients with a compromised immune system. Recent discoveries of other genes implicated in EV, including RHOH, MST‐1, and CORO1A, have complicated the classification of EV and EV‐like syndromes.MethodsWe review the available data on epidermodysplasia verruciformis in the literature in order to propose a new classification system to encompass current and future developments on EV and EV‐like syndromes.ResultsWe propose classifying EV into: (1) classic genetic EV, (2) non‐classic genetic EV, and (3) acquired EV.ConclusionThe proposed categorization scheme provides a simple and logical way to organize the different cases of EV that have been described in the literature. This system organizes EV by its cause, allowing for a better understanding of the disease and helps differentiate EV from other causes of generalized verrucosis.
Absolute bounds of list algorithms for parallel machines scheduling with unavailability periods
Authors: Mahjoub Amine , Kaabi Jihene , Harrath Youssef 
Published: August 2018

AbstractWe address the problem of scheduling a set of independent tasks on m parallel and identical machines subject to an arbitrary number of unavailability periods. The objective is to minimize the makespan. The problem was already investigated and was proved to be strongly hard. Moreover, when the number of unavailability periods per machine exceeds 1, there is no bound for the problem. We proved the existence of tight absolute bounds when there is only one unavailability period per machine. In the general case, we proposed an efficient binary linear program and proved that the list algorithm based on the largest processing time (LPT rule) has a high performance. This study was motivated by grid scheduling, where a large number of independent jobs is sent to computing resources whose availability cannot be guaranteed.
Treating real people: Science and humanity
Authors: Loughlin Michael , Mercuri Mathew , Pârvan Alexandra , Copeland Samantha Marie , Tonelli Mark , Buetow Stephen 
Published: August 2018

AbstractSomething important is happening in applied, interdisciplinary research, particularly in the field of applied health research. The vast array of papers in this edition are evidence of a broad change in thinking across an impressive range of practice and academic areas. The problems of complexity, the rise of chronic conditions, overdiagnosis, co‐morbidity, and multi‐morbidity are serious and challenging, but we are rising to that challenge. Key conceptions regarding science, evidence, disease, clinical judgement, and health and social care are being revised and their relationships reconsidered: Boundaries are indeed being redrawn; reasoning is being made “fit for practice.” Ideas like “person‐centred care” are no longer phrases with potential to be helpful in some yet‐to‐be‐clarified way: Theorists and practitioners are working in collaboration to give them substantive import and application.
Predictive modeling for 5‐hydroxymethylfurfural formation by some application conditions of high hydrostatic pressure, namely glucose concentration and application temperature, in high glucose containing model beverages
Authors: Altuner Ergin Murat , Alpas Hami 
Published: August 2018

AbstractHigh hydrostatic pressure (HHP) is a nonthermal food processing technology. Many studies have shown that HHP may be used as a process to increase the shelf life of beverages, which are inherently containing glucose or subsequently glucose added. Depending on food processing technologies and storage conditions 5‐hydroxymethylfurfural (5‐HMF) formation from glucose in foods occurs. There are some limitations about the amount of the 5‐HMF present in foods based on World Health Organization and various International Standards, such as European Commission Directive 2007/196/EC. The aim of this study is to present the effect of glucose concentration and HHP in 5‐HMF formation in model beverages with different glucose concentrations (10, 40, and 70 g/200 mL). A strong positive correlation was observed between 5‐HMF formation and glucose concentration (R = 0.6055) and application temperature (R = 0.6774). Also a predictive analysis model was fitted to the 5‐HMF formation response by response surface model (RSM).Practical applicationsThe equation obtained as a model in this study can be used to calculate the formation of 5‐HMF for a glucose containing beverages processed by HHP as a response of glucose concentration and application temperature within the conditions of the study. The model was calibrated and validated on glucose containing model beverages, which are representatives of some high glucose containing beverages. HMF content is an important parameter and should be included as one of the quality parameters for commercial beverages. Because of that, this equation has an importance especially for the beverage producers, who process their product by HHP, to predict 5‐HMF formation by controlling glucose concentration and HHP treatment conditions. Moreover, developed model can easily be adapted to the standard procedures of academic and industrial applications.
Pancreatic exocrine insufficiency and cardiovascular risk in patients with chronic pancreatitis: A prospective, longitudinal cohort study
Authors: de la Iglesia Daniel , Vallejo‐Senra Nicolau , López‐López Andrea , Iglesias‐Garcia Julio , Lariño‐Noia Jose , Nieto‐García Laura , Domínguez‐Muñoz Juan Enrique 
Published: August 2018

AbstractBackground and AimPrevious studies have suggested that chronic pancreatitis (CP) is associated with increased risk of cardiovascular (CV) disease independently of other major risk factors. We evaluated the risk of CV events in a well‐phenotyped cohort of patients with CP and its association with pancreatic exocrine insufficiency (PEI) among other CV risk factors.MethodsThis was a prospective, longitudinal cohort study of patients with CP, followed up at the Pancreas Unit of the University Hospital of Santiago de Compostela, Spain.ResultsFour hundred thirty patients were included (mean 47.8 ± 14.4 years of age, 79.1% male). Mean follow‐up was 8.6 ± 4.6 years. CP etiology was toxic (alcohol and/or smoking) in 290 patients (67.4%). PEI and pancreatogenic diabetes mellitus (DM) were present in 29.3% and 29.5% of the patients, respectively. A total of 45 CV events was recorded (10.5%); 21 patients had a major CV event (stroke or myocardial infarction) and 27 developed clinically relevant peripheral arterial disease. A higher incidence of CV events was recorded in patients with PEI than in those without (incidence rate ratio 3.67, 95% confidence interval [CI] 1.92–7.24; P < 0.001). In the multivariate analysis, PEI without DM (OR 4.96; 95% CI 1.68 to 14.65), coexistence of PEI and DM (OR 6.54; 95% CI 2.71 to 15.77), arterial hypertension (OR 3.40; 95% CI 1.50 to 7.72), and smoking (OR 2.91, 95% CI 1.07 to 7.97) were independently associated with increased CV risk.ConclusionsTogether with known major CV risk factors like smoking and hypertension, PEI is significantly associated with the risk of CV events in patients with CP.
Core nursing competency assessment tool for graduates of outcome‐based nursing education in South Korea: A validation study
Authors: Ko YuKyung , Yu Soyoung 
Published: August 2018

AbstractAimTo develop a competency assessment instrument for nurses who have completed an outcome‐based educational program based on national standards and to assess the content‐, construct‐, and criterion‐related validity of that instrument.MethodsIn the development stage, the competencies of nurses with 1–3 years' clinical experience after the completion of nursing education and training programs, based on national standards, were identified. A systematic literature review was conducted to derive the competencies in addition to the 12 national standard competencies. In the evaluation stage, the content‐, construct‐, and criterion‐related validity of the developed tool were verified. For verification of the content validity at each stage, the participants were 10 nurse managers of general hospitals and 10 nurse professors. A factor analysis was conducted to assess the construct validity and the Cronbach's alpha coefficients and item‐total correlation were used to assess the reliability of the developed scale. For the factor analysis, the participants were 141 nurses with 1–3 years' clinical experience who were recruited from four general hospitals. In order to evaluate the construct‐ and criterion‐related validity, the correlations between a nursing performance measurement scale, a self‐leadership tool, and the developed scale were examined.ResultsA competency assessment instrument, consisting of 19 items on a 4‐point scale, was developed and validated for assessing the competencies among nurses with 1–3 years' experience.ConclusionsNursing research, policy awareness, and leadership competencies were required by the Korean Accreditation Board of Nursing Education for nursing college graduates, but were removed due to poor content validity, indicating a need for nursing professionals to bridge the gap between educational standards in nursing colleges and clinical settings.
Fingolimod (FTY720) is not protective in the subacute MPTP mouse model of Parkinson's disease and does not lead to a sustainable increase of brain‐derived neurotrophic factor
Authors: Komnig Daniel , Dagli Toruntay Cem , Habib Pardes , Zeyen Thomas , Schulz Jörg B. , Falkenburger Björn H. 
Published: August 2018

AbstractParkinson's disease (PD) is characterized by the loss of midbrain dopaminergic neurons and aggregates of α‐synuclein termed Lewy bodies. Fingolimod (FTY720) is an agonist of sphingosine‐1 phosphate receptors and an approved oral treatment for multiple sclerosis. Fingolimod elevates brain‐derived neurotrophic factor (BDNF), an important neurotrophic factor for dopaminergic neurons. BDNF and fingolimod are beneficial in several animal models of PD. In order to validate the therapeutic potential of fingolimod for the treatment of PD, we tested its effect in the subacute MPTP mouse model of PD. MPTP or vehicle was applied i.p. in doses of 30 mg/kg MPTP on five consecutive days. In order to recapitulate the combination of dopamine loss and α‐synuclein aggregates found in PD, MPTP was first administered in Thy1‐A30P‐α‐synuclein transgenic mice. Fingolimod was administered i.p. at a dose of 0.1 mg/kg every second day. Nigrostriatal degeneration was assayed by stereologically counting the number of dopaminergic neurons in the substantia nigra pars compacta, by analysing the concentration of catecholamines and the density of dopaminergic fibres in the striatum. MPTP administration produced a robust nigrostriatal degeneration, comparable to previous studies. Unexpectedly, we found no difference between mice with and without fingolimod treatment, neither at baseline, nor at 14 or 90 days after MPTP. Also, we found no effect of fingolimod in the subacute MPTP mouse model when we used wildtype mice instead of α‐synuclein transgenic mice, and no effect with an increased dose of 1 mg/kg fingolimod administered every day. In order to explain these findings, we analysed BDNF regulation by fingolimod. We did find an increase of BDNF protein after a single injection of fingolimod 0.1 or 1.0 mg/kg, but not after multiple injections, indicating that the BDNF response to fingolimod is unsustainable over time. Taken together we did not observe a neuroprotective effect of fingolimod in the subacute MPTP mouse model of PD. We discuss possible explanations for this discrepancy with previous findings and conclude fingolimod might be beneficial for the nonmotor symptoms of PD.Open Science BadgesThis article has received a badge for *Open Materials* and *Open Data* because it provided all relevant information to reproduce the study in the manuscript and because it made the data publicly available. The data can be accessed at https://osf.io/6xgfn/. The complete Open Science Disclosure form for this article can be found at the end of the article. More information about the Open Practices badges can be found at https://cos.io/our-services/open-science-badges/.
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Longitudinal study of rat volar fat pad fixation and ethanol storage: implications for the use of fluid‐preserved specimens in morphological studies
Authors: Kingston Amanda K. 
Published: August 2018

AbstractMuseum fluid collections preserve important biological specimens for study. Tissues are often fixed in 10% buffered formalin to halt metabolic activities and transferred to a solution of ethanol for long‐term storage. This process, however, forces water from the tissues and has been shown to alter the morphology of preserved specimens in ways that may influence the biological interpretation of results. The degree to which fluid preservation alters morphology is linked to multiple biological factors, such as tissue size and composition, and should therefore be examined prior to functional analysis. This study is undertaken as part of a more inclusive examination of mammalian volar morphology. A sample of five adult male and five adult female rats (Rattus norvegicus) was utilized to evaluate longitudinal changes in the dimensions of the volar pads across fixation in 10% buffered formalin and preservation in 70% ethanol for 1 year. No significant changes to the measured dimensions of the rat volar pads were present across stages of fixation and preservation, and no significant interactions of specimen size or sex were noted. These findings indicate that small mammalian volar pads that have been fixed in 10% buffered formalin and stored in 70% ethanol are appropriate for morphological study using the measurements described here without corrective algorithms. This finding is rare among preservation studies but highlights the variability of tissue behavior during chemical preservation and the necessity of preliminary investigations of preservation artifacts. Concurrence here between the preserved and unpreserved samples is likely related to the anhydrous nature of the volar pads and the supporting skeletal structure, and their confined position between major joints of the hands and feet.
Foreign body granuloma treatment with 22‐MHz ultrasound‐guided corticoid infiltration
Authors: Pompeu Marcelo , Lima Vanessa , Magalhaes Hugo Leornardo , Regattieri Neysa , Costa Izelda Maria Carvalho 
Published: August 2018

SummaryIntralesional corticoid infiltration guided by 22‐MHz ultrasound is a new, noninvasive, and safe dermatological method for the treatment of foreign body granuloma. The great advantage of the procedure is that the medication is delivered straight to the desired target, preventing adverse treatment effects in noninjured areas.
Two‐phase delivery using a horse oil and adenosine‐loaded dissolving microneedle patch for skin barrier restoration, moisturization, and wrinkle improvement
Authors: Yang Huisuk , Kim Suyong , Jang Mingyu , Kim Hyeonjun , Lee Seunghee , Kim Youseong , Eom Younghyon Andrew , Kang Geonwoo , Chiang Liching , Baek Ji Hwoon , Ryu Ja Hyun , Lee Ye Eun , Koh Jaesuk , Jung Hyungil 
Published: August 2018

SummaryBackgroundDissolving microneedles (DMNs) have been used for skin restoration and wrinkle improvement. Although lipophilic compounds, for example, natural oils or ceramides, enrich the skin barrier, their delivery via DMNs is challenging because of DMN fabrication difficulties.ObjectivesIn the present study, we combined a topical formulation and a DMN patch to perform two‐phase delivery comprising a lipophilic formulation and hydrophilic compound‐loaded DMNs to improve skin barrier status and the efficacy of drug delivery.MethodsHorse oil‐spread and adenosine‐loaded DMN arrays were developed in a single patch (HOS‐Ad‐DMN patch). In vitro analysis was conducted to confirm the successful delivery of the compositions. Clinical assessments were conducted on the lateral canthus of 20 women to compare the efficacy of HOS‐Ad‐DMN patches with that of adenosine‐loaded DMN patches (Ad‐DMN patches).ResultsAdenosine was delivered via the DMNs after skin penetration and horse oil was delivered successfully into the skin through the microchannels created by the Ad‐DMNs. Compared with Ad‐DMN patches, HOS‐Ad‐DMN patches significantly improved skin elasticity, hydration, dermal density, and wrinkles. No adverse events were observed.ConclusionHOS‐Ad‐DMN patches are a safe and efficient system for skin restoration and wrinkle improvement.
Impact of clinical decision support on empirical antibiotic prescribing for children with community‐acquired pneumonia
Authors: Mostaghim Mona , Snelling Tom , McMullan Brendan , Ewe Yean H , Bajorek Beata 
Published: August 2018

AimTo assess the impact of a computerised clinical decision support system (CDSS) on antibiotic use in hospitalised children with a presumptive diagnosis of uncomplicated community‐acquired pneumonia (CAP).MethodsCodes associated with lower respiratory tract infection were used to identify cases of presumed uncomplicated CAP requiring admission to a tertiary paediatric hospital. Random sampling of the periods between 1 October 2010 and 30 September 2012 (pre‐CDSS) and 1 October 2012 and 30 September 2014 (post‐CDSS) determined the sequence of case assessment by two independent investigators. Initial antibiotic therapy, associated CDSS approvals and documented signs of clinical deterioration prior to antibiotic decision‐making were recorded.ResultsStatistically significant differences between cases pre‐ and post‐CDSS implementation were minimal. High fever was observed in 57.5% (77/134) cases pre‐CDSS and 45.8% (49/107) cases post‐CDSS (P = 0.07). Supplemental oxygen was used in 30.6% pre‐CDSS and 54.2% post‐CDSS cases (P < 0.001). Narrow‐spectrum penicillins were prescribed most often, with no statistically significant change post‐CDSS implementation (81.3% pre‐CDSS, 77.6% post‐CDSS, P = 0.47). Macrolides were used consistently throughout the study period (53.7% pre‐CDSS, 61.7% post‐CDSS; P = 0.21).ConclusionCDSS implementation did not reduce already low rates of broad‐spectrum antibiotic use for uncomplicated CAP.
Assessment of the cytotoxic potential of an aqueous-ethanolic extract from Thalassia testudinum angiosperm marine grown in the Caribbean Sea
Authors: Rodeiro Idania , Hernández Ivones , Herrera José A , Riera Mario , Donato Maria T , Tolosa Laia , González Kethia , Ansoar Yadira , Gómez-Lechón Maria J , Vanden Berghe Wim , Lopes Miriam 
Published: August 2018

Abstract

Objectives
Reported antioxidant, anti-inflammatory and neuroprotective properties for one aqueous-ethanolic extract from Thalassia testudinum which grows in the Caribbean Sea compelled us to explore about extract cytotoxic effects.

Methods
Cell viability was assayed on tumour (HepG2, PC12, Caco-2 and 4T1) and non-tumour (VERO, 3T3, CHO, MCDK and BHK2) cell lines. The extract effects upon primary cultures of rat and human hepatocytes and human lymphocytes were assayed.

Key findings
The extract exhibited cytotoxicity against cancer cells compared to normal cells, and the IC50 values were 102 μg/ml for HepG2, 135 μg/ml for PC12, 165 μg/ml for Caco-2 and 129 μg/ml for 4T1 cells after 48 h, whereas IC50 could not be calculated for normal cells. Additional data from a high-content screening multiparametric assay indicated that after 24-h exposure, the extract (up to 100 μg/ml) induced death in HepG2 cells through oxidative stress-associated mechanism, DNA damage and hypercalcaemia. Comet assay corroborated extract-induced DNA damage.

Conclusions
Thalassia testudinum extract is more cytotoxic and produced more DNA damage on human hepatoma cells than to other non-tumour cells. A possible mechanism is suggested for extract-induced cytotoxicity based on oxidative stress, nuclear damage and hypercalcaemia in HepG2 cells. T. testudinum may be a source for antitumour agents.
Securigera securidaca seed medicinal herb supplementation of diets improves pulmonary hypertensive response in broiler chickens reared at high altitude
Authors: Ahmadipour Behnam 
Published: August 2018

AbstractThis experiment was conducted to evaluate the effects of dietary Securigera securidaca seed powder on growth performance, haematological parameters, cardiac indices, electrocardiographic parameters and expression of catalase (CAT), endothelin 1 (ET‐1) and inducible nitric oxide synthase (iNOS) genes in the lung in the broilers reared at high altitude (2,100 m above sea level). A total number of 200‐day‐old male broilers (Ross 308) were randomly assigned to five treatments including different levels of S. securidaca 0, 1, 2, 3 and 4 g/kg in a 42‐day trial. The results of this experiment showed that the dietary inclusion of S. securidaca powder improvement in feed conversion ratio (p < 0.05). The dietary utilization of 2–4 g/kg S. securidaca significantly increased concentrations of nitric oxide (NO), although significantly lower serum concentrations of malondialdehyde (MDA) and significantly decrease T, R, S electrocardiogram waves compared with control group. Also, the dietary inclusion of 2–4 g/kg S. securidaca prevented right ventricular hypertrophy and increased the expression of iNOS and CAT genes in lung tissue of broilers. On the other hand, S. securidaca significantly suppressed the expression of ET‐1 in lung tissue. Generally, the results of this study showed that the use of 3 g/kg of medicinal plant S. securidaca can be beneficial in prevention of pulmonary hypertension syndrome (PHS) in broiler chickens reared at high altitudes.