bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of Tiotropium in Reducing Exacerbations of Chronic Obstructive Pulmonary Disease When Combined With Long‐Acting β2‐Agonists and Inhaled Corticosteroids: The OUTPUL Study
Authors: Ferroni Eliana , Belleudi Valeria , Cascini Silvia , Di Martino Mirko , Kirchmayer Ursula , Pistelli Riccardo , Patorno Elisabetta , Formoso Giulio , Fusco Danilo , Perucci Carlo A. , Davoli Marina , Agabiti Nera ,   the OUTPUL Study Group
Published: April 2016

AbstractCombined inhaled therapy in chronic obstructive pulmonary disease (COPD) is commonly used, but its benefits remain controversial. We assessed the effect of tiotropium in reducing COPD exacerbations when combined with long‐acting β2 agonists (LABA) and/or inhaled corticosteroids (ICS). This new‐user cohort study is based on administrative data from 3 Italian regions. We identified adults hospitalized for COPD from 2006 to 2009 who were newly prescribed a fixed LABA/ICS combination (double therapy). We classified patients according to whether tiotropium was also prescribed (triple therapy), using both intention‐to‐treat and as‐treated approaches, and followed them for 1 year. COPD exacerbations were measured as outcomes. Multivariate and propensity score‐adjusted hazard ratios (HRs, 95%CI) were calculated with Cox regression models. We identified 5717 new users of LABA/ICS of which 31.9% initiated triple therapy. In the intention‐to‐treat analysis, the multivariate adjusted HR for moderate, severe, and any exacerbations were 1.02 (95%CI 0.89‐1.16), 0.92 (95%CI 0.76‐1.12), and 1.08 (95%CI 0.91‐1.28), respectively. The propensity score adjustment produced similar results. In the subcohort of patients with previous exacerbations, triple therapy was significantly associated with reduced risk of moderate exacerbations, compared to double therapy (HR 0.68, 95%CI 0.48‐0.98 in intention‐to‐treat approach). In conclusion, the addition of tiotropium to LABA/ICS did not reduce COPD exacerbations compared to LABA/ICS alone. A protective role for moderate exacerbations was found in patients at risk of frequent exacerbations. Given the impact of exacerbations on health status and prognosis, it is crucial to target COPD patients for optimal treatment.
Patterns of cortical thinning in nondemented Parkinson's disease patients
Authors: Uribe Carme , Segura Barbara , Baggio Hugo Cesar , Abos Alexandra , Marti Maria Jose , Valldeoriola Francesc , Compta Yaroslau , Bargallo Nuria , Junque Carme 
Published: April 2016

ABSTRACTBackgroundClinical variability in the Parkinson's disease phenotype suggests the existence of disease subtypes. We investigated whether distinct anatomical patterns of atrophy can be identified in Parkinson's disease using a hypothesis‐free, data‐driven approach based on cortical thickness data.MethodsT1‐weighted 3‐tesla MRI and a comprehensive neuropsychological assessment were performed in a sample of 88 nondemented Parkinson's disease patients and 31 healthy controls. We performed a hierarchical cluster analysis of imaging data using Ward's linkage method. A general linear model with cortical thickness data was used to compare clustering groups.ResultsWe observed 3 patterns of cortical thinning in patients when compared with healthy controls. Pattern 1 (n = 30, 34.09%) consisted of cortical atrophy in bilateral precentral gyrus, inferior and superior parietal lobules, cuneus, posterior cingulate, and parahippocampal gyrus. These patients showed worse cognitive performance when compared with controls and the other 2 patterns. Pattern 2 (n = 29, 32.95%) consisted of cortical atrophy involving occipital and frontal as well as superior parietal areas and included patients with younger age at onset. Finally, in pattern 3 (n = 29, 32.95%), there was no detectable cortical thinning. Patients in the 3 patterns did not differ in disease duration, motor severity, dopaminergic medication doses, or presence of mild cognitive impairment.ConclusionsThree cortical atrophy subtypes were identified in nondemented Parkinson's disease patients: (1) parieto‐temporal pattern of atrophy with worse cognitive performance, (2) occipital and frontal cortical atrophy and younger disease onset, and (3) patients without detectable cortical atrophy. These findings may help identify prognosis markers in Parkinson's disease. © 2016 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society
Copy number variation sequencing‐based prenatal diagnosis using cell‐free fetal DNA in amniotic fluid
Authors: Qi Qingwei , Lu Sijia , Zhou Xiya , Yao Fengxia , Hao Na , Yin Guangjun , Li Wenhui , Bai Junjie , Li Ning , Cram David S. 
Published: April 2016

AbstractObjectiveThe study aimed to determine whether cell‐free fetal DNA (cffDNA) present in amniotic fluid supernatant can be used as a surrogate for amniocyte‐based diagnosis of fetal chromosomal abnormalities.MethodAmniocentesis was performed on 28 high‐risk pregnancies. Amniocytes and the cffDNA fraction were prepared from the amniotic fluid samples. Chromosomal analysis of amniocytes was performed by either karyotyping or single nucleotide polymorphism (SNP) arrays. The corresponding cffDNA samples were blindly analyzed by copy number variation (CNV) sequencing in an independent laboratory.ResultsIn the 28 matching amniocyte and cffDNA samples, there was a high diagnostic concordance for detection of euploidy, aneuploidy and CNVs. From ten samples referred for karyotyping, two aneuploidies (20%) were identified. From 18 samples referred for SNP array analysis, three pathogenic CNVs (16.7%) were identified. CNV sequencing of the 28 cffDNA samples also detected the two aneuploidies and the three pathogenic CNVs, giving an overall concordance rate of 100% for detection of pathogenic chromosome abnormalities. Compared with SNP array analysis, CNV sequencing returned a higher yield of benign or variants of unknown significance.ConclusionCopy number variation sequencing of cffDNA represents an alternative approach to conventional prenatal diagnostic methods for reliable and accurate detection of clinically significant chromosomal abnormalities. © 2016 John Wiley & Sons, Ltd.
Synthesis of a TLR4 Agonist‐Carbohydrate Antigen Conjugate As A Self‐Adjuvanting Cancer Vaccine
Authors: Lewicky Jordan D. , Ulanova Marina , Jiang Zi‐Hua 
Published: April 2016

AbstractTumour‐associated carbohydrate antigens (TACAs) are promising targets for therapeutic cancer vaccination efforts. However, an inherent limitation of this approach is the poor immunogenicity of carbohydrate epitopes. In an effort to overcome this problem, a self‐adjuvanting TACA has been targeted and synthesized herein, in which a Toll‐like receptor 4 activating lipid A mimic is employed as an immunostimulant and covalently linked to a broadly expressed TACA, the Thomsen‐Freidenreich (TF) antigen. Individual components were first prepared, including the lipid A mimic, the Galβ(1‐3)GalNAc disaccharide building block, and the tetraethylene glycol‐derived linker. The linker was then coupled with the TF disaccharide, and then with the lipid A mimic, both under HBTU‐mediated peptide coupling condition, to provide the conjugated precursor. Global debenzylation via catalytic hydrogenation afforded the designed self‐adjuvanting TF antigen in overall good yield.
Activation of β‐adrenergic receptors in rat visual cortex expands astrocytic processes and reduces extracellular space volume
Authors: Sherpa Ang Doma , Xiao Fanrong , Joseph Neethu , Aoki Chiye , Hrabetova Sabina 
Published: April 2016

ABSTRACTBrain extracellular space (ECS) is an interconnected channel that allows diffusion‐mediated transport of signaling molecules, metabolites, and drugs. We tested the hypothesis that β‐adrenergic receptor (βAR) activation impacts extracellular diffusion‐mediated transport of molecules through alterations in the morphology of astrocytes. Two structural parameters of ECS—volume fraction and tortuosity—govern extracellular diffusion. Volume fraction (α) is the volume of ECS relative to the total tissue volume. Tortuosity (λ) is a measure of the hindrance that molecules experience in the ECS, compared to a free medium. The real‐time iontophoretic (RTI) method revealed that treatment of acutely prepared visual cortical slices of adult female rats with a βAR agonist, DL‐isoproterenol (ISO), decreases α significantly, from 0.22 ± 0.03 (mean ± SD) for controls without agonist to 0.18 ± 0.03 with ISO, without altering λ (control: 1.64 ± 0.04; ISO: 1.63 ± 0.04). Electron microscopy revealed that the ISO treatment significantly increased the cytoplasmic area of astrocytic distal endings per unit area of neuropil by 54%. These findings show that norepinephrine decreases α, in part, through an increase in astrocytic volume following βAR activation. Norepinephrine is recognized to be released within the brain during the awake state and increase neurons’ signal‐to‐noise ratio through modulation of neurons’ biophysical properties. Our findings uncover a new mechanism for noradrenergic modulation of neuronal signals. Through astrocytic activation leading to a reduction of α, noradrenergic modulation increases extracellular concentration of neurotransmitters and neuromodulators, thereby facilitating neuronal interactions, especially during wakefulness. Synapse 70:307–316, 2016. © 2016 Wiley Periodicals, Inc.
Multifunctional platinum‐based nanoparticles for biomedical applications
Authors: Cheng Qinqin , Liu Yangzhong 
Published: April 2016

Platinum‐based anticancer drugs play a central role in current cancer therapy. However, their applicability and efficacy are limited by drug resistance and adverse effects. Nanocarrier‐based platinum drug delivery systems are promising alternatives to circumvent the disadvantages of bare platinum drugs. The various properties of nanoparticle chemistry allow for the trend toward multiple functionality. Nanoparticles preferentially accumulate at the tumor site through passive targeting, and the attachment of tumor targeting moieties further enhances their tumor‐specific localization as well as tumor cell uptake. The introduction of stimuli‐responsive groups into drug delivery systems can further achieve spatially and temporally controlled drug release in response to specific stimuli. Combination therapy strategies have been used to promote synergetic efficacy and overcome the resistance of platinum drugs. The tumor‐localized drug delivery strategies exhibit benefits for preventing local tumor recurrence. In addition, the combination of platinum drugs and imaging agents in one unity allows the cancer diagnostics for real‐time monitoring the distribution of drug‐loaded nanoparticles inside the body and tumor. This review discusses recent scientific advances in multifunctional nanoparticle formulations of platinum drugs, and these designs exhibit new potential of multifunctional nanoparticles for delivering platinum‐based anticancer drugs.WIREs Nanomed Nanobiotechnol2017, 9:e1410. doi: 10.1002/wnan.1410This article is categorized under:Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
A Review on Spinal Muscular Atrophy: Awareness, Knowledge, and Attitudes
Authors: Moultrie Rebecca R. , Kish‐Doto Julia , Peay Holly , Lewis Megan A. 
Published: April 2016

AbstractSpinal Muscular Atrophy (SMA) is one of the most common genetic causes of infant death. There is presently no cure, but the therapeutic pipeline is promising. Given the prevalence of SMA coupled with the potential for new treatment options, universal carrier screening, and newborn screening, we conducted a literature review of the awareness, knowledge, and attitudes held by the public and non‐geneticist clinicians about various aspects of SMA. We then identify recommendations for targeting additional research, training, and educational efforts to increase awareness. In the limited available literature, we found that the public is generally unfamiliar with SMA but has favorable views of carrier and newborn screening. Clinicians also had limited understanding of SMA. Further research into knowledge and attitudes of healthcare providers and the general public will help develop a better understanding of education gaps and inform outreach efforts. These educational efforts are needed to complement the momentum as treatments are being developed and tested. Furthermore, professional societies are proposing routine carrier screening and SMA may achieve newborn screening status, which will change the SMA landscape for genetics professionals and families. Thus, it is important to explore knowledge and attitudes about SMA to allow us to prepare for when SMA attains higher public and clinician recognition.
Parents’ Experiences of Receiving the Initial Positive Newborn Screening (NBS) Result for Cystic Fibrosis and Sickle Cell Disease
Authors: Chudleigh Jane , Buckingham Sarah , Dignan Jo , O'Driscoll Sandra , Johnson Kemi , Rees David , Wyatt Hilary , Metcalfe Alison 
Published: April 2016

AbstractThe clinical advantages of the newborn screening programme (NBS) in the UK are well described in the literature. However, there has been little exploration of the psychosocial impact on the family. This study followed the principles of grounded theory to explore parents’ experiences of receiving the initial positive NBS result for their child with cystic fibrosis (CF) or sickle cell disease (SCD). Semi‐structured, qualitative interviews were conducted with 22 parents (12 mothers and 10 fathers) whose children had been diagnosed with CF or SCD via NBS and were under the age of 1 year at the time of interview. The main themes that arose from the data were; parents previous knowledge of the condition and the NBS programme, the method of delivery and parental reactions to the result, sharing the results with others, the impact on parental relationships and support strategies. Study conclusions indicate that most parents thought initial positive NBS results should be delivered by a health professional with condition specific knowledge, preferably with both parents present. Genetic counselling needs to include a focus on the impact of NBS results on parental relationships. Careful consideration needs to be given to strategies to support parents of babies who have positive NBS results both in terms of the psychological health and to assist them in sharing the diagnosis.
Screening of promising chemotherapeutic candidates from plants extracts
Authors: Kinjo Junei , Nakano Daisuke , Fujioka Toshihiro , Okabe Hikaru 
Published: April 2016

Abstract
Over the course of our studies investigating anti-proliferative properties of compounds originating from plants against human gastric adenocarcinoma (MK-1), human uterine carcinoma (HeLa), murine melanoma (B16F10), and two human T cell lymphotropic virus type 1 (HTLV-1)-infected T-cell lines (MT-1 and MT-2), we have screened 582 extracted samples obtained from a variety of parts from 370 plants. A few extracts showed anti-proliferative activity against all cell lines, but upon further investigation, toxicity toward selected cell lines was recognized. After activity-guided fractionation, isolation of the active principles was achieved. Structure–activity relationship studies identified the components and functionalities responsible for the specific selectivity against each cancer cell line. The effect of polyacetylenes against MK-1 cells was more potent than against HeLa and B16F10 cells. The compound having a 3,4-dihydroxyphenethyl group also showed an anti-proliferative effect against B16F10 cells. Some 6-methoxyflavone derivatives and 8-hydroxy furanocoumarins were good inhibitors of HeLa cell growth. The 17 compounds whose EC50 values were less than 1 nM did not show specific cellular selectivity. Because the cytotoxic effect of 24, 25-dihydrowithanolide D toward control cells was observed at a concentration about 100 times higher than those for the cancer cell lines, withanolide was identified as the most promising chemotherapeutic candidate in our experiments.
Detailed Compositional Analysis of Vegetable Oil Metathesis Products Using Microfluidic Switching Multidimensional Gas Chromatography
Authors: Pease B. , Dreyer B. , Pauls R. E. 
Published: April 2016

AbstractOlefin metathesis provides an attractive and versatile route for the catalytic transformation of triglyceride‐based fats and oils into renewable chemical intermediates. Cross‐metathesis reaction of triglycerides with α‐olefins followed by transesterification leads to a complex array of olefins, fatty acid methyl esters, and fatty acid dimethyl esters. In order to evaluate the commercial value of these mixtures and to optimize process conditions, it is necessary to obtain detailed, quantitative, compositional information. With standard, one‐dimensional, gas chromatographic approaches, complete resolution of all components of interest with short analysis times is difficult to achieve. In this report we describe a rapid, microfluidic, two‐dimensional gas chromatographic methodology suitable for the detailed componential analysis of these complex mixtures. The precision of this method for individual components, as measured by the relative standard deviation, is on the order of 1 % or less, and the recovery of known blends of esters and olefins averaged 100 %.
Peripheral Female Genital Arousal as Assessed by Thermography Following Topical Genital Application of Alprostadil vs Placebo Arousal Gel: A Proof-of-Principle Study Without Visual Sexual Stimulation
Authors: Goldstein Sue W. , Gonzalez Joshua R. , Gagnon Catherine , Goldstein Irwin 
Published: April 2016

Abstract

Introduction
Female sexual arousal disorder is a pathophysiologic state characterized clinically by persistent or recurrent inability to attain or maintain an adequate lubrication-swelling response of sexual excitement until completion of sexual activity. Prior clinical experience with alprostadil products for men with erectile dysfunction supports its use in women with female sexual arousal disorder.

Aim
To compare the effect of topical alprostadil with over-the-counter (OTC) lubricant on female genital arousal in the absence of visual sexual stimuli.

Methods
Healthy premenopausal women without sexual dysfunction were recruited from the community to participate in the study. Of 17 women who consented, 10 were enrolled and completed the trial. The mean age of subjects was 32 years (range = 27–43). Study drug or placebo was applied topically to the genitals. Continuous temperature monitoring was performed. Participants completed questionnaires assessing genital sensation, effect, intensity, and duration.

Main Outcome Measures
Change in temperature from baseline in vestibule, clitoris and vulva.

Results
In all 10 subjects, topical alprostadil induced a statistically significant increase in temperature of the vestibule, clitoris, and vulva compared with the OTC lubricant. The most rapid difference in genital temperature between placebo and alprostadil was seen on the vulva, which demonstrated a significant difference at approximately 9 minutes. There was a significant difference in temperature seen for the vestibule and clitoris at 11 and 19 minutes, respectively. Sixty percent of women reported being aware or conscious of genital sensations with topical alprostadil, but not with OTC lubricant. Discordance was noted in 30% of subjects who reported being aware or conscious of genital sensations with the two treatments and 10% who reported not being aware or conscious of genital sensations with either treatment.

Conclusion
Topical alprostadil administered to healthy premenopausal women induced statistically significant, sustained increases in genital temperatures of the vestibule, clitoris, and vulva within 20 minutes compared with OTC lubricant.
Serum levels of SOD and risk of autism spectrum disorder: A case‐control study
Authors: Wang Lixuan , Jia Jianpu , Zhang Junling , Li Kuo 
Published: April 2016

AbstractBackgroundAutism is a severe developmental disorder with poorly understood etiology. This study examined the clinical significance of serum superoxide dismutase (SOD) level, a marker of oxidative stress, in children with autism spectrum disorder (ASD) and typically‐developing children between the ages of 2 and 6 years.MethodsNinety‐six children diagnosed with ASD and 96 sex and age matched typically‐developing children were assessed for serum levels of SOD at admission. S0D were assayed by colorimetry, and severity of ASD was evaluated with the Childhood Autism Rating Scale (CARS) Score. The influence of serum SOD levels on ASD was performed by conditional logistic regression analysis, which allows adjustment for confounding factors.ResultsThe median serum SOD levels were significantly (P < 0.001) lower in children with ASD as compared to typically‐developing children [146 (IQR: 133–165) U/ml and 180 (168–199) U/ml, respectively]. Levels of SOD increased with decreasing severity of ASD as defined by the CARS score (r = −0.432, P < 0.0001). After adjusting for all other possible covariates, SOD remained can be seen as an independent indictor of ASD with an adjusted odds ratio (OR) of 0.955 (95% confidence interval [CI], 0.942–0.969; P < 0.001). Based on the receiver operating characteristic (ROC) curve, the optimal cutoff value of serum level of SOD as an indicator for auxiliary diagnosis of ASD was projected to be 160U/ml, which yielded a sensitivity of 84.7% and a specificity of 71.4%, with the area under the curve at 0.811 (95%CI, 0.747–0.874).ConclusionsOur data suggests that the decreased serum SOD levels could be implicated in the pathophysiology and progression of autism in Chinese children and can be used as an independent risk indicator of ASD.
Meningococcal disease epidemiology in Australia 10 years after implementation of a national conjugate meningococcal C immunization programme
Authors: LAWRENCE G. L. , WANG H. , LAHRA M. , BOOY R. , McINTYRE P. B. 
Published: April 2016

SUMMARYAustralia implemented conjugate meningococcal C immunization in 2003 with a single scheduled dose at age 12 months and catch-up for individuals aged 2–19 years. Several countries have recently added one or more booster doses to their programmes to maintain disease control. Australian disease surveillance and vaccine coverage data were used to assess longer term vaccine coverage and impact on invasive serogroup C disease incidence and mortality, and review vaccine failures. Coverage was 93% in 1-year-olds and 70% for catch-up cohorts. In 10 years, after adjusting for changes in diagnostic practices, population invasive serogroup C incidence declined 96% (95% confidence interval 94–98) to 0·4 and 0·6 cases/million in vaccinated and unvaccinated cohorts, respectively. Only three serogroup C deaths occurred in 2010–2012vs.68 in 2000–2002. Four (<1/million doses) confirmed vaccine failures were identified in 10 years with no increasing trend. Despite published evidence of waning antibody over time, an ongoing single dose of meningococcal C conjugate vaccine in the second year of life following widespread catch-up has resulted in near elimination of serogroup C disease in all age groups without evidence of vaccine failures in the first decade since introduction. Concurrently, serogroup B incidence declined independently by 55%.