bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparisons between a self‐microemulsifying system and lipid nanoparticles of oxyresveratrol on the physicochemical properties and Caco‐2 cell permeability
Authors: Sangsen Yaowaporn , Wiwattanawongsa Kamonthip , Likhitwitayawuid Kittisak , Sritularak Boonchoo , Wiwattanapatapee Ruedeekorn 
Published: May 2016

The lipid‐based formulations including an oily self‐microemulsifying drug delivery system (SMEDDS), solid lipid nanoparticles (SLN), and nanostructured lipid carriers (NLC) were developed for the oral delivery of oxyresveratrol (OXYR). Each system was successfully formulated using different optimized compositions and methods. The obtained SMEDDS appeared as a yellow oily liquid, while the SLN and NLC as low viscous suspensions. The physical properties, cytotoxicity, and drug permeability across the Caco‐2 monolayer of the different systems were compared. The non‐aqueous SMEDDS had about a 13‐fold higher drug loading than the lipid nanoparticles. The particle sizes (26.94 ± 0.08 nm) of OXYR‐SMEDDS were significantly smaller than that of the NLC and SLN (p < 0.05). Also, a narrow size distribution of the SMEDDS (PDI, 0.073 ± 0.010) was obtained compared to the lipid nanoparticles (PDI, 0.2–0.3). By using the MTT assay, the OXYR‐SMEDDS showed a fourfold greater toxicity on the Caco‐2 cells than the SLN and NLC containing OXYR. At the non‐toxic concentration of 100 μM of OXYR, the SMEDDS and the lipid nanoparticles had 2.5–3‐fold enhanced permeability and 1.3–1.8‐fold reduced efflux transport compared to the unformulated OXYR (p < 0.05).Practical applications: The improvement of the in vitro oral absorption of the lipid‐based formulations resulted from the increased permeability and inhibited efflux mediated mechanisms. These lipid‐based systems have raised the possibility of the oral OXYR in treating and preventing some importance diseases in future. In addition, these systems could also be used as a potential carrier for oral delivery of other compounds which are substrates for efflux transporters. However, in vivo studies are needed to further investigate oral drug bioavailability. Moreover, for use as a commercial product, it is necessary to improve the storage stability and the toxicity of the oily SMEDDS.The lipid nanoparticles (SLN and NLC) and self‐microemulsifying drug delivery systems (SMEDDS) of oxyresveratrol (OXYR) were produced using different compositions and methods. The appearance and characteristics of the lipid‐based systems were different. However, all of three lipid‐based formulations significantly improved intestinal permeability and reduced efflux transport of OXYR. Therefore, these systems could be used as a potential carrier for oral delivery of OXYR or other compounds which are substrates for efflux transporters.
Early synaptic dysfunction in Parkinson's disease: Insights from animal models
Authors: Schirinzi Tommaso , Madeo Graziella , Martella Giuseppina , Maltese Marta , Picconi Barbara , Calabresi Paolo , Pisani Antonio 
Published: May 2016

ABSTRACTThe appearance of motor manifestations in Parkinson's disease (PD) is invariably linked to degeneration of nigral dopaminergic neurons of the substantia nigra pars compacta. Traditional views on PD neuropathology have been grounded in the assumption that the prime event of neurodegeneration involves neuronal cell bodies with the accumulation of metabolic products. However, this view has recently been challenged by both clinical and experimental evidence. Neuropathological studies in human brain samples and both in vivo and in vitro models support the hypothesis that nigrostriatal synapses may indeed be affected at the earliest stages of the neurodegenerative process. The mechanisms leading to either structural or functional synaptic dysfunction are starting to be elucidated and include dysregulation of axonal transport, impairment of the exocytosis and endocytosis machinery, altered intracellular trafficking, and loss of corticostriatal synaptic plasticity. The aim of this review is to try to integrate different lines of evidence from both pathogenic and genetic animal models that, to different extents, suggest that early synaptic impairment may represent the key event in PD pathogenesis. Understanding the molecular and cellular events underlying such synaptopathy is a fundamental step toward developing specific biomarkers of early dopaminergic dysfunction and, more importantly, designing novel therapies targeting the synaptic apparatus of selective, vulnerable synapses. © 2016 International Parkinson and Movement Disorder Society
The Influence of the Appendiceal Base Diameter on Appendix Stump Closure in Laparoscopic Appendectomy
Authors: Delibegović Samir , Mehmedović Zlatan 
Published: May 2016

AbstractBackgroundClosure of the appendiceal stump is the most critical part of laparoscopic appendectomy. Establishing the average diameter of the inflamed appendix, and forming the appropriate size of clip, endoloop or stapler length, would make this critical phase of laparoscopic appendectomy easier.MethodsOne hundred and fifty consecutive patients, with the diagnosis of acute appendicitis, were included in this study and divided into three groups according to the histological verification of the status of the infection, as follows: phlegmonous, gangrenous and perforated forms of acute appendicitis. The external diameter of the appendiceal base was measured, and the widest part of the appendix with the mesoappendix and the tip, with the help of Vernier callipers, and the measurement was expressed in millimetres.ResultsThe average size of the appendiceal base in the phlegmonous form was 10.29 ± 3.13, in the gangrenous form 12.41 ± 3.56, and in the perforated form 12.42 ± 3.64. The maximal size of base was observed in the perforated form, 23.13 mm. The dimensions of the appendiceal base, the central part and the tip in the phlegmonous form were statistically significantly smaller than in the gangrenous and perforated forms of acute appendicitis. The size of the appendix did not differ statistically significantly in the gangrenous and perforated forms of acute appendicitis.ConclusionIn view of the price, the size of the opening, radiological advantage and biocompatibility, the Hem‐o‐lok clip is the most effective, although its internal diameter should be increased. The DS clip is also effective, but the size of the opening sometimes makes application difficult, and possibly increasing the length of the legs and the opening would make this clip ideal. Staplers have the best characteristics, but their price means they are an option only for forms where it is not possible to close the stump using other methods.
Why Do Parents Want to Know their Child's Carrier Status? A Qualitative Study
Authors: Vears Danya F , Delany Clare , Massie John , Gillam Lynn 
Published: May 2016

AbstractWhen a child is identified with a genetic condition, some parents want to know the carrier status of their other children. There has been little exploration of why parents want this information. To address this question, semi‐structured interviews were conducted with parents of 32 children with cystic fibrosis, haemophilia, and Duchenne muscular dystrophy who wanted to know the carrier status of their other children. Data was analyzed using inductive content analysis. Parents expressed a range of reasons for desiring their child's carrier status, which fell into two broad categories: 1) benefit for the parents and 2) perceived benefit to the child. Parents discussed the desire for certainty and peace of mind derived from having knowledge of their child's status. The most commonly expressed reason for wanting to know their child's carrier status was in order to communicate the information to their child to provide them with the ability to make informed reproductive decisions. These reasons suggest parents are seeking their children's carrier information both as a coping strategy and to communicate carrier information as part of their role as a parent. This has important implications for genetic counseling practice, especially as international guidelines generally recommend against carrier testing in children.
KNOWING HOW TO PUT KNOWLEDGE FIRST IN THE THEORY OF JUSTIFICATION
Authors: Silva Paul 
Published: May 2016

AbstractIn what follows I offer a novel knowledge-first account of justification that avoids the pitfalls of existing accounts while preserving the underlying insight of knowledge-first epistemologies: that knowledge comes first. The view is, roughly, this: justification is grounded in our practical knowledge (know-how) concerning the acquisition of propositional knowledge (knowledge-that). The upshot is a virtue-theoretic, knowledge-first view of justification that is internalist-friendly and able to explain more facts about justification than any other available view.
Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data
Authors: Fengler S. , Roeske S. , Heber I. , Reetz K. , Schulz J. B. , Riedel O. , Wittchen H.U. , Storch A. , Linse K. , Baudrexel S. , Hilker R. , Mollenhauer B. , Witt K. , Schmidt N. , Balzer-Geldsetzer M. , Dams J. , Dodel R. , Gräber S. , Pilotto A. , Petrelli A. , Fünkele S. , Kassubek J. , Kalbe E. 
Published: May 2016

BackgroundData on gender-specific profiles of cognitive functions in patients with Parkinson's disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered.MethodThe LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-correctedZscores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration,l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates.ResultsRaw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning,p= 0.02; recall,p= 0.03), while men outperformed women in visuoconstruction (p= 0.002) and figural memory (p= 0.005). In contrast, gender-correctedZscores showed that men were superior in verbal memory (word list learning,p= 0.02; recall,p= 0.02; recognition,p= 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis.ConclusionsNormative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.
Bias in emerging biomarkers for bipolar disorder
Authors: Carvalho A. F. , Köhler C. A. , Fernandes B. S. , Quevedo J. , Miskowiak K. W. , Brunoni A. R. , Machado-Vieira R. , Maes M. , Vieta E. , Berk M. 
Published: May 2016

BackgroundTo date no comprehensive evaluation has appraised the likelihood of bias or the strength of the evidence of peripheral biomarkers for bipolar disorder (BD). Here we performed an umbrella review of meta-analyses of peripheral non-genetic biomarkers for BD.MethodThe Pubmed/Medline, EMBASE and PsycInfo electronic databases were searched up to May 2015. Two independent authors conducted searches, examined references for eligibility, and extracted data. Meta-analyses in any language examining peripheral non-genetic biomarkers in participants with BD (across different mood states) compared to unaffected controls were included.ResultsSix references, which examined 13 biomarkers across 20 meta-analyses (5474 BD cases and 4823 healthy controls) met inclusion criteria. Evidence for excess of significance bias (i.e. bias favoring publication of ‘positive’ nominally significant results) was observed in 11 meta-analyses. Heterogeneity was high for (I2 ⩾ 50%) 16 meta-analyses. Only two biomarkers met criteria for suggestive evidence namely the soluble IL-2 receptor and morning cortisol. The median power of included studies, using the effect size of the largest dataset as the plausible true effect size of each meta-analysis, was 15.3%.ConclusionsOur findings suggest that there is an excess of statistically significant results in the literature of peripheral biomarkers for BD. Selective publication of ‘positive’ results and selective reporting of outcomes are possible mechanisms.
LATERAL BRANCHING OXIDOREDUCTASEacts in the final stages of strigolactone biosynthesis inArabidopsis
Authors: Brewer Philip B. , Yoneyama Kaori , Filardo Fiona , Meyers Emma , Scaffidi Adrian , Frickey Tancred , Akiyama Kohki , Seto Yoshiya , Dun Elizabeth A. , Cremer Julia E. , Kerr Stephanie C. , Waters Mark T. , Flematti Gavin R. , Mason Michael G. , Weiller Georg , Yamaguchi Shinjiro , Nomura Takahito , Smith Steven M. , Yoneyama Koichi , Beveridge Christine A. 
Published: May 2016

SignificanceStrigolactone hormones regulate many plant growth and developmental processes and are particularly important in regulating growth in response to nonoptimal conditions. Plants produce a range of bioactive strigolactone-like compounds, suggesting that the biosynthesis pathway is complex. Despite this complexity, only one type of enzyme, the MORE AXILLARY GROWTH1 (MAX1) cytochrome P450, has been attributed to the diversity of strigolactones. Using transcriptomics and reverse genetics, we discovered a previously uncharacterized gene that encodes a 2-oxoglutarate and Fe(II)-dependent dioxygenase involved in strigolactone production downstream of MAX1. Studies with the corresponding mutant have shown that previously identified strigolactone-type compounds inArabidopsisare not the major strigolactone-type shoot branching hormone in this model species.
Introduction
Authors: Howard-Grenville Jennifer , Rerup Claus , Langley Ann , Tsoukas Haridimos 
Published: May 2016

Abstract
Over the past fifteen years, organizational routines increasingly have been investigated from a process perspective to challenge the idea that routines are stable entities that are mindlessly enacted. This chapter summarizes what constitutes a process perspective on organizational routines, and document some of the major areas of recent inquiry, including change in routines, the role of artifacts in routine performances, and emergence of routines. Three other themes emerge from the various chapters that constitute this volume: (1) zooming out to understand routines in larger contexts; (2) zooming in to reveal actor dispositions and skill; and (3) innovation, creativity, and routines in ambiguous contexts. The chapters also inspire future research that can extend a process perspective on routines by further zooming out and in, and by potentially using this metaphor to connect distinct findings by scholars studying routines from different perspectives.
OISTER optical and near-infrared observations of the super-Chandrasekhar supernova candidate SN 2012dn: Dust emission from the circumstellar shell
Authors: Yamanaka Masayuki , Maeda Keiichi , Tanaka Masaomi , Tominaga Nozomu , Kawabata Koji S. , Takaki Katsutoshi , Kawabata Miho , Nakaoka Tatsuya , Ueno Issei , Akitaya Hiroshi , Nagayama Takahiro , Takahashi Jun , Honda Satoshi , Omodaka Toshihiro , Miyanoshita Ryo , Nagao Takashi , Watanabe Makoto , Isogai Mizuki , Arai Akira , Itoh Ryosuke , Ui Takahiro , Uemura Makoto , Yoshida Michitoshi , Hanayama Hidekazu , Kuroda Daisuke , Ukita Nobuharu , Yanagisawa Kenshi , Izumiura Hideyuki , Saito Yoshihiko , Masumoto Kazunari , Ono Rikako , Noguchi Ryo , Matsumoto Katsura , Nogami Daisaku , Morokuma Tomoki , Oasa Yumiko , Sekiguchi Kazuhiro 
Published: May 2016

Abstract
We present extensively dense observations of the super-Chandrasekhar supernova (SC SN) candidate SN 2012dn from −11 to +140 d after the date of its B-band maximum in the optical and near-infrared (NIR) wavelengths conducted through the OISTER ToO (Optical and Infrared Synergetic Telescopes for Education and Research Target of Opportunity) program. The NIR light curves and color evolutions up to 35 days after the B-band maximum provided an excellent match with those of another SC SN 2009dc, providing further support to the nature of SN 2012dn as an SC SN. We found that SN 2012dn exhibited strong excesses in the NIR wavelengths from 30 d after the B-band maximum. The H- and Ks-band light curves exhibited much later maximum dates at 40 and 70 d after the B-band maximum, respectively, compared with those of normal SNe Ia. The H- and Ks-band light curves subtracted by those of SN 2009dc displayed plateaued evolutions, indicating an NIR echo from the surrounding dust. The distance to the inner boundary of the dust shell is limited to 4.8–6.4 × 10−2 pc. No emission lines were found in its early phase spectra, suggesting that the ejecta–circumstellar material interaction could not occur. On the other hand, we found no signature that strongly supports the scenario of dust formation. The mass-loss rate of the pre-explosion system is estimated to be 10−6–10−5 M⊙ yr−1, assuming that the wind velocity of the system is 10–100 km s−1, which suggests that the progenitor of SN 2012dn could be a recurrent nova system. We conclude that the progenitor of this SC SN could be explained by the single-degenerate scenario.
Cumulative Risk Impact of RET, SEMA3, and NRG1 Polymorphisms Associated With Hirschsprung Disease in Han Chinese
Authors: Li Qi , Zhang Zhen , Diao Mei , Gan Liang , Cheng Wei , Xiao Ping , Su Lin , Shangguan Shaofang , Jiang Qian , Li Long 
Published: May 2016

ABSTRACTObjectives:Hirschsprung disease (HSCR) is a congenital aganglionosis of myenteric and submucosal plexuses affecting a variable length of the intestine. The incidence of HSCR is approximately 1 of 5000 live births; however, the risk shows remarkable individual variation caused by single nucleotide polymorphisms (SNPs) at the RET, SEMA3, and NRG1 loci. The present study investigated the effects of these variants on the disease development and phenotype in a Chinese population.Methods:In total, 6 SNPs were genotyped in a cohort consisting of 115 patients with HSCR and 117 unaffected controls using a TaqMan genotyping assay. Histological identification of the affected‐segment length (short, long, or total colonic aganglionosis) was performed for all of the samples before DNA extraction.Results:Significant genetic risk was imparted by rs2435357 and rs2506030 at RET and by rs12707682 at SEMA3. In addition, the average cumulative risk score in the patients with HSCR was significantly higher than that in the controls. Through the assessment of risk alleles by effect size, individuals were classified into 3 weighted risk score groups: low (⩽3), medium (4), and high (≥5). Individuals in the high group were significantly more susceptible to HSCR than those in the low group with an odds ratio of 7.7 (95% confidence interval 3.7–16.3).Conclusions:Cumulative genetic risk varied >35‐fold between newborns with zero and >5 accumulated susceptibility alleles. The SNPs rs2435357, rs2506030, and rs12707682 may be useful for stratifying the Chinese population into distinct risk groups.
Early-Onset Dementia
Authors: Konijnenberg Elles , Fereshtehnejad Seyed-Mohammad , Kate Mara ten , Eriksdotter Maria , Scheltens Philip , Johannsen Peter , Waldemar Gunhild , Visser Pieter Jelle 
Published: May 2016

Background:
Early-onset dementia (EOD) is a rare condition, with an often atypical clinical presentation, and it may therefore be challenging to diagnose. Specialized memory clinics vary in the type of patients seen, diagnostic procedures applied, and the pharmacological treatment given. The aim of this study was to investigate quality-of-care indicators in subjects with EOD from 3 tertiary memory clinics in 3 European countries.

Methods:
We included 1325 newly diagnosed EOD patients, ages 65 years or younger, between January 1, 2007 and December 31, 2013, from the Danish Dementia Registry (Rigshospitalet, Copenhagen), the Swedish Dementia Registry (“SveDem”, Karolinska University Hospital, Stockholm), and the Amsterdam Dementia Cohort (VU University Medical Center).

Results:
The frequency of EOD among all dementia patients was significantly lower in Copenhagen (410, 20%) and Stockholm (284, 21%) compared with Amsterdam (631, 48%). Not all quality indicator targets were met, such as the time to diagnosis, the mini-mental state examination score available, and the prescription of cholinesterase inhibitors. Cerebrospinal fluid sampling, registered in 2 sites, was performed in over 80% of the subjects.

Conclusions:
In tertiary referral centers in Copenhagen, Stockholm, and Amsterdam, quality indicators were not always met for patients with EOD. Results partly reflect differences in referral pattern, the application of diagnostic criteria, and local best practices. Standardized international procedures for patients with EOD may reduce this variability.
Time-dependent fitness effects can drive bet-hedging populations extinct
Authors: Libby Eric , Ratcliff William 
Published: May 2016

AbstractTo survive unpredictable environmental change, many organisms adopt bet-hedging strategies that trade short-term population growth for long-term fitness benefits. Because the benefits of bet-hedging may manifest over long time intervals, bet-hedging strategies may be out-competed by strategies maximizing short-term fitness. Here, we investigate the interplay between two drivers of selection, environmental fluctuations and competition for limited resources, on different bet-hedging strategies. We consider an environment with frequent disasters that switch between which phenotypes they affect in a temporally-correlated fashion. We determine how organisms that stochastically switch between phenotypes at different rates fare in both competition and survival. When disasters are correlated in time, the best strategy for competition is among the worst for survival. Since the time scales over which the two agents of selection act are significantly different, environmental fluctuations and resource competition act in opposition and lead populations to evolve diversification strategies that ultimately drive them extinct.
PackIO and EphysViewer: software tools for acquisition and analysis of neuroscience data
Authors: Watson Brendon O. , Yuste Rafael , Packer Adam M. 
Published: May 2016

AbstractWe present an open-source synchronization software package, PackIO, that can record and generate voltage signals to enable complex experimental paradigms across multiple devices. This general purpose package is built on National Instruments data acquisition and generation hardware and has temporal precision up to the limit of the hardware. PackIO acts as a flexibly programmable master clock that can record experimental data (e.g. voltage traces), timing data (e.g. event times such as imaging frame times) while generating stimuli (e.g. voltage waveforms, voltage triggers to drive other devices, etc.). PackIO is particularly useful to record from and synchronize multiple devices, for example when simultaneously acquiring electrophysiology while generating and recording imaging timing data. Experimental control is easily enabled by an intuitive graphical user interface. We also release an open-source data visualisation and analysis tool, EphysViewer, written in MATLAB, as well as a module to import data into Python. These flexible and programmable tools allow experimenters to configure and set up customised input and output protocols in a synchronized fashion for controlling, recording, and analysing experiments.