bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted metabolomic analysis of nitric oxide/L-arginine pathway metabolites in dementia: association with pathology, severity, and structural brain changes
Authors: Fleszar Mariusz G. , Wiśniewski Jerzy , Zboch Marzena , Diakowska Dorota , Gamian Andrzej , Krzystek-Korpacka Małgorzata 
Published: September 2019

AbstractL-Arginine/NO pathway is altered in Alzheimer disease (AD). Its clinical relevance and pathway status in vascular dementia (VaD) are unknown. Using targeted metabolomics (a liquid chromatography-mass spectrometry) we assessed L-arginine, L-citrulline, dimethylamine (DMA), asymmetric dimethyl arginine (ADMA) and symmetric dimethylarginine (SDMA) in AD (n = 48), mixed-type dementia (MD; n = 34), VaD (n = 40) and non-demented individuals (n = 140) and determined their clinical relevance (the association with dementia pathology, cognitive impairment, and structural brain damage). L-Arginine, ADMA, L-arginine/ADMA, and L-citrulline levels were decreased in dementia and L-arginine, L-citrulline, age and sex were its independent predictors correctly classifying 91% of cases. L-Arginine and L-arginine/ADMA were differentiating between VaD and AD with moderate accuracy. L-Arginine, L-arginine/ADMA, SDMA, and DMA reflected structural brain changes. DMA and L-citrulline were elevated in patients with strategic infarcts and SDMA, L-arginine/ADMA, and DMA were independent predictors of Hachinski ischemic score. ADMA and SDMA accumulation reflected severity of cognitive impairment. In summary, L-Arginine/NO pathway is altered in neurodegenerative and vascular dementia in association with neurodegenerative and vascular markers of brain damage and severity of cognitive impairment.
Bankruptcy is an inevitable fate of repeated investments with leverage
Authors: Nii Momoka , Okabe Takuya , Ito Hiromu , Morita Satoru , Yasuda Yosuke , Yoshimura Jin 
Published: September 2019

AbstractDue to the globalization and computerization of financial and economic activities, numerous repetitive leveraged investments have become possible in stock markets and currency exchanges. In reality, repeated leveraged investments up to 100 times/day are possible via online access. With computer-aided programs, this repetition number may easily increase 1000 times/day. The possibility of bankruptcy in repeated leveraged investments has never been considered in actual practices because the probability of bankruptcy in a single investment trial is almost negligible. Here, we show that the extremely numerous repetitions have a considerable chance of bankruptcy overall, even if the probability of bankruptcy for a single investment is extremely close to zero. The exact relationship between the repetitions and the probability of bankruptcy is approximated well by n(0.63) = m, where 10n is the number of repetitions, 10−m is the bankruptcy probability of a single investment, and n(0.63) is the 63% chance of bankruptcy. Thus, extremely rare events can always lead to bankruptcy in continuously repeated investment, even if the possibility of such an event is almost null. We suggest that the avoidance measure of bankruptcy is necessary in numerous repeated investments even if a single trial is almost certain to win.
No evidence for viral small RNA production and antiviral function of Argonaute 2 in human cells
Authors: Schuster Susan , Overheul Gijs J. , Bauer Lisa , van Kuppeveld Frank J. M. , van Rij Ronald P. 
Published: September 2019

AbstractRNA interference (RNAi) has strong antiviral activity in a range of animal phyla, but the extent to which RNAi controls virus infection in chordates, and specifically mammals remains incompletely understood. Here we analyze the antiviral activity of RNAi against a number of positive-sense RNA viruses using Argonaute-2 deficient human cells. In line with absence of virus-derived siRNAs, Sindbis virus, yellow fever virus, and encephalomyocarditis virus replicated with similar kinetics in wildtype cells and Argonaute-2 deficient cells. Coxsackievirus B3 (CVB3) carrying mutations in the viral 3A protein, previously proposed to be a virus-encoded suppressor of RNAi in another picornavirus, human enterovirus 71, had a strong replication defect in wildtype cells. However, this defect was not rescued in Argonaute-2 deficient cells, arguing against a role of CVB3 3A as an RNAi suppressor. In agreement, neither infection with wildtype nor 3A mutant CVB3 resulted in small RNA production with the hallmarks of canonical vsiRNAs. Together, our results argue against strong antiviral activity of RNAi under these experimental conditions, but do not exclude that antiviral RNAi may be functional under other cellular, experimental, or physiological conditions in mammals.
Usp26 mutation in mice leads to defective spermatogenesis depending on genetic background
Authors: Sakai Kohei , Ito Chizuru , Wakabayashi Mizuki , Kanzaki Satoko , Ito Toshiaki , Takada Shuji , Toshimori Kiyotaka , Sekita Yoichi , Kimura Tohru 
Published: September 2019

AbstractSpermatogenesis is a reproductive system process that produces sperm. Ubiquitin specific peptidase 26 (USP26) is an X chromosome-linked deubiquitinase that is specifically expressed in the testes. It has long been controversial whether USP26 variants are associated with human male infertility. Thus, in the present study, we introduced a mutation into the Usp26 gene in mice and found that Usp26 mutant males backcrossed to a DBA/2 background, but not a C57BL/6 background, were sterile or subfertile and had atrophic testes. These findings indicate that the effects of the Usp26 mutation on male reproductive capacity were influenced by genetic background. Sperm in the cauda epididymis of Usp26 mutant mice backcrossed to a DBA/2 background were decreased in number and showed a malformed head morphology compared to those of wild-type mice. Additionally, histological examinations of the testes revealed that the number of round and elongated spermatids were dramatically reduced in Usp26 mutant mice. The mutant mice exhibited unsynapsed chromosomes in pachynema and defective chiasma formation in diplonema, which presumably resulted in apoptosis of metaphase spermatocytes and subsequent decrease of spermatids. Taken together, these results indicate that the deficiencies in fertility and spermatogenesis caused by mutation of Usp26 were dependent on genetic background.
Characterization of artificially re-pigmented ARPE-19 retinal pigment epithelial cell model
Authors: Hellinen Laura , Hagström Marja , Knuutila Heidi , Ruponen Marika , Urtti Arto , Reinisalo Mika 
Published: September 2019

AbstractMelanin pigment has a significant role in ocular pharmacokinetics, because many drugs bind at high extent to melanin in the retinal pigment epithelial cells. Most retinal pigment epithelial cell lines lack pigmentation and, therefore, we re-pigmented human ARPE-19 cells to generate a pigmented cell model. Melanosomes from porcine retinal pigment epithelium were isolated and co-incubated with ARPE-19 cells that spontaneously phagocytosed the melanosomes. Internalized melanosomes were functionally integrated to the cellular system as evidenced by correct translocation of cellular Rab27a protein to the melanosomal membranes. The pigmentation was retained during cell cultivation and the level of pigmentation can be controlled by altering the amount of administered melanosomes. We used these cells to study melanosomal uptake of six drugs. The uptake was negligible with low melanin-binders (methotrexate, diclofenac) whereas most of the high melanin-binders (propranolol, chloroquine) were extensively taken up by the melanosomes. This cell line can be used to model pigmentation of the retinal pigment epithelium, while maintaining the beneficial cell line characteristics, such as fast generation of cultures, low cost, long-term maintenance and good reproducibility. The model enables studies at normal and decreased levels of pigmentation to model different retinal conditions.
An intron-derived motif strongly increases gene expression from transcribed sequences through a splicing independent mechanism in Arabidopsis thaliana
Authors: Gallegos Jenna E. , Rose Alan B. 
Published: September 2019

AbstractCertain introns significantly increase mRNA accumulation by a poorly understood mechanism. These introns have no effect when located upstream, or more than ~1 Kb downstream, of the start of transcription. We tested the ability of a formerly non-stimulating intron containing 11 copies of the sequence TTNGATYTG, which is over-represented in promoter-proximal introns in Arabidopsis thaliana, to affect expression from various positions. The activity profile of this intron at different locations was similar to that of a natural intron from the UBQ10 gene, suggesting that the motif increases mRNA accumulation by the same mechanism. A series of introns with different numbers of this motif revealed that the effect on expression is linearly dependent on motif copy number up to at least 20, with each copy adding another 1.5-fold increase in mRNA accumulation. Furthermore, 6 copies of the motif stimulated mRNA accumulation to a similar degree from within an intron or when introduced into the 5′-UTR and coding sequences of an intronless construct, demonstrating that splicing is not required for this sequence to boost expression. The ability of this motif to substantially elevate expression from several hundred nucleotides downstream of the transcription start site reveals a novel type of eukaryotic gene regulation.
Aktivierende Pflege für Menschen mit Demenz
Authors: Seiler Bianca , Morgenstern Ulrike 
Published: September 2019

ZusammenfassungAktivierende Pflege ist wichtig, um die Alltagskompetenzen und die Lebensqualität
von älteren Menschen mit Demenz so lange wie möglich zu erhalten. Wir stellen
Ihnen 3 Konzepte vor: die Reminiszenztherapie, das Brain-Gym®-Konzept
und die Ergotherapie.
Lager-brewing yeasts in the era of modern genetics
Authors: Gorter de Vries Arthur R , Pronk Jack T , Daran Jean-Marc G 
Published: September 2019

ABSTRACT
The yeast Saccharomyces pastorianus is responsible for the annual worldwide production of almost 200 billion liters of lager-type beer. S. pastorianus is a hybrid of Saccharomyces cerevisiae and Saccharomyces eubayanus that has been studied for well over a century. Scientific interest in S. pastorianus intensified upon the discovery, in 2011, of its S. eubayanus ancestor. Moreover, advances in whole-genome sequencing and genome editing now enable deeper exploration of the complex hybrid and aneuploid genome architectures of S. pastorianus strains. These developments not only provide novel insights into the emergence and domestication of S. pastorianus but also generate new opportunities for its industrial application. This review paper combines historical, technical and socioeconomic perspectives to analyze the evolutionary origin and genetics of S. pastorianus. In addition, it provides an overview of available methods for industrial strain improvement and an outlook on future industrial application of lager-brewing yeasts. Particular attention is given to the ongoing debate on whether current S. pastorianus originates from a single or multiple hybridization events and to the potential role of genome editing in developing industrial brewing yeast strains.
Negative Predictive Value of Biopsy Margins in Keratinocyte Carcinoma: A Literature Review
Authors: Purnell Joseph Chase , Duncan James Robert , Stratton Michael Slade , Huang Conway , Phillips Carlton Blake 
Published: September 2019

BACKGROUND
Pathologists sometimes include commentary on margin involvement in shave biopsy reports of keratinocyte carcinoma (KC). This practice can lead to confusion regarding the need for further treatment. There is limited literature evaluating the reliability of reported histologic margin status in shave biopsies of KC.

OBJECTIVE
To evaluate the negative predictive value (NPV) of reported clear shave biopsy margins in basal and squamous cell carcinomas to determine whether this assessment is a reliable predictor of complete tumor removal.

METHODS
A literature review was performed using the PubMed database. The data were compiled, NPVs were calculated by the tumor subgroup, and a statistical analysis was performed.

RESULTS
Four studies met inclusion criteria. Two hundred twenty-one KCs were identified (n = 221). All specimens had negative-reported histologic margins (39 squamous cell carcinoma [SCC] and 182 BCC). Fifty-five cases initially noted to have negative margins on biopsy were found to have residual tumor on subsequent analysis: 5 SCC and 50 BCC, translating to 12.8% of all SCC (5/39) and 27.5% for BCC (50/182). Negative predictive values were found to be 75.1% for all KCs, 87.2% for SCC, and 72.5% for BCC.

CONCLUSION
Negative histologic margin status on shave biopsy specimens of KC has a poor NPV and is an inadequate predictor for complete tumor removal.
Discussion of “Dynamic Modeling and Projection-Based Reduction Methods for Bladed Disks With Nonlinear Frictional and Intermittent Contact Interfaces” (Mitra, M., Epureanu, B. I., 2018, ASME Appl. Mech. Rev., 71(5), p. 050803)
Authors: Wallaschek Jörg , Willeke Sebastian , Panning-von Scheidt Lars 
Published: September 2019

Abstract
Mitra and Epureanu have written a very good and complete overview on nonlinear vibrations of turbine blades. Nonlinearities due to friction and contact mechanics are the main focus. Questions related to modeling and model reduction are particularly addressed. This paper begins with an investigation of the vibration behavior of cyclic linear structures, in which a variety of considerations about the occurrence of standing and propagating waves play an important role. Subsequently, several methods of model-order reduction are presented, where cyclic sectors of tuned bladed disks are assumed. The classification of the linear vibration modes according to their nodal diameters (NDs) is explained in detail. Large models with a high number of degrees-of-freedom (DOF) occurring in the field of turbomachinery dynamics lead to very high computational cost. In this context, the authors consider model-order reduction with projection-based methods to be of particular interest. They give an overview of modern projection-based methods and compare them with regard to their respective advantages and disadvantages in the context of bladed disks with nonlinear friction and intermittent contact.
An observational study to examine how cumulative impact zones influence alcohol availability from different types of licensed outlets in an inner London Borough
Authors: Sharpe Carolyn A , Poots Alan , Watt Hilary , Williamson Chris , Franklin David , Pinder Richard J 
Published: September 2019

ObjectivesCumulative impact zones (CIZs) are a widely implemented local policy intended to restrict alcohol availability in areas proliferated with licensed outlets. Limited previous research has questioned their effectiveness and suggested they may play a more nuanced role in shaping local alcohol environments. This study evaluates the association between CIZ implementation and the number of licence applications made, and the number issued, relative to a control region.DesignA quantitative observational study.SettingThe inner London Borough of Southwark, which currently enforces three CIZs.PopulationLicence applications received by Southwark Council’s Licensing Authority between 1 April 2006 and 31 March 2017 (n=1254).InterventionsCIZ implementation.Primary outcome measuresFive outlet types were categorised and evaluated: drinking establishments, eateries, takeaways, off sales and other outlets. Primary outcome measures were the number of applications received and the number of licences issued. These were analysed using Poisson regression of counts over time.ResultsAcross all CIZs, implementation was associated with greater increases in the number of eateries in CIZ regions (incidence rate ratio (IRR)=1.58, 95% CI: 1.02–2.45, p=0.04) and number of takeaway venues (IRR=3.89, 95% CI: 1.32–11.49, p=0.01), relative to the control area. No discernible association was found for the remaining outlet types. Disaggregating by area indicated a 10-fold relative increase in the number of new eateries in Peckham CIZ (IRR=10.38, 95% CI: 1.39–77.66, p=0.02) and a fourfold relative increase in the number of newly licensed takeaways in Bankside CIZ (IRR=4.38, 95% CI: 1.20–15.91, p=0.03).ConclusionsCIZs may be useful as policy levers to shape local alcohol environments to support the licensing goals of specific geographical areas and diversify the night-time economy.
Qualitative study exploring patients experiences of being diagnosed and living with primary bone cancer in the UK
Authors: Martins Ana , Whelan Jeremy S , Bennister Lindsey , Fern Lorna A , Gerrand Craig , Onasanya Maria , Storey Lesley , Wells Mary , Windsor Rachael , Woodford Julie , Taylor Rachel M 
Published: September 2019

ObjectiveThe aim of this study is to explore the experiences of patients with primary bone cancer.DesignQualitative study design using semistructured interviews and focus groups.SettingHospitals across the UK and recruitment through UK sarcoma charities and support groups.MethodsSemistructured telephone/face-to-face interviews and focus groups with a purposive sample of 26 participants. Data were analysed using Framework Analysis.ParticipantsPatients (n=26) with primary bone cancer aged 13–77 years. The majority were male (69%), white (85%); diagnosed within 4 years (54%); and had lower limb sarcoma (65%). Ten participants had undergone an upper/lower limb amputation (39%).ResultsThe health-related quality-of-life domains of physical, emotional and social well-being and healthcare professionals’ role were the overarching themes of analysis. The physical domain anchored patient experiences. The intensity and length of treatment, the severity of side-effects, the level of disability after surgery and the uncertainty of their prognosis had an impact on patient’s self-image, confidence, mood and identity, and caused disruption to various aspects of the patients’ social life, including their relationships (emotional and sexual) and participation in work/school and leisure activities. Adaptation was influenced by the way patients dealt with stress and adversity, with some finding a new outlook in life, and others struggling with finding their ‘new normal’. Family and friends were the main source of support. Healthcare professional’s expertise and support was critical. Rehabilitation services had a considerable role in patient’s physical and emotional well-being, but inequitable access to these services was apparent.ConclusionsThis study described the impact of primary bone cancer on patients’ well-being and adjustment over time with the identification of influencing factors of better/worse experiences. It showed that impact was felt after end of treatment and affected patients at different life stages. Holistic models of survivorship care are needed.
How European primary care practitioners think the timeliness of cancer diagnosis can be improved: a thematic analysis
Authors: Harris Michael , Thulesius Hans , Neves Ana Luísa , Harker Sophie , Koskela Tuomas , Petek Davorina , Hoffman Robert , Brekke Mette , Buczkowski Krzysztof , Buono Nicola , Costiug Emiliana , Dinant Geert-Jan , Foreva Gergana , Jakob Eva , Marzo-Castillejo Mercè , Murchie Peter , Sawicka-Powierza Jolanta , Schneider Antonius , Smyrnakis Emmanouil , Streit Sven , Taylor Gordon , Vedsted Peter , Weltermann Birgitta , Esteva Magdalena 
Published: September 2019

BackgroundNational European cancer survival rates vary widely. Prolonged diagnostic intervals are thought to be a key factor in explaining these variations. Primary care practitioners (PCPs) frequently play a crucial role during initial cancer diagnosis; their knowledge could be used to improve the planning of more effective approaches to earlier cancer diagnosis.ObjectivesThis study sought the views of PCPs from across Europe on how they thought the timeliness of cancer diagnosis could be improved.DesignIn an online survey, a final open-ended question asked PCPs how they thought the speed of diagnosis of cancer in primary care could be improved. Thematic analysis was used to analyse the data.SettingA primary care study, with participating centres in 20 European countries.ParticipantsA total of 1352 PCPs answered the final survey question, with a median of 48 per country.ResultsThe main themes identified were: patient-related factors, including health education; care provider-related factors, including continuing medical education; improving communication and interprofessional partnership, particularly between primary and secondary care; factors relating to health system organisation and policies, including improving access to healthcare; easier primary care access to diagnostic tests; and use of information technology. Re-allocation of funding to support timely diagnosis was seen as an issue affecting all of these.ConclusionsTo achieve more timely cancer diagnosis, health systems need to facilitate earlier patient presentation through education and better access to care, have well-educated clinicians with good access to investigations and better information technology, and adequate primary care cancer diagnostic pathway funding.
Observational constraints on reheating in braneworld inflation
Authors: Sakhi Z. , Safsafi A. , Ferricha-Alami M. , Chakir H. , Bennai M. 
Published: September 2019

The reheating era after inflation is analyzed in the framework of the braneworld models. We study reheating by calculating the reheating temperature in a braneworld inflation for various cosmological parameters. The variation of reheating [Formula: see text]-folding number and reheating temperature were obtained and analyzed as function of a spectrum of perturbation for a polynomial potential [Formula: see text]. We have applied the slow-roll approximation in the high energy limit to constraint the parameter potentials by confronting our results to recent Planck 2018 observations. We have shown that in general the best values of the predicted reheating temperature is of the order [Formula: see text] GeV, with a brane tension [Formula: see text] GeV4. We have also shown that the polynomial potential in the case [Formula: see text] provides the best fit results with recent observational constraints.