bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neuroprotective effects of the anti‐cancer drug sunitinib in models of HIV neurotoxicity suggests potential for the treatment of neurodegenerative disorders
Authors: Wrasidlo Wolf , Crews Leslie A , Tsigelny Igor F , Stocking Emily , Kouznetsova Valentina L , Price Diana , Paulino Amy , Gonzales Tania , Overk Cassia R , Patrick Christina , Rockenstein Edward , Masliah Eliezer 
Published: August 2014

Background and PurposeAnti‐retrovirals have improved and extended the life expectancy of patients with HIV. However, as this population ages, the prevalence of cognitive changes is increasing. Aberrant activation of kinases, such as receptor tyrosine kinases (RTKs) and cyclin‐dependent kinase 5 (CDK5), play a role in the mechanisms of HIV neurotoxicity. Inhibitors of CDK5, such as roscovitine, have neuroprotective effects; however, CNS penetration is low. Interestingly, tyrosine kinase inhibitors (TKIs) display some CDK inhibitory activity and ability to cross the blood–brain barrier.Experimental ApproachWe screened a small group of known TKIs for a candidate with additional CDK5 inhibitory activity and tested the efficacy of the candidate in in vitro and in vivo models of HIV‐gp120 neurotoxicity.Key ResultsAmong 12 different compounds, sunitinib inhibited CDK5 with an IC50 of 4.2 μM. In silico analysis revealed that, similarly to roscovitine, sunitinib fitted 6 of 10 features of the CDK5 pharmacophore. In a cell‐based model, sunitinib reduced CDK5 phosphorylation (pCDK5), calpain‐dependent p35/p25 conversion and protected neuronal cells from the toxic effects of gp120. In glial fibrillary acidic protein‐gp120 transgenic (tg) mice, sunitinib reduced levels of pCDK5, p35/p25 and phosphorylated tau protein, along with amelioration of the neurodegenerative pathology.Conclusions and ImplicationsCompounds such as sunitinib with dual kinase inhibitory activity could ameliorate the cognitive impairment associated with chronic HIV infection of the CNS. Moreover, repositioning existing low MW compounds holds promise for the treatment of patients with neurodegenerative disorders.
Protons modulate perivascular axo‐axonal neurotransmission in the rat mesenteric artery
Authors: Takatori Shingo , Hirai Kazuhiro , Ozaki Shuichiro , Tangsucharit Panot , Fukushima‐Miyashita Satoko , Goda Mitsuhiro , Hashikawa‐Hobara Narumi , Ono Nobufumi , Kawasaki Hiromu 
Published: August 2014

Background and PurposePrevious studies have demonstrated that nicotine releases protons from adrenergic nerves via stimulation of nicotinic ACh receptors and activates transient receptor potential vanilloid‐1 (TRPV1) receptors located on calcitonin gene‐related peptide (CGRP)‐containing (CGRPergic) vasodilator nerves, resulting in vasodilatation. The present study investigated whether perivascular nerves release protons, which modulate axon‐axonal neurotransmission.Experiment ApproachPerfusion pressure and pH levels of perfusate in rat‐perfused mesenteric vascular beds without endothelium were measured with a pressure transducer and a pH meter respectively.Key ResultsPeriarterial nerve stimulation (PNS) initially induced vasoconstriction, which was followed by long‐lasting vasodilatation and decreased pH levels in the perfusate. Cold‐storage denervation of the preparation abolished the decreased pH and vascular responses to PNS. The adrenergic neuron blocker guanethidine inhibited PNS‐induced vasoconstriction and effects on pH, but not PNS‐induced vasodilatation. Capsaicin (CGRP depletor), capsazepine and ruthenium red (TRPV1 inhibitors) attenuated the PNS‐induced decrease in pH and vasodilatation. In denuded preparations, ACh caused long‐lasting vasodilatation and lowered pH; these effects were inhibited by capsaicin pretreatment and atropine, but not by guanethidine or mecamylamine. Capsaicin injection induced vasodilatation and a reduction in pH, which were abolished by ruthenium red. The use of a fluorescent pH indicator demonstrated that application of nicotine, ACh and capsaicin outside small mesenteric arteries reduced perivascular pH levels and these effects were abolished in a Ca2+‐free medium.Conclusion and ImplicationThese results suggest that protons are released from perivascular adrenergic and CGRPergic nerves upon PNS and these protons modulate transmission in CGRPergic nerves.
Concerns and hopes among adolescents attending adolescent psychiatric outpatient clinics
Authors: Anttila Katriina , Anttila Minna , Kurki Marjo , Hätönen Heli , Marttunen Mauri , Välimäki Maritta 
Published: August 2014

BackgroundMental disorders affect the well‐being of adolescents. This study aims to describe adolescents' concerns and hopes from their own perspective when referred to adolescent psychiatric outpatient treatment.MethodThe qualitative data consisted of adolescents' (n = 70) short essays gathered using the Depis.Net Internet program and analyzed with inductive thematic analysis.ResultsThe adolescents described their concerns and hopes regarding their relationships, daily actions, identity, and well‐being.ConclusionsAdolescents share their concerns and find solutions if they find a safe channel to do so. Professionals should find new ways to help adolescents share their life experiences and information technology may be a promising tool.
PD‐1 expression on peripheral blood T‐cell subsets correlates with prognosis in non‐small cell lung cancer
Authors: Waki Kayoko , Yamada Teppei , Yoshiyama Koichi , Terazaki Yasuhiro , Sakamoto Shinjiro , Matsueda Satoko , Komatsu Nobukazu , Sugawara Shunichi , Takamori Shinzo , Itoh Kyogo , Yamada Akira 
Published: August 2014

PD‐1 expression in peripheral blood T‐cells has been reported in several kinds of cancers, including lung cancer. However, the relationship between PD‐1 expression in peripheral blood T‐cells and prognosis after treatment with a cancer vaccine has not been reported. To elucidate this relationship, we analyzed PD‐1 expression in the peripheral blood T‐cells of patients with non‐small cell lung cancer. The blood samples used in this study were obtained from patients enrolled in phase II clinical trials of a personalized peptide vaccine. Seventy‐eight samples obtained before and after a single vaccination cycle (consisting of six or eight doses) were subjected to the analysis. PD‐1 was expressed on lymphocytes in the majority of samples. The relative contents of PD1+CD4+ T‐cells against total lymphocytes before and after the vaccination cycle correlated with overall survival (OS) with a high degree of statistical significance (P < 0.0001 and P = 0.0014). A decrease in PD‐1+CD8+ T‐cells after one cycle of vaccination also correlated with longer OS (P = 0.032). The IgG response to the non‐vaccinated peptides suggested that the epitope spreading seemed to occur more frequently in high‐PD‐1+CD4+ T‐cell groups. Enrichment of CD45RA−CCR7− effector‐memory phenotype cells in PD‐1+ T‐cells in PBMCs was also shown. These results suggest that PD‐1 expression on the peripheral blood T‐cell subsets can become a new prognostic marker in non‐small cell lung cancer patients treated with personalized peptide vaccination.
Beneficial metabolic phenotypes caused by loss‐of‐function APOC3 mutations
Authors: Gibson W. T. 
Published: August 2014

Loss‐of‐function mutations in APOC3, triglycerides, and coronary disease.TG & HDL Working Group of the NHLBI Exome Sequencing Project (2014)N Engl J Med 371:22–31Loss‐of‐function mutations in APOC3 and risk of ischemic vascular disease.Jørgensen et al. (2014)N Engl J Med 371:32–41
Cost‐Effectiveness of Using Small Vertebrates as Indicators of Disturbance
Authors: PECK MIKA ROBERT , MADDOCK SIMON T. , MORALES JORGE NOE , OÑATE HUGOLINO , MAFLA‐ENDARA PAOLA , PEÑAFIEL VANESSA AGUIRRE , TORRES‐CARVAJAL OMAR , POZO‐RIVERA WILMER E. , CUEVA‐ARROYO XAVIER A. , TOLHURST BRYONY A. 
Published: August 2014

AbstractIn species‐rich tropical forests, effective biodiversity management demands measures of progress, yet budgetary limitations typically constrain capacity of decision makers to assess response of biological communities to habitat change. One approach is to identify ecological‐disturbance indicator species (EDIS) whose monitoring is also monetarily cost‐effective. These species can be identified by determining individual species’ responses to disturbance across a gradient; however, such responses may be confounded by factors other than disturbance. For example, in mountain environments the effects of anthropogenic habitat alteration are commonly confounded by elevation. EDIS have been identified with the indicator value (IndVal) metric, but there are weaknesses in the application of this approach in complex montane systems. We surveyed birds, small mammals, bats, and leaf‐litter lizards in differentially disturbed cloud forest of the Ecuadorian Andes. We then incorporated elevation in generalized linear (mixed) models (GL(M)M) to screen for EDIS in the data set. Finally, we used rarefaction of species accumulation data to compare relative monetary costs of identifying and monitoring EDIS at equal sampling effort, based on species richness. Our GL(M)M generated greater numbers of EDIS but fewer characteristic species relative to IndVal. In absolute terms birds were the most cost‐effective of the 4 taxa surveyed. We found one low‐cost bird EDIS. In terms of the number of indicators generated as a proportion of species richness, EDIS of small mammals were the most cost‐effective. Our approach has the potential to be a useful tool for facilitating more sustainable management of Andean forest systems.Rentabilidad del Uso de Pequeños Vertebrados como Indicadores de Perturbaciones
How does Family Control Influence Firm Strategy and Performance? A Meta‐Analysis of US Publicly Listed Firms
Authors: van Essen Marc , Carney Michael , Gedajlovic Eric R. , Heugens Pursey P. M. A. R. 
Published: August 2014

AbstractManuscript TypeEmpiricalResearch Question/IssueA contentious and prominent research question in the management literature is whether publicly listed family firms (FFs) outperform other types of corporations. Through a research synthesis of all available studies on the performance of US FFs, we address this question directly. We also extend the debate by raising three salient follow‐up questions. First, is the performance differential between FFs and non‐FFs attributable to a unique set of strategic choices? Second, do FF performance effects persist across generational transitions in FF control? Third, are performance differentials across generations attributable to intergenerational shifts in corporate governance and strategy?Research Findings/InsightsWith respect to our primary research question, we find that the balance of evidence indicates that (US) FFs outperform other types of public corporations. We also evaluate competing narratives regarding which strategies are characteristic of FFs, and demonstrate that their diversification, internationalization, and financing strategies mediate the FF‐performance relationship in manners consistent with the narratives advanced by certain leading FF scholars, but not others. Further, we find that the performance of (US) FFs drops dramatically after the first generation and show that this negative performance differential is due to the much more conservative patterns of strategic decision making enacted by successor generations.Theoretical/Academic ImplicationsIn addition to providing the most comprehensive evidence to date regarding the performance attributes of FFs, we nuance several theoretical debates concerning the propensity of FFs to diversify, internationalize, and leverage their equity capital.Practitioner/Policy ImplicationsWe identify value‐creating strategic choices of FFs related to internationalization, diversification, and capital structure. We also identify strategic choices often made in successor‐led FFs which reduce value. Both sets of findings are relevant to FF executives and consultants. The policy implications of the study are that in advanced liberal market economies high‐quality capital market institutions are likely to contribute to FF outperformance vis‐à‐vis other types of publicly listed firms, but these findings may not hold in other types of national governance systems or in emerging markets.
Different Implication of Elevated B‐Type Natriuretic Peptide Level in Patients with Heart Failure with Preserved Ejection Fraction and in Those with Reduced Ejection Fraction
Authors: Ishigaki Takako , Yoshida Takashi , Izumi Hiromi , Fujisawa Yoshihisa , Shimizu Shoko , Masuda Kasumi , Asanuma Toshihiko , Okabe Hidetoshi , Nakatani Satoshi 
Published: August 2014

BackgroundThere have been no reports that show significant direct relationship between echocardiographic parameters and B‐type natriuretic peptide (BNP) level. This could be due to the heterogeneous pathophysiology of heart failure and a lack of appropriate echocardiographic parameters. We sought to determine the best echocardiographic parameter that described elevated BNP level in patients with heart failure with and without systolic dysfunction.Methods and ResultsWe studied 111 consecutive heart failure patients. They were divided into patients with heart failure and preserved ejection fraction (HFPEF, n = 61) and that with heart failure and reduced ejection fraction (HFREF, n = 50). Conventional and new echocardiographic parameters including myocardial strains were measured. BNP did not reflect any single echocardiographic parameter in patients with heart failure in total. The ratio of early diastolic transmitral flow velocity and mitral annular velocity had strong positive correlation with BNP level in the HFPEF group but not in the HFREF group. In the group of HFREF, global longitudinal and circumferential strains were positively correlated. Multivariate analysis revealed that predicted factors for BNP value in HFPEF and in HFREF were different.ConclusionHigh BNP level may indicate high filling pressure when ejection fraction is preserved and may indicate myocardial dysfunction when it is reduced.
Cardiac Strain during Upright Cycle Ergometry in Adolescent Males
Authors: Unnithan Viswanath B. , Rowland Thomas , Lindley Martin R. , Roche Denise M. , Garrard Max , Barker Piers 
Published: August 2014

Little evidence exists with regard to changes in cardiac strain that occur during submaximal exercise in young males. The aims of the study were to evaluate the changes that occur in longitudinal (L), radial (R), and endocardial circumferential (EC) strain during submaximal upright cycle ergometry and to examine the test–retest reproducibility of these measurements. Fourteen recreationally active, adolescent (age: 17.9 ± 0.7 years) males volunteered for the study. All subjects underwent an incremental (40 W) submaximal cycle ergometer test. L, R, and EC strain values were obtained using speckle tracking, from two‐dimensional B‐mode images of the left ventricle (LV) during rest and the initial stages of submaximal exercise (40 and 80 W). The average of 6 LV segments was used to determine both peak wall deformation (%) and the time to peak deformation (ms). There was a statistically (P < 0.05) significant increase from rest to submaximal exercise for peak deformation for L, R, and EC strain. There was a statistically significant (P < 0.05) decrease from rest to submaximal exercise for time to peak for L and R and EC strain and between submaximal workloads for time to peak for L strain and EC strain. Coefficients of variation demonstrated reproducibility for upright strain and strain rate measurements similar to published supine measurements. This study has demonstrated that changes in left ventricular wall deformation (L, R and EC strain) that occur during the transition from rest to submaximal exercise can be reliably measured and confirm that a healthy LV has a hyperdynamic response to exercise.
Serum 25‐hydroxyvitamin D and cognitive decline in the very old: the Newcastle 85+ Study
Authors: Granic A. , Hill T. R. , Kirkwood T. B. L. , Davies K. , Collerton J. , Martin‐Ruiz C. , von Zglinicki T. , Saxby B. K. , Wesnes K. A. , Collerton D. , Mathers J. C. , Jagger C. 
Published: August 2014

Background and purposeStudies investigating the association between 25‐hydroxyvitamin D [25(OH)D] and cognition in the very old (85+) are lacking.MethodsCross‐sectional (baseline) and prospective data (up to 3 years follow‐up) from 775 participants in the Newcastle 85+ Study were analysed for global (measured by the Standardized Mini‐Mental State Examination) and attention‐specific (measured by the attention battery of the Cognitive Drug Research test) cognitive performance in relation to season‐specific 25(OH)D quartiles.ResultsThose in the lowest and highest season‐specific 25(OH)D quartiles had an increased risk of impaired prevalent (1.66, 95% confidence interval 1.06–2.60, P = 0.03; 1.62, 95% confidence interval 1.02–2.59, P = 0.04, respectively) but not incident global cognitive functioning or decline in functioning compared with those in the middle quartiles adjusted for sociodemographic, health and lifestyle confounders. Random effects models showed that participants belonging to the lowest and highest 25(OH)D quartiles, compared with those in the middle quartiles, had overall slower (log‐transformed) attention reaction times for Choice Reaction Time (lowest, β = 0.023, P = 0.01; highest, β = 0.021, P = 0.02), Digit Vigilance Task (lowest, β = 0.009, P = 0.05; highest, β = 0.01, P = 0.02) and Power of Attention (lowest, β = 0.017, P = 0.02; highest, β = 0.022, P = 0.002) and greater Reaction Time Variability (lowest, β = 0.021, P = 0.02; highest, β = 0.02, P = 0.03). The increased risk of worse global cognition and attention amongst those in the highest quartile was not observed in non‐users of vitamin D supplements/medication.ConclusionLow and high season‐specific 25(OH)D quartiles were associated with prevalent cognitive impairment and poorer overall performance in attention‐specific tasks over 3 years in the very old, but not with global cognitive decline or incident impairment.
High‐Frequency Exchange Rate Forecasting
Authors: Cai Charlie X. , Zhang Qi 
Published: August 2014

AbstractPredictability of exchange rate movement is of great interest to both practitioners and regulators. We examine the predictability of exchange rate movement in the high‐frequency domain. To this end, we apply a model designed for modelling high‐frequency and irregularly spaced data, the autoregressive conditional multinomial–autoregressive conditional duration (ACM–ACD) model. Studying three pairs of currencies, we find strong predictability in the high‐frequency quote change data, with the rate of correct predictions varying from 54 to 70%. We demonstrate that filtering the data, by increasing the threshold of mid‐quote price change, in combination with dynamic learning, can improve forecasting performance.
Baicalein induces autophagic cell death through AMPK/ULK1 activation and downregulation of mTORC1 complex components in human cancer cells
Authors: Aryal Pramod , Kim Kijoong , Park Pil‐Hoon , Ham Seongho , Cho Junghee , Song Kyung 
Published: August 2014

Baicalein, a flavonoid and aglycon hydrolyzed from baicalin, has anticancer properties in several human carcinomas, but its molecular mechanisms of action remain unclear. Here, we show that baicalein leads to human cancer cell death by inducing autophagy rather than apoptosis, because cell death induced by baicalein was completely reversed by suppressing the expression levels of key molecules in autophagy such as Beclin 1, vacuolar protein sorting 34 (Vps34), autophagy‐related (Atg)5 and Atg7, but not by pan‐caspase inhibitor. Our data revealed that baicalein significantly increased the number of green fluorescence protein–cytosol‐associated protein light chain 3 (GFP–LC3)‐containing puncta and LC3B‐II expression levels, which were further enhanced by chloroquine treatment. Furthermore, a luciferase‐based reporter assay showed that the ratio of RLuc–LC3wt/RLuc–LC3G120A was greatly reduced. The data suggested that baicalein induced not only autophagosome formation, but also autophagic flux. Experiments using short interfering RNAs and pharmacological inhibitors revealed that Beclin 1, Vps34, Atg5, Atg7 and UNC‐51 (Caenorhabditis elegans)‐like kinase 1 (ULK1) play pivotal roles in mediating baicalein‐induced autophagy. Moreover, baicalein activated AMP‐activated protein kinase (AMPK)α, leading to ULK1 activation through phosphorylation at Ser555, whereas both protein and mRNA levels of mammalian target of rapamycin (mTOR) and Raptor, upstream inhibitors of ULK1 and autophagy, were markedly downregulated by baicalein. Our data suggest that the anticancer effects of baicalein are mainly due to autophagic cell death through activation of the AMPK/ULK1 pathway and inhibition of mTOR/Raptor complex 1 expression. These results provide new mechanistic insights into the anticancer functions of autophagy inducers, such as baicalein, which may be used as potential therapeutics for cancer treatment.
The effect of tooth loss on gait stability of community‐dwelling older adults
Authors: Brand Christina , Bridenbaugh Stephanie A. , Perkovac Mateja , Glenz Fabienne , Besimo Christian E. , Sendi Pedram , Kressig Reto W. , Marinello Carlo P. 
Published: August 2014

ObjectiveTo investigate the effects of tooth loss on gait stability in a healthy elderly population.MethodsA case–control study was conducted among healthy and prosthetically well‐restored seniors over the age of 65 years. The test group comprised 24 edentulous participants who were restored with complete dentures in the upper jaw and an overdenture fixed on two implants in the lower jaw. The control group comprised 25 dentate participants who either still had their natural teeth or were restored with conventional fixed partial dentures. Gait stability was evaluated by measuring the parameters ‘gait velocity’ and ‘cycle‐time variability’ during self‐selected normal walking speed and under dual‐task performance conditions. Measurements were conducted using the GAITRite® electronic walkway system.ResultsDentated and fixed restored participants (the control group) had a significantly higher gait velocity compared with denture wearers (the test group) under both normal walking (p = 0.03) and dual‐task performance conditions (p = 0.01). In each test condition, among edentulous participants, gait velocity did not significantly differ according to whether the participant wore their dentures.ConclusionThe present results suggest that tooth loss in healthy seniors is associated with lower gait velocity and therefore may have a negative impact on gait stability.
Peromyscus leucopus mice: a potential animal model for haematological studies
Authors: Sun Yu , Desierto Marie J. , Ueda Yasutaka , Kajigaya Sachiko , Chen Jichun , Young Neal S. 
Published: August 2014

SummaryPeromyscus leucopus mice share physical similarities with laboratory mice Mus musculus (MM) but have higher agility and longer lifespan. We compared domesticated P. leucopus linville (PLL) and M. musculus C57BL/6 (MMB6) mice for cellular composition of peripheral blood (PB), bone marrow (BM) and spleen. PLL mice had significantly fewer platelets and significantly more monocytes in the blood, and notably fewer megakaryocytes in the BM. Spleens of PLL mice were significantly smaller, with 50% fewer cells and reduced ‘red pulp’. There was no obvious haematological change in PLL mice between 2–8 and 16–26 months of age, except for a significant increase in blood monocytes. Cellular reactive oxygen species (ROS) content showed no change with age but differed significantly between different cell types. Treating two to eight month‐old PLL mice with antioxidant N‐acetylcysteine in drinking water for three months did not affect cellular ROS content, but increased blood leucocytes especially the concentration of monocytes. The low platelets, low megakaryocytes, high monocytes and low splenic erythropoiesis in PLL mice resemble human measurements better than the values seen in MMB6.