bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical activity and 22‐year all‐cause and coronary heart disease mortality
Authors: Krause Niklas , Arah Onyebuchi A. , Kauhanen Jussi 
Published: September 2017

BackgroundThis study explores the effects of occupational (OPA) and leisure time physical activity (LTPA) on mortality relative to cardiorespiratory fitness and pre‐existing coronary heart disease (CHD).MethodsAssociations between OPA, measured as energy expenditure (kcal/day) and relative aerobic workload (%VO2max), LTPA, and 22‐year mortality among 1891 Finnish men were assessed by Cox regression models stratified by CHD and adjusted for 19 confounders.ResultsIn fully adjusted models, each 10% of relative aerobic workload increased all‐cause mortality by 13% and CHD mortality 28% (P < 0.01). Compared to healthy subjects, men with CHD experienced lower mortality risks due to OPA and higher risks due to LTPA. While LTPA had no effect among healthy men, in men with CHD each weekly hour of conditioning LTPA increased all‐cause mortality risks by 10% and CHD mortality by14%.ConclusionOPA was positively associated with both all‐cause and CHD mortality. LTPA was not protective. Among men with CHD, LTPA increased mortality risks.
Knee Alignment Is Quantitatively Related to Periarticular Bone Morphometry and Density, Especially in Patients With Osteoarthritis
Authors: Lo Grace H. , Merchant Mehveen G. , Driban Jeffrey B. , Duryea Jeffrey , Price Lori Lyn , Eaton Charles B. , McAlindon Timothy E. 
Published: September 2017

ObjectiveStatic alignment influences knee loading and predicts osteoarthritis (OA) progression. Periarticular bone is important in dispersing forces across the knee, and there is substantial evidence for molecular crosstalk between cartilage and subchondral bone. The aim of this study was to evaluate the relationship between periarticular trabecular bone morphology and bone mineral density (BMD) and knee alignment in OA.MethodsThis was a cross‐sectional analysis of participants in the Osteoarthritis Initiative Bone Ancillary Study. Dual x‐ray absorptiometry (DXA) was performed to measure tibial periarticular bone mineral density (paBMD). Magnetic resonance imaging of knee trabecular bone was performed to calculate the apparent bone volume fraction (aBVF), apparent trabecular number (aTbN), apparent trabecular spacing (aTbSp), and apparent trabecular thickness (aTbTh). Static alignment was assessed by measuring the hip–knee–ankle (HKA) angle on long‐limb films.ResultsThe study group comprised 436 participants (mean ± SD age 65.4 ± 9.2 years, 46% female, mean ± SD body mass index 29.6 ± 4.6 kg/m2), 71% of whom had OA. Correlations between the HKA angle and medial:lateral paBMD, medial paBMD, aBVF, aTbN, aTbTh, and aTbSp were –0.63, –0.34, –0.29, –0.32, –0.22, and 0.30, respectively. More varus alignment was associated with higher medial:lateral paBMD, medial paBMD, aBVF, aTbN, aTbTh, and lower aTbSp. In OA knees, the results were more pronounced. In non‐OA knees, the most consistent association was with medial:lateral paBMD.ConclusionStatic alignment was associated with medial:lateral paBMD in all knees and with medial paBMD and trabecular morphometry in OA knees only. Aberrant knee loading may lead to increased relative subchondral bone density, which is partly related to a higher aBVF and a greater number of thicker trabeculae with smaller intertrabecular spacing. Knee DXA may be a useful early biomarker of knee OA.
HMPA‐Promoted Siladifluoromethylation of Di‐, and Triarylmethanes with the Ruppert–Prakash Reagent
Authors: Ji Xinfei , Zhao Xianghu , Shi Hongyan , Cao Song 
Published: September 2017

AbstractA mild and efficientmethod for the synthesis of α‐siladifluoromethylated di‐, and triarylmethanes via the reaction of di‐, and triarylmethanes with Ruppert–Prakash reagents, using LDA and HMPA at room temperature, was developed.
Executive function and functional and structural brain differences in middle‐age adults with autism spectrum disorder
Authors: Braden B. Blair , Smith Christopher J. , Thompson Amiee , Glaspy Tyler K. , Wood Emily , Vatsa Divya , Abbott Angela E. , McGee Samuel C. , Baxter Leslie C. 
Published: September 2017

There is a rapidly growing group of aging adults with autism spectrum disorder (ASD) who may have unique needs, yet cognitive and brain function in older adults with ASD is understudied. We combined functional and structural neuroimaging and neuropsychological tests to examine differences between middle‐aged men with ASD and matched neurotypical (NT) men. Participants (ASD, n = 16; NT, n = 17) aged 40–64 years were well‐matched according to age, IQ (range: 83–131), and education (range: 9–20 years). Middle‐age adults with ASD made more errors on an executive function task (Wisconsin Card Sorting Test) but performed similarly to NT adults on tests of delayed verbal memory (Rey Auditory Verbal Learning Test) and local visual search (Embedded Figures Task). Independent component analysis of a functional MRI working memory task (n‐back) completed by most participants (ASD = 14, NT = 17) showed decreased engagement of a cortico‐striatal‐thalamic‐cortical neural network in older adults with ASD. Structurally, older adults with ASD had reduced bilateral hippocampal volumes, as measured by FreeSurfer. Findings expand our understanding of ASD as a lifelong condition with persistent cognitive and functional and structural brain differences evident at middle‐age. Autism Res 2017, 10: 1945–1959. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryWe compared cognitive abilities and brain measures between 16 middle‐age men with high‐functioning autism spectrum disorder (ASD) and 17 typical middle‐age men to better understand how aging affects an older group of adults with ASD. Men with ASD made more errors on a test involving flexible thinking, had less activity in a flexible thinking brain network, and had smaller volume of a brain structure related to memory than typical men. We will follow these older adults over time to determine if aging changes are greater for individuals with ASD.
Adaptive behavior in autism: Minimal clinically important differences on the Vineland‐II
Authors: Chatham C. H. , Taylor K. I. , Charman T. , Liogier D'ardhuy X. , Eule E. , Fedele A. , Hardan A. Y. , Loth E. , Murtagh L. , del Valle Rubido M. , San Jose Caceres A. , Sevigny J. , Sikich L. , Snyder L. , Tillmann J. E. , Ventola P. E. , Walton‐Bowen K. L. , Wang P. P. , Willgoss T. , Bolognani F. 
Published: September 2017

Autism Spectrum Disorder (ASD) is associated with persistent impairments in adaptive abilities across multiple domains. These social, personal, and communicative impairments become increasingly pronounced with development, and are present regardless of IQ. The Vineland Adaptive Behavior Scales, Second Edition (Vineland‐II) is the most commonly used instrument for quantifying these impairments, but minimal clinically important differences (MCIDs) on Vineland‐II scores have not been rigorously established in ASD. We pooled data from several consortia/registries (EU‐AIMS LEAP study, ABIDE‐I, ABIDE‐II, INFOR, Simons Simplex Collection and Autism Treatment Network [ATN]) and clinical investigations and trials (Stanford, Yale, Roche) resulting in a data set of over 9,000 individuals with ASD. Two approaches were used to estimate MCIDs: distribution‐based methods and anchor‐based methods. Distribution‐based MCID [d‐MCID] estimates included the standard error of the measurement, as well as one‐fifth and one‐half of the covariate‐adjusted standard deviation (both cross‐sectionally and longitudinally). Anchor‐based MCID [a‐MCID] estimates include the slope of linear regression of clinician ratings of severity on the Vineland‐II score, the slope of linear regression of clinician ratings of longitudinal improvement category on Vineland‐II change, the Vineland‐II change score maximally differentiating clinical impressions of minimal versus no improvement, and equipercentile equating. Across strata, the Vineland‐II Adaptive Behavior Composite standardized score MCID estimates range from 2.01 to 3.2 for distribution‐based methods, and from 2.42 to 3.75 for sample‐size‐weighted anchor‐based methods. Lower Vineland‐II standardized score MCID estimates were observed for younger and more cognitively impaired populations. These MCID estimates enable users of Vineland‐II to assess both the statistical and clinical significance of any observed change. Autism Res 2018, 11: 270–283. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.Lay SummaryThe Vineland Adaptive Behavior Scales (2nd edition; Vineland‐II) is the most widely used scale for assessing day‐to‐day “adaptive” skills. Yet, it is unknown how much Vineland‐II scores must change for those changes to be regarded as clinically significant. We pooled data from over 9,000 individuals with ASD to show that changes of 2–3.75 points on the Vineland‐II Composite score represent the “minimal clinically‐important difference.” These estimates will help evaluate the benefits of potential new treatments for ASD.
Amine oxidase from Euphorbia characias: Kinetic and structural characterization
Authors: Pintus Francesca , Sabatucci Annalaura , Maccarrone Mauro , Dainese Enrico , Medda Rosaria 
Published: September 2017

AbstractThis minireview focuses on a plant copper/2,4,5‐trihydroxyphenyl alanine quinone amine oxidase isolated from the latex of the shrub Euphorbia characias (ELAO). This enzyme has been investigated in terms of both molecular structure and kinetic mechanism. The characterization of this enzyme allowed us to identify specific amino acids and domains that play a key role in modulating substrate access into the active site not only for ELAO but also for other plant and mammalian amine oxidases. As mammalian amine oxidases are implicated in several physiological and pathological conditions, the deep structural characterization of their active site accession mechanisms could be the starting point for the development of enzyme modulators with high therapeutic potential. Thus, this paper gives structural/functional insights that open new perspectives in the research about the whole amine oxidase family.
Dissipative Stahlblechverbindungen für aussteifende Wandscheiben aus Brettsperrholz
Authors: Schmidt Tobias , Blaß Hans Joachim 
Published: September 2017

AbstractVerglichen mit anderen Holzbausystemen sind Brettsperrholzelemente aufgrund ihrer ausgezeichneten mechanischen Eigenschaften besonders geeignet, um Einwirkungen in Scheibenebene abzutragen und damit Gebäude auszusteifen. Die Duktilität und Energiedissipation einer Tragstruktur aus Brettsperrholz ergibt sich primär aus den mechanischen Eigenschaften der Verbindungsmittel. Üblicherweise kommen stiftförmige metallische Verbindungsmittel wie Nägel, Schrauben und Klammern zum Einsatz. Die Dissipationsfähigkeit dieser Verbindungen bei zyklischer Beanspruchung nimmt bereits bei geringer Zyklenanzahl signifikant ab. Für Erdbebeneinwirkungen sind jedoch Verbindungen wünschenswert, die ähnlich wie reine Stahlverbindungen über nahezu konstante Hystereseeigenschaften verfügen. Um dieses Ziel zu erreichen, wurden neuartige Stahlblechverbindungen entwickelt, wissenschaftlich untersucht und Gleichungen zur Bemessung sowie konstruktive Regeln hergeleitet. In diesem Beitrag werden die Ergebnisse der experimentellen, numerischen und analytischen Untersuchungen vorgestellt.Das Anordnen einer Lücke im Verbindungsnahbereich ermöglicht es, das Last‐Verschiebungsverhalten der Stahlblech‐Holzverbindung so zu beeinflussen, dass eine hochduktile, robuste und kostengünstige Verbindung entsteht, die stabile Hystereseeigenschaften aufweist.
Sleep disturbances in Taiwanese patients with Parkinson's disease
Authors: Lin Yi‐Ying , Chen Rou‐Shayn , Lu Chin‐Song , Huang Ying‐Zu , Weng Yi‐Hsin , Yeh Tu‐Hsueh , Lin Wey‐Yil , Hung June 
Published: September 2017

AbstractIntroductionSleep disturbance is a common nonmotor symptom of Parkinson's disease (PD) and strongly affects patients’ quality of life. The relationship between excessive daytime sleepiness (EDS) and nighttime problems remains uncertain. Arguments persist regarding the risk factors for sleep disturbance among patients with PD. Furthermore, the prevalence of EDS appears to be lower in Asian countries. Herein, we conducted the study to describe the characteristics of sleep problems in a sample of Taiwanese PD patients and delineate the difference with reported sleep disturbances in Caucasian PD patients from the literature.MethodsPatients with PD were recruited from the outpatient clinic of a tertiary medical center and were evaluated using standardized assessment protocols, including the Parkinson's Disease Sleep Scale (PDSS), the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale (ESS), and 39‐Item Parkinson's Disease Questionnaire (PDQ‐39).ResultsA total of 225 patients with PD were recruited. The mean age of patients with PD was 65.7 years old and the mean disease duration was 8.18 years. Among the patients, 53.8% were defined as poor sleepers (PSQI > 5) and 26.3% had EDS. Seventy‐one percent of the poor sleepers used hypnotic medications. The poor sleepers were worse in the scores of Unified Parkinson's Disease Rating Scale (UPDRS), PDSS, and the PDQ‐39, and received higher levodopa daily dosage. A PDSS score of <126 indicate that a patient with PD was a poor sleeper. EDS was positively correlated with advanced Hoehn and Yahr stages and use of dopamine agonists but not with levodopa daily dosage and levodopa equivalent daily dosage.ConclusionsTaiwanese patients with PD had a lower prevalence of EDS compared with the literatures reported in Caucasian patients. We identify and suggest that PDSS total score, rather than subcategory items, should be used to predict poor sleep among patients with PD.
Efficacy of biological response modifier lentinan with chemotherapy for advanced cancer: a meta‐analysis
Authors: Wang Hui , Cai Yong , Zheng Yue , Bai Qixuan , Xie Dongling , Yu Jiufei 
Published: September 2017

AbstractLentinan is a common biological response modifier. This study was sought to evaluate the efficacy of adjuvant lentinan combined with chemotherapy for advanced cancer. A meta‐analysis of published prospective controlled trials investigating the effects of lentinan for kinds of advanced cancer was performed. Sensitivity analysis, inverted funnel plots, and trial sequence analysis were conducted to explore the reliability and stability of results. Seventeen clinical studies were identified containing 1423 patients. Twelve trials included gastrointestinal cancer (GIC), three trials included lung cancer (LC), and two trials included the two cancers. There was a increase in survival rate in 1 year (risk ratios [RR], 1.46, P = 0.001) and overall response rate including both complete and partial response (RR, 1.28, P = 0.005). There was also a reduction in progressive disease (RR, 0.57, P = 0.0005), nonsevere adverse events (RR, 0.88, P = 0.004), and severe adverse events (RR, 0.73, P = 0.007). Similar results were shown in the two subgroups of GIC and LC. Limited trials reported the data of median overall survival and time to treatment failure, and the data were insufficient for quantitative analysis, and no significant difference were found in 2‐year survival rate. Adjuvant lentinan used with chemotherapy achieved improvements in 1‐year survival rate, response rate, and adverse events in advanced cancer. The effect seemed to be similar irrespective of cancer type. However, its sustained efficacy on survival was still unclear.
Expression of P62 in hepatocellular carcinoma involving hepatitis B virus infection and aflatoxin B1 exposure
Authors: Xiang Xiao , Qin Hong‐Gui , You Xue‐Mei , Wang Yan‐Yan , Qi Lu‐Nan , Ma Liang , Xiang Bang‐De , Zhong Jian‐Hong , Li Le‐Qun 
Published: September 2017

AbstractThis study aims to clarify the relationship and mechanism between expression of autophagy‐related protein P62 and prognosis of patients with hepatocellular carcinoma (HCC) involving chronic hepatitis B virus (HBV) infection and aflatoxin B1 (AFB1) exposure. HCC patients who underwent resection were divided into three groups: HBV(+)/AFB1(+) (n = 26), HBV(+)/AFB1(−) (n = 68), and HBV(−)/AFB1(−) (n = 14). The groups were compared in terms of mRNA and protein levels of P62, disease‐free survival (DFS), and overall survival (OS) and the expression of NRF2, Nqo1, and AKR7A3 in P62 high‐expression and low‐expression group. HBV(+)/AFB1(+) group has lower DFS and OS, and higher P62 expression than in the other two groups. P62 expression generally correlated with elevated NRF2 and Nqo1 expression, and reduced AKR7A3 expression. Patients expressing high levels of P62 showed significantly lower DFS and OS rates than patients expressing low levels. HCC involving HBV infection and AFB1 exposure is associated with relatively high risk of tumor recurrence, and this poor prognosis may relate to high P62 expression. High P62 expression activates the NRF2 pathway, promotes tumor recurrence. The downregulation of AKR7A3 also reduced liver detoxification of aflatoxin B1.
Metabolomic and transcriptomic profiling of hepatocellular carcinomas in Hras12V transgenic mice
Authors: Fan Tingting , Rong Zhuona , Dong Jianyi , Li Juan , Wang Kangwei , Wang Xinxin , Li Huiling , Chen Jun , Wang Fujin , Wang Jingyu , Wang Aiguo 
Published: September 2017

AbstractActivation of the Ras/MAPK pathway is prevalently involved in the occurrence and development of hepatocellular carcinoma (HCC). However, its effects on the deregulated cellular metabolic processes involved in HCC in vivo remain unknown. In this study, a mouse model of HCC induced by hepatocyte‐specific expression of the Hras12V oncogene was investigated using an integrative analysis of metabolomics and transcriptomics data. Consistent with the phenotype of abundant lipid droplets in HCC, the lipid biosynthesis in HCC was significantly enhanced by (1) a sufficient supply of acetyl‐CoA from enhanced glycolysis and citrate shuttle activity; (2) a sufficient supply of NADPH from enhanced pentose phosphate pathway (PPP) activity; (3) upregulation of key enzymes associated with lipid biosynthesis; and (4) downregulation of key enzymes associated with bile acid biosynthesis. In addition, glutathione (GSH) was significantly elevated, which may result from a sufficient supply of 5‐oxoproline and L‐glutamate as well as an enhanced reduction in the process of GSSG being turned into GSH by NADPH. The high level of GSH along with elevated Bcl2 and Ucp2 expression may contribute to a normal level of reactive oxygen species (ROS) in HCC. In conclusion, our results suggest that the lipid metabolism, glycolysis, PPP, tricarboxylic acid (TCA) cycle, citrate shuttle activity, bile acid synthesis, and redox homeostasis in the HCC induced by ras oncogene are significantly perturbed, and these altered metabolic processes may play crucial roles in the carcinogenesis, development, and pathological characteristics of HCC.
Preanalytical blood sample workup for cell‐free DNA analysis using Droplet Digital PCR for future molecular cancer diagnostics
Authors: van Ginkel Joost H. , van den Broek Daan A. , van Kuik Joyce , Linders Dorothé , de Weger Roel , Willems Stefan M. , Huibers Manon M. H. 
Published: September 2017

AbstractIn current molecular cancer diagnostics, using blood samples of cancer patients for the detection of genetic alterations in plasma (cell‐free) circulating tumor DNA (ctDNA) is an emerging practice. Since ctDNA levels in blood are low, highly sensitive Droplet Digital PCR (ddPCR) can be used for detecting rare mutational targets. In order to perform ddPCR on blood samples, a standardized procedure for processing and analyzing blood samples is necessary to facilitate implementation into clinical practice. Therefore, we assessed the technical sample workup procedure for ddPCR on blood plasma samples. Blood samples from healthy individuals, as well as lung cancer patients were analyzed. We compared different methods and protocols for sample collection, storage, centrifugation, isolation, and quantification. Cell‐free DNA (cfDNA) concentrations of several wild‐type targets and BRAF and EGFR‐mutant ctDNA concentrations quantified by ddPCR were primary outcome measurements. Highest cfDNA concentrations were measured in blood collected in serum tubes. No significant differences in cfDNA concentrations were detected between various time points of up to 24 h until centrifugation. Highest cfDNA concentrations were detected after DNA isolation with the Quick cfDNA Serum & Plasma Kit, while plasma isolation using the QIAamp Circulating Nucleic Acid Kit yielded the most consistent results. DdPCR results on cfDNA are highly dependent on multiple factors during preanalytical sample workup, which need to be addressed during the development of this diagnostic tool for cancer diagnostics in the future.
Strong antitumor efficacy of a pancreatic tumor‐targeting oncolytic adenovirus for neuroendocrine tumors
Authors: Yamamoto Yuki , Nagasato Masaki , Rin Yosei , Henmi Marina , Ino Yoshinori , Yachida Shinichi , Ohki Rieko , Hiraoka Nobuyoshi , Tagawa Masatoshi , Aoki Kazunori 
Published: September 2017

AbstractAlthough oncolytic adenoviruses are promising cancer therapy agents, for effective oncolytic activity, viruses need to specifically infect and effectively replicate in cancer cells but not in normal cells. We have previously identified a pancreatic cancer‐targeting ligand, SYENFSA (SYE), by screening an adenovirus library displaying random peptides against human pancreatic cancer cells and reported that a survivin promoter‐regulated adenovirus, displaying the SYE ligand (AdSur‐SYE), provided effective oncolysis of pancreatic ductal adenocarcinoma (PDAC) in a preclinical study. As we examined the infectivity of AdSur‐SYE in human surgical specimens of various pancreatic tumors, we unexpectedly found that AdSur‐SYE showed high gene transduction efficiency for pancreatic neuroendocrine tumors (PNETs) as well as for PDAC, 9.1‐ and 6.2‐fold, respectively, compared to that of the nontargeting virus (AdSur). The infectivity of both vectors was almost the same in other cancers and organs such as the pancreas. Immunostaining indicated that the cells infected with AdSur‐SYE were PNET cells but not stromal cells. AdSur‐SYE showed a significantly higher oncolytic potency than that of AdSur in human PNET cell lines, and intratumoral infection with AdSur‐SYE completely diminished subcutaneous tumors in a murine model, in which AdSur‐SYE effectively proliferated and spread. AdSur‐SYE exerted a stronger oncolytic effect in primary PNET cells cocultured with mouse embryonic fibroblasts than AdSur did. Thus, AdSur‐SYE shows promise as a next‐generation therapy for PNET.
Ensuring faculty success in online competency‐based education programs
Authors: Newbold Curtis , Seifert Christine , Doherty Brooks , Scheffler Anthony , Ray April 
Published: September 2017

BackgroundThe growth of competency‐based programs means faculty are facing new challenges that require different institutional support than traditional programs.MethodThis article identifies how faculty roles are changing and discusses specific challenges for faculty in three diverse institutions, Rasmussen College, Westminster College, and Valdosta State University.Results and ConclusionThe article recommends actions institutions can implement to better support CBE faculty.