bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vedolizumab use is not associated with increased malignancy incidence: GEMINI LTS study results and post‐marketing data
Authors: Card Timothy , Ungaro Ryan , Bhayat Fatima , Blake Aimee , Hantsbarger Gary , Travis Simon 
Published: November 2019

SummaryBackgroundVedolizumab is a gut‐selective antibody to α4β7 integrin approved to treat moderate‐to‐severe Crohn's disease and ulcerative colitis in adults. Inflammatory bowel disease (IBD) and immunosuppressant use are associated with increased risk of malignancy.AimTo analyse the incidence of malignancy with vedolizumab treatment in the GEMINI long‐term safety (LTS) study and post‐marketing (PM) setting.MethodsMalignancy data from the LTS study (May 2009 to May 2018), and data from the vedolizumab Global Safety Database (20 May 2014 to 19 May 2018), were identified using Medical Dictionary for Regulatory Activities coding. The number of patients experiencing malignancies in the LTS study (excluding malignancies within 1 year following vedolizumab initiation) was indirectly standardised against the number expected, using age‐ and sex‐specific rates in patients with IBD from Optum's Clinformatics™ Data Mart (CDM) database.ResultsAmong 1785 patients with ≥1 year of follow‐up post‐vedolizumab initiation in the LTS study (total 5670 patient‐years), observed numbers of malignancies were similar to those expected compared with CDM data (31 vs 29; ratio of observed to expected events = 1.08; P = 0.71; 95% confidence intervals [CI] 0.73, 1.53). The most common malignancies were renal and bladder (6). PM, 293 patients reported 299 malignancies (including malignancies within 1 year following vedolizumab initiation), in approximately 208 050 patient‐years of vedolizumab exposure. Lower gastrointestinal malignancies were most common (59).ConclusionsThe number of malignancies in the LTS study was similar to that expected from an IBD population with no statistically significant differences, although few confounders could be corrected for. Limitations of PM safety reporting require consideration; however, the number of malignancies with vedolizumab appeared low.
Population pharmacokinetic modeling of plasma Δ9‐tetrahydrocannabinol and an active and inactive metabolite following controlled smoked cannabis administration
Authors: Sempio Cristina , Huestis Marilyn A. , Mikulich‐Gilbertson Susan K. , Klawitter Jost , Christians Uwe , Henthorn Thomas K. 
Published: November 2019

AimsPopulation pharmacokinetic models of Δ9‐tetrahydrocannabinol (THC) have been developed for THC plasma and blood concentration data. Often, only the metabolites of THC are measurable when blood samples are obtained. Therefore, we performed a population pharmacokinetic analysis of THC, 11‐OH‐THC and THCCOOH plasma concentration data from a Phase I clinical trial of THC smoking.MethodsFrequently obtained plasma THC, 11‐OH‐THC and THCCOOH concentration data were obtained over 168 h from 6 subjects who smoked low (15.8 mg) and high dose (33.8 mg) THC cigarettes on 2 occasions. Bayesian estimates of the THC pharmacokinetic model from each individual for each dose were fixed prior to the sequential pharmacokinetic analysis of the metabolites.ResultsA 3‐compartment model of THC was developed that has a steady‐state volume of distribution (VdSS) of 3401 ± 788 L and a clearance of 0.72 ± 0.10 L/min. 11‐OH‐THC was characterized by 50 ± 6% of the THC being directly cleared to a 3‐compartment model with a VdSS of 415.2 ± 4.3 L and clearance of 0.78 ± 0.05 L/min. The THCCOOH model shared the central compartment of the 11‐OH‐THC model with a VdSS of 29.1 ± 0.05 L and a clearance of 0.12 ± 0.02 L/min. First order kinetics were observed for THC and THCCOOH between the low and high doses, but a nonlinear pattern was observed for 11‐OH‐THC.ConclusionWe describe the pharmacokinetics of THC, 11‐OH‐THC and THCCOOH including inter‐ and intraindividual variability of the parameter estimates of the model.
P7TP3 inhibits tumor development, migration, invasion and adhesion of liver cancer through the Wnt/β‐catenin signaling pathway
Authors: Zhao Jing , Wang Yun , Han Ming , Lu Hongping , Chen Xiaofan , Liu Shunai , Yuan Xiaoxue , Han Kai , Liang Pu , Cheng Jun 
Published: November 2019

AbstractThe effect of hepatitis C virus p7 trans‐regulated protein 3 (P7TP3) in the development of hepatocellular carcinoma (HCC) is still unknown. The present study aimed to investigate the role and mechanism of P7TP3 in HCC. P7TP3 was significantly decreased in HCC tissues when compared with corresponding liver tissues immediately around the tumor (LAT) from seven HCC patients. Fewer and smaller colonies originated from HepG2‐P7TP3 cells when compared to HepG2‐NC cells. Overexpression of P7TP3 in HepG2 cells significantly repressed the growth of HCC xenografts in nude mice. Furthermore, wound‐healing tests, Transwell assays, Matrigel Transwell assays, adhesion assays, CCK‐8 assays, flow cytometry and western blotting analysis showed that P7TP3 protein expression inhibited migration, invasion, adhesion, proliferation and cell cycle progression in HCC cell lines. Moreover, P7TP3 suppressed the activity of the Wnt/β‐catenin signaling pathway, and was restored by Wnt3a, which is an activator of the Wnt/β‐catenin signaling pathway. Consistently, β‐catenin was highly expressed by P7TP3 silencing, and restored by XAV939, an inhibitor of the Wnt/β‐catenin signaling pathway. Finally, microRNA (miR)‐182‐5p suppressed the expression of target gene P7TP3 by directly interacting with the 3′‐UTR region. Taken together, P7TP3, the direct target gene of miR‐182‐5p, inhibited HCC by regulating migration, invasion, adhesion, proliferation and cell cycle progression of liver cancer cell through the Wnt/β‐catenin signaling pathway. These findings provide strong evidence that P7TP3 functions as a new promising tumor suppressor in HCC.
Lactate‐fueled oxidative metabolism drives DNA methyltransferase 1‐mediated transcriptional co‐activator with PDZ binding domain protein activation
Authors: Huang Tao , Zhou Xinglu , Mao Xike , Yu Chenxi , Zhang Zhijian , Yang Jianke , Zhang Yao , Su Tianyu , Chen Chenchen , Cao Yuxiang , Wei Huijun , Wu Zhihao 
Published: November 2019

AbstractActivity of transcriptional co‐activator with PDZ binding domain (TAZ) protein is strongly implicated in the pathogenesis of human cancer and is influenced by tumor metabolism. High levels of lactate concentration in the tumor microenvironment as a result of metabolic reprogramming are inversely correlated with patient overall survival. Herein, we investigated the role of lactate in the regulation of the activity of TAZ and showed that glycolysis‐derived lactate efficiently increased TAZ expression and activity in lung cancer cells. We showed that the reactive oxygen species (ROS) generated by lactate‐fueled oxidative phosphorylation (OXPHOS) in mitochondria activated AKT and thereby inhibited glycogen synthase kinase 3 beta/beta‐transducin repeat‐containing proteins (GSK‐3β/β‐TrCP)‐mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1). Upregulation of DNMT1 by lactate caused hypermethylation of TAZ negative regulator of the LATS2 gene promoter, leading to TAZ activation. Moreover, TAZ binds to the promoter of DNMT1 and is necessary for DNMT1 transcription. Our study showed a molecular mechanism of DNMT1 in linking tumor metabolic reprogramming to the Hippo‐TAZ pathway and functional significance of the DNMT1‐TAZ feedback loop in the migratory and invasive potential of lung cancer cells.
On Demand Solid Texture Synthesis Using Deep 3D Networks
Authors: Gutierrez J. , Rabin J. , Galerne B. , Hurtut T. 
Published: November 2019

AbstractThis paper describes a novel approach for on demand volumetric texture synthesis based on a deep learning framework that allows for the generation of high‐quality three‐dimensional (3D) data at interactive rates. Based on a few example images of textures, a generative network is trained to synthesize coherent portions of solid textures of arbitrary sizes that reproduce the visual characteristics of the examples along some directions. To cope with memory limitations and computation complexity that are inherent to both high resolution and 3D processing on the GPU, only 2D textures referred to as ‘slices’ are generated during the training stage. These synthetic textures are compared to exemplar images via a perceptual loss function based on a pre‐trained deep network. The proposed network is very light (less than 100k parameters), therefore it only requires sustainable training (i.e. few hours) and is capable of very fast generation (around a second for 2563 voxels) on a single GPU. Integrated with a spatially seeded pseudo‐random number generator (PRNG) the proposed generator network directly returns a color value given a set of 3D coordinates. The synthesized volumes have good visual results that are at least equivalent to the state‐of‐the‐art patch‐based approaches. They are naturally seamlessly tileable and can be fully generated in parallel.
Bone‐implant‐contact and new bone formation around implants placed in FDB blocks compared to placement at the adjunction of particulate FDB
Authors: Anavi Lev Karen , Chaushu Liat , Schwarz Frank , Artzi Zvi 
Published: November 2019

AbstractBackgroundThe efficacy of human freeze‐dried bone (h‐FDB) as particulate vs block forms as a proper onlay augmented bone graft material to accommodate implants is undetermined.PurposeTo evaluate osseointegration and new bone formation at implants placed in FDB blocks (BL group) and those at the adjunction of particulate FDB (PR group).Materials and MethodsTwelve pairs of h‐FDB blocks were stabilized bilaterally to the calvaria of 12 rabbits. Twenty‐four SLA implants were placed at the remodeled grafted blocks, 4 months later. A circumferential gap was created around one implant in each pair and packed with particulate h‐FDB. Section biopsies were obtained at 2‐month post implant placement (6 months post‐block grafting). Bone‐to‐implant contact (BIC) and bone‐area fraction (BAF) were histomorphometrically calculated.ResultsThe mean BIC was 34.4% and 33.5% for the BL and PR groups, respectively. The mean BAF was 23.9% and 26.4% for the corresponding groups, respectively. Osseointegration and newly formed bone were evident mostly between the threaded portions of the implants in proximity to the host rabbit calvaria compared to its cervical neck.ConclusionThe particulate and the cancellous block h‐FDB forms yielded similar BIC and BAF outcome. Full revascularization/revitalization is questioned.
Watershed complexity increases the capacity for salmon–wildlife interactions in coastal ecosystems
Authors: Armstrong Jonathan B. , Schindler Daniel E. , Cunningham Curry J. , Deacy William , Walsh Patrick 
Published: November 2019

AbstractHabitat alteration and species exploitation are fundamental issues in conservation, yet their interacting effects on food webs are rarely considered. We used a foraging model based on the Wood River basin (Alaska, USA) to explore how watershed development and commercial fisheries affect energy flow from sockeye salmon to brown bears. We found that, where salmon are abundant, fisheries can harvest large fractions of runs without substantially reducing bear consumption of salmon, but that watershed development could strongly reduce bear consumption if it shortens the duration of foraging opportunities by reducing population‐level variation in salmon spawn timing. Habitats with the lowest resource abundance (small streams) were particularly profitable for bear foraging because they offer salmon at unique times of the season. This result challenges environmental impact assessments that assume ecological effects respond solely to changes in resource abundance.
Blockade of adrenergic β‐receptor activation through local delivery of propranolol from a 3D collagen/polyvinyl alcohol/hydroxyapatite scaffold promotes bone repair in vivo
Authors: Wu Hao , Song Yue , Li Junqin , Lei Xing , Zhang Shuaishuai , Gao Yi , Cheng Pengzhen , Liu Bin , Miao Sheng , Bi Long , Yang Liu , Pei Guoxian 
Published: November 2019

AbstractObjectivesActivation of the sympathetic system and adrenergic β‐receptors following traumatic bone defects negatively impairs bone regeneration. Whether preventing β‐receptor activation could potentially improve bone defect repair is unknown. In this study, we investigated the effect of systematic administration and local delivery of propranolol through composite scaffolds on bone healing.Materials and methodsCollagen/PVA/propranolol/hydroxyapatite（CPPH）composite scaffolds were fabricated with 3D printing technique and characterized by scanning electron microscope (SEM). Micro‐CT analysis and bone formation histology were performed to detect new bone formation. Osteogenic differentiation of bone marrow stromal cells (BMSCs) and osteoclastogenesis of bone marrow monocytes cultured with scaffolds extract were performed for further verification.ResultsIntraperitoneal injection of propranolol did not significantly improve bone repair, as indicated by micro‐CT analysis and bone formation histology. However, CPPH scaffolds exhibited sustained release of propranolol in vitro and significantly enhanced bone regeneration compared with vehicle collagen/PVA/hydroxyapatite (CPH) scaffolds in vivo. Moreover, in vitro experiments indicated the scaffolds containing propranolol promoted the osteogenic differentiation and migration of rat BMSCs and inhibited osteoclastogenesis by preventing β‐receptor activation.ConclusionsThis study demonstrates that local adrenergic β‐receptor blockade can effectively enhance the treatment of bone defects by stimulating osteogenic differentiation, inhibiting osteoclastogenesis and enhancing BMSCs migration.
Coagulation factor IV is an indicator of symptomatic pulmonary embolism in patients with primary lung cancer
Authors: Xiong Wei , Zhao Yunfeng , Xiong Yifan , Xu Mei , Pudasaini Bigyan , Du He , Guo Xuejun 
Published: November 2019

AbstractBackgroundCoagulation factor IV, also known as serum ionised calcium (SIC), participates in coagulative process and tends to elevate in patients with primary lung cancer. It may be an indicator of symptomatic pulmonary embolism (PE) due to primary lung cancer (LC).MethodsA total of 388 patients who underwent CTPA and/or radionuclide ventilation perfusion scanning due to PE‐suspected symptoms were stratified into LCPE (lung cancer and PE) group (n = 95), PE group (n = 99), LC group (n = 98) and control group (n = 96). At admission, the level of SIC and STC (serum total calcium) was compared among four groups. At discharge, the level change of SIC and STC from admission to discharge was compared among four groups. The coefficients analysis between SIC as well as STC and the possibility of PE were performed.ResultsThe SIC of LCPE group was the highest among four groups at admission (P < 0.001). The level change of SIC from admission to discharge in LCPE group was the highest among four groups (P = 0.001). A ROC curve analysis demonstrated that the sensitivity and specificity of SIC for a diagnosis of PE among LC patients were 71.9% and 86.0%, respectively. The area under curve (AUC) was 0.781. Along with the increase of 0.1 mmol/L in SIC level, the risk ratio for a PE was 2.165 (1.537‐2.849) (P < 0.001).ConclusionsSerum ionised calcium may be an indicator of pulmonary embolism in patients with primary lung cancer.
Assessing the limit of detection of Fourier‐transform infrared spectroscopy and immunoassay strips for fentanyl in a real‐world setting
Authors: McCrae Karen , Tobias Samuel , Grant Cameron , Lysyshyn Mark , Laing Richard , Wood Evan , Ti Lianping 
Published: November 2019

AbstractIntroduction and AimsDrug checking is a harm reduction intervention increasingly used in the context of the opioid overdose epidemic. The aim of the study was to determine the limit of detection for fentanyl of two point‐of‐care drug checking technologies.Design and MethodsSamples tested at point‐of‐care using Bruker Fourier transform infrared (FTIR) spectroscopy and BTNX fentanyl immunoassay strips were sent for confirmatory laboratory analysis using quantitative nuclear magnetic resonance (qNMR) spectroscopy. Concentrations by weight were determined and compared to results obtained with point‐of‐care methods.ResultsIn total, 283 samples were sent for qNMR analysis; among these, 173 (61.1%) tested positive for fentanyl. As determined by qNMR, fentanyl concentration by weight ranged from 1% to 91%. Among these 173 samples, fentanyl was not detected in 30 (17.3%) samples by FTIR and in 4 (2.3%) samples by test strip. Samples containing fentanyl that went undetected by FTIR had concentrations ≤10%. The four samples containing fentanyl that went undetected by test strip had concentrations ≤5% (i.e. 1%, 3%, 4%, 5%).Discussion and ConclusionsFentanyl immunoassay strips were able to consistently detect the presence of fentanyl in samples at lower concentrations than FTIR spectroscopy. Given that FTIR spectroscopy is able to quantify content, mixture and concentrations on an array of compounds beyond just fentanyl but requires concentrations generally greater than 10%, these findings provide evidence for use of FTIR spectroscopy and immunoassay strips in combination to compensate for the limitations of each technology alone.
Interest rate risk of life insurers: Evidence from accounting data
Authors: Möhlmann Axel 
Published: November 2019

AbstractLife insurers are exposed to interest rate risk as their liability side is typically more sensitive to interest rate changes than their asset side. This paper explores why insurers assume this risk using a new accounting‐based method to measure the interest rate sensitivity of assets and liabilities. Calculation at the insurer level yields a wide duration gap with pronounced heterogeneity in the cross‐section. This could be explained by alternative investment strategies, such as asset insulation, which are at odds with interest rate risk management. Using a 2014–2018 panel, factors associated with interest rate risk support this view.
Grazing intensity significantly changes the C : N : P stoichiometry in grassland ecosystems
Authors: He Miao , Zhou Guiyao , Yuan Tengfei , van Groenigen Kees Jan , Shao Junjiong , Zhou Xuhui 
Published: November 2019

AbstractAimLivestock grazing can alter carbon (C), nitrogen (N) and phosphorus (P) cycles, thereby affecting the C : N : P stoichiometry in grasslands. In this study, we aimed to examine mechanisms underlying the impacts of grazing on grassland C : N : P stoichiometry, focusing on belowground processes and their linkages with aboveground vegetation properties.LocationGlobal.Time period1900–2018.Major taxa studiedGrassland ecosystems.MethodsWe conducted a meta‐analysis based on 129 published studies to synthesize the effects of grazing on the C : N : P stoichiometry of leaves, stems, litter, roots, microbial biomass, and soil in grassland ecosystems.ResultsGrazing significantly affected the C, N and P pools, and then the C : N : P stoichiometry in grassland ecosystems. Grazing effects on C : N : P stoichiometry varied strongly with grazing intensity. Specifically, heavy grazing decreased all C : N : P stoichiometry except litter N : P and root C : N ratios, while light and moderate grazing caused less negative or positive effects. Grazing effects on litter C : N ratio were negatively correlated with grazing effects on soil C : N ratios under light and moderate grazing, but this relationship was positive under heavy grazing. In contrast, grazing effects on root C : P and soil C : P were positively correlated under light and moderate grazing but negatively correlated under heavy grazing. Importantly, grazing significantly decreased the soil N pool by 10.0% but increased the soil P pool by 3.6%, indicating differential mechanisms for grazing impact on N and P cycles in grasslands.Main conclusionsOur results strongly suggest that grazing intensity regulates the biogeochemical cycles of C, N and P in grassland ecosystems by affecting plant nutrient use efficiency and soil physicochemical processes. Therefore, incorporating grazing intensity into Earth system models may improve predictions of climate–grassland feedbacks in the Anthropocene.
Basic survey for the prevention of intraoral residual medication in older adults: A pilot study
Authors: Hasegawa Yoko , Sakuramoto-Sadakane Ayumi , Yoshida Mitsuyoshi , Yoshikawa Mineka , Nozaki Sonoko , Hikasa Shinichi , Horii Nobuhide , Sugita Hideyuki , Ono Takahiro , Shinmura Ken , Kishimoto Hiromitsu 
Published: November 2019

AbstractObjectiveThis study aimed to assess the relationship between oral hygiene/stomatognathic function and residual intraoral medication in older adults and to identify the oral factors associated with residual oral medication.MethodsThe study included 309 older adults (77 men, 232 women, mean age: 74.1 ± 7.4 years) who were prescribed medications at regular intervals. The following survey items were assessed: overall physical condition, intraoral condition and oral function. Participants prescribed oral medication were classified into groups with and without residual medication in the oral cavity. Statistical analysis was performed using univariate analysis for each of the factors contributing to the presence of residual medication.ResultsOnly 1.9% of all patients had residual medication, which suggests that older adults in this survey had a low risk of residual intraoral medication. However, greater attention should be given to residual intraoral medication in older adults receiving long‐term care. Powdered‐form oral medications were more likely to remain in the oral cavity. Older adults with residual medication had a tendency to have less occlusal support, poor tongue hygiene and poor tongue movement. Oral function, particularly functions that are closely related to swallowing, was significantly lower in the residual intraoral medication group when compared to those of the group without residual intraoral medication.ConclusionsReduced oral function and powered medication were associated with greater residual intraoral medication in this sample of older Japanese adults.
Influence of oral health literacy on dissatisfaction with oral health among older people
Authors: Tenani Carla Fabiana , De Checchi Maria Helena Ribeiro , Bado Fernanda Maria Rovai , Ju Xiangqun , Jamieson Lisa , Mialhe Fábio Luiz 
Published: November 2019

AbstractObjectiveTo investigate the influence of oral health literacy (OHL) and associated factors on dissatisfaction with oral health (DOH) among older people.BackgroundOral health literacy is a recent field of research that has been considered an important mediator between socioeconomic variables and oral health outcomes. However, there are few studies with older people.Materials and methodsA cross‐sectional study was conducted with 535 non‐institutionalised older people aged 60‐100 years from Brazil. Individuals completed a questionnaire on general health, sociodemographic information and usual reason for dental visit. OHL was assessed using the Health Literacy in Dentistry questionnaire (HeLD‐14), validated in Brazil. DOH was the outcome of interest. Poisson regression with robust standard errors was applied as a statistical model to estimate bivariate and multivariable relationships of DOH with OHL after adjusting for sex, age, social characteristics and general health using the P‐value of ≤ .05.ResultsThe overall prevalence of DOH was 21.1%. Multivariable regression analysis showed that older people with low OHL (HeLD‐14 score ≤35) had 1.28 times the odds of having DOH than those with high OHL (HeLD14 score >46), after adjusting for sociodemographic, economic and health outcomes.ConclusionsDissatisfaction with oral health in older people is a complex issue associated with OHL, social and behavioural factors. Health services should give greater attention to developing health literacy competences in older adults in order to empower them to achieve optimal oral health.