bluuebunny/crossref_metadata_2025_split huggingface dataset:
Near‐infrared spectroscopy is a promising noninvasive technique for monitoring the effects of feeding regimens on the cerebral and splanchnic regions
Authors: Grometto Alice , Pizzo Benedetta , Strozzi Maria Chiara , Gazzolo Francesca , Gazzolo Diego 
Published: September 2017

AbstractAimThe effects of different milk and, or, administration regimens on cerebro‐splanchnic perfusion are still a matter of debate. We investigated the effects of the bolus administration of breast milk or formula on cerebro‐splanchnic oximetry, function and perfusion, assessed by near‐infrared spectroscopy (NIRS).MethodsThis observational study of 30 infants fed with breast (n = 15) or formula (n = 15) milk, and matched for gestational age and birth weight, was carried out in the neonatal intensive care unit of the C Arrigo Children's Hospital, Alessandria, Italy, a tertiary‐level referral centre, from October 2015 to December 2016. NIRS monitoring parameters, such as cerebral and splanchnic oximetry, fraction of tissue oxygen extraction and the cerebral–splanchnic ratio, were recorded before, during and after feeding.ResultsBreast milk led to a significant increase in cerebro‐splanchnic oximetry and tissue oxygen extraction (p < 0.001) during and after feeding, and the cerebro‐splanchnic perfusion ratio was significantly higher (p < 0.001) in the breast than formula group.ConclusionOur study results suggest that breast milk was better tolerated than formula, requiring lower energy expenditure and lower cerebro‐splanchnic haemodynamic redistribution. The findings could prompt investigations using NIRS as a promising noninvasive tool for cerebral and splanchnic longitudinal monitoring during neonatal feeding.
Population pharmacodynamic modelling of midazolam induced sedation in terminally ill adult patients
Authors: Franken Linda G. , de Winter Brenda C. M. , Masman Anniek D. , van Dijk Monique , Baar Frans P. M. , Tibboel Dick , Koch Birgit C. P. , van Gelder Teun , Mathot Ron A. A. 
Published: September 2017

AimsMidazolam is the drug of choice for palliative sedation and is titrated to achieve the desired level of sedation. A previous pharmacokinetic (PK) study showed that variability between patients could be partly explained by renal function and inflammatory status. The goal of this study was to combine this PK information with pharmacodynamic (PD) data, to evaluate the variability in response to midazolam and to find clinically relevant covariates that may predict PD response.MethodA population PD analysis using nonlinear mixed effect models was performed with data from 43 terminally ill patients. PK profiles were predicted by a previously described PK model and depth of sedation was measured using the Ramsay sedation score. Patient and disease characteristics were evaluated as possible covariates. The final model was evaluated using a visual predictive check.ResultsThe effect of midazolam on the sedation level was best described by a differential odds model including a baseline probability, Emax model and interindividual variability on the overall effect. The EC50 value was 68.7 μg l–1 for a Ramsay score of 3–5 and 117.1 μg l–1 for a Ramsay score of 6. Comedication with haloperidol was the only significant covariate. The visual predictive check of the final model showed good model predictability.ConclusionWe were able to describe the clinical response to midazolam accurately. As expected, there was large variability in response to midazolam. The use of haloperidol was associated with a lower probability of sedation. This may be a result of confounding by indication, as haloperidol was used to treat delirium, and deliria has been linked to a more difficult sedation procedure.
Experimental Design for Multi-drug Combination Studies Using Signaling Networks
Authors: Huang Hengzhen , Fang Hong-Bin , Tan Ming T. 
Published: September 2017

SummaryCombinations of multiple drugs are an important approach to maximize the chance for therapeutic success by inhibiting multiple pathways/targets. Analytic methods for studying drug combinations have received increasing attention because major advances in biomedical research have made available large number of potential agents for testing. The preclinical experiment on multi-drug combinations plays a key role in (especially cancer) drug development because of the complex nature of the disease, the need to reduce development time and costs. Despite recent progresses in statistical methods for assessing drug interaction, there is an acute lack of methods for designing experiments on multi-drug combinations. The number of combinations grows exponentially with the number of drugs and dose-levels and it quickly precludes laboratory testing. Utilizing experimental dose–response data of single drugs and a few combinations along with pathway/network information to obtain an estimate of the functional structure of the dose–response relationship in silico, we propose an optimal design that allows exploration of the dose–effect surface with the smallest possible sample size in this article. The simulation studies show our proposed methods perform well.
Fully Bayesian Spectral Methods for Imaging Data
Authors: Reich Brian J. , Guinness Joseph , Vandekar Simon N. , Shinohara Russell T. , Staicu Ana-Maria 
Published: September 2017

Summary
Medical imaging data with thousands of spatially correlated data points are common in many fields. Methods that account for spatial correlation often require cumbersome matrix evaluations which are prohibitive for data of this size, and thus current work has either used low-rank approximations or analyzed data in blocks. We propose a method that accounts for nonstationarity, functional connectivity of distant regions of interest, and local signals, and can be applied to large multi-subject datasets using spectral methods combined with Markov Chain Monte Carlo sampling. We illustrate using simulated data that properly accounting for spatial dependence improves precision of estimates and yields valid statistical inference. We apply the new approach to study associations between cortical thickness and Alzheimer's disease, and find several regions of the cortex where patients with Alzheimer's disease are thinner on average than healthy controls.
Treatment of gastric eosinophilia by epicutaneous immunotherapy in piglets sensitized to peanuts
Authors: Mondoulet L. , Kalach N. , Dhelft V. , Larcher T. , Delayre‐Orthez C. , Benhamou P. H. , Spergel J. , Sampson H. A. , Dupont C. 
Published: September 2017

SummaryBackgroundEosinophilic gastrointestinal disorders (EGIDs) are hypersensitivity disorders frequently triggered by food allergy and manifested by mucosal eosinophilic infiltration at any level of the gastrointestinal tract. This study established a model of gastric eosinophilia in peanut‐sensitized piglets to evaluate the efficacy of epicutaneous immunotherapy (EPIT) for its treatment.MethodsExperiments were carried out in piglets first sensitized by three intra‐peritoneal injections of peanut protein extract (PPE) with adjuvant, and then given PPE orally for 10 days, a sequence leading to gastric eosinophilia assessed by endoscopy. For 3 months, eight piglets received active EPIT, using Viaskin® loaded with PPE, applied daily on the ear, while eight received placebo EPIT (Placebo). Piglets were exposed to a second 10‐day period of PPE orally. Lesions were scored by endoscopy on the last day of PPE exposure. After killing, all parts of the digestive tract were analysed by a pathologist unaware of the piglets’ status. IgE response was measured, and mechanistic parameters were analysed in the spleen.ResultsAfter sensitization, a significant increase of total IgE was observed in sensitized compared to naive animals (61.1 ± 13.3 vs 27.8 ± 6 ng/mL, P < .01). Following oral intake of PPE, sensitized piglets developed moderate gastritis compared to naive piglets (1.5 vs 1.0, median score). After 3 months of immunotherapy, median IgE was significantly reduced in EPIT vs placebo piglets (61.4 ± 16.3 vs 105.9 ± 25.6 ng/mL, P < .01). Active EPIT significantly reduced gastric mucosal lesions induced by PPE oral intake (macroscopic score 0 [0‐2] vs 2 [1‐3], P < .01, respectively, active vs placebo) and gastric mucosa eosinophils counts (239 eosinophils/mm2 [59‐645] vs 2554 eosinophils/mm2 [462‐8057], P < .01, respectively active vs placebo). GATA‐3, IL‐5 and eotaxin mRNA expression decreased significantly after EPIT (P < .05).ConclusionsThis study describes a large animal model of gastric eosinophil in peanut‐sensitized piglets. Utilizing this model, we demonstrated the efficacy of EPIT in treating peanut‐induced EGIDs.
Increased prevalence of fracture and hypoglycaemia in young adults with concomitant type 1 diabetes mellitus and coeliac disease
Authors: Thong Eleanor P. , Wong Phillip , Dev Anouk , Ebeling Peter R. , Teede Helena J. , Milat Frances 
Published: September 2017

SummaryBackgroundBoth Type 1 diabetes mellitus (T1DM) and coeliac disease (CD) are independently associated with reduced bone mineral density (BMD) and increased fracture risk. Whilst poorer glycaemic control and increased microvascular complications have been described, the literature examining bone health and fractures in adults with concomitant T1DM and CD (T1DM + CD) is limited.ObjectiveTo evaluate fracture prevalence and explore associations with glycaemic control, hypoglycaemia and microvascular disease in T1DM + CD compared with T1DM alone.MethodsWe conducted a retrospective cross‐sectional study of young adults with T1DM, who attended diabetes clinics at a large tertiary referral centre between August 2016 and February 2017. Clinical information, radiological and biochemistry results were extracted from medical records. Patients with comorbid chronic kidney disease, glucocorticoid use, hypogonadism and untreated hyperthyroidism were excluded.ResultsA total of 346 patients with T1DM alone (median age 23 years) and 49 patients with T1DM + CD (median age 24 years) were included. Median age, gender distribution, BMI, haemoglobin A1c, daily insulin dose and serum 25‐hydroxyvitamin D levels were similar between groups. Higher adjusted fracture risk was observed in T1DM + CD compared with T1DM (12.2% vs 3.5%; OR 3.50, 95% CI 1.01‐12.12, P = .01), yet BMD was only measured in 6% of patients. The adjusted risk of hypoglycaemia ≥2/week was greater for T1DM + CD (55% vs 38%, OR 3.28, 95% CI 1.61‐6.69, P = .001); however, this was not independently associated with fractures. Replete vitamin D (≥ 50 nmol/L) was associated with less hypoglycaemia (OR 0.48, 95% CI 0.29‐0.80; P = .005), but not with fractures.ConclusionsCoeliac disease status was independently associated with increased fracture prevalence in young adults with T1DM. Recurrent hypoglycaemia was also increased in T1DM + CD, although hypoglycaemia was not independently associated with fractures. Prospective studies are required to determine the long‐term impacts of CD on bone health and glycaemic control in patients with T1DM.
Utilization of high donor sequence number grafts in cardiac transplantation
Authors: Squiers John J. , DiMaio J. Michael , Saracino Giovanna , Qin Huanying , Felius Joost , Chamogeorgakis Themistokles , MacHannaford Juan C. , Rafael Aldo E. , Kale Parag , Joseph Susan M. , Hall Shelley A. , Gonzalez‐Stawinski Gonzalo V. , Lima Brian 
Published: September 2017

AbstractDonor sequence number (DSN) represents the number of candidates to whom a graft was offered and declined prior to acceptance for transplantation. We sought to investigate the outcomes of patients receiving high DSN grafts. Consecutive isolated adult cardiac transplantations performed at a single‐center were reviewed. Recipients were grouped into standard (≤75th percentile) DSN and high (>75th percentile) DSN. A previously validated donor risk index was used to quantify the risk associated with donor grafts, and recipient outcomes were assessed. Overall, 254 patients were included: 194 standard DSN (range 1‐79) and 60 high DSN (range 82‐1723). High DSN grafts were harvested at greater distance (P < .001) with increased ischemia time (P < .001), resulting in a modest increase in donor risk index (1 point median difference, P = .014). High DSN recipients were less frequently listed as UNOS status 1A (P < .001). Despite a nonsignificant trend toward increased in‐hospital/30‐day mortality in high DSN recipients, there were no differences in primary graft dysfunction or 1‐year survival (high DSN 89% vs standard DSN 88%, P = .82). After adjustment for risk factors, high DSN was not associated with increased 1‐year mortality (hazard ratio 1.18, 95%‐CI 0.54‐2.58, P = .68).
Epithelial oral mucosal cells: Do they behave differently when exposed to oral carcinogens?
Authors: da Silva A. D. , Daroit N. B. , Cardoso F. B. , Laureano N. K. , Maraschin B. J. , Bündrich L. , Danilevicz C. K. , Magnusson A. S. , Visioli F. , Rados P. V. 
Published: September 2017

ObjectiveTo assess the level of maturation and proliferation of epithelial cells and the correlation with immunocytochemical expression of adhesion (E‐cadherin) and cell differentiation (involucrin) markers.MethodsCytopathological samples were obtained from four groups of patients: control (CG, n=30); alcohol/tobacco (ATG, n=31), leucoplakia (LG, n=31), and squamous cell carcinoma (SCCG, n=22). Cytopathological smears were collected from all groups for AgNOR, Papanicolaou and immunocytochemical staining.ResultsThere was an increase in anucleated cells in ATG compared to CG and in LG compared to lesion‐free groups (P<.05). In addition, there was a higher rate of intermediate cells in lesion‐free groups than in LG (P=.001). When these findings were correlated with positive E‐cadherin expression, there was a smaller number of anucleated and intermediate cells (P<.05). The proliferation rate was higher in the SCCG than in the CG (P<.05) and in the ATG compared to LG (P<.05). Moreover, cell proliferation increased in the presence of positive E‐cadherin expression in the ATG and LG. No statistically significant results were obtained for involucrin analysis.ConclusionCytopathology combined with quantitative techniques such as Papanicolaou, AgNOR, and immunocytochemical expression of E‐cadherin detects changes associated with oral carcinogenesis. The innovative approach used in this study allows assessing the expression of cell adhesion (E‐cadherin) and differentiation (involucrin) markers by means of oral mucosal cytopathology. The E‐cadherin imunocytochemical expression indicated changes associated with the oral carcinogenesis process. An increase in cell proliferation rate in oral squamous cell carcinoma group was associated with the lower immunoexpression of E‐cadherin. Cytopathology combined with quantitative techniques and immunocytochemical expression of E‐cadherin may detect early alterations associated with oral carcinogenesis.
Influence of thickness, color, and polishing process of ethylene‐vinyl‐acetate sheets on surface roughness and microorganism adhesion
Authors: Almeida Mariane Hemerly , Ceschim Geovana Ventorim , Iorio Natalia Lopes Pontes Póvoa , Póvoa Helvécio Cardoso Corrêa , Cajazeira Marlus Roberto Rodrigues , Guimarães Glaucio Serra , Antunes Leonardo Santos , Antunes Lívia Azeredo Alves 
Published: September 2017

AbstractBackground/AimThe surface roughness of dental materials can make cleaning difficult, thus facilitating retention of food debris and accumulation of microorganisms. The aim of this study was to assess whether thickness, color, and the polishing process influence the surface roughness of ethylene‐vinyl‐acetate (EVA) sheets and the amount of microorganisms that adhere to them.Materials and MethodsA total of 180 samples of EVA (5 × 5 mm) were divided into 9 groups according to thickness (G1 = 2 mm; G2 = 3 mm; and G3 = 4 mm), color (G4 = black and G5 = white), and type of polishing (G6 = Scheu™; G7 = Scheu™ associated with hot‐air burner; G8 = Erkodent™ and G9 = Erkodent™ associated with hot‐air burner). Mean value of 3 roughness parameters was assessed: Ra, Rq, and Rz (one‐way ANOVA test and Tukey's test, P < .05). Seven samples of each group (n = 63) were inoculated with saliva for 2 hours to promote microbial adhesion and count the number of colony‐forming units (CFUs) (one‐way ANOVA test, P < .05). Scanning electron microscopy (SEM) of microbial adhesion and the effects of the polishing process on the surface was assessed.ResultsOnly the polishing parameter presented less roughness (G2, G7 and G9; P < .05) as also observed on SEM. SEM characterized microbial adhesion but the CFU count was not statistically significant, independent of the assessed parameters.ConclusionThe polishing systems, Scheu™ and Erkodent™ in association with a hot‐air burner, were effective in decreasing the surface roughness without influencing the amount of adhered microorganisms.
Effect of atrial fibrillation duration on plasma von Willebrand factor level
Authors: Wysokinski Waldemar E. , Cohoon Kevin P. , Konik Ewa A. , Melduni Rowlens M. , Ammash Naser M. , Asirvatham Samuel J. , McBane Robert D. 
Published: September 2017

AbstractAimsvon Willebrand factor (VWF) is an independent risk factor for adverse events in patients with non‐valvular atrial fibrillation (NVAF). However, it is unclear if VWF level remains elevated and predictive of stroke during entire course of NVAF.Methods and ResultsIn order to determine if VWF is a time‐dependent blood variable, VWF antigen measured by latex immunoassay in 425 NVAF patients and 100 controls with normal sinus rhythm (NSR) was analyzed according to NVAF duration (<1 month: n = 76, 1‐12 months: n = 98, and >12 months: n = 251). The mean VWF antigen level in NVAF patients with <1‐month duration (167 ± 59%) was not different compared to those with 1‐12 months (157 ± 50%, P = .24) and >12 months duration (156 ± 54%, P = .11) but higher compared to NSR controls (143 ± 48%, P = .003). Higher VWF level correlated with higher CHADS2 scores and with progressing intensity of blood stasis in the left atrium and thrombus formation in all three time periods of atrial fibrillation duration. Patients not treated with warfarin had VWF 30% higher in the first month compared to following months.Conclusionsvon Willebrand Factor is steadily elevated throughout the course of dysrhythmia in NVAF patients treated with warfarin and in those with higher intensity of left atrium blood stasis.
Eryptosis in autoimmune haemolytic anaemia
Authors: Bartolmäs Thilo , Mayer Beate , Balola Abdelwahab H. , Salama Abdulgabar 
Published: September 2017

AbstractObjectiveHaemolysis and anaemia related to autoimmune haemolytic anaemia (AIHA) of warm type (wAIHA) and of cold type (cAIHA) are believed to be solely due to antibody and/or complement‐mediated destruction and clearance of red blood cells (RBCs). There is evidence that RBCs of affected patients may also undergo eryptosis, the suicidal death of RBCs.MethodRBCs from 24 patients with wAIHA, 7 patients with chronic cAIHA and one patient with AIHA of mixed type were analysed for exposed phosphatidylserine (PS) by treatment with phycoerythrin‐labelled Annexin V, and cell‐associated fluorescence was measured using a MACSQuant flow cytometer.ResultsPS‐exposing RBCs were detected in 7 of 13 patients with clinically significant wAIHA. Haemolysis was mostly related to IgM or IgA autoantibodies (aab) in those patients. In contrast, PS exposure in 11 patients with wAIHA in complete remission was comparable to that in healthy blood donors. All patients with chronic cAIHA and the patient with AIHA of mixed type showed haemolytic activity and high numbers of PS‐exposing RBCs. Patients with decompensated AIHA appear to respond to treatment with erythropoietin, which is a known inhibitor of eryptosis.ConclusionEryptosis may frequently occur in AIHA related to IgM or IgA aab. Inhibition of eryptosis with erythropoietin may represent a new therapeutic option in the treatment of AIHA.
Potential years lost and life expectancy in adults with newly diagnosed epilepsy
Authors: Granbichler Claudia A. , Zimmermann Georg , Oberaigner Willi , Kuchukhidze Giorgi , Ndayisaba Jean‐Pierre , Taylor Alexandra , Luef Gerhard , Bathke Arne C. , Trinka Eugen 
Published: September 2017

SummaryObjectiveStudies using relative measures, such as standardized mortality ratios, have shown that patients with epilepsy have an increased mortality. Reports on more direct and absolute measure such as life expectancy are sparse. We report potential years lost and how life expectancy has changed over 40 years in a cohort of patients with newly diagnosed epilepsy.MethodsWe analyzed life expectancy in a cohort of adult patients diagnosed with definite epilepsy between 1970 and 2010. Those with brain tumor as cause of epilepsy were excluded. By retrospective probabilistic record linkage, living or death status was derived from the national death registry. We estimated life expectancy by a Weibull regression model using gender, age at diagnosis, epilepsy etiology, and year of diagnosis as covariates at time of epilepsy diagnosis, and 5, 10, 15, and 20 years after diagnosis. Results were compared to the general population, and 95% confidence intervals are given.ResultsThere were 249 deaths (105 women, age at death 19.0–104.0 years) in 1,112 patients (11,978.4 person‐years, 474 women, 638 men). A substantial decrease in life expectancy was observed for only a few subgroups, strongly depending on epilepsy etiology and time of diagnosis: time of life lost was highest in patients with symptomatic epilepsy diagnosed between 1970 and 1980; the impact declined with increasing time from diagnosis. Over half of the analyzed subgroups did not differ significantly from the general population. This effect was reversed in the later decades, and life expectancy was prolonged in some subgroups, reaching a maximum in those with newly diagnosed idiopathic and cryptogenic epilepsy between 2001 and 2010.SignificanceLife expectancy is reduced in symptomatic epilepsies. However, in other subgroups, a prolonged life expectancy was found, which has not been reported previously. Reasons may be manifold and call for further study.
Solar and lunar influences on the spawning activity of Pacific bluefin tuna (Thunnus orientalis) in the south‐western North Pacific spawning ground
Authors: Shimose Tamaki , Aonuma Yoshimasa , Tanabe Toshiyuki , Suzuki Nobuaki , Kanaiwa Minoru 
Published: September 2017

AbstractPacific bluefin tuna (Thunnus orientalis) migrate to the south‐western North Pacific spawning grounds (area off Taiwan and the Ryukyu Islands) from mid‐April to early July. Reproductive traits of the species in this area have been studied for some time; however, temporal changes in spawning activity during this season are not well understood. In this study, the spawning fraction (proportion of females with post‐ovulatory follicles to total mature females) in relation to solar calendar date and lunar day was investigated using a generalized linear model. Sampling was conducted almost every day throughout the fishing season at Ishigaki Fishing Port (24°21′N, 124°09′E), southern Japan between 2012 and 2014, and a total of 212 ovaries were histologically observed. Spawning fraction continued to increase from the beginning to the end of the season. This indicates that the peak season of occurrence in the area and the peak of spawning activity did not co‐occur. Spawning fraction also changed with the lunar day and significantly increased around the new moon. Eggs and early larvae hatched around the new moon may have reduced the predation risk during night‐time. These findings improve the current knowledge of reproductive biology and resource evaluation of Pacific bluefin tuna and indicate that spawning activity is not constant, and has two or three peaks in each season.