bluuebunny/crossref_metadata_2025_split huggingface dataset:
Simplified approaches for estimating vitamin A stores and β‐carotene bioconversion in humans (39.6)
Authors: Park Hyunjin , Lietz Georg , Oxley Anthony , Boddy Alan , Berry Phil , Wyss Adrian , Schalch Wolfgang , Green Michael 
Published: June 2021

Better methods are needed to assess vitamin A (VA) status and the efficiency of bioconversion of β‐carotene (BC) to retinol (ROH). Data on plasma ROH kinetics from 2 h to 14 d after an oral tracer dose of [13C10]BC and [13C10]retinyl acetate (RAc) to 33 healthy young adults were analyzed using model‐based compartmental analysis (WinSAAM, the Windows version of the Simulation, Analysis and Modeling software). The 6‐compartment model that fit data for all subjects predicted 5.3 pools of plasma ROH were transferred into extravascular stores each day, with ~17%/d recycling back to plasma; 6.5%/day was irreversibly lost and total body VA stores (TBS) were 146 ± 89 μmol (mean ± SD). We derived a simplified isotope dilution (“Olson”) equation for TBS, eliminating several factors and assumptions: TBS = F * (1 / SA), where F (fraction of dose [FD] absorbed and retained) was estimated as 0.61 from the kinetic data and SA (specific activity) is FD 13C10[ROH] in plasma 3 d after dosing / plasma ROH pool (μmol). TBS calculated using the equation was 149 ± 85 μmol, essentially the same as the value predicted by the model. BC bioconversion, calculated as FD 13C5[ROH] (derived from BC) / 13C10[ROH] (derived from RAc) at 2 d, averaged 23 ± 11% and was significantly correlated (R=0.942) with WinSAAM’s estimate based on areas under the curves (26 ± 12%). Our results indicate that both TBS and BC conversion to ROH can be estimated based on blood samples taken 3 and 2 d, respectively, after dosing. With further refinement, one sample at 3 d may suffice.Grant Funding Source: BBSRC, U.K. and DSM, Basel, Switzerland
Child‐directed marketing within and around fast‐food restaurants (390.1)
Authors: Ohri‐Vachaspati Punam , Zeynep Isgor , Rimkus Leah , Powell Lisa 
Published: June 2021

Fast food is the second‐largest source of calories among youth. Children who eat fast food consume more calories and have poor diet quality. The fast‐food industry spends over $700 million to market products to youth each year. Using validated instruments, data were collected from 6710 fast‐food restaurants located in a nationally representative sample of public middle‐ and high‐school enrollment areas between 2010 and 2012. Child‐directed marketing was defined as the presence of one or more of eight components inside or on the exterior of the restaurant. Over a fifth of all types of fast‐food restaurants and a third of chain fast‐food restaurants used child‐directed marketing within and/or around their buildings. Fast‐food restaurants that offered kids’ meals were significantly more likely to use child‐directed marketing than those that didn’t offer kids’ meals. Indoor display of kids’ meal toys was the most often used strategy and prevalence was highest among restaurants that participate in the Children’s Food and Beverage Advertising Initiative (CFBAI [84.6% in 2012]). Results from multivariate analysis indicate that all fast‐food restaurants in mid‐low income neighborhoods, and CFBAI member fast‐food restaurants in black neighborhoods, had significantly higher odds of using child directed marketing compared to those located in highest income and white neighborhoods, respectively. Child‐directed marketing was more prevalent in communities that are disproportionately affected by obesity. Popularity of kids’ meals toy displays to advertise to children meals that have been shown to be of poor nutritional quality is of concern. It is important to limit children’s exposure to unhealthy food advertising.Grant Funding Source: Robert Wood Johnson Foundation
A comparison of the nutritional quality of kids’ versus adult meals from chain sit‐down restaurants (390.2)
Authors: Scourboutakos Mary , L'Abbe Mary 
Published: June 2021

The objectives were to compare the nutritional quality of restaurant meals from regular (adult) menus in contrast to meals from kids’ menus, and to compare the nutritional quality of meals marketed as being “healthy kids’ meals” in contrast to “healthy adult meals”. Nutrition information was collected from Canadian chain restaurant websites in 2010. Nutrient levels (including calories, sodium, sugar, saturated fat, fiber, protein and trans fat) and Ofcom nutrient profile scores in 1630 adult meals and 248 kids’ meals from seven restaurant chains were analyzed. In addition, 46 “healthy kids’ meals” and 20 “healthy adult meals” were compared. On average, kids’ meals had a significantly lower nutritional quality in comparison to adult meals (p<0.01). However, the difference varied depending on the restaurant. “Healthy kids’ meals” had significantly higher amounts of calories, sugar, trans and saturated fat (both per serving and per 100g, p<0.05) when compared to “healthy adult meals”. Additionally, “healthy kids’ meals” had two‐times more saturated fat, almost three‐times more sugar and a significantly higher percentage of total energy coming from fat (33% [healthy kids’ meals] vs 25% [healthy adult meals]), saturated fat (11% vs 7%) and sugar (23% vs 11%). In conclusion, kids’ meals are often nutritionally worse than adult meals, and there is a gap between what is being marketed as a “healthy meal” for kids versus adults.Grant Funding Source: Supported By: Vanier Canada Graduate Scholarship, CIHR/HSF PICDP Fellowship, OGS, McHenry Grant
Front‐of‐pack symbols are not a reliable indicator of products with healthier nutrient profiles (390.7)
Authors: Emrich Teri , Qi Ying , Cohen Joanna , Lou Wendy , L'Abbe Mary 
Published: June 2021

Front‐of‐pack (FOP) nutrition rating symbols are used on food labels worldwide. Without standardized criteria for their use, it is unclear if FOP symbols are being used to promote products that are more nutritious than products without symbols. Objective: To compare the amount of calories, saturated fat, sodium, and sugar in products with FOP symbols to products without symbols. Design: A 2010‐2011 database of 10,487 Canadian packaged food labels was used. Nutrient content differences were compared using Wilcoxon rank‐sum test; differences greater than 25% were deemed nutritionally relevant. Results: Products with FOP symbols were not uniformly lower in calories, saturated fat, sodium, and sugar per reference amount than products without these symbols in any of the 10 food categories or in 59/60 subcategories. None of the different FOP system types (nutrient‐specific, summary indicatory, or food group information) examined were used to market products with overall better nutritional profiles (i.e. lower in calories, saturated fat, sodium, and sugar) than products without this type of marketing. Conclusion: FOP symbols are being used to market foods that are no more nutritious than foods without this type of marketing. As FOP symbols may influence consumer product perceptions and purchases, it may be a useful public health strategy to set minimum nutritional standards for products using FOP symbols.Grant Funding Source: Canadian Institutes of Health Research
Mathematical modeling and correlation of histopathology with perfusion‐contrast CT for prediction of vascular permeability and chemotherapeutic diffusion parameters (397.7)
Authors: Bearer Elaine , Wang Zhihui , Cristini Vittorio 
Published: June 2021

Tumor perfusion influences the ability of chemotherapeutic drugs to penetrate and kill cancers. Further, the physical properties of the microenvironment moderates the penetration of drugs from the vasculature into tumors. Here, we develop a mathematical model based on histopathology to predict the outcome of chemotherapy based on the physical laws of diffusion. The most important parameters in the model are the volume fraction occupied by tumor blood vessels (BVF) and their average diameter. Drug delivery to cells, and kill thereof, are mediated by these micro‐environmental properties and affected by the diffusion penetration distance after extravasation. To calculate parameter values we fit the model to histopathology measurements of the fraction of tumor killed after chemotherapy in human patients with colorectal cancer (CRC) metastatic to liver (coefficient of determination R2 = 0.94). To validate the model in a different tumor type, we input patient‐specific model parameter values from glioblastoma (GBM); the model successfully predicts extent of tumor kill after chemotherapy (R2 = 0.7‐0.91). Towards prospective clinical translation, we calculate BVF parameter values from in vivo contrast‐CT perfusion imaging from a separate cohort of patients with CRC metastatic to liver, and demonstrate accurate model predictions of individual patient responses (average relative error = 15%). Here, patient‐specific data from either in‐vivo imaging or histopathology drives output of the model’s formulas. Values obtained from histopathologic analysis for each individual are entered into the model dmonstrating accurate prediction of tumor kill after chemotherapy in a retrospective study of 24 subjects. Application of this model will enable rational design of individualized treatment strategies such as amount, frequency and delivery platform of drug and the need for ancillary non‐drug‐based treatment.Grant Funding Source: NCI CA153825, NIGMS P50GM085273, NINDS NS062184
Low‐fat dairy reduces inflammatory genes and liver enzymes in adults with metabolic syndrome (40.5)
Authors: AGuilar David , Dugan Christine , Park Young‐Ki , Lee Ji‐Young , Fernandez Maria Luz 
Published: June 2021

We evaluated the effect of low‐fat dairy (LFD) intake on plasma inflammatory markers, gene expression of these markers in peripheral blood mononuclear cells (PBMC) and liver enzymes in individuals with metabolic syndrome (MetS). Subjects (13 male, 22 female) with low dairy intake (<1.5 ser/dairy/day) were randomly assigned to receive LFD (296 mL low‐fat milk, 170 g yogurt, 510 g cheese stick, 3 servings of dairy/day) or isocaloric control foods (CON) (42 g granola bar, 177 mL juice) daily for 6‐wk. After a 4‐wk wash‐out, subjects were allocated to the alternate treatment. Participants had lower concentrations of both hepatic alanine aminotransferase (ALT) (p < 0.05) and aspartate aminotransferase (AST) (p< 0.005) as well as lower concentrations of plasma monocyte chemoattractant protein (MPC‐1) (p<0.05) after the LFD period. Gene expression was evaluated in a subset of subjects (n = 17). IL‐1b and IL‐6 were reduced by 46 and 63%, respectively compared to the control period. Protein and gene expression of tumor necrosis factor (TNF)‐alpha was not altered by diet. These results indicate that consumption of three dairy servings per day improve both liver inflammatory markers and systemic inflammation in subjects with MetS.Grant Funding Source: Dairy Council
lmpact of various dietary oils on expression levels of inflammatory genes: a randomized crossover controlled nutritional intervention (40.6)
Authors: Labonté Marie‐Eve , Couture Patrick , Vohl Marie‐Claude , Jenkins David , Connelly Philip , West Sheila , Kris‐Etherton Penny , Jones Peter , Lamarche Benoît 
Published: June 2021

Consumption of a docosahexaenoic acid (DHA)‐enriched canola oil was shown to have anti‐inflammatory effects compared with a control diet rich in linoleic acid (LA) and a diet rich in flax oil and alpha‐linolenic acid (ALA). We further investigated the impact of these oils on the expression of key inflammatory genes in whole blood cells as part of the Canola Oil Multicenter Intervention Trial (COMIT). A total of 118 men and women with abdominal obesity and at least one other criterion for metabolic syndrome consumed 5 isoenergetic diets for 4 weeks each according to a randomized, crossover design. Each diet provided 60 g/3000 kcal of various experimental oils. Here we report the impact of 3 of these 5 oils: 1‐ CONTROL high LA corn/safflower oil (LA 41.6 g; ALA 0.2 g; n6/n3 ratio 208:1), 2‐ FLAX oil (LA 22.5 g; ALA 19.2 g; n6/n3 ratio 1.2:1), 3‐ High DHA canola (DHA‐CAN; LA 7.6 g; ALA 1.2 g; DHA 3.5 g; n6/n3 ratio 1.2:1). Inflammatory gene expression in whole blood cells at the end of each diet was assessed by real‐time PCR in a subset of 66 individuals. DHA‐CAN lowered mRNA expression of interleukin(IL)‐1β compared with CONTROL (fold change 0.90, P=0.03) and FLAX (fold change 0.89, P=0.03). There was no between‐diet difference in the expression of other inflammatory genes and transcription factors. These data suggest that anti‐inflammatory effects of DHA compared with n3 and n6 polyunsaturated fatty acid rich oils from plant sources occur at least in part through a reduction in the expression of IL‐1β.Grant Funding Source: Supported by the Canola Council of Canada, Flax 2015 and Agriculture and Agri‐Food Canada
Vitamin D status positively associates with interleukin‐6 and tumour necrosis factor alpha in healthy young children (40.8)
Authors: Brett Neil , Agellon Sherry , Vanstone Catherine , Weiler Hope 
Published: June 2021

Vitamin D status associates with immune function and duration of illness. The objective was to examine interleukin‐6 (IL‐6) and tumor necrosis factor alpha (TNF) in relation to vitamin D status in healthy children. Children (n=457; 1.8‐5.8 y) were recruited from randomly selected daycares in Montreal. Body mass index Z‐scores for age (BAZ) were calculated using the WHO growth standard. Capillary plasma samples were measured for IL‐6, TNF and C‐related peptide (CRP) (Multiplex assays; Millipore Corp. USA); CRP values > 10 mg/L were excluded. Vitamin D status (chemiluminescence; Liaison, Diasorin Inc.) was categorized using plasma 25‐hydroxyvitamin D (25(OH)D) values <50.0 nmol/L (low; n=52), 50.0‐74.9 nmol/L (adequate; n=189) and 蠅75.0 nmol/L (robust; n=216). Differences among vitamin D status categories were tested using mixed model ANOVA (random effects: age, sex, BMI Z‐score and season) and Tukey’s post hoc test; data are mean ± SD. Average age was 3.7 ± 1.0 y, BAZ 0.5 ± 1.0 kg/m2 and CRP 0.9 ± 1.6 mg/L. By design all pair‐wise differences in 25(OH)D (nmol/L) were observed (low: 40.8 ± 6.7; adequate: 63.4 ± 7.6; robust 100.3 ± 22.4, P<0.001). Highest IL‐6 (low: 9.9 ± 13.0; adequate 9.9 ± 12.9; robust 14.0 ± 14.9 ng/L, P<0.02) and TNF (low: 6.8 ± 3.5; adequate 7.1 ± 3.1; robust 7.8 ± 3.4 ng/L, P<0.03) were observed in the robust group. The data suggests that robust vitamin D status supports innate immune function.Grant Funding Source: Supported by Dairy Farmers of Canada
CFC1 gene mutation in tetralogy of Fallot and dextro‐transposition of great arteries in Pakistani population. (404.2)
Authors: Arif Afsheen , Zehra Sitwat , Qamarunissa Syeda , Patel Najma , Azhar Abid 
Published: June 2021

Background: Congenital heart diseases (CHDs) are the most common of all birth defects and one of the leading causes of mortality in the first year of life. CFC1 gene is a cell signaling protein is a co receptor in nodal signaling pathway and involve in right and left axis determination during gastrulation.Materials and Methods: This is a case‐control study, recruited 225 non syndromic patients and 140 controls, healthy unrelated individuals. The study, after formal approval includes patients from various pediatric cardiology centers in three years. A detailed family history was taken to elucidate the genetic and environmental factors. Pediatric cardiologist confirmed the diagnosis on the basis of all standard testing like chest X‐ray, CBC, ECG, ECHO, cardiac catherization reports etc. DNA extraction and sequencing was done and data was interpreted by multiple sequence alignment software. Statistical data was done by SPSS 17.0.Results: The mean age for controls was 3.14±1.82 years, for TOF; 2.97±1.21, and for DTGA patients 1.84±2.26 years. TOF and DTGA were frequent in males. The study demonstrates frequency of this disease; with its variation in Pakistani population. Consanguinity affects the rate of CHDs, as it is 62% in patients and 25% in controls. Two novel mutations were found in CFC 1 gene.First in exon 5 at c. 396 C>A and second in exon 6 at c. 548 C>T.Conclusions: The study demonstrates frequency and prevalence for TOF, and DTGA, there variation and association with other cardiac defects. Environmental factors are taken into consideration and consanguinity proves to be an element for the increasing number of disease. CFC1 plays a key role in cardiac malformation and its mutations.
Caveolin‐1 deficiency enhances cancer cell transendothelial migration and promotes lung metastasis through upregulation of VCAM‐1 in lung endothelial cells (405.2)
Authors: Fu Wei , Wang Chen , Liu Ziyang , Wang Enhua , Liu Jun 
Published: June 2021

Caveolin‐1 (Cav1) has been shown to play an important role in oncogene‐induced cell transformation and tumorigenesis. It has been reported that the level of Cav1 expression in tumors affected tumor cell proliferation, invasion and metastasis. In this study, we employed Cav1 knockout mice and tested whether genetic depletion of Cav1 in endothelial cells would affect cancer metastasis. Melanoma (B16F10) and Lewis lung cancer (LLC1) cells were inoculated in both wild‐type and Cav1 knockout mice. Tumor growth and metastasis in the lungs and livers were monitored for a period of four weeks. Although there was no significant difference of the onset and burden of the primary tumors between wild‐type and Cav1 knockout mice, Cav1 depletion significantly promoted tumor metastasis to the lungs and livers. Consequently, the survival rate was significantly lower in Cav1 knockout mice than the control group. Upon TNFα stimulation, Cav1 knockout endothelial cells showed more than 2‐fold increase in the expression of vascular cell adhesion molecule‐1 (VCAM‐1) over wild‐type cells. The increased VCAM‐1 expression was translated to a dramatic increase in the adhesion of B16F10 cells to Cav1 deficient endothelial cells by 5‐fold more than wild‐type cells. Furthermore, Cav1 deficiency resulted in an increase in the transendothelial migration of B16F10 cells. Our results suggest that the levels of Cav1 expression in endothelial cells plays important role in cancer metastasis by enhancing the interaction of cancer cells with endothelial cells and cancer cell extravasation.Grant Funding Source: Supported by the American Cancer Society
Mice heterozygous for the F508del mutation in the cystic fibrosis transmembrane conductance regulator anion channel display attenuated cardiopulmonary dysfunction and lung injury after influenza H1N1 infection (406.4)
Authors: Aeffner Famke , Joseph Lisa , Amer Amal , Hickman‐Davis Judy , Davis Ian 
Published: June 2021

Influenza A viruses cause a highly‐contagious respiratory disease associated with significant morbidity and mortality. The purpose of this study was to utilize F508del CFTR‐heterozygous mice to determine the contribution of CFTR‐mediated Cl‐ secretion to influenza pathogenesis and to evaluate CFTR as a therapeutic target.F508del CFTR‐heterozygous progeny (HETs) and wild‐type (WT) littermate controls were infected intranasally with 50 μl virus diluent (mock) or with 10,000 FFU/mouse influenza A/WSN/33 (H1N1) for 1‐6 days. Body weight, lung mechanics, cardiopulmonary function and levels of pulmonary inflammatory mediators were determined over the time of disease.Relative to WT littermate controls, infection‐induced hypoxemia and bradycardia were attenuated in HETs at 2‐6 days post‐infection (d.p.i.), although weight loss and viral replication did not differ. At 2 and 6 d.p.i., alterations in lung function in infected WT mice were absent in HETs at both 2 and 6 d.p.i. Bronchoalveolar lavage fluid from influenza‐infected HETs contained approximately 3‐fold greater numbers of alveolar macrophages and more than 10‐fold higher IL‐6 levels at 6 d.p.i.Reduced CFTR expression resulting from F508del CFTR heterozygosity significantly alters influenza pathogenesis. CFTR‐mediated Cl‐ secretion is therefore a potential therapeutic target to decrease lung injury after influenza H1N1 infection.Grant Funding Source: Supported by C. Glenn Barber Fund and NHLBI R01‐HL102469
SerpinA3N accelerates wound closure in a murine model of impaired wound healing (413.1)
Authors: Hsu Ivy , Zhao Hongyan , Bleackley Chris , Granville David 
Published: June 2021

Granzyme B (GzmB) is a serine protease that accumulates in the extracellular milieu during chronic inflammation and cleaves many extracellular matrix (ECM) proteins that are essential for proper wound healing to ensue. We hypothesized that GzmB contributes to the pathogenesis of impaired wound healing observed in the diabetic population through excessive degradation of the ECM. On the dorsal back of genetically‐induced type II diabetic db/db mice, 10 mm excisional wounds were created and covered with semi‐transparent dressing. SerpinA3N, a GzmB inhibitor, was administered topically and/or subcutaneously on the wounds every 3 days. GzmB was found to co‐localize with mast cells in wound sites at the dermal‐epidermal junction. In addition, preliminary results suggest that administration of serpinA3N accelerates wound closure as by day 35, 100% of serpinA3N‐treated compared to 55% of vehicle‐treated mice have fully re‐reepithelialized. In serpinA3N‐treated animals, an increase in full‐length ECM proteins involved in collagen fibrillogenesis was observed along with fewer cleavage fragments by immunostaining. These findings suggest that GzmB contributes to the pathogenesis of diabetic wound healing through the proteolytic cleavage of ECM proteins that are essential for normal wound closure.Grant Funding Source: Supported by Canadian Diabetes Association and Canadian Institutes of Health Research
Intestinal epithelial ecto‐5’‐nucleotidase CD73 regulates invasion by Salmonella typhimurium (488.4)
Authors: Kao Daniel , Saeedi Bejan , Vickery Thad , Wilson Kelly , Colgan Sean , Kominsky Douglas 
Published: June 2021

Previous work has shown that adenosine is a key mediator of bacterial‐epithelial cell interactions. CD73 is an ecto‐5'‐nucleotidase expressed abundantly on the apical surface of intestinal epithelial cells (IEC) that catalyzes the conversion of 5’‐adenosine monophosphate (AMP) to adenosine (Ado). Here, we hypothesized that CD73 activity is important in invasion of IECs by the enteric pathogen Salmonella typhimurium. In this work, we demonstrate that pharmacologic inhibition of CD73 activity and lentiviral‐mediated knockdown of CD73 expression significantly attenuated Ado production by cultured T84 human colonic epithelial cells (approximately 7‐fold reduction in the ability to convert etheno‐AMP to etheno‐Ado). Furthermore, inhibition of CD73 activity by these two methods diminished invasion of T84 cells by Salmonella typhimurium. Based on these in vitro data, a transgenic mouse was generated with IEC‐specific knockout of CD73 (CD73f/f x Villin‐Cre). These CD73 tissue‐specific knockout mice were protected in an S. typhimurium model of infectious colitis compared to control animals. IEC‐specific knockout animals revealed attenuated weight loss and diminished histopathological severity of colitis at 24 and 48 hours after infection. Correspondingly, there was a significant decrease in disseminated bacteria isolated from mesenteric lymph nodes and spleen, demonstrating attenuated bacterial invasion in the absence of CD73. In conclusion, these results demonstrate that CD73 is a key regulator of infection by the enteric invasive pathogen S. typhimurium and implicates a prominent role for extracellular adenosine in Salmonella interactions with IEC.Grant Funding Source: Supported by NIH and CCFA