bluuebunny/crossref_metadata_2025_split huggingface dataset:
The bioactivity of flavonoids is likely the result of cumulative low exposure to a variety of structurally similar phenolic metabolites
Authors: Kay Colin , de Gesso Jessica , Warner Emily , Amin Hiren , de Ferrars Rachel , Edwards Michael , Zang Qing , O'Hagan David , O'Connell Maria 
Published: June 2021

Activities of 21 flavonoid metabolites were investigated relative to their unmetabolized structures, utilizing 20 assays of vascular reactivity, inflammation and cellular adhesion, in endothelial (HUVEC), smooth muscle (AVSMC) and monocyte (THP‐1) cells, at physiologically relevant concentrations (0.1‐10µM). Unmetabolized flavonoids were generally less active than their phenolic metabolites. In vascular screens no metabolites altered expression of endothelin‐1 or nitric oxide, 3 metabolites induced eNOS, 2metabolites reduced angiotensin‐II induced superoxide, no metabolites induced NOX or p47phox, 1 metabolite upregulated p22phox and 3 metabolites induced HO‐1. In vascular inflammation and adhesion screens in HUVEC, 10, 9 and 6 metabolites reduced IL‐6 following CD40L, oxLDL or TNF‐α stimulation, respectively. 10 and 6 metabolites reduced sVCAM‐1 following CD40L or TNF‐α stimulation, respectively. 2 metabolites attenuated IL‐1β‐stimulated phosphorylation of NF‐κB p65, 1 metabolite induced Nrf2. In monocyte activity assays, 5 metabolites reduced LPS‐induced TNF‐α, 1 metabolite induced IL1B, no metabolites were active on HO‐1, tissue factor, NFkB or nfKB. The evidence suggests that bioactivity of flavonoids in vivo results from low exposure to a variety of structurally similar metabolites modifying inflammation and cellular adhesion pathways.Support: UK Biotechnology and Biological Sciences Research Council (BB/I006028/1, BB/H004963/1).
Improving Infant and Young Child Feeding in Ethiopia through Community Based Grain Banks Using Local Foods
Authors: Roche Marion , Sako Binta , Osendarp Saskia , Adish Abdulaziz , Tolossa Azeb 
Published: June 2021

BackgroundInadequate infant and young child feeding practices contribute to the concerning malnutrition situation in Ethiopia. To improve availability, accessibility and quality of complementary foods, development partners in Ethiopia supported women's groups to produce complementary food by processing local grains and legumes at community grain banks. Flour was sold in the semi‐urban communities and a subsidized barter system was created in the rural areas. ObjectiveTo assess the acceptability, perceived impact, feasibility and sustainability for local grain bank interventions to improve infant and young child nutrition, in four regions of Ethiopia. MethodsA total of 51 key informant interviews and 33 focus group discussions (n=237) were conducted based on a purposive sampling framework of project stakeholders. ResultsThe grain bank flour was valued for its quality and diverse locally grown ingredients. Mothers were motivated to give the flour because of perceived benefits to their child's health; while the community grain bank was credited as labor saving for women. The grain bank flour offered improved dietary diversity; however, further micronutrient interventions including dietary modification or fortification are needed to improve diet adequacy. The greatest risks to sustainability were dependence on external resources to subsidize the barter model and reliance on volunteer work from women's groups in the rural context. ConclusionsIntegrated agricultural and health interventions leveraging local crops can appeal to diverse stakeholders and may offer an acceptable approach to improving infant and young child feeding.Funding: UNICEF & Micronutrient Initiative
A Comparison of the Healthfulness of Prepackaged Children's Foods from Participants and Non‐Participants of the Canadian Voluntary Code on Marketing to Children
Authors: Murray Chelsea , L'Abbé Mary 
Published: June 2021

This study's purpose was to determine whether children's food and beverage products from companies participating in the Canadian voluntary code on marketing to children (CAI), which does not cover product packaging, were healthier than children's products from non‐participating companies. All products marketed to children (n=415) were identified in a database of Canadian food products (n=10,488). The Ofcom nutrient profiling method was used to calculate a summary score of the healthfulness of each children's product based on its content of specific nutrients. These scores, ranging from 1 to 100 (where 1 is least healthy), were compared between children's products from CAI participants (n=164) and non‐participants (n=251). The Ofcom model provides a cutoff score for products to be classified as “healthier”; the proportion of products meeting this “healthier” cutoff was compared between products from CAI participants and non‐participants. The median healthfulness score of children's products from CAI participants was 43 (interquartile range 37‐66); this score was not significantly different compared to children's products from non‐participants, which scored 54 (interquartile range 38‐64). However, a significantly lower proportion of children's products from CAI participants were considered “healthier”, 14% of products, compared to 23% from non‐participants; p = .02. These results indicate that voluntary codes, such as the CAI, in which companies commit to reduce the marketing of unhealthy foods and beverages to children, should also apply to all components of their marketing, including product packaging.Supported by McHenry Chair grant (ML); and OGS, CIHR Master's, and CIHR PICDP graduate scholarships (CM)
Dietary Fiber and Added Fiber
Authors: Gordon Dennis 
Published: June 2021

The challenges to achieve more dietary fiber (DF) in foods and beverages, and achieving recommended intakes, can be traced to IOM recommendation to have two categories or definitions of DF. Objective: Recommend and justify the use of “Added Fiber” (AF) in foods and beverages.MethodsDocument current non‐reported use of AF in foods.
ResultsQuantitate and contrast current total DF intakes (endogenous DF and AF) in meeting recommended Adequate Intakes (AI).ConclusionsReport disparity, and recommend how, AF can help meet AI, with advantages, disadvantages and risks. Dietary fiber remains a nutrient of great interest to the consumer and the health community. This interest is attributed to the consumer's strong belief in DF benefits and quest to find and consume more foods with DF, and the IOM's recommended AI levels at approximately twice current intakes.. The average DF intake is 16 g/day, and AI recommendations are 38 and 25 g/day for men and women, respectively. The IOM defined “Dietary Fiber” as that endogenous in foods and “Added Fiber” is that extracted and or modified and added to foods. While of academic and taxonomical interest, two DF definitions, and specifically use of the term “Added Fiber” are limiting and possibly discriminating to the science of DF, the consumer and food labeling. The FDA in proposing changes to the food label has decided there will be only one term on food labels, “Dietary Fiber”. For “Added Fiber” to be included in this term, is must have demonstrated beneficial physiological effects for human health. While increased whole grain (WG) consumption is recommended, most WG foods as presently available and consumed are not a good source of DF. (No support)
Determination of the Tolerable Upper Intake Level of Leucine in Healthy Elderly (70‐75y)
Authors: Rasmussen Betina , Turki Abrar , Madden Kenneth , Elango Rajavel 
Published: June 2021

Leucine, a branched‐chain amino acid, has been shown to stimulate muscle protein synthesis, and thus it has been proposed to prevent age related muscle atrophy (sarcopenia). Therefore, leucine supplementation may have potential benefits in elderly populations. The UL (tolerable upper intake level) for leucine intake in young men has been recently determined to be 500 mg/kg/day, and increases in ammonia concentrations were seen at intake levels above 500/mg/kg/day. The objective of the current study was to determine the UL for leucine in healthy elderly men, as this is currently unknown. Five healthy elderly men (70 – 76 yrs) received graded stepwise increases in leucine intakes ranging from 50 ‐ 650 mg/kg/day, provided on eight separate study days. The UL of leucine was identified by measurements of plasma and urinary biochemical variables, including blood ammonia, glucose and insulin concentrations. Further, the participants received an oral primed‐continuous protocol of 1‐13C‐leucine on all study days to measure changes in leucine oxidation. None of the participants reported any adverse physical symptoms on study days. Leucine oxidation appears to plateau with increasing leucine intakes. Blood ammonia concentrations above normal values (35 µmol/L) were observed at leucine intake of 350mg/kg/day and above. Plasma glucose stayed within normal ranges. These preliminary results suggest that the UL for leucine in healthy elderly men may be lower than the current UL of 500 mg/kg/d for healthy young men.(Supported by ICAAS)
Feeding of infant formula at birth links with feeding of infant formula and discontinuation of breastfeeding in Vietnam
Authors: Nguyen Tuan , Frongillo Edward , Hajeebhoy Nemat 
Published: June 2021

Few studies have examined the association between feeding infant formula at birth and future feeding patterns. This study was conducted to examine the association between feeding infant formula in the first 3 days after birth (IF3d) and current feeding infant formula (IFcur), as well as discontinuation of breastfeeding (noBF). In a cross‐sectional survey, we interviewed 10,681 mothers with children aged 0−23.9 mo in Vietnam about current breastfeeding practices and feeding practices during 3 days after birth. The prevalence of feeding IF3d was 52%, higher in those with cesarean delivery (78%) than vaginal delivery (45%, P < 0.01). The prevalence of IFcur in children 0−0.9, 3−3.9, 4−8.9, and 9−23.9 mo fed with IF3d was 31%, 40%, 50% and 50%, which was statistically higher than those who were not fed IF3d (5%, 15%, 30%, and 40%, respectively). The stratified analysis by delivery mode showed a similar trend. At 12 to 14.9 mo, the noBF prevalence was higher in infants fed IF3d than who were not. IF3d was associated with increased prevalence of IFcur (OR: 1.76; 95% CI: 1.58, 1.95) and noBF (OR: 1.32; 95% CI: 1.14, 1.53), which was stronger in the younger infants. Structural equation modeling shows that a) IF3d was associated with higher IFcur (std β: 0.244), which in turn linked with noBF (std β: 0.285) and b) IF3d was associated with cesarean delivery (std β: 0.627), intention of feeding formula at birth (std β: 0.556), and lack of professional breastfeeding support at birth (std β: 0.213; P < 0.01 for all). Support for exclusive breastfeeding in the first 3 days of life can reduce early introduction of infant formula and early cessation of breastfeeding.Funding: Bill & Melinda Gates Foundation, through Alive & Thrive, managed by FHI 360
WAVE Pilot Study: Feasibility of Using Emails and Short Message Service (SMS) with High School Soccer Players to Reinforce Compliance in an Obesity Prevention Intervention
Authors: Wong Siew Sun , Meng Yu , Moissinac Béatrice , Scaffidi Christopher , Manore Melinda 
Published: June 2021

ObjectiveEvaluate the feasibility of using emails/SMS with high school (HS) soccer players for increasing compliance at group classes, completion of questionnaires, and 7‐day tracking of eating behavior and physical activity. MethodCustomized emails/SMS using Google Voice and WavePipe (a custom data collection system that sends emails) were sent to remind and encourage compliance in 52 youth (14‐19y) enrolled in the WAVE Pilot Study. Prior to each activity, coaches and youth received emails/SMS about enrollment session, class schedule (intervention group [IG] only), and baseline assessments. During a subsequent 7‐day tracking period, youth received a daily email/SMS with a unique link to the behavioral checklist (BC) online and a reminder to wear the Fitbit.ResultsOverall, the IG was more compliant in all aspects of data collection and attending group sessions. The enrollment and survey completion rate was 76% in the IG (n=25) vs. 51% in the control group (CG) (n=27) (p<0.05). On average, the IG wore Fitbits for 6.0 d vs. 4.9 d for the CG (p<0.05); 98% Fitbits were returned. The IG completed the online BC for 3.7 d vs. 1.4 d by the CG (p<0.05). Failure to receive daily emails significantly reduced the BC response rate; 44% of the CG reported not noticing 蠅1 daily email/SMS. Other reasons include wrong contacts. Youth generally preferred SMS over emails as reminders. ConclusionEmails, particularly SMS, during intervention increased active HS soccer players' compliance. Sponsor: NIFA AFRI Award No. 2013‐67001‐20418
Physical Activity is Associated with Lower Adiposity Independent of Diet Quality in Adolescent Girls
Authors: Vassallo Danielle , Thomson Cynthia , Funk Janet , Jacobs Elizabeth , Blew Robert , Lee Vinson , Going Scott 
Published: June 2021

BACKGROUNDTotal and site‐specific adiposity, such as visceral and skeletal muscle fat, have been associated with increased cardiovascular disease risk in adults, but data are lacking for youth. Calorically dense diets are major contributors to the development of childhood obesity and metabolic diseases.OBJECTIVETo assess the relationships between diet quality (DQ), measured by the Youth Healthy Eating Index (YHEI), physical activity (PA), and measures of total and site‐specific adiposity in 211 healthy girls aged 8‐13 years.METHODSMuscle density (MD, mg/cm3), surrogate for fat infiltration, was measured at tibia and femur sites using peripheral quantitative computed tomography. Total body and android fat (surrogate for visceral fat) were measured by dual energy x‐ray absorptiometry. Diet was assessed using the validated semi‐quantitative Harvard Youth/Adolescent Food Frequency Questionnaire (YAQ). DQ was assessed from the YHEI, developed based on the YAQ. PA was assessed using a past year PA questionnaire.RESULTSMultiple linear regressions with DQ, maturity, total energy intake, and PA were used to predict MD, total body fat (BF), android fat (AF), and body mass index (BMI) in separate models. DQ was not a significant predictor of adiposity. PA was positively associated with calf MD (p 蠄 0.01, β=0.62) and thigh MD (p 蠄 0.01, β=0.77) and negatively associated with BMI (p蠄0.05, β=‐0.02), AF (p蠄0.01, β=‐4.82), and BF (p蠄0.01, β=‐3.74).CONCLUSIONPA is associated with lower adiposity independent of DQ, total energy intake, ethnicity, and maturation.Grant Funding Source: NIH: HD050775
PAR2 Activation Protects Against Colitis but Inhibits Epithelial Wound Healing
Authors: Trusevych Elizabeth , Iablokov Vadim , Dicay Michael , Beck Paul , MacNaughton Wallace 
Published: June 2021

AimsProtease‐activated receptor (PAR)2 activation increases the expression of cyclooxygenase (COX)‐2 in intestinal epithelial cells. We tested the hypothesis that PAR2‐induced COX‐2 regulates intestinal inflammation and modulates epithelial wound healing.MethodsPAR2 was activated using the selective activating peptide 2f‐LIGRLO. Circular wounds in Caco2 cell monolayers were monitored with live‐cell imaging. In vivo, epithelial damage was induced by giving WT and PAR2 KO (C57Bl/6) mice 2.5% DSS for 5‐7 days.ResultsActivation of PAR2 in Caco2 cells significantly increased COX‐2 protein (4.2‐fold) and PGE2 metabolites (9.6‐fold). In vivo, preliminary results showed less COX‐2 protein in PAR2 KO mice given DSS compared to WT mice. The PAR2 KO mice also lost significantly more weight and had higher histological damage scores compared to WT mice. We next determined the effect of PAR2‐induced COX‐2 on epithelial wound healing in vitro. Surprisingly, PAR2 activation significantly inhibited the rate of wound closure over 48 hr (79.3±2.5% wound closure) compared to control (94.3±0.5%), independently of COX‐2 activity. PAR2 activation had no effect on proliferation, but significantly inhibited cell migration.ConclusionsPAR2 activation was shown to be protective in vivo, which correlated with the expression of COX‐2. We also uncovered a novel COX‐2‐independent effect of PAR2, reducing the rate of wound healing by inhibiting cell migration. Our results show that PAR2 plays differential roles in regulating epithelial response to injury and inflammation.Support: Crohn's and Colitis Canada, Alberta IBD Consortium, Alberta Cancer Foundation.
Mutations of Nrf2 are an early and frequent event in the development of rat hepatocellular carcinoma
Authors: Columbano Amedeo , Giordano Silvia , Perra Andrea , Kowalik Marta , Ledda‐Columbano Giovanna , Petrelli Annalisa , Menegon Silvia , Quagliata Luca , Terracciano Luigi , Zavattari Patrizia 
Published: June 2021

Hepatocellular carcinoma (HCC) is a multistage process, but the nature of the molecular changes associated to the different steps, particularly the very early ones, is unknown. The Nrf2–Keap1 pathway is now recognized as a major cellular defense mechanism against oxidative and electrophilic stresses; however, its exact role in cancer development is unclear.To unveil the role of Nrf2 in HCC, we used the Resistant‐Hepatocyte (R‐H) rat model, which identifies distinct lesions (preneoplastic foci, dysplastic nodules, early and advanced HCCs) at well‐defined timings.The results showed that mutations of Nrf2 are very frequent in early preneoplastic lesions positive for the putative progenitor cell marker cytokeratin‐19 (KRT‐19), which are considered to be the precursor cell population of HCC in this model. All the mutations were missense, involved the Nrf2‐Keap1‐ binding regions and were associated with a strong increase of expression of the Nrf2‐target genes (Nqo1, Gclc,Gst4), in both pre‐ and neoplastic lesions. KRT‐19 positive HCCs arising 10 and 14 months later also showed a high percentage of Nrf2 mutations (70 and 56%, respectively), suggesting that mutation of this gene is critical for HCC development. Nrf2 silencing inhibited the ability of rat tumorigenic cells to grow in soft agar and to develop HCC when injected into syngeneic rats.ConclusionThis study demonstrates that Nrf2 mutation is a very early and frequent event, suggesting that dysregulation of the Nrf2‐Keap1 pathway is likely essential for the clonal expansion of KRT‐19+ preneoplastic hepatocytes to HCC.
PPARα: A Novel Target in Pancreatic Cancer
Authors: Hua Alexander , Casper Jessica , Bielenberg Diane , Schmidt Birgitta , Kieran Mark , Panigrahy Dipak , Gus‐Brautbar Yael 
Published: June 2021

BackgroundThe tumor stroma is increasingly implicated in pancreatic cancer. Pancreatic cancer is characterized by a highly fibrotic tumor microenvironment resulting in stromal resistance to chemotherapy. Peroxisome proliferator activated receptor alpha (PPARα), a ligand‐activated nuclear receptor/transcription factor, is a key negative regulator of inflammation. In PPARα deficient mice, stromal processes inhibited tumor growth resulting in dormant tumors. We hypothesized that blocking the PPARα pathway with a small molecule PPARα antagonist (NXT00120) may inhibit pancreatic cancer by targeting inflammation and cell signaling pathways that regulate cell cycle progression.ResultsSystemic administration of the PPARα antagonist, NXT00120, inhibited primary human pancreatic cancer cancer (HPAF‐II) and ascites formation in an aggressive orthotopic pancreatic cancer model. Combination of NXT00120 with gemcitabine induced sustained tumor regression in an orthotopic model of pancreatic cancer (PancOH7). NXT00120 reduced levels of phospho‐AKT, AKT, PCNA, Cyclin‐D1, RB protein levels.ConclusionWe demonstrated NXT00120 induced proliferation arrest by negatively modulating cell cycle regulatory proteins. Targeting pancreatic cancer with a PPARα antagonist is an entirely novel approach to complement chemotherapy to combat pancreatic cancer.Research Support: ROCA148633
High MUC2 Production in Goblet Cells Induces ER Stress and Exhibit Increase Susceptibility to Apoptosis
Authors: Tawiah Adelaide , Moreau France , Chadee Kris 
Published: June 2021

MUC2 is a large glycoprotein produced by goblet cells (GC) that form the protective mucus blanket overlying the intestinal epithelium. During pathological conditions such as IBD or colonic cancers, MUC2 biosynthesis and secretion are accelerated. Little information is known on how MUC2 production is regulated and whether GC undergoes endoplasmic reticulum (ER) stress following high MUC2 biosynthesis. We studied the role of MUC2 in GC stress using a high MUC2 producing GC line, HT29‐H, and a clone of HT29‐H (HT29‐L) in which MUC2 was stably silenced using lentivirus shRNA. Cells were treated with the ER stressor, tunicamycin (TUN) and markers for ER stress (GRP78, ATF4, CHOP, sXBP1) and apoptosis (caspase 3 and PARP cleavage) quantified by western blotting and RT‐qPCR. Compared to HT29‐L, HT29‐H cells showed significant increase in ER stress and apoptosis in response to TUN. Over expressing MUC2 in non‐MUC2‐producing SKCO15 cells also increased ER stress and apoptosis confirming specificity of MUC2. Pre‐treatment of cells with reactive oxygen species (ROS) inhibitor, diphenyleneiodonium, abrogated basal stress levels, TUN‐induced ER stress and apoptosis. HT29‐H constitutively produced significantly more ROS than HT29‐L cells indicating that high MUC2 production specifically increases ROS production that drives ER stress and apoptosis. These findings were corroborated in isolated colonic epithelial cells and colonic tissues from Wt and Muc2‐/‐ mice that showed significant increase in ER stress in Wt as compared to Muc2‐/‐ mice. We conclude that high MUC2 production by GC induces ER stress and apoptosis that could subsequently lead to diminished mucus barrier function in disease pathogenesis.Grant: CIHR
A biomedical synthesis of the zygoma: bone elastic properties, morphology and function, and reconstructive medicine
Authors: Dechow Paul , Wang Qian , Pryor Smith Leslie 
Published: June 2021

The zygomas form the prominent anterolateral structure of the midfacial skeleton. Functionally different from most cranial bones, the zygoma is subject to large strains because of the forces of the masseter muscle attached to the zygomatic arch, in addition to the indirect support of molar bite forces due to articulation between the zygomatic body and the maxilla. Clinically, there is a high tendency of the zygoma to fracture during trauma, which affects the integrity of the facial skeleton, demanding careful reconstruction. Thus, bone characters in the zygoma are of special importance in functional analysis and reconstructive medicine. Using ultrasonic techniques, microCT, cone beam radiography, and histological techniques, our laboratory has studied the material properties, and microstructure of the zygoma in a variety of primates including humans. Results have shown that across taxa the arch is the most anisotropic region of the cranial skeleton. Surprisingly, there is much inconsistency in the trabecular structure of the zygoma, with some taxa having little trabeculae and a nearly solid bony structure. This is not the case in humans where the bone is highly trabeculated and thus relatively weaker than in some primate species, suggesting that the human zygoma is more prone to injuries; a multidisciplinary approach considering both external and internal bone structures would promote functional recovery.Supported by the NSF Physical Anthropology HOMINID program NSF BCS 0725141.