bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Anatomy Schema Network
Authors: Nyamse Victor , Parker Caroline 
Published: June 2021

The Anatomical Schema network (ASN) is proposed as a framework that defines how anatomical information is stored in memory of an anatomy learner and serves as an indicator of the learner's competency. Information stored in Long Term Memory plays a vital role in all aspect of education and schema theory is seen as one of the most effective ways of conceptualizing information storage. It proposes that information is stored in memory as mental structures called schemata that consists of individual units and the interlinks between them. Based on this understanding, the anatomical schema (AS) is proposed as a hypothetical mental structure that stores anatomical information in units relating to an anatomical structure or region and the interlinks between those units.ASN groups these AS into three levels based on the nature of information in the individual units and the complexity of the interlinks between the units. AS in the first level have information units on a single anatomical structure and have a maximum of three interlinks. The second level contains AS with information units related to more than one anatomical structure and less than six interlinks. Units of AS in the third and final level have an infinite number of interlinks and contain information relevant to a particular professional context. The framework has been applied to anatomical taxonomies for learning activities (ALA), textual representation AI. A similar philosophy is applied in IAPP for assessments.
Topoisomerase‐Induced DNA Cleavage at Ribonucleotide Misincorporation Sites
Authors: Pommier Yves , Huang Shar‐Yin , Williams Jessica , Kunkel Thomas 
Published: June 2021

An estimated two ribonucleotides (rNMPs) per kilobase are mis‐incorporated into DNA due to high ratios of rNTP/dNTP pools in vivo, placing rNMPs as the most frequent source of DNA damage to date (Williams and Kunkel, 2014). The main pathway for rNMPs removal is the RNaseH2‐dependent pathway. When RNaseH2 is deleted in yeast, a specific topoisomerase I (Top1)‐dependent mutator effect develops: accumulation of short deletions within tandem repeats at genomic ribonucleotide sites generated by Top1 (Kim et al., 2011). We will discuss how ribonucleotide misincorporations induce replication stress and hyper‐recombination phenotype, which are alleviated upon deletion of the Top1 gene. On the other hand, ribonucleotide misincorporation is aggravated by inactivation of homologous repair (HR) in yeast strains. These in vivo data suggest that HR is important in the repair of Top1‐induced DNA damage in the presence of high levels of rNMPs. Using oligonucleotides with rNMPs incorporated at different positions, we show that Top1 can generate frequent DNA nicks with 3′ blocking ends (2′,3′‐cyclophosphates). In addition, we will demonstrate how a single rNMP is sufficient to generate recombination products and double‐strand breaks, a potential source of replication stress in vivo. Finally, we will show that faulty religation by Top1 generated 2‐nucleotide deletion, and the deletion products no longer contained rNMPs. Together these findings demonstrate the potential danger of Top1 activity at ribonucleotide misincorporation sites· Kim, N., Huang, S. Y., Williams, J. S., Li, Y. C., Clark, A. B., Cho, J. E., Kunkel, T. A., Pommier, Y., and Jinks‐Robertson, S. (2011). Mutagenic processing of ribonucleotides in DNA by yeast topoisomerase I. Science 332, 1561‐1564· Williams, J. S., and Kunkel, T. A. (2014). Ribonucleotides in DNA: origins, repair and consequences. DNA Repair (Amst) 19, 27‐37.
Glycemic and insulinemic responses are blunted by the consumption of a smoothie‐type beverage containing a whole‐grain fiber composite ingredient
Authors: O'Connor Lauren , Campbell Wayne 
Published: June 2021

This study assessed the effects of consuming a novel co‐processed composite ingredient comprised of a viscous fiber and whole‐grain high‐amylose maize flour, a rich source of resistant starch, on glycemic and insulinemic responses to meals. It was hypothesized that a smoothie‐type beverage containing the ingredient would blunt the post‐prandial responses in serum glucose and insulin concentrations compared to a beverage containing maltodextrin (MD). Nineteen healthy men and women (26 ± 3 years, BMI 24.3 ± 2.8 kg/m2) participated in 2 testing days (randomized crossover design) separated by at least 1 week. Subjects were counseled to consume a standard low‐fiber diet on each day prior to testing. On each testing day, blood samples were collected at baseline and incrementally for 8 hours after consuming a standardized low‐fiber meal with a beverage containing the composite ingredient or MD; a standard low‐fiber meal (without the composite ingredient or MD) was consumed 4 hours after the first meal. The composite ingredient blunted the post‐prandial glycemic (AUC0‐8h 3548 ± 1722 vs. 5352 ± 3564 mg/dL•480 min) and insulinemic (AUC0‐8h 7612 ± 3799 vs. 9769 ± 5156 µU/mL•480 min) responses (p<0.05) versus MD. Glycemic and insulinemic responses were lowered by 53 and 78%, respectively, after the first meal and by 17 and 11% after the second meal (p<0.05) with consumption of the composite ingredient. These findings support the use of this composite ingredient for insulin‐mediated glucose control.SupportIngredion Incorporated; NIH UL1TR001108; Purdue University
A Nutrient Profiling System for the (Re)Formulation of a Global Food & Beverage Portfolio
Authors: Vlassopoulos Antonios , Masset Gabriel , Leroy Fabienne , Drewnowski Adam 
Published: June 2021

BACKGROUNDOne goal of nutrient profiling models is to help the food industry reformulate its products for better public health. The Nestle Nutrition Profiling System (NNPS) was developed to help screen a global product portfolio for improved nutrient density.METHODFor nutrient profiling purposes,products in the portfolio were assigned to 3 main food groups and 32 food categories, based on consumer research data, patterns of food use, and insights from food technology. The groups were larger and smaller meal components (n=6 & n=18, respectively), and accessories (n=6). Nutrient targets were linked to age‐adjusted dietary guidelines. Nutrient density was assessed per serving. The NNPS algorithm ensured that excessive amounts of disqualifying nutrients could not be compensated for. An external expert board provided feedback during NNPS development.RESULTSNutrient targets for larger meal components were based on energy and nutrients per serving (% of energy or %DV), whereas those for snacks and accessories were based only on %DV of nutrients per serving. Maximum energy targets per serving were set to drive optimal serving sizes. The NNPS outcome was set as pass/fail, largely based on the presence of excess disqualifying nutrients. The relative distance of portfolio products from desired target goals then became the basis for product reformulation. Analysis of 14 randomly selected products showed that reformulation using NNPS resulted in a reduction of the content in all disqualifying nutrients.

Nestlé After vs Before

Added Sugars
SFA
Sodium
Total Fat

Chicken soup (250mL)
‐100%
‐100%
‐6%
‐47%

Chocolate milk (200mL)
‐14%
‐4%
0%
‐3%

Vegetable Lasagna (225g)
0%
‐42%
‐15%
‐25%

Vanilla Ice Cream Sandwich (70g)
‐50%
‐75%
‐39%
‐79%

Chocolate cereal bar (20g)
‐66%
‐97%
‐58%
‐92%

Apple drink (240mL)
‐54%
0%
‐75%
0%

Bacon slices (20g)
‐60%
‐42%
‐73%
‐44%

Water ice (85g)
‐35%
‐
0%
‐

Pepperoni pizza (143g)
25%
‐14%
‐13%
‐30%

Mousse type dessert (75g)
1%
‐63%
‐63%
‐68%

Puff pastry (28g)
‐42%
‐11%
10%
‐6%

Mayonnaise (15g)
‐80%
‐1%
1%
0%

Fruit Jellies (22g)
‐10%
‐
‐61%
‐

CONCLUSIONThe NNPS can help ensure that each product delivered to the consumer is (re)formulated to address public health needs and assist in the adoption of a balanced diet.
Serum Metabolomic Response to Vitamin E Supplementation in a Controlled Cancer Prevention Trial
Authors: Albanes Demetrius , Moore Steven , Weinstein Stephanie , Mondul Alison 
Published: June 2021

The Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study found that vitamin E supplementation led to 32% lower prostate cancer incidence, but two subsequent trials were not confirmatory. To increase our understanding of the effects of α‐tocopherol supplementation on cancer risk by searching for novel biochemical signatures, we examined the on‐study change in serum metabolomic profiles of men randomized to receive the ATBC α‐tocopherol supplement. Fifty men were randomly selected from each of the four trial groups: α‐tocopherol (as all‐rac‐α‐tocopheryl acetate), ß‐carotene, both supplements, and placebo. Metabolomic profiling of baseline and follow‐up fasting serum was conducted at Metabolon, Inc. (Durham, NC) using ultrahigh‐performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy. Of the 500 metabolites we identified, 24 changed in response to supplementation with α‐tocopherol at p<0.05. After correction for multiple comparisons with a threshold of p<0.00021, the top five metabolite signals were for α‐CEHC sulfate (β=1.512, p=1.5x10‐38), α‐CEHC glucuronide (β=1.412, p=1.0x10‐31), α‐tocopherol (β=0.974, p=2.2x10‐13), γ‐tocopherol (β=‐0.902, p=1.8x10‐11), and β‐tocopherol (β=‐0.731, p=9.4x10‐8). Interestingly, three amino acids were also altered by the α‐tocopherol supplementation, but below the Bonferroni level of statistical significance: beta‐alanine, ornithine, and N6‐acetyllysine (β=‐0.4, p=10‐2‐10–3). Comparison of the metabolomic profile found here to those in other vitamin E prevention trials may shed light on their apparently discordant findings.Research support: Intramural Research Program of the National Cancer Institute, NIH.
Omega‐3 Fatty Acids Modify Treatment Effect of High‐Dose B Vitamins in Cognitively Impaired Elderly
Authors: Jernerén Fredrik , Elshorbagy Amany , Oulhaj Abderrahim , Smith Stephen , Refsum Helga , Smith David 
Published: June 2021

ObjectiveTo investigate whether plasma omega‐3 fatty acid (FA) concentrations (eicosapentaenoic acid, EPA; docosahexaenoic acid, DHA) modify the treatment effect of homocysteine‐lowering B vitamins on brain atrophy rates and cognitive decline in a placebo‐controlled trial.DesignThe effect of high‐dose B vitamins in the previously reported VITACOG trial [PLoS ONE 5(9) 2010: e12244] was analysed according to baseline omega‐3 FA concentrations. This study included 168 elderly (蠅70 y) with Mild Cognitive Impairment randomly assigned either to placebo, or to B vitamins.ResultsThere was a significant interaction (P = 0.024) between B vitamin treatment and plasma combined omega‐3 FA (EPA+DHA) on brain atrophy rates. In subjects with high baseline omega‐3 FA (˃590 μmol/L), B‐vitamin treatment slowed the mean atrophy rate by 40% compared with placebo (P = 0.023). B‐vitamin treatment had no significant effect on rate of atrophy among subjects with low baseline omega‐3 FA (<390 μmol/L). High baseline omega‐3 FA were associated with a slower rate of brain atrophy in the B‐vitamin group, but not in the placebo group. A similar interaction was found between omega‐3 FA and the beneficial cognitive effects of B vitamin treatment.ConclusionThe beneficial effect of B vitamin treatment on brain atrophy and cognitive decline was observed only in subjects with high plasma omega‐3 FA. It is also suggested that the beneficial effect of omega‐3 FA may be confined to subjects with good B vitamin status.
Elevations in Serum Anti‐flagellin and Anti‐lipopolysaccharide Immunoglobulins are Related to Underweight in Young Tanzanian Children
Authors: McDonald Christine , Tran Hao , Gosselin Kerri , Manji Karim , Gewirtz Andrew , Kisenge Rodrick , Aboud Said , Fawzi Wafaie , Duggan Christopher 
Published: June 2021

BackgroundAntibodies to lipopolysaccharide (LPS) and flagellin have been described as indirect measures of increased gastrointestinal permeability and may be markers of environmental enteric dysfunction (EED), a condition linked to poor child growth. ObjectiveTo assess whether serum LPS‐ and flagellin‐specific immunoglobulin concentrations are associated with poor growth among young Tanzanian children at risk of EED. MethodsBlood samples were obtained from 590 children at age 6 wks, 6 and 12 mths. Serum LPS‐ and flagellin‐specific immunoglobulin levels (IgA and IgG) were measured by ELISA. Growth was measured monthly for 18 mths. ResultsAt 6 wks, compared to infants with LPS‐IgA, LPS‐IgG, flagellin‐IgA, and flagellin‐IgG levels in the lowest quartile, those with values in the highest quartile were, respectively, 1.93 (95% CI 1.06, 3.51), 2.89 (1.49, 5.61), 2.09 (1.11, 3.91), and 2.67 (1.38, 5.16) times more likely to become underweight (WAZ <‐2) after adjusting for covariates (p <0.05). These 6 wk markers were not related to the risk of stunting (LAZ <‐2). There was no association between any of the markers at 6 or 12 mths and subsequent underweight or stunting. ConclusionEED in early infancy, as measured by serum levels of LPS‐ and flagellin‐specific immunoglobulins, is associated with underweight. The relationship between these markers and other EED diagnostic tests requires further study.
Sensitivity and Specificity of Serum Retinol in Determining Vitamin A Deficiency
Authors: Suri Devika , Tanumihardjo Jake , Gannon Bryan , Tanumihardjo Sherry 
Published: June 2021

Vitamin A deficiency (VAD) afflicts 190 million children worldwide, increasing the risk of morbidity, mortality and blindness. Serum retinol concentration (SR), a common indicator of VA, is not always associated with liver VA reserves due to homeostatic control and during infection. Sensitivity and specificity are used to evaluate the utility of clinical tests to determine presence of disease. Our objective was to determine the sensitivity and specificity of SR as an indicator of VAD in two rural populations of children from Zambia and Thailand.VA deficiency was based on cutoffs of <0.1 umol/g for liver VA stores (LVA) calculated using stable isotope dilution and <0.7 umol/L for SR. No Zambian children were found deficient using LVA, but 17% were deficient using SR; no children were deficient using SR in the Thai children, but 68% had VAD using LVA. Because there were no true positive cases of VAD in the Zambia children, sensitivity could not be calculated. Specificity was 83%, meaning that 83% of true negative VAD cases were identified, but 27% were false positives. Conversely in the Thai children there were no VAD cases identified by SR, so there were no true or false positives and thus sensitivity was 0%. Specificity was 100%, meaning that all cases identified as not VAD were true negatives. If there was presence of infection as indicated by elevated CRP, AGP or malaria, specificity was reduced; that is, SR was less likely to identify false positives in children without infection in Zambia.We found that specificity of SR as an indicator of VAD was between 83‐100%, but sensitivity could not be calculated because in these populations there were no children with VAD as identified by both SR and LVA. Presence of infection reduced the specificity of SR for determining VA status.
Feeding Practices Associated with Toddler Dietary Intake
Authors: Edelson Lisa , Mokdad Cassandra , Martin Nathalie 
Published: June 2021

ObjectiveTo explore the relationship between parents' observed feeding practices during a typical day of meals and the toddler's usual intake of food groups.MethodsSixty families of 12‐36 mo.‐old children recorded all of children's meals for one full day, plus an additional meal at which they introduced a new fruit or vegetable. These videos were coded for parent and child behavior during mealtimes. Three months later, each family completed three 24‐hr dietary recall interviews, from which intakes of food groups were extracted.ResultsEncouragements: Parents' encouragements of vegetable intake during main meals and the novel vegetable were both positively correlated with typical vegetable intake. There was a trend for encouragements of fruit during main meals to be correlated with children's fruit intake, but no association with encouragements of a new fruit. Significant subtypes of encouragements for fruits at main meals were reasoning, modeling, and pressure; for vegetables, reasoning, modeling, and neutral encouragements.Other behaviors: Parents who served vegetables at least once during main meals had children with significantly higher typical intakes of fruit, and a trend for eating more whole grains and vegetables. Children of parents who used restriction ate significantly more refined grain and had a trend for eating less fish. Correlations between additional parent behaviors and intake will also be presented.Environment: Compared to those who did not watch TV during meals, children who had a TV/screen on during at least one meal ate less fruit, fish, and alternative proteins, with a trend for eating less whole grain and more dairy.ConclusionsMealtime practices such as how new foods are introduced and TV viewing during meals are associated with children's intake of many food groups.
Excess Body Weight Is Not Associated with Colorectal Cancer Survival: The Multiethnic Cohort
Authors: Maskarinec Gertraud , Harmon Brook , Ollberding Nicholas , Wilkens Lynne , Henderson Brian , Kolonel Laurence , Le Marchand Loic 
Published: June 2021

PurposeExcess body weight has been associated with a higher risk for colorectal cancer (CRC) and may also adversely affect mortality in CRC patients. The current study examined the relation of prediagnostic body mass index (BMI) with CRC‐specific and all‐cause mortality in the Multiethnic Cohort (MEC).MethodsAmong the 5 major ethnic groups, 4204 invasive cases of CRC were diagnosed between cohort entry and 2010. Cox regression was applied to estimate hazard ratios (HR) and 95% confidence intervals (CI) while adjusting for relevant covariates. Using self‐reports at baseline and after 5.7±0.8 years (73% of participants), BMI was treated as time‐varying exposure.ResultsOf the 2258 men and 1946 women, 1674 (40%) were overweight and 939 (22%) were obese at baseline. After 6.0±4.7 years of follow‐up, 1976 overall deaths and 1095 deaths due to CRC occurred. No significant association with CRC‐specific mortality was detected in men (HR=0.94; 95%CI: 0.84, 1.04) and women (HR=0.98; 95%CI: 0.89, 1.08) per 5 units of BMI. In men, all‐cause mortality showed no relation with BMI (HR=0.97; 95%CI: 0.90, 1.06), whereas it was elevated in women (HR=1.10; 95%CI: 1.03, 1.31). Interactions of BMI with ethnicity were not significant, but risk estimates varied across groups.ConclusionsLittle evidence for an adverse effect of excess body weight on survival was detected within a multiethnic group of CRC cases although some variations in mortality were seen after stratification by sex and ethnicity.
Trefoil Factor Family 1 (TFF1) Inhibit the Invasion of Tumor Cells of the Pancreas
Authors: Yamaguchi Junpei , Kokuryo Toshio , Yokoyama Yukihiro , Nagino Masato 
Published: June 2021

ObjectiveThe tumor suppressive role of TFF has been recently reported in gastric tumorigenesis. Here we aimed to clarify the role of TFF1 as tumor suppressor in pancreatic tumorigenesis.MethodsBy immunohistochemistry, the expression pattern of TFF1 was analyzed in surgically resected specimen of PDAC (Pancreatic Ductal Adenocarcinoma; n=14), invasive IPMN (Intraductal Papillary Mucinous Neoplasms: n=12) and non‐invasive IPMN (n=10). Human pancreatic cancer cell line was treated by TFF1‐siRNA to evaluate the role of TFF1 in vitro.ResultsTFF1 expression is not found in normal pancreatic ductal epithelium. Pancreatic Intraductal Neoplasm (PanIN) has high expression of TFF1, suggesting that up‐regulation of TFF1 is the early event of pancreatic tumorigenesis. While TFF1 is also expressed in the intraductal compartment of PDAC and IPMN, it is frequently lost in the invasive compartment (50% (7/14) in PDAC and 58.3% (7/12) in invasive IPMN). The expressions of TFF1 in human pancreatic cancer cell lines were evaluated and Panc1 was found to have TFF1 mRNA. Suppression of TFF1 in Panc1 cells by siRNA does not change the proliferative rate of Panc1 cells; however, it was found to induce the higher invasive ability (55.2% of invasive area in control, 94.9% in TFF1‐siRNA; p<0.01) by Boyden chamber assay.ConclusionWhile acquisition of TFF1 seems to be the early event of pancreatic tumorigenesis, loss of TFF1 may result in the invasive transformation of pancreatic tumor.
Modulating Neutrophil‐Derived MPO‐Endothelial Surface Binding with CORMs
Authors: Patterson Eric , Fraser Douglas , Inoue Ken , Cepinskas Gediminas 
Published: June 2021

Myeloperoxidase (MPO) binds to vascular endothelial cells (EC) through a mechanism that, at least in part, involves interactions with glycosaminoglycans expressed on the endothelial surface. MPO that is closely associated with endothelial cells can directly damage them through its catalytic activity. Our previous work demonstrated that carbon monoxide‐releasing molecule 3 (CORM‐3) inhibits MPO catalytic activity and can thereby mitigate its detrimental effects during severe inflammation. The effects and mechanisms of CORM‐dependent modulation of MPO‐vascular EC binding are not yet investigated.We have employed in vitro assays to study neutrophil‐derived MPO binding to human umbilical vein EC (HUVEC) following treatment with two structurally different CORMs; CORM‐3 and CORM‐401, synthesized based on Ru or Mn transition metals, respectively.Our results indicate that at equimolar concentrations CORM‐3, but not CORM‐401 inhibits MPO‐endothelial surface binding. Inactivated CORM‐3 (iCORM‐3) did not inhibit MPO binding to ECWe conclude that in addition to CORM‐3‐dependent suppression of MPO catalytic activity, reduced MPO binding to EC in the presence of CORM‐3 may provide an additional mechanism that contributes to CORM‐dependent suppression of inflammation and endothelial damage.
Entamoeba histolytica Induces Pro‐Inflammatory Mediator HMGB1 Release in Early Contact with Macrophage
Authors: Begum Sharmin , St‐Pierre Joëlle , Moreau France , Chadee Kris 
Published: June 2021

Entamoeba histolytica (Eh) is an invasive extracellular parasite that causes amebiasis in ~10% of infected individuals resulting in 105 deaths/year. The host and/or parasite factors that influence disease susceptibility remain unknown. Interaction between Eh and host macrophages has been shown to trigger a strong pro‐inflammatory response characterized by IL‐1β and TNF‐α release. High Mobility Group Box1 (HMGB1) is a non‐histone nuclear protein secreted by macrophages upon stimulation with various bacterial, viral and cellular components. HMGB1 binds TLRs (TLR‐2 and 4) and induce pro‐inflammatory responses in neighboring cells. In this study, we investigated whether Eh could trigger the release of the pro‐inflammatory molecule HMGB1 as an early “alarmin” signal and the putative parasitic virulent factors involved. Only stimulation with live Eh but not Eh components triggered prompt (1‐5min) and robust secretion of HMGB1 in human macrophages. This event was contact‐dependent as inhibiting Eh adhesin, Gal‐lectin with exogenous galactose abrogated HMGB1 release. HMGB1 secretion was independent of the major surface virulent factor cysteine proteinase 5 (EhCP5) as CP5‐deficient Eh, or cysteine protease inhibitor pretreatment of Wt Eh had no effect. HMGB1 secretion was independent of caspase‐1 activation, as revealed by using pan caspase inhibitor, Z‐VAD‐fmk. Eh‐induced HMGB1 release upon contact with macrophage acts as a sensor for the host to detect invasive Eh that can attract bystander cells to amplify innate host defenses and/or promote an acute pro‐inflammatory response critical in disease pathogenesis.Grant Support: NSERC