bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interrogation of novel biomarkers for the treatment of inflammatory diseases: Raf‐1 kinase inhibitor protein as a case study (146.10)
Authors: Wright Kyle , Vella Anthony 
Published: June 2021

Through cutting edge proteomics, our lab has identified Raf‐1 kinase inhibitor protein (RKIP), a molecule previously described as a regulator of MAPK and NF‐κB signaling, as a new potential therapeutic target for immune regulation of inflammatory disorders. We are currently investigating the breadth and mechanism of RKIP function within the immune system, and how this can be applied to future therapeutic intervention. Experimentally, we have illustrated that RKIP is critical for T cell receptor signaling and IFNγ production from antigen‐specific T cells in a model of systemic inflammatory response syndrome (SIRS). This was evidenced by a 50% reduction in IFNγ+ T cells in RKIP‐/‐ mice after SIRS initiation and a 70% reduction in IFNγ from wild type T cells after blockade of RKIP with a small molecule inhibitor. Additionally, RKIP seems to play a role in proper toll‐like receptor (TLR) signaling in antigen presenting cells (exemplified by its rapid downregulation on immunoblot after stimulation with TLR ligands), and is necessary for maintaining the type I interferon signaling architecture in B cells as we observed a 2‐4 fold decrease in important transcripts by RNAseq in RKIP‐/‐ B cells (Table I). Taken together, our data suggest that RKIP is a critical player in driving cytokine responses from immune cells and provides a potential new target for the development of future therapeutics against inflammatory diseases.
Table I: RKIP‐/‐ B cells have an altered Type I Interferon signature by RNASeq

Gene
Location
Log2(change)
Fold Change
p value

Traf3
chr. 12
‐1.56
‐2.95
.0027

Irf3
chr. 7
‐1.86
‐3.63
.0027

Irf5
chr. 6
‐1.27
‐2.41
.0017

Irf7
chr. 7
‐1.93
‐3.81
.0018

Ifnar1
chr. 16
‐1.26
‐2.39
.0030

Grant Funding Source: Supported by grants from NIH (RO1 AI042858, Project 3 PO1 AI05172, and T32 AI007080)
Plasma metabolomic profiling in adults with cystic fibrosis and cystic fibrosis‐related diabetes (248.1)
Authors: Alvarez Jessica , Frediani Jennifer , Jones Dean , Grossmann Ruth , Uppal Karan , Tangpricha Vin , Ziegler Thomas 
Published: June 2021

Background: Advances in metabolomics enable broad exploration of metabolism in cystic fibrosis (CF) and cystic fibrosis‐related diabetes (CFRD).Methods: Plasma from 30 CF adults hospitalized for pulmonary symptoms (15 with CFRD) and 17 healthy controls were analyzed by high‐resolution LC‐MS. Data was analyzed in R using an in‐house pipeline that performs log2‐transformation, quantile normalization, FDR analysis using limma, and hierarchal clustering analysis (HCA). The METLIN Database was used to match ions to known metabolites. A targeted metabolome‐wide association study (MWAS) with serum 25‐hydroxyvitamin D (25(OH)D) levels was also done.Results: Of 11,736 metabolites, 4,522 significantly differed between CF and controls (q = 0.01). HCA revealed 55 distinct metabolomic clusters differentiating CF and control subjects. Derivatives of vitamin D3 and several acylcarnitines were lower in CF. MWAS identified 268 metabolites associated with serum 25(OH)D levels, including octanoylcarnitine (r = 0.51, P = 0.01). A total of 74 metabolites significantly differentiated CF patients ± CFRD (q = 0.05), including coenzyme A and ATP.Conclusions: Plasma metabolomic profiling can distinguish adults with or without CF and CF patients ± CFRD; other metabolites are linked with vitamin D status. These pilot data suggest fatty acid β‐oxidation pathways may be perturbed in certain CF patients.Grant Funding Source: Supported by National Institutes of Health (T32 DK007298‐32S1, K23 AR054334, and K24 RR023356).
Teens and greens: the effect of vegetable‐based smoothies on adolescent health and school performance (251.8)
Authors: Lefkowitz Sarah , Rockway Susie 
Published: June 2021

Teens and Greens: The Effect of Vegetable‐Based Smoothies on Adolescent Health and School Performance S Lefkowitz, S Rockway Capital Brands, 11755 Wilshire Blvd; LA CA 90025 ABSTRACT
Background: Children who eat breakfast are more likely to meet nutritional needs and perform better in school and on tests, yet many skip breakfast and do not meet their RDI for vegetable intake.Purpose: Introduce vegetables to high school students at breakfast by giving a variety of fresh produce and high‐powered blenders to make healthy, palatable smoothies.Design: Pre‐post design, 43 students from a local high school volunteered for a 3‐month pilot study. An RD met and encouraged students daily to make their own smoothie, ideally with 2 C veggies. Outcome measures were body composition, lipids and change in nutrient intake. Qualitative data were obtained at baseline and end of study via surveys regarding students’ views of health, focus and performance in school.Results: Of the 43 students, 21 completed. Waist circumference decreased by 3% on average; plasma HDL increased in 14 students, TC dropped 9% in 7 students. Energy improved in 13 students. Ten percent had better grades. Afternoon lethargy dropped from 35% to 22%. Change in nutrient profiles of smoothies: Total kcal decreased from 293 to 247; veg servings increased from 1.75 to 2.25; CHO decreased from 58 to 40.5g; protein intake increased 1g, fat increased from 6 to 8.5 g and no change in fiber intake.Conclusion: A daily vegetable‐based smoothie improved energy levels, focus, lipid profiles and body image in participating high school students.
Creation of a mobile‐phone application for assessing supermarket offerings for a Guatemalan‐based exploration of the Nutrient Environment Measurement Survey‐Stores (255.1)
Authors: Kanter Rebecca , Alvey Jeniece , Fuentes Déborah 
Published: June 2021

Background: Consumer nutrition environment measures are important to understanding the food environment, which affects individual diet. A paper version of the nutrition environment measures survey for supermarkets (NEMS‐S) was modified for use in Guatemala. However, a paper survey is not an inconspicuous data collection method and is not well equipped for multiple languages in the same version.Objective: To design, pilot test, and validate the paper NEMS‐S for Guatemala in the form of a mobile phone application (mobile app).Methods: CommCare, a free and open‐source software application, was used to design the NEMS‐S for Guatemala in the form of a mobile app. Two raters tested the mobile app in one Guatemalan supermarket. Both the inter‐rater and test‐retest reliability of the mobile app was determined using percent agreement and Cohen’s Kappa score; and compared to the paper version.Results: The inter‐rater reliability was very high between the paper survey and the mobile app (Cohen’s kappa > 0.90). Test‐retest reliability ranged from Kappa 0.78‐0.91. With experience, survey completion‐time using the mobile app was 5 min less than the paper form (35 vs 40 min).Conclusions: The NEMS‐S mobile app provides for more rapid data collection, with equivalent reliability and validity of the NEMS‐S paper version. And has advantages over a paper‐based survey of multiple language capability and concomitant data entry.
Residential property values: a novel GIS‐based metric to characterize obesogenic environments (255.8)
Authors: Aggarwal Anju , Rehm Colin , Cohen‐Cline Hannah , Hurvitz Phil , Moudon Anne , Drewnowski Adam 
Published: June 2021

Objective: To determine whether multiple attributes of obesogenic environments can be captured by the single objective measure of residential property values. Methods: The Seattle Obesity Study (SOS) was a cross‐sectional study on socioeconomic disparities in diets and health. A telephone survey of a geographically distributed sample of 2,001 King County adults was conducted in 2008‐09. Home addresses were geocoded. Residential property values at tax parcel level were obtained from King County tax assessor. Mean residential property values within a 10‐minute walk (833m buffer) were calculated. Perceptions toward neighborhood social and physical environment were collected by self‐report. Multivariable linear regression analyses examined the associations among multiple attributes of the neighborhood environment, property values and body mass index (BMI). Results: Perceived neighborhood attributes such as crime, heavy traffic and proximity to bars, liquor stores and fast foods were all associated with lower property values. By contrast, living in neighborhoods that were perceived as safe, quiet, clean and attractive was associated with higher property values. Higher property values were in turn associated with lower BMIs. The observed associations between perceived neighborhood characteristics and BMI were largely attenuated after accounting for property values. Conclusion: Environments, described as obesogenic in past studies, were consistently associated with lower property values. Further research, in additional locations, needs to explore whether residential property values act as a proxy for other neighborhood characteristics and socioeconomic status.Grant Funding Source: NIH grants P20 RR020774‐03, R01 DK076608‐04 and R21 DK020774
Differences among pulse grains and cereal grains in dietary fiber (259.5)
Authors: Thompson Henry , Echeverria Dimas , Brick Mark 
Published: June 2021

Pulses, i.e., dry beans, dry peas, chickpeas, and lentils, are grain legumes that serve as staple food crops for populations around the world. Since ancient times, pulses have been combined with cereal grains, primarily wheat, rice, or corn, or tubers such as potato or cassava to provide a balanced source of protein and carbohydrate and a nutritionally adequate diet when combined with seed oils, fruit and vegetables. In this setting, the established ratio of cereal grains to pulses to meet nutritional requirements is 2:1; however, over the last 60 years both production and consumption patterns, globally, have changed to 8:1. One consequence of these changes has been on a marked but largely unappreciated shift in dietary carbohydrate quality. This presentation focuses on differences among pulse crops in their amount and type of dietary fiber and how this relates to the amounts and types of dietary fiber provided by various cereal grains. Data will be reported using the AOAC 2011.25 Integrated Total Dietary Fiber Assay to quantify dietary fiber and oligosaccharide content. These data will be considered in the context of the pandemic of overweight and obesity that has swept the globe over the last 60 years since there has been virtually no scrutiny of the potential association between the decline in pulse consumption and the global rise in obesity and its associated metabolic disorders.Grant Funding Source: PHS R01‐ CA172375 and American Pulse Association
Maternal food insecurity, anemia, and social support are independently associated with prenatal depression among HIV‐positive and ‐negative women attending antenatal services in northern Uganda (268.2)
Authors: Natamba Barnabas , Achan Jane , Oyok Thomas , Mou Sophie , Gosh Shibani , Stoltzfus Rebecca , Griffiths Jeffrey , Young Sera 
Published: June 2021

Introduction: Limited data exist on prenatal depression in in high HIV burden resource‐poor settings.Population: 403 pregnant clinic attendees at Gulu Hospital, Uganda. HIV (+) women were oversampled in a ratio of 1 HIV (+): 2 HIV (‐).Methods. Depression was assessed using the Center for Epidemiological Studies‐Depression (CESD) scale. Maternal food insecurity (FI) was evaluated using an individually focused Food Insecurity Access Scale, anemia using a Hemocue® hemoglobinometer, and social support using the 10 item version of the Duke‐UNC functional social support instrument. We performed bivariate and multivariate analyses to identify variables associated with CESD scores keeping those with p <0.05 as well as theoretically or contextually important variables in the final model.Results: CESD scores ranged from 0‐57 (mean 20 + 13.2SD). 62.3% of study women had a major depressive episode (CESD score 蠅15). While being HIV (+) was linked to higher CESD scores in bivariate analyses, in multivariate linear regression maternal food insecurity (β=+0.663) and age (β=+0.227) were the only factors associated with higher CESD scores. Maternal social support (β=‐1.209) and higher hemoglobin (β=‐0.927) were linked to lower CESD scores.Conclusion: Interventions targeting depressed pregnant Ugandan women should better understand how age, food insecurity, anemia, and social support influence prenatal depression.Grant Funding Source: Supported by USAID Feed the Future grant to Tufts University
Tracking chromatin signatures in individual cells to trace vascular smooth muscle cell lineage in human atherosclerotic lesion (278.4)
Authors: Gomez Delphine , Shankman Laura , Owens Gary 
Published: June 2021

Atherosclerosis is a chronic disease of the arterial wall responsible for nearly 50% of deaths in developed countries. There is a strong correlation between ratio of smooth muscle cells (SMC) to macrophages and stability of atherosclerotic lesions; a high macrophage to SMC content associated with high risk of plaque rupture. Herein, we reevaluated the contribution of SMC within lesions that was underestimated due to lack of identification of SMC undergoing phenotypic switching (i.e loss of SMC marker gene expression). Using a SMC‐lineage tracing mouse, we show that traditional staining for SMC is unable to detect 86% of the SMC population within lesions of Apoe‐/‐ mice and that 25% of macrophages identified by traditional macrophage markers are of SMC origin. To validate these data in human, we developed a novel method of detection of histone modifications on gene loci in single cells using tissue sections. Our assay was based on studies showing that the histone modification H3K4dime on the SMC marker genes is a specific and stable epigenetic marker of the SMC lineage in vitro. First, H3K4dime on the SMC marker genes (PLA+ cells) was strictly restricted to SMC lineage in vivo. Then, we identified PLA+/macrophage markers+ cells in human lesions. In conclusion, we rigorously identified lesion cells of SMC origin and we provide exciting evidence that a fraction of macrophage‐like cells in human lesions are derived from SMC.Grant Funding Source: American Heart Association
An acute non‐lethal method to test leptin responsiveness in rats (371.3)
Authors: Desai Bhavna , Harris Ruth 
Published: June 2021

Continuous subcutaneous administration of leptin normalizes blood glucose levels in rodent models of type I and type II diabetes independent of changes in food intake, body weight and plasma insulin. We tested whether an acute intravenous leptin infusion changed blood glucose in normal and diet‐induced leptin resistant rats and determined if this could be used as a marker of leptin sensitivity. Leptin responsive, chow fed male Sprague Dawley rats and leptin resistant rats fed chow, lard and 30% sucrose or chow and 30% sucrose were fitted with jugular vein catheters. They were infused with either saline for 32 min, low dose (LD) leptin (1.9µg/kg/min) followed by high dose (HD) leptin (3.75µg/kg/min) for 16 min each, or only HD leptin for 16 min. Infusion of either LD leptin or HD leptin alone did not change blood glucose. Infusion of LD leptin followed by HD leptin decreased blood glucose in leptin responsive, but not leptin resistant rats. Leptin infusion increased serum leptin in all groups, but had no effect on serum insulin, glucagon, 18 hour weight gain or 18 hour energy intake in any rat. The leptin‐induced decrease in blood glucose correlated with leptin responsiveness measured as a leptin‐induced inhibition of food intake. This effect is consistent in control rats and absent in two rat models of leptin resistance. Thus, this acute non‐lethal test is a novel method of testing leptin responsiveness in rats.Grant Funding Source: Supported by NIH DK 53903
Adaptation and evaluation of the WillTry tool to assess willingness to try fruits and vegetables among children 3‐11y in Guam (380.6)
Authors: Aflague Tanisha , Leon Guerrero Rachael , Boushey Carol 
Published: June 2021

Children’s fruit & vegetable (FV) intake is mediated by a preference for FV or a willingness to try FV. Our aim was to adapt the validated WillTry (Thomson et al Appetite 2010) for interventions in Guam among children, 3‐11 y. Adaptations included novel and common FV unique to Guam. Children were shown images matching the 14 food questions during a one‐on‐one interview and a 2nd interview 3‐72 hrs later for reliability. Factor analyses determined components of willingness to try FV. We analyzed psychometric properties and reliability. Sixty‐five children from 2 camps completed the first interview and 64 did the second. Factor analyses revealed 3 dimensions, i.e., local novel (guava, breadfruit, eggplant, sweet sop, star apple, taro leaves), local common (carrot, papaya, long beans, salad greens), and imported (apple, canned peaches, canned corn). All but the imported scale had sufficient internal consistency (Cronbach’s α>0.69). Each food scale had substantial reliability (ICC>0.76). There were no significant differences by age, sex, or camp for any scale. Mean scores were 2.1 (local novel), 2.4 (local common), and 2.7 (imported) and all were significantly different. The adapted WillTry was culturally relevant and possessed similar psychometric properties as the original. An unexpected finding was the tool’s potential for documenting shifts from local to imported FV, a concern of the nutrition transition.Grant Funding Source: Supported by NCI 1U01CA130784‐01; USDA NIFA no 2011‐68001‐30335
Gender differences in impact of food stores in neighborhoods on children’s obesity status change: U.S. early childhood longitudinal study (390.4)
Authors: Chen Hsin‐Jen , Wang Youfa 
Published: June 2021

Objective: Examine influence of food stores in neighborhoods on children’s weight change by gender. Methods: Height and weight of a national representative sample of US schoolchildren were directly measured at 5th and 8th grades (n=7,090). Information of food store quantities in neighborhoods (supermarkets, convenience stores, takeaway restaurants) in the years of follow‐ups (2004 and 2007) was obtained from the US Zip‐code Business Pattern Data. Children’s weight status and neighborhood environment characteristics were linked via children’s residence zip code. Results: Mixed‐effect models showed that girls living in neighborhoods with 2 supermarkets had lower odds of becoming obese 3 years later (OR=0.44 [95% CI: 0.23‐0.83]) than did those living in neighborhoods without supermarket. Girls living in neighborhoods with more takeaway restaurants had greater odds of becoming obese 3 years later than those living in neighborhoods with 蠄1 takeaway restaurant (OR=4.45 [1.54, 12.83]). Decreased number of supermarkets in neighborhoods was associated with increased odds of obesity for girls (OR=1.68 [1.07, 2.64]). However, there was no significant finding for boys. Conclusions: Girls’ weight status change at the pubertal age, but not boys’, was associated with local food store environments.Grant Funding Source: NIH (R01DK081335‐02, R01HD064685‐02)
Inhibition of tumor growth by ERK1/2 inhibitors is associated with the induction of interferon‐γ production (397.3)
Authors: Ma Xingzhe , Wang Qixue , Duan Yajun , Han Jihong 
Published: June 2021

Inhibition of tumor growth by ERK1/2 inhibitors is associated with the induction of interferon‐γ productionXingzhe Ma, Qixue Wang, Yajun Duan, Jihong HanState Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, Nankai University, Tianjin 300071, ChinaERK1/2 plays an important role in cell survival, proliferation and differentiation. However, the high ERK1/2 activity has been linked to tumorigenesis. Several ERK1/2 inhibitors are in clinical trials to evaluate their effects on cancers. IFN‐γ is an important cytokine with anti‐tumorigenic function. So far, it has been remained unknown if the anti‐cancer action of ERK1/2 inhibitors is related to their effect on IFN‐γ expression. We previously reported that activation of LXR induces IFN‐γ expression and inhibits tumor growth, and ERK1/2 inhibitors can activate LXR‐targeted gene expression. Herein, we determined if ERK1/2 inhibitors can influence IFN‐γ expression, and the anti‐tumorigenic action of ERK1/2 inhibitors is completed, in part, by their effect on IFN‐γ production. We observed that ERK1/2 inhibitors increased IFN‐γ protein expression which was associated with increased IFN‐γ mRNA expression, promoter activity and formation of LXRE‐nuclear protein complexes. In vivo, U0126 increased mouse serum IFN‐γ levels and IFN‐γ expression in tissues. Animal study also demonstrated that U0126 inhibited inoculated LLC1 tumor growth in wild type but not in IFN‐γ‐/‐ mice indicating the inhibition is associated with IFN‐γ production. Our study suggests that ERK1/2 inhibitor induces IFN‐γ production and the induction can be partially attributed to their anti‐tumorigenic properties.
Human beta‐defensins‐1, ‐2, and ‐3 production by human amniotic epithelial cells in relation to human papillomavirus genotype (397.4)
Authors: Szukiewicz Dariusz , Alkhalayla Habib , Stangret Aleksandra , Szewczyk Grzegorz 
Published: June 2021

HPV is common sexually transmitted infection. Based on the oncogenic potential, low‐risk and high‐risk HPV types were distinguished among approximately 40 HPV genotypes identified within the mucosa of the anogenital tract. Epithelial HBDs act as a potent protein adjuvants promoting cellular and humoral immune responses in viral infections. Unlike alpha‐defensins, HBDs are upregulated in HPV infections. We compared strenght of this response in respect to oncogenic (types 16 and 18) and non‐oncogenic (6 and 11) HPVs (groups I and II, respectively). After normal pregnancies (N = 96) HAEC were isolated from the amnions using trypsinization and divided into three groups (including negative controls; group III), according to the results of the vaginal smear real‐time PCR test for detection of HPV DNA. HAEC stimulated with lipopolysaccharide (1μg/ml) were cultured in vitro for 5 days. HBD‐1, HBD‐2, and HBD‐3 were quantified by ELISA in the culture media samples. Observed mean increases for HBDs were 5.7‐, 3.4‐, and 4.6‐fold, compared to the controls. The mean increases in HBDs concentrations were weaker in the oncogenic HPV infection, compared to the non‐oncogenic HPVs, and the differences between group I and II reached statistical significance (p < 0.05) for HBD‐1 and HBD‐3. Thus, HPV‐related HBD overproduction depends on the virus genotype. Subdued response to oncogenic HPVs may be included in their pathomechanism.Grant Funding Source: Supported by WUM grant: 2M2‐W2‐13.