bluuebunny/crossref_metadata_2025_split huggingface dataset:
Group Coaching, Grounded in Theory and Evidence, Deployed through the National Research Mentoring Network (NRMN) to Complement Research Mentoring and Increase Diversity
Authors: McGee Richard 
Published: November 2023

Biomedical research training has historically relied almost exclusively on mentoring by research advisors as the vehicle for developing the talents of young scientists. Following an apprenticeship model, it affords almost a limitless array of permutations and combinations among mentors and trainees. It also allows for maximum variations in approaches to mentoring. However, it also leads to extreme variability in terms of what is ‘taught’ and opportunities made available to those in training, often leading to unpredictable outcomes, and/or underdevelopment or loss of scientific talent. This potential loss of talent can have especially high impact for individuals from underrepresented groups. As an alternative and complementary approach to more fully develop scientific talent, several variations of group coaching processes have been created and studied. All incorporate both practical and theoretical underpinnings and have established evidence of efficacy, and in one case intensive analysis through a randomized controlled trial. Based on both evidence of impact and theoretical strengths, they are now being expanded beyond their home institutions or limited missions to national impact through the National Research Mentoring Network (NRMN) funded by NIH.This presentation will highlight the theoretical basis, designs, and impacts to date of 4 different grant writing group coaching models being deployed and compared through NRMN. The presentation will also describe the career coaching group model with an expanded focus beyond grant writing that has evolved from a randomized controlled trial. The refined career coaching model is being tested in collaboration with the American Society for Pharmacology and Experimental Therapeutics (ASPET). All of the coaching models augment and complement research and other mentoring trainees are receiving. The models also all employ coaches who are highly skilled and successful scientists, usually with extensive mentoring experience, who are provided with additional training in the respective group coaching models. The models differ in the time each group operates (ranging from 3–12 months), and the career stages and readiness of participants to be actively writing a proposal. Unique to these group coaching models, they all acknowledge and make visible the underlying social science theories and practices that influence the environments where research training takes place. Evidence to date supports these group coaching models as valuable adjuncts to classical research mentoring, with the ability to positively impact maximal development of research talent and increase contributions from underrepresented groups.Support or Funding InformationSupported by NIH DP4 GM0096807, R01 GM107701, R35 GM118184, U54 GM119023 and ASPET Big Idea Award
Visualizing DNA Double Strand Break Repair with Single‐Molecule Microscopy
Authors: Loparo Joseph , Graham Thomas , Walter Johannes 
Published: November 2023

DNA double strand breaks are an extremely toxic form of DNA damage and must be repaired to maintain genome stability. In human cells the majority of DNA double strand breaks are repaired by nonhomologous end joining (NHEJ), a versatile pathway capable of directly ligating even complicated DNA end structures. This flexibility comes with a price as the NHEJ machinery joins difficult ends in an error‐prone manner. How the NHEJ machinery assembles on DNA ends, holds the ends together and maximizes the fidelity of end joining remain open questions. In this talk I will describe how my laboratory is using single‐molecule imaging approaches in Xenopus laevis egg extracts to follow the repair of double strand DNA breaks in real time with nanometer resolution. We have found that DNA ends pass through at least two distinct synaptic states during repair. Initially ends are tethered in a long‐range synaptic state that requires Ku and DNA‐PKcs. The catalytic activity of DNA‐PKcs along with XLF and XRCC4‐LIG4 are then required to transition the DNA ends into close alignment prior to ligation. In order to understand the role of XLF and XRCC4 in this complex I will describe how we are fluorescently labeling these components and visualizing them during repair.Support or Funding InformationThis work was supported by a National Institutes of Health grant (R01GM115487) to J.J.L.
Targeting epigenetic regulation of malaria blood‐stage infections
Authors: Duraisingh Manoj 
Published: November 2023

Epigenetic mechanisms control a variety of critical processes through the life‐cycle of the malaria parasite P. falciparum. In the blood‐stage of infection, this includes antigenic variation of proteins on the surface of parasite‐infected red blood cells that enable sequestration within the host microvasculature and organs, as well as the expression of genes required for transition to the transmissible sexual stage of the parasite. Key histone‐modifying enzymes have been identified as regulators of distinct transcriptional programs underlying these processes. We have focused our research on the histone deacetylases (HDACs) of P. falciparum, that enzymatically remove the acetyl group from histones to regulate transcription of specific gene sets. P. falciparum expresses one class I HDAC, two class II HDACs and two class III HDACs. We have been studying the functions of these HDACs in blood‐stage infections, to establish how they regulate different transcriptional programs and cellular processes in a ‘division of labor’. We are exploring how we can chemically target the essential functions of the P. falciparum HDACs to disrupt and halt proliferation and transmission of this deadly parasite.Support or Funding InformationBurroughs Wellcome Fund
Novel Methodological Considerations Regarding the Use of Visual Analog Scale (VAS) Questionnaires to Assess Appetite Control and Satiety
Authors: Douglas Steve M , Gwin Jess A. , Leidy Heather J. 
Published: November 2023

BackgroundVAS questionnaires are commonly used in appetite research to measure postprandial changes in hunger and fullness as markers of subsequent food intake. The current prevalence of smartphone usage provides an opportunistic platform to assess these questions. However, little is known with respect to whether the repetitive use of these questionnaires influence eating behavior or whether novel modifications in their delivery are warranted.ObjectivesTo compare VAS appetite and satiety questionnaires delivered through a smartphone application vs. a commonly used computerized program and to test whether the use of these questionnaires alter subsequent eating behavior.MethodsTwelve healthy young adults (age: 22±1 y; BMI: 22.1±0.9 kg/m2) completed the following randomized crossover design study. On five separate days, the participants came to the facility between 7–9 am and were placed in a room that was void of all time cues. Within 30 min after arrival, they were provided with a 130 kcal preload breakfast containing 30 g protein. During four of the five testing days, the participants completed VAS questionnaires (hunger, fullness, desire to eat, prospective food consumption) every 30 min for 4h using the respective appetite applications (ScaleKit) on an iPod Touch (Apple; Cupertino, CA) or netbook computer application (AVAS; Neurobehavioral Research Laboratory and Clinic; San Antonio, TX). At the end of the 4h periods, the participants were provided with an ad libitum pasta meal to consume until ‘comfortably full.’ To examine the influence of VAS assessment on subsequent eating behavior, no questionnaires were provided over the 4h period on one of the five testing days.ResultsNo differences in 4h postprandial hunger, fullness, desire to eat, or prospective food consumption were observed between the smartphone application and the computer program. Additionally, no differences in energy content consumed at the subsequent eating occasions were observed between the days that included the VAS questionnaires (484 ± 50 kcal) vs. no questionnaires (500 ± 53 kcal).ConclusionsThe use of a newly developed VAS smartphone application provides similar measures of reported appetite and satiety compared to a previously validated computer program and the use of VAS questionnaires does not influence subsequent eating behavior.Support or Funding InformationInternal Funds
Number of Episodes of Food Insecurity in Childhood Directly Impacts Risk of Overweight/Obesity by Eighth Grade
Authors: Mangini Lauren D , Zhu Yeyi , Dong Yongquan , Forman Michele R 
Published: November 2023

ObjectiveObesity and food insecurity represent significant public health challenges, yet their association in childhood is unclear. Our objective is to examine the relationship between the number of episodes of household food insecurity in early and mid‐childhood and risk of overweight/obesity in eighth grade.MethodsIn the prospective Early Childhood Longitudinal Study‐Kindergarten cohort, food insecurity, measured with the validated USDA 18‐item module, was quantified in episodes per year/wave, and examined across four waves. Anthropometrics were measured to calculate age‐ and sex‐specific BMI z‐scores categorized as normal or overweight/obese. BMI trajectory was analyzed by sex and episodes of food insecurity. Sex‐specific multivariable Poisson regression models estimated relative risks (RR) and 95% confidence intervals (CI) for overweight/obesity at the eighth grade, adjusting for covariates.ResultsBMI trends differed by sex and episodes of food insecurity. Compared with the food‐secure, boys with food insecurity ≥3 times had a 44% (95% CI 1.09, 1.92) higher risk of overweight/obesity at the eighth grade; and twice food‐insecure girls had a 50% (95% CI 1.10, 2.06) higher risk. Racial disparity in overweight/obesity risk only emerged among girls. High birthweight was associated with an increased risk of overweight/obesity regardless of sex, whereas low birthweight was associated with a decreased risk among girls.ConclusionsExposure to food insecurity predicted a higher BMIZ and was positively associated with risk of overweight/obesity dependent on sex and number of episodes of food insecurity. The American Academy of Pediatrics recommendation to screen for food insecurity is timely and may inform obesity prevention.Support or Funding InformationThis research did not receive any specific grant from funding agencies in the public, commercial, or not‐for‐profit sectors. Ms. Mangini and Dr. Forman are supported by the David Bruton, Jr. Centennial Professorship funds. David Bruton, Jr. had no role in the design, analysis or writing of this article.
MicroRNAs in the Pathogenesis of Lipogenic Diet Induced Hyperlipidemia and Insulin Resistance
Authors: Su Qiaozhu , Sud Neetu , Pan Kaichao 
Published: November 2023

Fructose is a highly lipogenic sugar which can alter energy metabolism and trigger metabolic disorders. MicroRNAs (miRNAs) are noncoding RNAs with a length of 19 to 25 nt and are involved in posttranscriptional gene regulation by binding to the 3′‐untranslated regions of their target mRNA and impacting diverse cellular processes, such as metabolic inflammation and energy metabolism. Regulation of miRNAs is tissue and cell type specific in which a single miRNA can target numerous mRNA sequences and each mRNA can be targeted by multiple miRNAs. This unique regulatory property enables miRNAs to simultaneously regulate several groups of mRNAs within a signaling pathway or network and generate powerful impact on diverse cellular processes. Thus, identification of miRNA expression profiles and their relevant target genes offers great potential to delineate the molecular pathogenesis of metabolic diseases. In this study, our objective was to comprehensively explore the regulatory roles of miRNAs in the onset of hyperlipidemia and insulin resistance induced by high fructose. Determination of the miRNA profile by illumina small RNA sequencing identified a set of miRNAs (forty six miRNAs) in mouse livers whose expression profiles were significantly altered by high‐fructose feeding. Among them, nineteen miRNAs were significantly upregulated whereas the other twenty six were downregulated compared to the control chow‐fed mice. Computational prediction and functional analysis further revealed that ten of these miRNAs, including miR‐19b‐3p, miR‐101a‐3p ‐3p, miR‐30a‐5p, miR‐223‐3p, miR‐378a‐3p, miR‐33‐5p, miR‐145a‐3p, miR‐128‐3p, miR‐125b‐5p and miR‐582‐3p, assembled as a regulatory network that collaboratively and repeatedly targets multiple key metabolic signaling molecules involved in inflammatory stress (e.g., PPARα and LXRα), lipid and lipoprotein metabolism (e.g., SREBP‐1/2 and apoB), and insulin signaling (e.g., IRS‐1 and FOXO1). Quantitative real‐time PCR analysis further confirmed that alterations of miRNAs were associated with the changes of the mRNA abundances of their target genes, indicating the pathogenic impact of the altered miRNAs on fructose induced metabolic disorders. Genetic depletion of miR‐378a protected mice from fructose induced insulin resistance whereas overexpression of miR‐378a resulted in inflammatory stress in hepatocytes. In conclusion, our study unveils a novel hepatic miRNA regulatory network that was altered by high‐fructose feeding. Manipulating the abundance of the key miRNAs in this network prevents the onset of hyperlipidemia and insulin resistance induced by high‐fructose diet. This novel finding provides mechanistic insights into the interaction between miRNAs and their target genes in the development of metabolic syndrome. It may further provide rationale for pharmaceutically targeting these miRNAs in the prevention and treatment of nutritional associated metabolic diseases.Support or Funding InformationP20 GM104320‐01A
Barriers to Healthcare Seeking and Provision Among African American Adults in the Rural Mississippi Delta: Community and Provider Perspectives
Authors: Connell Carol , Yadrick Kathy , Wang Sherry 
Published: November 2023

The objective of this project was to identify barriers to healthcare seeking and healthcare provision among rural African American adults in the Mississippi Delta from the perspective of volunteer community health advisors (CHAs), community residents, and healthcare providers. Ten focus groups (20 males, 37 females) were conducted with CHAs and community residents from nine counties in one public health district. An additional focus group was conducted with healthcare providers (3 males, 2 females, 4 African American, 1 Other) from medical clinics and a hospital located in the same public health district. Two key informant interviews were also conducted with a district public health officer and a chairman of a local health advocacy foundation board of directors. All interviews were transcribed and data were analyzed using the constant comparative method to identify major themes and sub‐themes related to barriers to healthcare seeking and provision. Findings were broadly categorized as structural and interpersonal barriers with structural barriers encompassing issues of poverty (unemployment/underemployment), lack of health insurance, rurality (such as lack of transportation and medical specialists), perceptions of racism, and medical mistrust. Interpersonal barriers included fear of a serious medical diagnosis, gender socialization (going to the doctor as a sign of weakness among men) and age (not going to see the doctor until age 50 for first screening). Differences also emerged in the perceptions between community members and healthcare providers. While both groups were critical of medical insurance, providers viewed insurance guidelines as restricting their ability to provide the most current treatment. Community members and some CHAs viewed providers as conspiring with insurance and pharmaceutical companies to receive “kick‐backs.” Additionally, whereas racism emerged as a major structural barrier in the community interviews, this topic was not mentioned in any of the provider interviews. Results indicate significant efforts are needed to overcome both structural and interpersonal barriers to healthcare seeking and provision in order to reduce health disparities.Support or Funding InformationThis project was funded through a Patient‐Centered Outcomes Research Institute (PCORI) Eugene Washington PCORI Engagement Award (1514‐USM). The statements presented in this abstract are solely the responsibility of the authors and do not necessarily represent the views of PCORI, its Board of Governors or Methodology Committee.
Dietary fat/cholesterol‐sensitive PKCbeta‐RB signaling: Potential role in diet‐induced NASH/HCC axis
Authors: Mehta Devina , Sif Said D , Jacob Samson T , Ghoshal Kalpana D , Mehta Kamal Deep , Huang Wei 
Published: November 2023

Hepatocellular carcinoma (HCC) is a frequent form of cancer with a poor prognosis. Recent studies suggest that abnormal lipid metabolism may play an essential role in nonalcoholic steatohepatitis (NASH) development and oncogenesis of HCC. Excess dietary cholesterol intake has been shown to cause development of experimental NASH in different animal models, especially in the setting of a concurrent high‐fat diet. Despite knowledge that Western‐style high‐fat and high‐cholesterol diet is a risk factor in the development of NASH and subsequent progression to HCC, diet‐induced signaling changes implicated in NASH/HCC axis are not well understood. Understanding molecular mechanisms altered by diet is crucial for developing preventive and therapeutic strategies. We previously assessed whether metabolic adaptation to high‐fat/cholesterol diet is associated with changes in hepatic PKCβ expression and also studied the consequence of PKCβ deficiency on diet‐induced hepatic cholesterol homeostasis. We reported that diets enriched with high‐fat and high‐cholesterol (with or without bile acid), shown to produce NASH and HCC, induce hepatic PKCβ expression, and a systemic loss of PKCβ promotes hepatic cholesterol accumulation in response to such diets. These results support the possibility that PKCβ is a physiological transducer of dietary fat/cholesterol and plays a critical role in hepatic adaptation to such diets. Here, we sought to determine how PKCβ and diet functionally interact during tumorigenesis. We examined effects of dietary fat/cholesterol on the PKCβ phosphorylation of retinoblastoma (RB) protein and family members, as well as compared PKCβ expression in human HCC versus normal tissue. We show that diet‐induced hepatic PKCβ expression is accompanied by increased phosphorylation of specific residues of RB protein in a time‐dependent manner. Intriguingly, PKCβ−/− livers exhibited reduced phospho‐RB and RB protein levels, which ultimately resulted in increased transcription of RB gene. It is also accompanied by reduced RBL‐1 with no significant effect on RBL‐2 protein level. To investigate the potential effect of PKCβ deficiency on DNA content of preneoplastic livers, flow cytometric analysis was conducted on hepatocytes obtained from high‐fat/cholesterol diet‐fed WT and PKCβ−/− mice. We also report reduced expression of PKCβ in HCC compared to an adjacent non‐tumorous liver in human patients. These results raise an interesting possibility that diet‐induced PKCβ activation represents an important mediator in the functional wiring of cholesterol metabolism and tumorigenesis through modulating stability of cell cycle‐associated proteins. Identification of PKCβ as a cellular relay in diet‐mediated change in RB functions can define the signaling events that could participate in diet‐induced oncogenesis.Support or Funding InformationThe Ohio State University College of Medicine Research Funds
Reduced Leucine Availability Inhibits the Growth of Bone Sarcomas by Stimulating the Fuel Sensing Enzyme AMPK
Authors: Martin Shailer , Boyer Michael , Ananieva Elitsa 
Published: November 2023

Bone sarcomas are tumors that commonly originate from the bone and the cartilage. Although rare, bone sarcomas are associated with high mortality in children and adolescents due to their unresponsiveness to traditional treatments. One novel approach to address this resistance is to explore the role of leucine metabolism in bone sarcoma cellular proliferation and protein synthesis. The essential amino acid, leucine, stimulates protein synthesis via complex 1 of the mammalian target of rapamycin (mTORC1) and is thus important for cell growth and proliferation. The intracellular concentrations of leucine are regulated at the level of leucine degradation. The first step in leucine degradation is the reversible transamination of leucine catalyzed by the mitochondrial (BCATm) and the cytosolic (BCATc) branched chain aminotransferases. The objective of this research was to explore whether changes in leucine availability enforced by inhibition of leucine uptake or leucine degradation would impact the growth and protein synthesis of the human bone sarcoma cell line 143B. We hypothesized that the leucine antagonist, N‐acetyl‐leucine‐amide (NALA), would inhibit the cellular growth and protein synthesis of the bone sarcoma cells, while the BCATc inhibitor, gabapentin, would have an effect opposite to that of NALA, through the inhibition of leucine degradation. To test this hypothesis, we treated 143B cells with different concentrations of NALA (0,12.5, 25, and 50mM) or gabapentin (0, 5, and 50mM) for twenty‐four hours, and measured the following: cellular growth, protein content, and the activation of mTORC1 and the fuel‐sensing enzyme AMP‐activated protein kinase (AMPK). Our results revealed that both NALA and gabapentin inhibited the bone sarcoma cellular growth and protein content in concentration dependent manner. However, while NALA stimulated AMPK, gabapentin inhibited AMPK, as evidenced by changes in the phosphorylation of AMPK. The observed changes in AMPK indicate that leucine may impact the energy status and the growth of bone sarcomas by modulating the activation state of AMPK. Because activation of AMPK inhibits anabolic processes and cancer growth, a therapeutic approach aimed at reducing leucine availability may be one novel solution to treat bone cancer patients.Support or Funding InformationIOER ‐startup, Des Moines University (Ananieva, EA)