Digital Commons Network^™

Longitudinal Single-Cell Profiling Reveals Molecular Heterogeneity And Tumor-Immune Evolution In Refractory Mantle Cell Lymphoma, Shaojun Zhang, Vivian Changying Jiang, Guangchun Han, Dapeng Hao, Junwei Lian, Yang Liu, Qingsong Cai, Rongjia Zhang, Joseph Mcintosh, Ruiping Wang, Minghao Dang, Enyu Dai, Yuanxin Wang, David Santos, Maria Badillo, Angela Leeming, Zhihong Chen, Kimberly Hartig, John Bigcal, Jia Zhou, Rashmi Kanagal-Shamanna, Chi Young Ok, Hun Lee, Raphael E Steiner, Jianhua Zhang, Xingzhi Song, Ranjit Nair, Sairah Ahmed, Alma Rodriquez, Selvi Thirumurthi, Preetesh Jain, Nicolaus Wagner-Bartak, Holly Hill, Krystle Nomie, Christopher Flowers, Andrew Futreal, Linghua Wang, Michael Wang

Faculty, Staff and Student Publications

The mechanisms driving therapeutic resistance and poor outcomes of mantle cell lymphoma (MCL) are incompletely understood. We characterize the cellular and molecular heterogeneity within and across patients and delineate the dynamic evolution of tumor and immune cell compartments at single cell resolution in longitudinal specimens from ibrutinib-sensitive patients and non-responders. Temporal activation of multiple cancer hallmark pathways and acquisition of 17q are observed in a refractory MCL. Multi-platform validation is performed at genomic and cellular levels in PDX models and larger patient cohorts. We demonstrate that due to 17q gain, BIRC5/survivin expression is upregulated in resistant MCL tumor cells and …

Effect Of Nano2, A Donor Of Nitric Oxide, On Glucose Mediated Oxidative Stress In Pancreaticb-Cells, Kazi Nazrul Islam, Rahib K. Islam, Mohammod B. Rashid, Branson Smith, Safa K. Islam

School of Medicine Faculty Publications

Annual Meeting of the Endocrine Society, ENDO 2024, June 1 - 4, 2024, Boston, MA

Identification Of An Ionic Mechanism For Erα-Mediated Rapid Excitation In Neurons, Meng Yu, Na Yin, Bing Feng, Peiyu Gao, Kaifan Yu, Hesong Liu, Hailan Liu, Yongxiang Li, Olivia Z Ginnard, Kristine M Conde, Mengjie Wang, Xing Fang, Longlong Tu, Jonathan C Bean, Qingzhuo Liu, Yue Deng, Yuxue Yang, Junying Han, Sanika V Jossy, Megan L Burt, Huey Zhong Wong, Yongjie Yang, Benjamin R Arenkiel, Yang He, Shaodong Guo, Pierre Gourdy, Jean-Francois Arnal, Francoise Lenfant, Zhao Wang, Chunmei Wang, Yanlin He, Yong Xu

Faculty, Staff and Students Publications

The major female ovarian hormone, 17β-estradiol (E2), can alter neuronal excitability within milliseconds to regulate a variety of physiological processes. Estrogen receptor-α (ERα), classically known as a nuclear receptor, exists as a membrane-bound receptor to mediate this rapid action of E2, but the ionic mechanisms remain unclear. Here, we show that a membrane channel protein, chloride intracellular channel protein-1 (Clic1), can physically interact with ERα with a preference to the membrane-bound ERα. Clic1-mediated currents can be enhanced by E2 and reduced by its depletion. In addition, Clic1 currents are required to mediate the E2-induced rapid excitations in multiple brain ERα …

Pulse Oximetry Accuracy In Children With Dark Skin Tones: Relevance To Acute Lower Respiratory Infection Care In Low- And Middle-Income Countries, Shubhada Hooli, Tim Colbourn, Manish I Shah, Kristy Murray, Anna Mandalakas, Eric D Mccollum

Faculty, Staff and Students Publications

Acute lower respiratory infections (ALRI) are the leading post-neonatal cause of death in children under 5 years old. There is a high prevalence of pediatric ALRI-related hypoxemia in low- and middle-income countries. The WHO defines clinically meaningful hypoxemia in children as a SpO2 (peripheral oxygen saturation) < 90%. Multiple studies put this convention into question and found SpO2 of 90% to 92% to be associated with child ALRI mortality. An evolving body of evidence suggests that pulse oximeters systematically overestimate oxygen saturation in individuals with dark skin tones. We conducted a narrative review of pediatric studies evaluating pulse oximeter accuracy in children without COVID-19. Four studies, one prospective, examined pulse oximeter accuracy in children of varying ages with dark skin tones. All studies had limitations that affect their generalizability. There is evidence that certain pulse oximeters may overestimate oxygen saturation in children with dark skin tones. Further prospective research is urgently needed to identify affected populations and clinical implications. Despite recognized challenges, we strongly urge continued and expanded use of pulse oximetry as its use will save lives.

The Role Of Nutrition In Modulating Neurodevelopmental And Mental Health Outcomes In Pediatric Populations: A Review, Athul M. Vikas

Senior Theses

Introduction: Neurodevelopmental and mental health disorders, including Attention-Deficit/Hyperactivity Disorder (ADHD), anxiety, and depression, have risen sharply in prevalence among children and adolescents, creating substantial public health concerns. Traditional interventions, primarily pharmacological and behavioral, offer critical but limited support, underscoring the need for integrated approaches. Recent findings suggest that nutrition may play a significant role in supporting brain development and mitigating mental health risks, offering preventive benefits that complement conventional therapies. This review aims to evaluate the influence of specific nutrients—such as folate, iron, DHA, zinc, and vitamin B12—on neurodevelopmental outcomes, emphasizing the importance of these nutrients during critical growth …

Aging Skeletal Muscle: Influence Of Obesity And Role Of The Exercise Responsive Nuclear Receptor Nor-1, Hector G. Paez

Alternative Theses and Dissertations (AETDs)

Skeletal muscle mass and function are critical components of overall health and quality of life. Advanced age is associated with skeletal muscle disease characterized by a loss of muscle mass, function, and quality. Indeed, low muscle mass and function is associated with poor disease outcomes and greater mortality, greater incidence of falls, and a high fiscal and societal cost. Aging contributes to a decline in skeletal muscle health through several intrinsic and extrinsic mechanisms including impaired nutrient sensing, mitochondrial dysfunction, inflammation, physical inactivity, and proteostatic imbalance. Obesity, an increasingly prominent public health concern, is becoming more common in the elderly …

Knockdown Of Ketohexokinase Versus Inhibition Of Its Kinase Activity Exert Divergent Effects On Fructose Metabolism, Se-Hyung Park, Taghreed Fadhul, Lindsey R. Conroy, Harrison A. Clarke, Ramon Sun, Kristina Wallenius, Jeremie Boucher, Gavin O'Mahony, Alessandro Boianelli, Marie Persson, Sunhee Jung, Cholsoon Jang, Analia S. Loria, Genesee J. Martinez, Zachary A. Kipp, Evelyn A. Bates, Terry D. Hinds Jr., Senad Divanovic, Samir Softic

Markey Cancer Center Faculty Publications

Excessive fructose intake is a risk factor for the development of obesity and its complications. Targeting ketohexokinase (KHK), the first enzyme of fructose metabolism, has been investigated for the management of metabolic dysfunction–associated steatotic liver disease (MASLD). We compared the effects of systemic, small molecule inhibitor of KHK enzymatic activity with hepatocyte-specific, N-acetylgalactosamine siRNA–mediated knockdown of KHK in mice on an HFD. We measured KHK enzymatic activity, extensively quantified glycogen accumulation, performed RNA-Seq analysis, and enumerated hepatic metabolites using mass spectrometry. Both KHK siRNA and KHK inhibitor led to an improvement in liver steatosis; however, via substantially different mechanisms, KHK …

Acute Changes In Liver Function Tests During Initiation Of Ketogenic Diet, Akshat Katyayan, Anuranjita Nayak, Gloria Diaz-Medina, Maureen Handoko, James John Riviello

Faculty, Staff and Students Publications

BACKGROUND: Ketogenic diet is an effective therapy for patients with medically refractory epilepsy. It is generally well tolerated, with the most common side effects being gastrointestinal. Hepatic toxicity has been described as an uncommon side effect of ketogenic diet, usually with long-term use. However, there are limited data to implicate ketogenic diet in acute liver toxicity.

METHODS AND RESULTS: We analyzed all patients who underwent elective inpatient ketogenic diet initiation at our institution from June 2019 to June 2022. Of the 25 patients reviewed, we found 6 patients who showed acute, asymptomatic changes in liver function tests during initiation, in …

Pulmonary Vascular Manifestations Of Hereditary Haemorrhagic Telangiectasia, Sarah Cullivan, Barry Kevane, Brian Mccullagh, Terry M O'Connor, Robin Condliffe, Sean Gaine

Children’s Nutrition Research Center Staff Publications

Hereditary haemorrhagic telangiectasia (HHT) is an autosomal dominant, multisystem disorder that manifests with a spectrum of disease including cardiopulmonary complications. HHT is characterised by aberrant signalling via the transforming growth factor β (TGFβ) pathway, with loss of vascular integrity, angiogenesis and vascular dysplasia. The disease has an estimated prevalence of 1 in 5000 persons and the penetrance increases with increasing age. HHT commonly presents with epistaxis and telangiectasia, while visceral arteriovenous malformations are not uncommon. Mutations in the ENG, ACVRL1 and MADH4 genes account for 97% of all HHT cases, and it is recommended that genetic tests are used in …

Benefits Of Calorie Restriction In Mice Are Mediated Via Energy Imbalance, Not Absolute Energy Or Protein Intake, Daniel L Smith, Sharon E Mitchell, Maria S Johnson, Victoria K Gibbs, Stephanie Dickinson, Beate Henschel, Rui Li, Kathryn A Kaiser, Daniella E Chusyd, Andrew W Brown, David B Allison, John R Speakman, Tim R Nagy

Children’s Nutrition Research Center Staff Publications

Caloric restriction (CR) results in reduced energy and protein intake, raising questions about protein restriction's contribution to CR longevity benefits. We kept ad libitum (AL)-fed male C57BL/6J mice at 27°C (AL27) and pair-fed (PF) mice at 22°C (22(PF27)). The 22(PF27) group was fed to match AL27 while restricted for calories due to cold-induced metabolism. The 22(PF27) mice had significantly lower body weight, lean mass, fat mass, leptin, IGF-1, and TNF-α levels than AL27 mice (p< 0.001 for all). Manipulations over ~11 weeks resulted in significant differences in body temperature, physical activity, and expression of key genes linked to hunger in the hypothalamus. Survival was significantly greater in 22(PF27) compared to AL27 overall (p< 0.001). CR in the context of equivalent energy and protein intake resulted in hormonal, metabolic, and physiological benefits and extended longevity. Hence, energy imbalance, rather than low energy or protein intake per se, mediates the benefits of CR.

Viability Discrimination Of Bacterial Microbiomes In Home Kitchen Dish Sponges Using Propidium Monoazide Treatment, Christina K Carstens, Joelle K Salazar, Shreela Sharma, Wenyaw Chan, Charles Darkoh

Faculty, Staff and Student Publications

Dish sponges are known to support the proliferation of human bacterial pathogens, yet they are commonly used by consumers. Exposure to foodborne pathogens via sponge use may lead to illness, a serious concern among susceptible populations. The extent of exposure risks from sponge use has been limited by constraints associated with culture-independent or dependent methods for bacterial community characterization. Therefore, five used dish sponges were characterized to evaluate the presence of viable bacterial foodborne pathogens using the novel application of propidium monoazide (PMA) treatment and targeted 16S rRNA gene amplicon sequencing. Select pathogen viability was confirmed using targeted selective enrichment. …

Mechanisms By Which The Intratumoral Microbiome May Potentiate Immunotherapy Response, Dalissa Negrón-Figueroa, Lauren E Colbert

Faculty, Staff and Student Publications

No abstract provided.

Exploring Age And Gender Disparities In Cardiometabolic Phenotypes And Lipidomic Signatures Among Chinese Adults: A Nationwide Cohort Study, Xiaojing Jia, Hong Lin, Ruizhi Zheng, Shuangyuan Wang, Yilan Ding, Chunyan Hu, Mian Li, Yu Xu, Min Xu, Guixia Wang, Lulu Chen, Tianshu Zeng, Ruying Hu, Zhen Ye, Lixin Shi, Qing Su, Yuhong Chen, Xuefeng Yu, Li Yan, Tiange Wang, Zhiyun Zhao, Guijun Qin, Qin Wan, Gang Chen, Meng Dai, Di Zhang, Bihan Qiu, Xiaoyan Zhu, Jie Zheng, Xulei Tang, Zhengnan Gao, Feixia Shen, Xuejiang Gu, Zuojie Luo, Yingfen Qin, Li Chen, Xinguo Hou, Yanan Huo, Qiang Li, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Yiming Mu, Shenghan Lai, Donghui Li, Weiguo Hu, Guang Ning, Weiqing Wang, Yufang Bi, Jieli Lu, 4c Study Group

Faculty, Staff and Student Publications

Understanding sex disparities in modifiable risk factors across the lifespan is essential for crafting individualized intervention strategies. We aim to investigate age-related sex disparity in cardiometabolic phenotypes in a large nationwide Chinese cohort. A total of 254,670 adults aged 40 years or older were selected from a population-based cohort in China. Substantial sex disparities in the prevalence of metabolic diseases were observed across different age strata, particularly for dyslipidemia and its components. Generalized additive models were employed to characterize phenotype features, elucidating how gender differences evolve with advancing age. Half of the 16 phenotypes consistently exhibited no sex differences, while …

Inhibition Of Hepatic Oxalate Overproduction Ameliorates Metabolic Dysfunction-Associated Steatohepatitis, Sandeep Das, Alexandra C Finney, Sumit Kumar Anand, Sumati Rohilla, Yuhao Liu, Nilesh Pandey, Alia Ghrayeb, Dhananjay Kumar, Kelley Nunez, Zhipeng Liu, Fabio Arias, Ying Zhao, Brenna H Pearson-Gallion, M Peyton Mckinney, Koral S E Richard, Jose A Gomez-Vidal, Chowdhury S Abdullah, Elizabeth D Cockerham, Joseph Eniafe, Andrew D Yurochko, Tarek Magdy, Christopher B Pattillo, Christopher G Kevil, Babak Razani, Md Shenuarin Bhuiyan, Erin H Seeley, Gretchen E Galliano, Bo Wei, Lin Tan, Iqbal Mahmud, Ida Surakka, Minerva T Garcia-Barrio, Philip L Lorenzi, Eyal Gottlieb, Eduardo Salido, Jifeng Zhang, A Wayne Orr, Wanqing Liu, Monica Diaz-Gavilan, Y Eugene Chen, Nirav Dhanesha, Paul T Thevenot, Ari J Cohen, Arif Yurdagul, Oren Rom

Faculty, Staff and Student Publications

The incidence of metabolic dysfunction-associated steatohepatitis (MASH) is on the rise, and with limited pharmacological therapy available, identification of new metabolic targets is urgently needed. Oxalate is a terminal metabolite produced from glyoxylate by hepatic lactate dehydrogenase (LDHA). The liver-specific alanine-glyoxylate aminotransferase (AGXT) detoxifies glyoxylate, preventing oxalate accumulation. Here we show that AGXT is suppressed and LDHA is activated in livers from patients and mice with MASH, leading to oxalate overproduction. In turn, oxalate promotes steatosis in hepatocytes by inhibiting peroxisome proliferator-activated receptor-α (PPARα) transcription and fatty acid β-oxidation and induces monocyte chemotaxis via C-C motif chemokine ligand 2. In …

Temporal Recording Of Mammalian Development And Precancer, Mirazul Islam, Yilin Yang, Alan J Simmons, Vishal M Shah, Krushna Pavan Musale, Yanwen Xu, Naila Tasneem, Zhengyi Chen, Linh T Trinh, Paola Molina, Marisol A Ramirez-Solano, Iannish D Sadien, Jinzhuang Dou, Andrea Rolong, Ken Chen, Mark A Magnuson, Jeffrey C Rathmell, Ian G Macara, Douglas J Winton, Qi Liu, Hamim Zafar, Reza Kalhor, George M Church, Martha J Shrubsole, Robert J Coffey, Ken S Lau

Faculty, Staff and Student Publications

Temporal ordering of cellular events offers fundamental insights into biological phenomena. Although this is traditionally achieved through continuous direct observations1,2, an alternative solution leverages irreversible genetic changes, such as naturally occurring mutations, to create indelible marks that enables retrospective temporal ordering3–5. Using a multipurpose, single-cell CRISPR platform, we developed a molecular clock approach to record the timing of cellular events and clonality in vivo, with incorporation of cell state and lineage information. Using this approach, we uncovered precise timing of tissue-specific cell expansion during mouse embryonic development, unconventional developmental relationships between cell …

A Simulation And Small-Group Pediatric Emergency Medicine Course For Generalist Healthcare Providers: Gastrointestinal And Nutrition Emergencies, Adeola Adekunbi Kosoko, Alicia E Genisca, Nicholas A Peoples, Connor Tompkins, Ryan Sorensen, Joy Mackey

Faculty, Staff and Student Publications

Audience and type of curriculum: This is a review curriculum utilizing multiple methods of education to enhance the skills of generalist healthcare providers in low- and middle-income countries (LMICs) in the identification and stabilization of pediatric respiratory emergencies. Our audience of implementation was Belizean generalist providers (nurses and physicians).

Length of curriculum: 8-10 hours.

Introduction: Early recognition and stabilization of critical pediatric patients can improve outcomes. Compared with resource-rich systems, many low-resource settings (i.e., LMICs) rely on generalists to provide most pediatric acute care. We created a curriculum for general practitioners comprising multiple educational modules focused on identifying and stabilizing …

Oligodendroglial Fatty Acid Metabolism As A Central Nervous System Energy Reserve, Ebrahim Asadollahi, Andrea Trevisiol, Aiman S Saab, Zoe J Looser, Payam Dibaj, Reyhane Ebrahimi, Kathrin Kusch, Torben Ruhwedel, Wiebke Möbius, Olaf Jahn, Jun Yup Lee, Anthony S Don, Michelle-Amirah Khalil, Karsten Hiller, Myriam Baes, Bruno Weber, E Dale Abel, Andrea Ballabio, Brian Popko, Celia M Kassmann, Hannelore Ehrenreich, Johannes Hirrlinger, Klaus-Armin Nave

Duncan NRI Faculty and Staff Publications

Brain function requires a constant supply of glucose. However, the brain has no known energy stores, except for glycogen granules in astrocytes. In the present study, we report that continuous oligodendroglial lipid metabolism provides an energy reserve in white matter tracts. In the isolated optic nerve from young adult mice of both sexes, oligodendrocytes survive glucose deprivation better than astrocytes. Under low glucose, both axonal ATP levels and action potentials become dependent on fatty acid β-oxidation. Importantly, ongoing oligodendroglial lipid degradation feeds rapidly into white matter energy metabolism. Although not supporting high-frequency spiking, fatty acid β-oxidation in mitochondria and oligodendroglial …

Metagenomic Study Of The Mesa: Detection Of Gemella Morbillorum And Association With Coronary Heart Disease, Kent D Taylor, Alexis C Wood, Jerome I Rotter, Xiuqing Guo, David M Herrington, W Craig Johnson, Wendy S Post, Russell P Tracy, Stephen S Rich, Shaista Malik

Faculty, Staff and Students Publications

BACKGROUND: Inflammation is a feature of coronary heart disease (CHD), but the role of proinflammatory microbial infection in CHD remains understudied.

METHODS AND RESULTS: CHD was defined in the MESA (Multi-Ethnic Study of Atherosclerosis) as myocardial infarction (251 participants), resuscitated arrest (2 participants), and CHD death (80 participants). We analyzed sequencing reads from 4421 MESA participants in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine program using the PathSeq workflow of the Genome Analysis Tool Kit and a 65-gigabase microbial reference. Paired reads aligning to 840 microbes were detected in >1% of participants. The association of the …

Discordance Between Aptt And Anti-Xa In Monitoring Heparin Anticoagulation In Mechanical Circulatory Support, Song Li, Ang Li, Jennifer A Beckman, Christopher Kim, Marian A Granich, John Mondin, Daniel E Sabath, David A Garcia, Claudius Mahr

Faculty, Staff and Students Publications

AIMS: It is unclear whether activated partial thromboplastin time (aPTT) or anti-Xa is more accurate for monitoring heparin anticoagulation in mechanical circulatory support (MCS) patients. This study investigates the relationship between aPTT and anti-Xa in MCS patients and identifies predictors of discordance.

METHODS AND RESULTS: aPTT and anti-Xa were simultaneously measured in a prospective cohort of MCS patients receiving unfractionated heparin at a tertiary academic medical centre. Therapeutic aPTT and anti-Xa levels were 60-100 s and 0.3-0.7 IU/mL, respectively, and concordance was defined as both levels being subtherapeutic, therapeutic, or supratherapeutic. To identify predictors of discordance, both a machine learning …

Pancreatic Enzyme Use Reduces Pancreatitis Frequency In Children With Acute Recurrent Or Chronic Pancreatitis: A Report From Insppire, Alvin Jay Freeman, Kenneth Ng, Fuchenchu Wang, Maisam A Abu-El-Haija, Ankur Chugh, Gretchen A Cress, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Praveen Goday, Tanja Y Gonska, Amit S Grover, Douglas Lindblad, Quin Y Liu, Asim Maqbool, Jacob A Mark, Brian A Mcferron, Megha S Mehta, Veronique D Morinville, Robert A Noel, Chee Y Ooi, Emily R Perito, Sarah Jane Schwarzenberg, Zachary M Sellers, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Dana K Andersen, Mark E Lowe, Aliye Uc, Consortium For The Study Of Chronic Pancreatitis, Diabetes, And Pancreatic Cancer (Cpdpc)

Faculty, Staff and Students Publications

Introduction: Among children who suffer from acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP), acute pancreatitis (AP) episodes are painful, often require hospitalization, and contribute to disease complications and progression. Despite this recognition, there are currently no interventions to prevent AP episodes. In this retrospective cohort study, we assessed the impact of pancreatic enzyme therapy (PERT) use on clinical outcomes among children with pancreatic-sufficient ARP or CP.

Methods: Children with pancreatic-sufficient ARP or CP in the INSPPIRE-2 cohort were included. Clinical outcomes were compared for those receiving vs not receiving PERT, as well as frequency of AP before and after …

What Would Happen In The United States If There Were No Cow Milk-Based Preterm Infant Nutritional Products: Historical Perspective And Evaluation Of Nutrient-Related Challenges, Steven A Abrams, Robert J Shulman

Faculty, Staff and Students Publications

Recent litigation has led to a situation where preterm cow milk-based infant nutritional products (PCMBPs) may soon have limited or no availability in the United States. Given their limited availability, similar products based only on human milk are unlikely to meet the needs of most preterm infants requiring such products, especially those born >1500 g or very preterm infants born at < 1500 g after they reach 34-35 wk postmenstrual age. Alternative nutritional strategies, used before the introduction of specialized preterm products, would require modular nutrient additions to a formula designed for full-term infants and donor or maternal milk. The addition of modular products would require careful calibration to provide needed macro and micronutrients which would expose infants to risks of contamination, poor growth, and limited bioavailability of some of these modulars. Substantial risks of metabolic derangements, and ultimately, poor outcomes would occur. In the long-term greater availability and support for the use of human milk-based products is needed. However, policymakers cannot assume that PCMBPs will not be critically needed and should identify strategies for their continued marketplace availability.

Changes In Conjunctival Mononuclear Phagocytes And Suppressive Activity Of Regulatory Macrophages In Desiccation Induced Dry Eye, Jehan Alam, Ebru Yaman, Cintia S De Paiva, De-Quan Li, Gerda Cristal Villalba Silva, Zhen Zuo, Stephen C Pflugfelder

Faculty, Staff and Students Publications

Purpose: To evaluate the effects of dry eye on conjunctival immune cell number and transcriptional profiles with attention to mononuclear phagocytes.

Methods: Expression profiling was performed by single-cell RNA sequencing on sorted conjunctival immune cells from non-stressed and C57BL/6 mice subjected to desiccating stress (DS). Monocle 3 modeled cell trajectory, scATAC-seq assessed chromatin accessibility and IPA identified canonical pathways. Inflammation and goblet cells were measured after depletion of MRC1+ MΦs with mannosylated clodronate liposomes.

Results: Mononuclear phagocytes (monocytes, MΦs, DCs) comprised 72 % of immune cells and showed the greatest changes with DS. Distinct DS induced gene expression patterns were …

Perineuronal Nets’ Role In Metabolism, Nan Zhang, Beite Song, Peng Bai, Li Du, Lulu Chen, Yong Xu, Tianshu Zeng

Faculty, Staff and Students Publications

Perineuronal nets (PNNs), specialized extracellular matrix (ECM) structures that envelop neurons, have recently been recognized as key players in the regulation of metabolism. This review explores the growing body of knowledge concerning PNNs and their role in metabolic control, drawing insights from recent research and relevant studies. The pivotal role of PNNs in the context of energy balance and whole body blood glucose is examined. This review also highlights novel findings, including the effects of astroglia, microglia, sex and gonadal hormones, nutritional regulation, circadian rhythms, and age on PNNs dynamics. These findings illuminate the complex and multifaceted role of PNNs …

Nongenetic And Genetic Factors Associated With White Matter Brain Aging: Exposome-Wide And Genome-Wide Association Study, Li Feng, Halley S Milleson, Zhenyao Ye, Travis Canida, Hongjie Ke, Menglu Liang, Si Gao, Shuo Chen, L Elliot Hong, Peter Kochunov, David K Y Lei, Tianzhou Ma

Faculty, Staff and Student Publications

BACKGROUND/OBJECTIVES: Human brain aging is a complex process that affects various aspects of brain function and structure, increasing susceptibility to neurological and psychiatric disorders. A number of nongenetic (e.g., environmental and lifestyle) and genetic risk factors are found to contribute to the varying rates at which the brain ages among individuals.

METHODS: In this paper, we conducted both an exposome-wide association study (XWAS) and a genome-wide association study (GWAS) on white matter brain aging in the UK Biobank, revealing the multifactorial nature of brain aging. We applied a machine learning algorithm and leveraged fractional anisotropy tract measurements from diffusion tensor …

High Fat, High Sucrose Diet Promotes Increased Expression Of Ace2 Receptor In The Siv-Infected Host: Implications For Sars-Cov-2 Infection, Elizabeth C. Delery, Danielle E. Levitt, Angela M. Amedee, Patricia E. Molina, Liz Simon

School of Graduate Studies Faculty Publications

Introduction: People with pre-existing conditions, including metabolic comorbidities, are at greater risk for complications of SARS-CoV-2 infection and expression of machinery required for viral entry into host cells may be a contributing factor. This study tested the hypothesis that high fat, high sucrose diet (HFSD) and alcohol use increase expression of angiotensin converting enzyme 2 (ACE2) receptor and transmembrane serine protease 2 (TMPRSS2) in tissues isolated from simian immunodeficiency virus (SIV) infected macaques, the most clinically relevant model for the study of HIV. Methods: Biospecimens obtained from a longitudinal study of SIV-infected, antiretroviral therapy (ART)-treated female rhesus macaques (Macaca mulatta) …

Hormone Replacement Therapy And Risk Of Pancreatic Cancer In Postmenopausal Women: Evidence From The Us National Inpatient Sample 2008–2018, Lei Liu, Xinyu Wang, Dekai Guo, Ruirui Ma, Haibing Gong, Congjun Wang

Faculty, Staff and Student Publications

BACKGROUND: Pancreatic cancer is a serious, usually fatal disease and one of the most aggressive malignancies. Research into whether hormone replacement therapy (HRT) might protect against pancreatic cancer has yielded mixed results. This study aimed to investigate the potential association between HRT and the risk of pancreatic cancer in postmenopausal women.

METHODS: This population-based, retrospective study extracted data from the US National Inpatient Sample (NIS) 2008-2018. Hospitalized females aged ≥55 years were eligible for inclusion. Associations between HRT, other study variables, and pancreatic cancer diagnosis were determined using univariate and multivariable regression analyses.

RESULTS: After 1:4 matching by age, data …

Untargeted Metabolomic Biomarker Discovery For The Detection Of Ectopic Pregnancy, Onur Turkoglu, Ayse Citil, Ceren Katar, Ismail Mert, Robert A Quinn, Ray O Bahado-Singh, Stewart F Graham

Faculty, Staff and Students Publications

Ectopic pregnancy (EP) is the leading cause of maternal morbidity and mortality in the first trimester. Using an untargeted metabolomic approach, we sought to identify putative plasma biomarkers using tandem liquid chromatography-mass spectrometry for the detection of tubal EP. This case-control study included the prospective recruitment of 50 tubal EP cases and 50 early intrauterine pregnancy controls. To avoid over-fitting, logistic regression models were developed in a randomly selected discovery group (30 cases vs. 30 controls) and validated in the test group (20 cases vs. 20 controls). In total, 585 mass spectral features were detected, of which 221 molecular features …

Molecular Testing Of Environmental Samples As A Potential Source To Estimate Parasite Infection, Rojelio Mejia, Barton Slatko, Cristina Almazan, Ruben Cimino, Alejandro Krolewiecki, Natalia Montellano Duran, Jacob Edwin Valera Aspetty, Paola Andrea Vargas, Chiara Cássia Oliveira Amorim, Stefan Michael Geiger, Ricardo Toshio Fujiwara, Juan David Ramirez, Luz Marina Llangarí-Arizo, Irene Guadalupe, Liliana E Villanueva-Lizama, Julio Vladimir Cruz-Chan, María Leticia Ojeda, Eva Mereles Aranda, Sandra Ocampos Benedetti, Maritza Dalí Camones Rivera, Eddyson Montalvo Sabino, Carlos Pineda, Eric J Wetzel, Philip J Cooper

Faculty, Staff and Students Publications

We discuss the potential usefulness of molecular testing of soil, dust, and water samples to detect medically important parasites, and where such testing could be used to supplement stool sampling in humans. A wide variety of parasites including protozoa and helminths, many of which are zoonotic, have an important infection reservoir in the environment. In some cases, this environmental period is essential for further parasite development. We describe the progress in implementing methods for the molecular detection of these parasites in soil across eight collaborating centers in Latin America and represent a variety of potential applications in improving our understanding …

Transient Elastography And Diffusion-Weighted Magnetic Resonance Imaging For Assessment Of Liver Fibrosis In Children With Chronic Hepatitis C, Mohamed A El-Guindi, Alif A Allam, Ahmed A Abdel-Razek, Gihan A Sobhy, Menan E Salem, Mohamed A Abd-Allah, Mostafa M Sira

Faculty, Staff and Student Publications

BACKGROUND: Chronic hepatitis C (CHC) is a health burden with consequent morbidity and mortality. Liver biopsy is the gold standard for evaluating fibrosis and assessing disease severity and prognostic purposes post-treatment. Noninvasive alternatives for liver biopsy such as transient elastography (TE) and diffusion-weighted magnetic resonance imaging (DW-MRI) are critical needs.

AIM: To evaluate TE and DW-MRI as noninvasive tools for predicting liver fibrosis in children with CHC.

METHODS: This prospective cross-sectional study initially recruited 100 children with CHC virus infection. Sixty-four children completed the full set of investigations including liver stiffness measurement (LSM) using TE and measurement of apparent diffusion …

Dense And Persistent Odor Representations In The Olfactory Bulb Of Awake Mice, Delaram Pirhayati, Cameron L Smith, Ryan Kroeger, Saket Navlakha, Paul Pfaffinger, Jacob Reimer, Benjamin R Arenkiel, Ankit Patel, Elizabeth H Moss

Children’s Nutrition Research Center Staff Publications

Recording and analysis of neural activity are often biased toward detecting sparse subsets of highly active neurons, masking important signals carried in low-magnitude and variable responses. To investigate the contribution of seemingly noisy activity to odor encoding, we used mesoscale calcium imaging from mice of both sexes to record odor responses from the dorsal surface of bilateral olfactory bulbs (OBs). The outer layer of the mouse OB is comprised of dendrites organized into discrete "glomeruli," which are defined by odor receptor-specific sensory neuron input. We extracted activity from a large population of glomeruli and used logistic regression to classify odors …