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Mechanisms By Which The Intratumoral Microbiome May Potentiate Immunotherapy Response, Dalissa Negrón-Figueroa, Lauren E Colbert Oct 2024

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 Oct 2024

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 Oct 2024

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 Oct 2024

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 Oct 2024

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 …


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 Oct 2024

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 Oct 2024

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 …


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 Oct 2024

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 …


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 Oct 2024

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 …


Acute Changes In Liver Function Tests During Initiation Of Ketogenic Diet, Akshat Katyayan, Anuranjita Nayak, Gloria Diaz-Medina, Maureen Handoko, James John Riviello Oct 2024

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 …


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 Oct 2024

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 …


Intercellular Mitochondrial Transfer Contributes To Microenvironmental Fate Redirection Of Mammary Cancer Cells, Julie Sofie Bjerring Oct 2024

Intercellular Mitochondrial Transfer Contributes To Microenvironmental Fate Redirection Of Mammary Cancer Cells, Julie Sofie Bjerring

Biomedical Sciences Theses & Dissertations

The dynamic cellular microenvironment, made up of resident cells and various macromolecules, differs markedly across tissues in the body. The multidirectional signals that cells receive from this microenvironment, along with the signaling they send back, heavily influence their physiology and behavior. Recent important findings have further validated this notion as the mammary microenvironment has been shown to suppress tumor progression by redirecting cancer cells to adopt a normal mammary epithelial progenitor fate in vivo. However, the mechanism(s) driving changes in metabolic reprogramming and cancer fate redirection is understudied. The work presented in this dissertation focuses on exploring the impact of …


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) Oct 2024

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 Oct 2024

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.


Sarkopenia Sebagai Faktor Risiko Varises Esofagus Risiko Tinggi Berdasarkan Stratifikasi Child-Pugh Pasien Sirosis Hati, Iwandheny Sepmeitutu, Juferdy Kurniawan, Hasan Maulahela, Ikhwan Rinaldi, Hamzah Shatri, Triyanta Yuli Pramana, Dadang Makmun, Cosmas Rinaldi A Lesmana, Rudy Hidayat, Purwita Wijaya Laksmi, Diana Sunardi Sep 2024

Sarkopenia Sebagai Faktor Risiko Varises Esofagus Risiko Tinggi Berdasarkan Stratifikasi Child-Pugh Pasien Sirosis Hati, Iwandheny Sepmeitutu, Juferdy Kurniawan, Hasan Maulahela, Ikhwan Rinaldi, Hamzah Shatri, Triyanta Yuli Pramana, Dadang Makmun, Cosmas Rinaldi A Lesmana, Rudy Hidayat, Purwita Wijaya Laksmi, Diana Sunardi

Jurnal Penyakit Dalam Indonesia

Background The high prevalence of sarcopenia in chronic liver disease negatively impacts the quality of life and increases the risk of various complications of cirrhosis, one of which is the development of esophageal varices. The aim of this study was to determine the prevalence of sarcopenia in cirrhosis patients based on the severity of liver cirrhosis and to explore the association of sarcopenia with high-risk esophageal varices stratified by Child-Pugh. Methods This observational cross-sectional study involved patients with liver cirrhosis at Cipto Mangunkusumo Hospital between January and September 2023. Sarcopenia was defined as a reduction in muscle mass accompanied by …


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 Sep 2024

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 …


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 Sep 2024

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 …


Understanding Necrotizing Enterocolitis Endotypes And Acquired Intestinal Injury Phenotypes From A Historical And Artificial Intelligence Perspective., Alain Cuna, Navin Kumar, Venkatesh Sampath Sep 2024

Understanding Necrotizing Enterocolitis Endotypes And Acquired Intestinal Injury Phenotypes From A Historical And Artificial Intelligence Perspective., Alain Cuna, Navin Kumar, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Necrotizing enterocolitis (NEC) remains a devastating disease in preterm and term neonates. Despite significant progress made in understanding NEC pathogenesis over the last 50 years, the inability of current definitions to discriminate the various pathophysiological processes underlying NEC has led to an umbrella term that limits clinical and research progress. In this mini review, we provide a historical perspective on how NEC definitions and pathogenesis have evolved to our current understanding of NEC endotypes. We also discuss how artificial intelligence-based approaches are influencing our knowledge of risk-factors, classification and prognosis of NEC and other neonatal intestinal injury phenotypes.


Catastrophic Spontaneous Uterine And Bladder Rupture In An Unscarred Uterus, Nathanael N. Hoskins Do, Kathryn Brandt Do, Tory Peterson Md Sep 2024

Catastrophic Spontaneous Uterine And Bladder Rupture In An Unscarred Uterus, Nathanael N. Hoskins Do, Kathryn Brandt Do, Tory Peterson Md

Transformative Medicine

Introduction:

Uterine rupture during pregnancy is a rare event which can be life-threatening for both the patient and the fetus. This case report describes a rare complication of uterine rupture which ultimately required a hysterectomy and extensive urologic reconstruction.

Case Description:

A 36-year-old patient presented to the hospital after term pre-labor rupture of membranes. The patient underwent induction of labor which ultimately resulted in a uterine rupture in an unscarred uterus. The rupture extended into the posterior bladder wall, right ureter, urethra, and anterior vaginal wall, resulting in a vesicovaginal fistula. The patient required a cesarean hysterectomy due to the …


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 Sep 2024

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 …


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 Sep 2024

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 …


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 Sep 2024

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 Sep 2024

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 …


A Bayesian Semi-Parametric Scalar-On-Function Regression With Measurement Error Using Instrumental Variables, Roger S Zoh, Yuanyuan Luan, Lan Xue, David B Allison, Carmen D Tekwe Sep 2024

A Bayesian Semi-Parametric Scalar-On-Function Regression With Measurement Error Using Instrumental Variables, Roger S Zoh, Yuanyuan Luan, Lan Xue, David B Allison, Carmen D Tekwe

Children’s Nutrition Research Center Staff Publications

Wearable devices such as the ActiGraph are now commonly used in research to monitor or track physical activity. This trend corresponds with the growing need to assess the relationships between physical activity and health outcomes, such as obesity, accurately. Device-based physical activity measures are best treated as functions when assessing their associations with scalar-valued outcomes such as body mass index. Scalar-on-function regression (SoFR) is a suitable regression model in this setting. Most estimation approaches in SoFR assume that the measurement error in functional covariates is white noise. Violating this assumption can lead to underestimating model parameters. There are limited approaches …


Lamina Cribrosa Microstructure In Nonhuman Primates With Naturally Occurring Peripapillary Retinal Nerve Fiber Layer Thinning, Palaiologos Alexopoulos, Arthur G Fernandes, Zeinab Ghassabi, Ronald Zambrano, Anse Vellappally, Eitan Shemuelian, Tingfang Lee, Jiyuan Hu, Armando Burgos-Rodriguez, Melween I Martinez, Joel S. Schuman, Amanda D Melin, James P Higham, John Danias, Gadi Wollstein Sep 2024

Lamina Cribrosa Microstructure In Nonhuman Primates With Naturally Occurring Peripapillary Retinal Nerve Fiber Layer Thinning, Palaiologos Alexopoulos, Arthur G Fernandes, Zeinab Ghassabi, Ronald Zambrano, Anse Vellappally, Eitan Shemuelian, Tingfang Lee, Jiyuan Hu, Armando Burgos-Rodriguez, Melween I Martinez, Joel S. Schuman, Amanda D Melin, James P Higham, John Danias, Gadi Wollstein

Wills Eye Hospital Papers

PURPOSE: The lamina cribrosa (LC) is hypothesized to be the site of initial axonal damage in glaucoma with the circumpapillary retinal nerve fiber layer thickness (RNFL-T) widely used as a standard metric for quantifying the glaucomatous damage. The purpose of this study was to determine in vivo, 3-dimensional (3D) differences in the microstructure of the LC in eyes of nonhuman primates (NHPs) with naturally occurring glaucoma.

METHODS: Spectral-domain optical coherence tomography (OCT) scans (Leica, Chicago, IL, USA) of the optic nerve head were acquired from a colony of 50 adult rhesus monkeys suspected of having high prevalence of glaucoma. The …


A Holistic Approach To Music For Stress Management During Pregnancy, Danielle Emily Dixon Sep 2024

A Holistic Approach To Music For Stress Management During Pregnancy, Danielle Emily Dixon

Doctoral Dissertations and Projects

Pregnancy is a transformative journey for women, but amidst the excitement and anticipation that most women experience, pregnancy often raises stress levels to profound heights for various reasons, which may include hormonal fluctuations, physical discomforts, concerns about the baby’s health, financial pressures, relationship changes, fear of labor and birth, life adjustments, and societal expectations. The purpose of this qualitative hermeneutic phenomenological study was to examine how music interventions impacted stress levels during pregnancy. This two-week study employed an in-person group experiment involving pregnant women. The study sample was selected via voluntary response sampling, where pregnant women volunteered to participate in …


Global Trends In Type 1 Diabetes In Adolescents And Young Adults (1990–2019), Jessy Louisa Silfer, Ksenia N. Tonyushkina Sep 2024

Global Trends In Type 1 Diabetes In Adolescents And Young Adults (1990–2019), Jessy Louisa Silfer, Ksenia N. Tonyushkina

Faculty Scholarship

The study by Gong et al. examines the increases in the incidence, prevalence, and burden trends of type 1 diabetes (T1D) in adolescents and young adults over a 30-year span (1990 – 2019) by age, sex, and geographical regions based on the data from the 204 countries and territories included in the Global Burden of Disease (GBD) collaborative.1 Burden is defined as a combination of mortality rates and disability adjusted life year (DALY) indexes. The results of this 3-decade study should be interpreted within the milieu of improvements in the diagnosis and treatment of T1D over this period as well …


14-Month-Old Female With Anti-Mda5 Juvenile Dermatomyositis Complicated By Liver Disease: A Case Report., Mitch Kinkor, Sameena Hameed, Alexander Kats, Voytek Slowik, Emily Fox, Maria Ibarra Sep 2024

14-Month-Old Female With Anti-Mda5 Juvenile Dermatomyositis Complicated By Liver Disease: A Case Report., Mitch Kinkor, Sameena Hameed, Alexander Kats, Voytek Slowik, Emily Fox, Maria Ibarra

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Juvenile Dermatomyositis (JDM) is a rare disorder with subtypes associated with different myositis-specific antibodies (MSAs) including anti-MDA5. Hepatic involvement in JDM is rare and has not previously been documented in anti-MDA5 JDM. There is a lack of formal research on treatment protocols for anti-MDA5 JDM, though tofacitinib is a highly regarded emerging therapy.

CASE PRESENTATION: A previously healthy 14-month-old Hispanic female presented to a pediatric rheumatology clinic with eight months of worsening rash, weakness, periorbital edema, intermittent fevers, and weight loss. Her physical exam was notable for fever, thinning of hair, heliotrope rash, periorbital edema, violaceous macules on her …


Detecting Altered Hepatic Lipid Oxidation By Mri In An Animal Model Of Masld, Marc Mcleod, Mario C Chang, Anna Rushin, Mukundan Ragavan, Rohit Mahar, Gaurav Sharma, Arshee Badar, Anthony Giacalone, Max E Glanz, Vinay R Malut, Dalton Graham, Nishanth E Sunny, James A Bankson, Kenneth Cusi, Matthew E Merritt Sep 2024

Detecting Altered Hepatic Lipid Oxidation By Mri In An Animal Model Of Masld, Marc Mcleod, Mario C Chang, Anna Rushin, Mukundan Ragavan, Rohit Mahar, Gaurav Sharma, Arshee Badar, Anthony Giacalone, Max E Glanz, Vinay R Malut, Dalton Graham, Nishanth E Sunny, James A Bankson, Kenneth Cusi, Matthew E Merritt

Faculty, Staff and Student Publications

Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of MASLD/MASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we develop a method for estimating hepatic β-oxidation from the metabolism of [D


Curcumin Alleviates Inflammatory Effects Of Ketamine Anesthesia In Postnatal Rats, Soroush Afshar Ghahremani, Abbas Raisi, Sohrab Minaei Beirami, Houman Kahroba, Mahnaz Mardani, Omid Dezfoulian, Vahideh Tarhriz Sep 2024

Curcumin Alleviates Inflammatory Effects Of Ketamine Anesthesia In Postnatal Rats, Soroush Afshar Ghahremani, Abbas Raisi, Sohrab Minaei Beirami, Houman Kahroba, Mahnaz Mardani, Omid Dezfoulian, Vahideh Tarhriz

School of Graduate Studies Faculty Publications

Curcumin has been employed in traditional medicine for over a millennium to treat various ailments, and its global use is now widespread. Chinese medicine relies heavily on curcumin as a primary element and uses it to cure infectious diseases, skin disorders, depression, and stress. It has cardioprotective, neuroprotective, and anti-diabetic properties, as well as pharmacological effects on disorders like type II diabetes, atherosclerosis, and human immunodeficiency virus replication. The anti-cancer activity of curcumin has been studied extensively with notable improvements in gastrointestinal, melanoma, urogenital, breast, and lung malignancies. We investigated the anti-inflammatory effects of curcumin on expression of tumor necrosis …