Digital Commons Network^™

Host Gastric Corpus Microenvironment Facilitates Ascaris Suum Larval Hatching And Infection In A Murine Model, Yifan Wu, Grace Adeniyi-Ipadeola, Mahliyah Adkins-Threats, Matthew Seasock, Charlie Suarez-Reyes, Ricardo Fujiwara, Maria Elena Bottazzi, Lizhen Song, Jason C Mills, Jill E Weatherhead

Faculty, Staff and Students Publications

Ascariasis (roundworm) is the most common parasitic helminth infection globally and can lead to significant morbidity in children including chronic lung disease. Children become infected with Ascaris spp. via oral ingestion of eggs. It has long been assumed that Ascaris egg hatching and larval translocation across the gastrointestinal mucosa to initiate infection occurs in the small intestine. Here, we show that A. suum larvae hatched in the host stomach in a murine model. Larvae utilize acidic mammalian chitinase (AMCase; acid chitinase; Chia) from chief cells and acid pumped by parietal cells to emerge from eggs on the surface of gastric …

Distribution Of P2y And P2x Purinergic Receptor Expression Within The Intestine, Kristen A Engevik, Francesca J Scribano, J Thomas Gebert, Jacob L Perry, Sue E Crawford, Joseph M Hyser

Faculty, Staff and Students Publications

Nucleotides are potent extracellular signaling molecules during homeostasis, infection, and injury due to their ability to activate purinergic receptors. The nucleotide ATP activates P2X receptors (P2RXs), whereas the nucleotides ADP, ATP, UTP, and UDP-glucose selectively activate different P2Y receptors (P2RYs). Several studies have established crucial roles for P2 receptors during intestinal inflammatory and infectious diseases, yet the most extensive characterization of purinergic signaling has focused on immune cells and the central and enteric nervous systems. As epithelial cells serve as the first barrier against irritants and infection, we hypothesized that the gut epithelium may express multiple purinergic receptors that respond …

Pediatric Cancer Incidence Among Individuals With Overgrowth Syndromes And Overgrowth Features: A Population-Based Assessment In Seven Million Children, Gillean K Connolly, Rachel D Harris, Charles Shumate, Surya P Rednam, Mark A Canfield, Sharon E Plon, Joanne Nguyen, Jeremy M Schraw, Philip J Lupo

Faculty, Staff and Students Publications

Background: Overgrowth syndromes (e.g., Beckwith-Wiedemann) are associated with an increased risk of pediatric cancer, although there are few population-based estimates of risk. There are also limited studies describing associations between other overgrowth features (e.g., hepatosplenomegaly) and pediatric cancer. Therefore, cancer risk among children with these conditions was evaluated with data from a large, diverse population-based registry linkage study.

Methods: This study includes all live births in Texas during the years 1999-2017. Children with overgrowth features and syndromes were identified from the Texas Birth Defects Registry; children with cancer were identified by linkage to the Texas Cancer Registry. Cox regression models …

Emotional Resilience Predicts Preserved White Matter Microstructure Following Mild Traumatic Brain Injury, Lanya T Cai, Benjamin L Brett, Eva M Palacios, Esther L Yuh, Ioanna Bourla, Jamie Wren-Jarvis, Yang Wang, Christine Mac Donald, Ramon Diaz-Arrastia, Joseph T Giacino, David O Okonkwo, Harvey S Levin, Claudia S Robertson, Nancy Temkin, Amy J Markowitz, Geoffrey T Manley, Murray B Stein, Michael A Mccrea, Ross D Zafonte, Lindsay D Nelson, Pratik Mukherjee, Track-Tbi Investigators

Faculty, Staff and Students Publications

Background: Adult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI. The present study hypothesized that white matter (WM) microstructure is better preserved in an emotionally resilient mTBI phenotype compared with a neuropsychiatrically distressed mTBI phenotype.

Methods: The present study used diffusion magnetic resonance imaging to investigate and compare WM microstructure in major association, projection, and commissural tracts between the two phenotypes and over time. …

A Machine Learning-Based Approach To Identify Peripheral Artery Disease Using Texture Features From Contrast-Enhanced Magnetic Resonance Imaging, Bijen Khagi, Tatiana Belousova, Christina M Short, Addison Taylor, Vijay Nambi, Christie M Ballantyne, Jean Bismuth, Dipan J Shah, Gerd Brunner

Faculty, Staff and Students Publications

Diagnosing and assessing the risk of peripheral artery disease (PAD) has long been a focal point for medical practitioners. The impaired blood circulation in PAD patients results in altered microvascular perfusion patterns in the calf muscles which is the primary location of intermittent claudication pain. Consequently, we hypothesized that changes in perfusion and increase in connective tissue could lead to alterations in the appearance or texture patterns of the skeletal calf muscles, as visualized with non-invasive imaging techniques. We designed an automatic pipeline for textural feature extraction from contrast-enhanced magnetic resonance imaging (CE-MRI) scans and used the texture features to …

The History Of Extracorporeal Membrane Oxygenation And The Development Of Extracorporeal Membrane Oxygenation Anticoagulation, Robert Bartlett, Deepa J Arachichilage, Meera Chitlur, Shiu-Ki Rocky Hui, Cindy Neunert, Andrew Doyle, Andrew Retter, Beverley J Hunt, Hoong Sern Lim, Arun Saini, Thomas Renné, Vadim Kostousov, Jun Teruya

Faculty, Staff and Students Publications

Extracorporeal membrane oxygenation (ECMO) was first started for humans in early 1970s by Robert Bartlett. Since its inception, there have been numerous challenges with extracorporeal circulation, such as coagulation and platelet activation, followed by consumption of coagulation factors and platelets, and biocompatibility of tubing, pump, and oxygenator. Unfractionated heparin (heparin hereafter) has historically been the defacto anticoagulant until recently. Also, coagulation monitoring was mainly based on bedside activated clotting time and activated partial thromboplastin time. In the past 50 years, the technology of ECMO has advanced tremendously, and thus, the survival rate has improved significantly. The indication for ECMO has …

Quality Assurance For Stereotactic Body Radiation Therapy For Gynecologic Malignancies, Samuel N Andersen, Mark D Bonnen, Michelle S Ludwig, Shraddha M Dalwadi

Faculty, Staff and Students Publications

The use of stereotactic body radiation therapy (SBRT) is not well studied or reported in the treatment of gynecologic malignancies, despite its success in the definitive management of other cancer sites. This report describes a rigorous quality assurance process for patients to undergo dose escalation to the pelvis via stereotactic photon beam irradiation. Patients who receive SBRT must be ineligible for conventional brachytherapy boost and undergo comprehensive informed consent. Fiducial placement, bowel prep, Foley catheter placement with standardized bladder filling, computerized tomography (CT) simulation with whole-body immobilization, magnetic resonance imaging (MRI)-assisted target delineation, planning aims based on the established brachytherapy …

Circadian Dysfunction Induces Nafld-Related Human Liver Cancer In A Mouse Model, Jennifer Padilla, Noha M Osman, Beatrice Bissig-Choisat, Sandra L Grimm, Xuan Qin, Angela M Major, Li Yang, Dolores Lopez-Terrada, Cristian Coarfa, Feng Li, Karl-Dimiter Bissig, David D Moore, Loning Fu

Faculty, Staff and Students Publications

BACKGROUND & AIMS: Chronic circadian dysfunction increases the risk of non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC), but the underlying mechanisms and direct relevance to human HCC have not been established. In this study, we aimed to determine whether chronic circadian dysregulation can drive NAFLD-related carcinogenesis from human hepatocytes and human HCC progression.

METHODS: Chronic jet lag of mice with humanized livers induces spontaneous NAFLD-related HCCs from human hepatocytes. The clinical relevance of this model was analysed by biomarker, pathological/histological, genetic, RNA sequencing, metabolomic, and integrated bioinformatic analyses.

RESULTS: Circadian dysfunction induces glucose intolerance, NAFLD-associated human HCCs, and human …

Sirt1 Safeguards Adipogenic Differentiation By Orchestrating Anti-Oxidative Responses And Suppressing Cellular Senescence, An Yu, Ruofan Yu, Haiying Liu, Chenliang Ge, Weiwei Dang

Faculty, Staff and Students Publications

Adipose tissue is an important endocrine organ that regulates metabolism, immune response and aging in mammals. Healthy adipocytes promote tissue homeostasis and longevity. SIRT1, a conserved NAD⁺-dependent deacetylase, negatively regulates adipogenic differentiation by deacetylating and inhibiting PPAR-γ. However, knocking out SIRT1 in mesenchymal stem cells (MSCs) in mice not only causes defects in osteogenesis, but also results in the loss of adipose tissues, suggesting that SIRT1 is also important for adipogenic differentiation.

Here, we report that severe impairment of SIRT1 function in MSCs caused significant defects and cellular senescence during adipogenic differentiation. These were observed only when inhibiting …

Leptin Reduction As A Required Component For Weight Loss, Shangang Zhao, Na Li, Wei Xiong, Guannan Li, Sijia He, Zhuzhen Zhang, Qingzhang Zhu, Nisi Jiang, Christian Ikejiofor, Yi Zhu, May-Yun Wang, Xianlin Han, Ningyang Zhang, Carolina Solis-Herrera, Christine Kusminski, Zhiqiang An, Joel K Elmquist, Philipp E Scherer

Faculty, Staff and Students Publications

Partial leptin reduction can induce significant weight loss, while weight loss contributes to partial leptin reduction. The cause-and-effect relationship between leptin reduction and weight loss remains to be further elucidated. Here, we show that FGF21 and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide rapidly induced a reduction in leptin. This leptin reduction contributed to the beneficial effects of GLP-1R agonism in metabolic health, as transgenically maintaining leptin levels during treatment partially curtailed the beneficial effects seen with these agonists. Moreover, a higher degree of leptin reduction during treatment, induced by including a leptin neutralizing antibody with either FGF21 or …

Nonchromosomal Birth Defects And Risk Of Childhood Acute Leukemia: An Assessment In 15 000 Leukemia Cases And 46 000 Controls From The Childhood Cancer And Leukemia International Consortium, Philip J Lupo, Tiffany M Chambers, Beth A Mueller, Jacqueline Clavel, John D Dockerty, David R Doody, Friederike Erdmann, Sameera Ezzat, Tommaso Filippini, Johnni Hansen, Julia E Heck, Claire Infante-Rivard, Alice Y Kang, Corrado Magnani, Carlotta Malagoli, Erin L Marcotte, Catherine Metayer, Helen D Bailey, Ana M Mora, Evangelia Ntzani, Eleni Th Petridou, Maria S Pombo-De-Oliveira, Wafaa M Rashed, Eve Roman, Joachim Schüz, Catharina Wesseling, Logan G Spector, Michael E Scheurer

Faculty, Staff and Students Publications

Although recent studies have demonstrated associations between nonchromosomal birth defects and several pediatric cancers, less is known about their role on childhood leukemia susceptibility. Using data from the Childhood Cancer and Leukemia International Consortium, we evaluated associations between nonchromosomal birth defects and childhood leukemia. Pooling consortium data from 18 questionnaire-based and three registry-based case-control studies across 13 countries, we used multivariable logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between a spectrum of birth defects and leukemia. Our analyses included acute lymphoblastic leukemia (ALL, n = 13 115) and acute myeloid leukemia …

The Ddhd2-Stxbp1 Interaction Mediates Long-Term Memory Via Generation Of Saturated Free Fatty Acids, Isaac O Akefe, Saber H Saber, Benjamin Matthews, Bharat G Venkatesh, Rachel S Gormal, Daniel G Blackmore, Suzy Alexander, Emma Sieriecki, Yann Gambin, Jesus Bertran-Gonzalez, Nicolas Vitale, Yann Humeau, Arnaud Gaudin, Sevannah A Ellis, Alysee A Michaels, Mingshan Xue, Benjamin Cravatt, Merja Joensuu, Tristan P Wallis, Frédéric A Meunier

Faculty, Staff and Students Publications

The phospholipid and free fatty acid (FFA) composition of neuronal membranes plays a crucial role in learning and memory, but the mechanisms through which neuronal activity affects the brain's lipid landscape remain largely unexplored. The levels of saturated FFAs, particularly of myristic acid (C14:0), strongly increase during neuronal stimulation and memory acquisition, suggesting the involvement of phospholipase A1 (PLA1) activity in synaptic plasticity. Here, we show that genetic ablation of the PLA1 isoform DDHD2 in mice dramatically reduces saturated FFA responses to memory acquisition across the brain. Furthermore, DDHD2 loss also decreases memory performance in reward-based learning and spatial memory …

Anticoagulation With Osocimab In Patients With Kidney Failure Undergoing Hemodialysis: A Randomized Phase 2 Trial, Jeffrey I Weitz, László B Tankó, Jürgen Floege, Keith A A Fox, Deepak L Bhatt, Ravi Thadhani, James Hung, Ákos F Pap, Dagmar Kubitza, Wolfgang C Winkelmayer

Faculty, Staff and Students Publications

Individuals with kidney failure undergoing hemodialysis are at elevated risk for thromboembolic events. Factor (F) XI, which is in the intrinsic pathway of coagulation, is emerging as an attractive target for new anticoagulants that may be safer than existing agents. Osocimab-an inhibitory FXIa antibody-is a potential treatment option for such patients. We conducted a phase 2b, double-blind, placebo-controlled trial, in which 704 participants (448 male, 256 female) with kidney failure undergoing hemodialysis were randomized to receive lower- or higher-dose osocimab or placebo. In total, 686 participants (436 male, 250 female) received treatment for ≤18 months (planned minimal treatment period of …

Correlates Of Risk For Disinhibited Behaviors In The Million Veteran Program Cohort, Peter B Barr, Tim B Bigdeli, Jacquelyn L Meyers, Roseann E Peterson, Sandra Sanchez-Roige, Travis T Mallard, Danielle M Dick, K Paige Harden, Anna Wilkinson, David P Graham, David A Nielsen, Alan C Swann, Rachele K Lipsky, Thomas R Kosten, Mihaela Aslan, Philip D Harvey, Nathan A Kimbrel, Jean C Beckham

Faculty, Staff and Students Publications

Importance: Many psychiatric outcomes share a common etiologic pathway reflecting behavioral disinhibition, generally referred to as externalizing (EXT) disorders. Recent genome-wide association studies (GWASs) have demonstrated the overlap between EXT disorders and important aspects of veterans' health, such as suicide-related behaviors and substance use disorders (SUDs).

Objective: To explore correlates of risk for EXT disorders within the Veterans Health Administration (VA) Million Veteran Program (MVP).

Design, setting, and participants: A series of phenome-wide association studies (PheWASs) of polygenic risk scores (PGSs) for EXT disorders was conducted using electronic health records. First, ancestry-specific PheWASs of EXT PGSs were conducted in the …

The Human Vaginal Microbiota: From Clinical Medicine To Models To Mechanisms, Samantha Ottinger, Clare M Robertson, Holly Branthoover, Kathryn A Patras

Faculty, Staff and Students Publications

The composition of the vaginal microbiota is linked to numerous reproductive health problems, including increased susceptibility to infection, pregnancy complications, and impaired vaginal tissue repair; however, the mechanisms contributing to these adverse outcomes are not yet fully defined. In this review, we highlight recent clinical advancements associating vaginal microbiome composition and function with health outcomes. Subsequently, we provide a summary of emerging models employed to identify microbe-microbe interactions contributing to vaginal health, including metagenomic sequencing, multi-omics approaches, and advances in vaginal microbiota cultivation. Last, we review new in vitro, ex vivo, and in vivo models, such as organoids and humanized …

Safety, Immunogenicity, And Mechanism Of A Rotavirus Mrna-Lnp Vaccine In Mice, Chenxing Lu, Yan Li, Rong Chen, Xiaoqing Hu, Qingmei Leng, Xiaopeng Song, Xiaochen Lin, Jun Ye, Jinlan Wang, Jinmei Li, Lida Yao, Xianqiong Tang, Xiangjun Kuang, Guangming Zhang, Maosheng Sun, Yan Zhou, Hongjun Li

Faculty, Staff and Student Publications

Rotaviruses (RVs) are a major cause of diarrhea in young children worldwide. The currently available and licensed vaccines contain live attenuated RVs. Optimization of live attenuated RV vaccines or developing non-replicating RV (e.g., mRNA) vaccines is crucial for reducing the morbidity and mortality from RV infections. Herein, a nucleoside-modified mRNA vaccine encapsulated in lipid nanoparticles (LNP) and encoding the VP7 protein from the G1 type of RV was developed. The 5' untranslated region of an isolated human RV was utilized for the mRNA vaccine. After undergoing quality inspection, the VP7-mRNA vaccine was injected by subcutaneous or intramuscular routes into mice. …

The Mef2c Gene Dose-Dependently Controls Hippocampal Neurogenesis And The Expression Of Autism-Like Behaviors, Sreetama Basu, Eun Jeoung Ro, Zhi Liu, Hyunjung Kim, Aubrey Bennett, Seungwoo Kang, Hoonkyo Suh

The Brown Foundation: Institute of Molecular Medicine

Mutations in the activity-dependent transcription factor MEF2C have been associated with several neuropsychiatric disorders. Among these, autism spectrum disorder (ASD)-related behavioral deficits are manifested. Multiple animal models that harbor mutations in Mef2c have provided compelling evidence that Mef2c is indeed an ASD gene. However, studies in mice with germline or global brain knock-out of Mef2c are limited in their ability to identify the precise neural substrates and cell types that are required for the expression of Mef2c-mediated ASD behaviors. Given the role of hippocampal neurogenesis in cognitive and social behaviors, in this study we aimed to investigate the role …

Blood Epigenome-Wide Association Studies Of Suicide Attempt In Adults With Bipolar Disorder, Salahudeen Mirza, Camila N C Lima, Alexandra Del Favero-Campbell, Alexandre Rubinstein, Natasha Topolski, Brenda Cabrera-Mendoza, Emese H C Kovács, Hilary P Blumberg, Jenny Gringer Richards, Aislinn J Williams, John A Wemmie, Vincent A Magnotta, Jess G Fiedorowicz, Marie E Gaine, Consuelo Walss-Bass, Joao Quevedo, Jair C Soares, Gabriel R Fries

Faculty, Staff and Student Publications

Suicide attempt (SA) risk is elevated in individuals with bipolar disorder (BD), and DNA methylation patterns may serve as possible biomarkers of SA. We conducted epigenome-wide association studies (EWAS) of blood DNA methylation associated with BD and SA. DNA methylation was measured at >700,000 positions in a discovery cohort of n = 84 adults with BD with a history of SA (BD/SA), n = 79 adults with BD without history of SA (BD/non-SA), and n = 76 non-psychiatric controls (CON). EWAS revealed six differentially methylated positions (DMPs) and seven differentially methylated regions (DMRs) between BD/SA and BD/non-SA, with multiple immune-related …

Management Of Infliximab Refractory Immune Checkpoint Inhibitor Gastrointestinal Toxicity: A Multicenter Case Series, Catriona Harvey, Kazi J Nahar, Janet Mckeown, Serigne N Lo, Sheima Farag, Nadia Yousaf, Kate Young, Liselotte Tas, Aafke Meerveld-Eggink, Christian Blank, Austin Thomas, Jennifer Mcquade, Bastian Schilling, Douglas B Johnson, Roberto Martín Huertas, Ana Arance, Joanna Lee, Lisa Zimmer, Georgina V Long, Matteo S Carlino, Yinghong Wang, Alexander Maxwell Menzies

Faculty, Staff and Student Publications

Background: Immune checkpoint inhibitor (ICI) gastrointestinal toxicity (gastritis, enteritis, colitis) is a major cause of morbidity and treatment-related death. Guidelines agree steroid-refractory cases warrant infliximab, however best management of infliximab-refractory ICI gastrointestinal toxicity (IRIGItox) is unknown.

Methods: We conducted an international multicenter retrospective case series. IRIGItox was defined as failure of symptom resolution ≤grade 1 (Common Terminology Criteria for Adverse Events V.5.0) following ≥2 infliximab doses or failure of symptom resolution ≤grade 2 after one dose. Data were extracted regarding demographics, steroid use, response to treatment, and survival outcomes. Toxicity was graded at symptom onset and time of infliximab failure. …

Association Between Regulatory T Cells And Ischemic Heart Disease: A Mendelian Randomization Study, Yucheng Hou, Ke Si, Jingyue Yang, Tan Liu, Basel Abdelazeem, Nonthikorn Theerasuwipakorn, Jingwei Zhao, Zhenya Shen

Faculty, Staff and Student Publications

BACKGROUND: An imbalance of innate and acquired immune responses is significantly involved in the pathophysiology of coronary atherosclerosis and the occurrence of ischemic heart disease (IHD). Regulatory T cells (Tregs) play an essential regulatory role in atherosclerotic plaque formation and maintenance; therefore, dysfunction of Tregs triggers the formation of atherosclerotic plaques and accelerates their progression. However, due to the inherent limitations of observational research, clinical evidence is limited concerning the relationship between the variation in peripheral Tregs and the risk of IHD, and the cause-and-effect relationship between these factors is unclear. Mendelian randomization (MR) uses genetic variation as a proxy …

Comprehensive Characterization Of Polyproline Tri-Helix Macrocyclic Nanoscaffolds For Predictive Ligand Positioning, Chia-Lung Tsai, Je-Wei Chang, Kum-Yi Cheng, Yu-Jing Lan, Yi-Cheng Hsu, Qun-Da Lin, Tzu-Yuan Chen, Orion Shih, Chih-Hsun Lin, Po-Hsun Chiang, Mantas Simenas, Vidmantas Kalendra, Yun-Wei Chiang, Chun-Hsien Chen, U-Ser Jeng, Sheng-Kai Wang

Faculty, Staff and Student Publications

Multivalent ligands hold promise for enhancing avidity and selectivity to simultaneously target multimeric proteins, as well as potentially modulating receptor signaling in pharmaceutical applications. Essential for these manipulations are nanosized scaffolds that precisely control ligand display patterns, which can be achieved by using polyproline oligo-helix macrocyclic nanoscaffolds via selective binding to protein oligomers and cell surface receptors. This work focuses on synthesis and structural characterization of different-sized polyproline tri-helix macrocyclic (PP3M) scaffolds. Through combined analysis of circular dichroism (CD), small- and wide-angle X-ray scattering (SWAXS), electron spin resonance (ESR) spectroscopy, and molecular modeling, a non-coplanar tri-helix loop structure with partially …

Expression Of Atoh1, Gfi1, And Pou4f3 In The Mature Cochlea Reprograms Nonsensory Cells Into Hair Cells, Melissa M Mcgovern, Ishwar V Hosamani, Yichi Niu, Ken Y Nguyen, Chenghang Zong, Andrew K Groves

Faculty, Staff and Students Publications

Mechanosensory hair cells of the mature mammalian organ of Corti do not regenerate; consequently, loss of hair cells leads to permanent hearing loss. Although nonmammalian vertebrates can regenerate hair cells from neighboring supporting cells, many humans with severe hearing loss lack both hair cells and supporting cells, with the organ of Corti being replaced by a flat epithelium of nonsensory cells. To determine whether the mature cochlea can produce hair cells in vivo, we reprogrammed nonsensory cells adjacent to the organ of Corti with three hair cell transcription factors: Gfi1, Atoh1, and Pou4f3. We generated numerous hair cell–like …

Frozen Tissue Coring And Layered Histological Analysis Improves Cell Type-Specific Proteogenomic Characterization Of Pancreatic Adenocarcinoma, Sara R Savage, Yuefan Wang, Lijun Chen, Scott Jewell, Chelsea Newton, Yongchao Dou, Qing Kay Li, Oliver F Bathe, Ana I Robles, Gilbert S Omenn, Mathangi Thiagarajan, Hui Zhang, Galen Hostetter, Bing Zhang

Faculty, Staff and Students Publications

BACKGROUND: Omics characterization of pancreatic adenocarcinoma tissue is complicated by the highly heterogeneous and mixed populations of cells. We evaluate the feasibility and potential benefit of using a coring method to enrich specific regions from bulk tissue and then perform proteogenomic analyses.

METHODS: We used the Biopsy Trifecta Extraction (BioTExt) technique to isolate cores of epithelial-enriched and stroma-enriched tissue from pancreatic tumor and adjacent tissue blocks. Histology was assessed at multiple depths throughout each core. DNA sequencing, RNA sequencing, and proteomics were performed on the cored and bulk tissue samples. Supervised and unsupervised analyses were performed based on integrated molecular …

The Role Of Family Support In The Self-Rated Health Of Older Adults In Eastern Nepal: Findings From A Cross-Sectional Study, Ivan Fumagalli, Stefano Pagani, Christian Vergara, Luca Dede', Dilachew A Adebo, Maurizio Del Greco, Antonio Frontera, Giovanni Battista Luciani, Gianluca Pontone, Roberto Scrofani, Alfio Quarteroni

Faculty, Staff and Student Publications

BACKGROUND AND OBJECTIVE: Computational models of the cardiovascular system allow for a detailed and quantitative investigation of both physiological and pathological conditions, thanks to their ability to combine clinical-possibly patient-specific-data with physical knowledge of the processes underlying the heart function. These models have been increasingly employed in clinical practice to understand pathological mechanisms and their progression, design medical devices, support clinicians in improving therapies. Hinging upon a long-year experience in cardiovascular modeling, we have recently constructed a computational multi-physics and multi-scale integrated model of the heart for the investigation of its physiological function, the analysis of pathological conditions, and to …

Leveraging Trop2 Antibody-Drug Conjugates In Solid Tumors, Blessie Elizabeth Nelson, Funda Meric-Bernstam

Faculty, Staff and Student Publications

Antibody-drug conjugates (ADCs) have become the cornerstone of effective therapeutics in solid and hematological malignancies by harnessing potent cytotoxic payloads with targeted tumoricidal delivery. Since the monumental shift occurred with HER2-targeted ADCs, the discovery of the TROP2 antigen has revolutionized the landscape of ADC development. Moving beyond the traditional ADC design, multiple novel ADCs have successfully shaped and improved survival outcomes in patients with various tumor histologies. Here we review and contrast the clinical impact of the well-known TROP2 ADCs currently in clinical use. We also shed light on upcoming investigational TROP2 ADCs showing promise with novel ADC platforms.

Patient-Derived Models Of Cancer In The Nci Pdmc Consortium: Selection, Pitfalls, And Practical Recommendations, Amber N Habowski, Deepthi P Budagavi, Sandra D Scherer, Arin B Aurora, Giuseppina Caligiuri, William F Flynn, Ellen M Langer, Jonathan R Brody, Rosalie C Sears, Giorgia Foggetti, Anna Arnal Estape, Don X Nguyen, Katerina A Politi, Xiling Shen, David S Hsu, Donna M Peehl, John Kurhanewicz, Renuka Sriram, Milagros Suarez, Sophie Xiao, Yuchen Du, Xiao-Nan Li, Nora M Navone, Estefania Labanca, Christopher D Willey

Faculty, Staff and Student Publications

For over a century, early researchers sought to study biological organisms in a laboratory setting, leading to the generation of both in vitro and in vivo model systems. Patient-derived models of cancer (PDMCs) have more recently come to the forefront of preclinical cancer models and are even finding their way into clinical practice as part of functional precision medicine programs. The PDMC Consortium, supported by the Division of Cancer Biology in the National Cancer Institute of the National Institutes of Health, seeks to understand the biological principles that govern the various PDMC behaviors, particularly in response to perturbagens, such as …

Ahp Db: A Reference Database Of Proteins In The Human Aqueous Humor, Tae Jin Lee, Arnav Goyal, Garrett Jones, Joshua Glass, Vishal Doshi, Kathryn Bollinger, Lane Ulrich, Saleh Ahmed, Sai Karthik Kodeboyina, Amy Estes, Marc Töteberg-Harms, Wenbo Zhi, Shruti Sharma, Ashok Sharma

Faculty, Staff and Student Publications

The aqueous humor (AH) is a low-viscosity biofluid that continuously circulates from the posterior chamber to the anterior chamber of the eye. Recent advances in high-resolution mass-spectrometry workflows have facilitated the study of proteomic content in small-volume biofluids like AH, highlighting the potential clinical implications of the AH proteome. Nevertheless, in-depth investigations into the role of AH proteins in ocular diseases have encountered challenges due to limited accessibility to these workflows, difficulties in large-scale AH sample collection and the absence of a reference AH proteomic database. In response to these obstacles, and to promote further research on the involvement of …

Adult Neuromuscular Choristoma, A Rare Peripheral Nerve Pathology: Illustrative Case, Ashley Ricciardelli, Alex Flores, Hsiang-Chih Lu, Ekin Guney, Arie Perry, Joey Grochmal

Faculty, Staff and Students Publications

Background: Neuromuscular choristomas (NMCs) are rare tumors involving aberrant intercalation of muscle fibers into peripheral nerves, most commonly the sciatic nerve. Although benign, these lesions risk developing into NMCs with desmoid-type fibrosis (NMC-DTFs), aggressive lesions potentially requiring amputation. Currently, information on NMCs and the link between NMCs and NMC-DTFs is limited in adults, with the majority of cases reported in children. We present the case of a 66-year-old male with a sciatic NMC alongside a Preferred Reporting Items for Systematic Reviews and Meta-Analyses-based systematic review of similar cases to better characterize this lesion in the adult population.

Observations: A male …

Important Features For Protein Foldings In Two Acyl Carrier Proteins From Enterococcus Faecalis, Seoyeong Yoo, Jiwon Yeon, Eunhee Kim, Yangmee Kim

Faculty, Staff and Student Publications

The emergence of multi-drug resistant Enterococcus faecalis raises a serious threat to global public health. E. faecalis is a gram-positive intestinal commensal bacterium found in humans. E. faecalis can endure extreme environments such as high temperature, pressure, and high salt, which facilitates them to cause infection in hospitals. E. faecalis has two acyl carrier proteins, AcpA (EfAcpA) in de novo fatty acid synthesis (FAS) and AcpB (EfAcpB) which utilizes exogenous fatty acids. Previously, we determined the tertiary structures of these two ACPs and investigated their structure-function relationships. Solution structures revealed that overall folding of these two ACPs is similar to …

Circulating Microrna Expression And Nonalcoholic Fatty Liver Disease In Adolescents With Severe Obesity, Yi-Jie Li, Brittney O Baumert, Nikos Stratakis, Jesse A Goodrich, Hao-Tian Wu, Jing-Xuan He, Yin-Qi Zhao, Max T Aung, Hong-Xu Wang, Sandrah P Eckel, Douglas I Walker, Damaskini Valvi, Michele A La Merrill, Justin R Ryder, Thomas H Inge, Todd Jenkins, Stephanie Sisley, Rohit Kohli, Stavra A Xanthakos, Andrea A Baccarelli, Rob Mcconnell, David V Conti, Lida Chatzi

Faculty, Staff and Students Publications

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases in children and adolescents. NAFLD ranges in severity from isolated hepatic steatosis to nonalcoholic steatohepatitis (NASH), wherein hepatocellular inflammation and/or fibrosis coexist with steatosis. Circulating microRNA (miRNA) levels have been suggested to be altered in NAFLD, but the extent to which miRNA are related to NAFLD features remains unknown. This analysis tested the hypothesis that plasma miRNAs are significantly associated with histological features of NAFLD in adolescents.

AIM: To investigate the relationship between plasma miRNA expression and NAFLD features among adolescents with NAFLD.

METHODS: This …