Digital Commons Network^™

Thinking Through How Race, Disability, And Gender Work Together, Rosemarie Garland-Thomson, Desiree Valentine

Philosophy Faculty Research and Publications

No abstract provided.

Update On Recommendations For Surveillance For Children With Predisposition To Hematopoietic Malignancy, Luke D Maese, Marcin W Wlodarski, Sun Young Kim, Alison A Bertuch, Gaelle Bougeard, Vivian Y Chang, Lucy A Godley, Payal P Khincha, Roland P Kuiper, Harry Lesmana, Rose B Mcgee, Lisa J Mcreynolds, Julia Meade, Sharon E Plon, Sharon A Savage, Sarah R Scollon, Hamish S Scott, Michael F Walsh, Kim E Nichols, Christopher C Porter

Center for Medical Ethics and Health Policy Staff Publications

Children harboring certain germline gene variants have an increased risk of developing myelodysplastic syndrome (MDS) and other hematopoietic malignancies (HM), such as leukemias and lymphomas. Recent studies have identified an expanding number of these predisposition genes, with variants most prevalent in children with MDS but also found in children with other HM. For some hematopoietic malignancy predispositions (HMP), specifically those with a high risk of MDS, early intervention through hematopoietic stem cell transplantation can favorably impact overall survival, providing a rationale for rigorous surveillance. A multidisciplinary panel of experts at the 2023 AACR Childhood Cancer Predisposition Workshop reviewed the latest …

Human Embryonic Genetic Mosaicism And Its Effects On Development And Disease, Sarah M Waldvogel, Jennifer E Posey, Margaret A Goodell

Center on Aging Staff Publications

Nearly every mammalian cell division is accompanied by a mutational event that becomes fixed in a daughter cell. When carried forward to additional cell progeny, a clone of variant cells can emerge. As a result, mammals are complex mosaics of clones that are genetically distinct from one another. Recent high-throughput sequencing studies have revealed that mosaicism is common, clone sizes often increase with age and specific variants can affect tissue function and disease development. Variants that are acquired during early embryogenesis are shared by multiple cell types and can affect numerous tissues. Within tissues, variant clones compete, which can result …

Breakdown Of Boltzmann-Type Models For The Alignment Of Self-Propelled Rods, Patrick Murphy, Misha Perepelitsa, Ilya Timofeyev, Matan Lieber-Kotz, Brandon Islas, Oleg A. Igoshin

Faculty Research, Scholarly, and Creative Activity

Studies in the collective motility of organisms use a range of analytical approaches to formulate continuous kinetic models of collective dynamics from rules or equations describing agent interactions. However, the derivation of these kinetic models often relies on Boltzmann's “molecular chaos” hypothesis, which assumes that correlations between individuals are short-lived. While this assumption is often the simplest way to derive tractable models, it is often not valid in practice due to the high levels of cooperation and self-organization present in biological systems. In this work, we illustrated this point by considering a general Boltzmann-type kinetic model for the alignment of …

A Top Model Of Urban Residents’ Subjective Well-Being In China, Bing Pan, Deborah Kerstetter, Xiaoli Yi, Gaojun Zhang, Rui Li, Jie Gao, Xiangyou Sharon Shen, Guangming Li

Faculty Research, Scholarly, and Creative Activity

Past research on subjective well-being (SWB) in Western society and China has revealed various contributing factors. This study conducted a series of interviews with Chinese urban residents to systematically analyze those factors based on Bronfenbrenner’s Ecological System Theory. The results revealed that 5 layers, 23 factors, and 55 elements, many of which had distinct Chinese characteristics, contributed to Chinese urban residents’ SWB. The Top Model of SWB, visualized as a spinning top or gyroscope, showcased the interdependent layers of factors impacting Chinese urban residents’ SWB. At its vertical axis is a time dimension as residents often reflect on factors by …

Dean's Update, October 2024, Neil W. Schluger

SOM Dean's Research Newsletter

No abstract provided.

Transcription And Post-Translational Mechanisms: Dual Regulation Of Adiponectin-Mediated Occludin Expression In Diabetes, Yanru Duan, Demin Liu, Huahui Yu, Shihan Zhang, Yihua Xia, Zhiyong Du, Yanwen Qin, Yajing Wang, Xin-Liang Ma, Huirong Liu, Yunhui Du

Department of Emergency Medicine Faculty Papers

BACKGROUND: Occludin, a crucial component of tight junctions, has emerged as a promising biomarker for the diagnosis of acute ischemic disease, highlighting its significant potential in clinical applications. In the diabetes, Occludin serves as a downstream target gene intricately regulated by the adiponectin (APN) signaling pathway. However, the specific mechanism by which adiponectin regulates Occludin expression remains unclear.

METHODS AND RESULTS: Endothelial-specific Ocln knockdown reduced APN-mediated blood flow recovery after femoral artery ligation and nullified APN's protection against high-fat diet (HFD)-triggered apoptosis and angiogenesis inhibition in vivo. Mechanically, we have meticulously elucidated APN's regulatory role in Occludin expression through a …

Chemometric Processing Of Ecstasy Tablet Thermal Profiles Using Machine Learning Methods, Ali Arif Ibrahim

Theses

Ecstasy is an amphetamine-type substance scientifically known as MDMA (3,4- methylenedioxymethamphetamine) that belongs to a group of illicit drugs called “club drugs” that are widespread and distributed illegally (Maione et al., 2016). Its ever-growing popularity and variety in multiple forms, shapes, and colors complicates the identification and tracking process to law enforcement and forensic analysts. The current study focused on integrating data analytics and advanced chemometric methods to Differential Scanning Calorimetry (DSC) to analyze the thermal profiles of ecstasy tablets. This approach aims to discriminate between tablets linked to different suspects and origins through thermal profiling, which will provide law …

Resistance To Acetyl Coenzyme A Carboxylase (Accase) Inhibitor In Lolium Multiflorum: Effect Of Multiple Target-Site Mutations, Gulab Rangani, Ana Claudia Langaro, Shilpi Agrawal, Reiofeli Algodon Salas-Perez, Juan Camilo Velasquez, Christopher E. Nelson, Nilda Roma-Burgos

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Italian ryegrass (Lolium multiflorum Lam.) is a persistent weed species that poses significant management challenges in key agricultural crops such as wheat, corn, cotton, and soybean. This study investigated the prevalence of resistance to ACCase inhibitor herbicides, specifically diclofop and pinoxaden, among field-collected Italian ryegrass populations. The survey revealed widespread resistance to diclofop and emerging cross-resistance to pinoxaden. To elucidate the physiological mechanism of ACCase herbicide resistance, we investigated mutations in the carboxyl-transferase (CT) domain of the ACCase enzyme, a critical region for herbicide sensitivity. Using dCAPS assays and CT domain sequencing, several known resistance-conferring mutations were detected in …

Oxyfluorfen Use In Combination With Clomazone Or Quinclorac, Jason K. Norsworthy, Casey H. Arnold, Thomas R. Butts, Chad W. Shelton

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Oxyfluorfen is a herbicide that inhibits protoporphyrinogen IX oxidase and has shown significant potential in its ability to control barnyardgrass. Oxyfluorfen is categorized as a Group 14 herbicide by the Herbicide Resistance Action Committee (HRAC)/Weed Science Society of America (WSSA). Despite its current lack of labeling for use on rice in the mid-southern United States due to its potential to cause crop injury, the introduction of a trait in rice that confers resistance to oxyfluorfen could provide producers with an effective alternative site of action for weed control. Field experiments were conducted during the 2021 and 2022 growing seasons near …

Clomazone And Oxyfluorfen Combinations In A Flooded Rice System, Jason K. Norsworthy, Casey H. Arnold, Thomas R. Butts, Trenton L. Roberts, Chad W. Shelton

Crop, Soil and Environmental Sciences Faculty Publications and Presentations

Rice producers battle herbicide-resistant weeds worldwide while producing rice for ≥50% of the world’s population. Oxyfluorfen can provide rice producers with an alternative site of action for barnyardgrass control, as there are no documented cases of grass weeds being resistant to the herbicide in the mid-southern United States. Oxyfluorfen is anticipated to be labeled in the Roxy Rice Production System and may be sold as a clomazone/oxyfluorfen premixture; hence, experiments were conducted in 2021 and 2022 to evaluate preemergence-applied clomazone/oxyfluorfen ratios compared to clomazone alone on silt loam and clay soils. All ratios of the herbicides caused less than 7% …

A Coupled Spatial-Network Model: A Mathematical Framework For Applications In Epidemiology, Hannah Kravitz, Christina Duron, Moysey Brio

Mathematics and Statistics Faculty Publications and Presentations

There is extensive evidence that network structure (e.g., air transport, rivers, or roads) may significantly enhance the spread of epidemics into the surrounding geographical area. A new compartmental modeling framework is proposed which couples well-mixed (ODE in time) population centers at the vertices, 1D travel routes on the graph’s edges, and a 2D continuum containing the rest of the population to simulate how an infection spreads through a population. The edge equations are coupled to the vertex ODEs through junction conditions, while the domain equations are coupled to the edges through boundary conditions. A numerical method based on spatial finite …

A Mouse Model For Conditional Expression Of Activated Β-Catenin In Epidermal Keratinocytes, Vineet K Maurya, Yan Ying, John P Lydon

Faculty, Staff and Students Publications

We report the generation and characterization of the K5: CAT bigenic mouse in which the constitutively activated form of β-catenin (ΔN89 β-catenin) is conditionally expressed in cytokeratin-5 (K5) positive epidermal keratinocytes. Following short-term doxycycline intake during the telogen resting phase, the adult K5: CAT bigenic develops enlarged pilosebaceous units that expand deep into the dermis, an expansion usually observed during the anagen growth phase. Prolonged doxycycline treatment results in significant thickening and folding of the K5: CAT epidermis. During this persistent induction period, there is clear evidence of increased keratinocyte proliferation, particularly in the epidermal basal cell layer and the …

Disruption Of Neural Periodicity Predicts Clinical Response After Deep Brain Stimulation For Obsessive-Compulsive Disorder, Nicole R Provenza, Sandesh Reddy, Anthony K Allam, Sameer V Rajesh, Nabeel Diab, Gabriel Reyes, Rose M Caston, Kalman A Katlowitz, Ajay D Gandhi, Raphael A Bechtold, Huy Q Dang, Ricardo A Najera, Nisha Giridharan, Katherine E Kabotyanski, Faiza Momin, Mohammed Hasen, Garrett P Banks, Brian J Mickey, Brent M Kious, Ben Shofty, Benjamin Y Hayden, Jeffrey A Herron, Eric A Storch, Ankit B Patel, Wayne K Goodman, Sameer A Sheth

Faculty, Staff and Students Publications

Recent advances in surgical neuromodulation have enabled chronic and continuous intracranial monitoring during everyday life. We used this opportunity to identify neural predictors of clinical state in 12 individuals with treatment-resistant obsessive-compulsive disorder (OCD) receiving deep brain stimulation (DBS) therapy ( NCT05915741 ). We developed our neurobehavioral models based on continuous neural recordings in the region of the ventral striatum in an initial cohort of five patients and tested and validated them in a held-out cohort of seven additional patients. Before DBS activation, in the most symptomatic state, theta/alpha (9 Hz) power evidenced a prominent circadian pattern and a high …

Mouse Corneal Immune Cell Heterogeneity Revealed By Single-Cell Rna Sequencing, Ebru Yaman, Nicole Heyer, Cintia S De Paiva, Mary Ann Stepp, Stephen C Pflugfelder, Jehan Alam

Faculty, Staff and Students Publications

PURPOSE: This study aimed to define the heterogeneity, spatial localization, and functional roles of immune cells in the mouse cornea using single-cell RNA sequencing (scRNA-seq) and immunofluorescent staining.

METHODS: Enriched mouse corneal immune cells (C57BL/6 strain, age 16-20 weeks) underwent single-cell RNA sequencing library preparation, sequencing, and analysis with Seurat, Monocle 3, and CellChat packages in R. Pathway analysis used Qiagen Ingenuity Pathway Analysis software. Immunostaining confirmed cell distribution.

RESULTS: We identified 14 distinct immune cell clusters (56% myeloid and 44% lymphoid). Myeloid populations included resident macrophages, conventional dendritic cells (cDC2s), Langerhans cells, neutrophils, monocytes, and mast cells. Additionally, lymphocyte …

Pkmyt1 Is A Marker Of Treatment Response And A Therapeutic Target For Cdk4/6 Inhibitor-Resistance In Er+ Breast Cancer, Anran Chen, Beom-Jun Kim, Aparna Mitra, Craig T Vollert, Jonathan T Lei, Diana Fandino, Meenakshi Anurag, Matthew V Holt, Xuxu Gou, Jacob B Pilcher, Matthew P Goetz, Donald W Northfelt, Susan G Hilsenbeck, C Gary Marshall, Marc L Hyer, Robert Papp, Shou-Yun Yin, Carmine De Angelis, Rachel Schiff, Suzanne A W Fuqua, Cynthia X Ma, Charles E Foulds, Matthew J Ellis

Faculty, Staff and Students Publications

Endocrine therapies (ET) with cyclin-dependent kinase 4/6 (CDK4/6) inhibition are the standard treatment for estrogen receptor-α-positive (ER+) breast cancer, however drug resistance is common. In this study, proteogenomic analyses of patient-derived xenografts (PDXs) from patients with 22 ER+ breast cancer demonstrated that protein kinase, membrane-associated tyrosine/threonine one (PKMYT1), a WEE1 homolog, is estradiol (E2) regulated in E2-dependent PDXs and constitutively expressed when growth is E2-independent. In clinical samples, high PKMYT1 mRNA levels associated with resistance to both ET and CDK4/6 inhibition. The PKMYT1 inhibitor lunresertib (RP-6306) with gemcitabine selectively and synergistically reduced the viability of ET and palbociclib-resistant ER+ breast …

Tau Is Required For Glial Lipid Droplet Formation And Resistance To Neuronal Oxidative Stress, Lindsey D Goodman, Isha Ralhan, Xin Li, Shenzhao Lu, Matthew J Moulton, Ye-Jin Park, Pinghan Zhao, Oguz Kanca, Ziyaneh S Ghaderpour Taleghani, Julie Jacquemyn, Joshua M Shulman, Kanae Ando, Kai Sun, Maria S Ioannou, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

The accumulation of reactive oxygen species (ROS) is a common feature of tauopathies, defined by Tau accumulations in neurons and glia. High ROS in neurons causes lipid production and the export of toxic peroxidated lipids (LPOs). Glia uptake these LPOs and incorporate them into lipid droplets (LDs) for storage and catabolism. We found that overexpressing Tau in glia disrupts LDs in flies and rat neuron-astrocyte co-cultures, sensitizing the glia to toxic, neuronal LPOs. Using a new fly tau loss-of-function allele and RNA-mediated interference, we found that endogenous Tau is required for glial LD formation and protection against neuronal LPOs. Similarly, …

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 …

Does Glial Lipid Dysregulation Alter Sleep In Alzheimer’S And Parkinson’S Disease?, Lindsey D Goodman, Matthew J Moulton, Guang Lin, Hugo J Bellen

Duncan NRI Faculty and Staff Publications

In this opinion article, we discuss potential connections between sleep disturbances observed in Alzheimer's disease (AD) and Parkinson's disease (PD) and the dysregulation of lipids in the brain. Research using Drosophila has highlighted the role of glial-mediated lipid metabolism in sleep and diurnal rhythms. Relevant to AD, the formation of lipid droplets in glia, which occurs in response to elevated neuronal reactive oxygen species (ROS), is required for sleep. In disease models, this process is disrupted, arguing a connection to sleep dysregulation. Relevant to PD, the degradation of neuronally synthesized glucosylceramides by glia requires glucocerebrosidase (GBA, a PD-associated risk factor) …

Piezo Ion Channels: Force Sensors Of The Interoceptive Nervous System, Yasmeen M F Hamed, Britya Ghosh, Kara L Marshall

Duncan NRI Faculty and Staff Publications

Many organs are designed to move: the heart pumps each second, the gastrointestinal tract squeezes and churns to digest food, and we contract and relax skeletal muscles to move our bodies. Sensory neurons of the peripheral nervous system detect signals from bodily tissues, including the forces generated by these movements, to control physiology. The processing of these internal signals is called interoception, but this is a broad term that includes a wide variety of both chemical and mechanical sensory processes. Mechanical senses are understudied, but rapid progress has been made in the last decade, thanks in part to the discovery …

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 …

Novel Genes Of The Male Reproductive System: Potential Roles In Male Reproduction And As Non-Hormonal Male Contraceptive Targets, Thomas X Garcia, Martin M Matzuk

Faculty, Staff and Students Publications

The development of novel non-hormonal male contraceptives represents a pivotal frontier in reproductive health, driven by the need for safe, effective, and reversible contraceptive methods. This comprehensive review explores the genetic underpinnings of male fertility, emphasizing the crucial roles of specific genes and structural variants (SVs) identified through advanced sequencing technologies such as long-read sequencing (LRS). LRS has revolutionized the detection of structural variants and complex genomic regions, offering unprecedented precision and resolution over traditional next-generation sequencing (NGS). Key genetic targets, including those implicated in spermatogenesis and sperm motility, are highlighted, showcasing their potential as non-hormonal contraceptive targets. The review …

Addressing Platelet Insecurity – A National Call To Action, Eric A Gehrie, Pampee P Young, Sridhar V Basavaraju, Arthur W Bracey, Andrew P Cap, Liz Culler, Nancy M Dunbar, Mary Homer, Iris Isufi, Rob Macedo, Tanya Petraszko, Glenn Ramsey, Christopher A Tormey, Richard M Kaufman, Edward L Snyder

Faculty, Staff and Students Publications

No abstract provided.

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 …

Characterization And Visualization Of Tandem Repeats At Genome Scale, Egor Dolzhenko, Adam English, Harriet Dashnow, Guilherme De Sena Brandine, Tom Mokveld, William J Rowell, Caitlin Karniski, Zev Kronenberg, Matt C Danzi, Warren A Cheung, Chengpeng Bi, Emily Farrow, Aaron Wenger, Khi Pin Chua, Verónica Martínez-Cerdeño, Trevor D Bartley, Peng Jin, David L Nelson, Stephan Zuchner, Tomi Pastinen, Aaron R Quinlan, Fritz J Sedlazeck, Michael A Eberle

Faculty, Staff and Students Publications

Tandem repeat (TR) variation is associated with gene expression changes and numerous rare monogenic diseases. Although long-read sequencing provides accurate full-length sequences and methylation of TRs, there is still a need for computational methods to profile TRs across the genome. Here we introduce the Tandem Repeat Genotyping Tool (TRGT) and an accompanying TR database. TRGT determines the consensus sequences and methylation levels of specified TRs from PacBio HiFi sequencing data. It also reports reads that support each repeat allele. These reads can be subsequently visualized with a companion TR visualization tool. Assessing 937,122 TRs, TRGT showed a Mendelian concordance of …

Cancer Drug-Tolerant Persister Cells: From Biological Questions To Clinical Opportunities, Mariangela Russo, Mengnuo Chen, Elisa Mariella, Haoning Peng, Sumaiyah K Rehman, Elena Sancho, Alberto Sogari, Tzen S Toh, Nathalie Q Balaban, Eduard Batlle, Rene Bernards, Mathew J Garnett, Matthew Hangauer, Eleonora Leucci, Jean-Christophe Marine, Catherine A O'Brien, Yaara Oren, E Elizabeth Patton, Caroline Robert, Susan M Rosenberg, Shensi Shen, Alberto Bardelli

Faculty, Staff and Students Publications

The emergence of drug resistance is the most substantial challenge to the effectiveness of anticancer therapies. Orthogonal approaches have revealed that a subset of cells, known as drug-tolerant 'persister' (DTP) cells, have a prominent role in drug resistance. Although long recognized in bacterial populations which have acquired resistance to antibiotics, the presence of DTPs in various cancer types has come to light only in the past two decades, yet several aspects of their biology remain enigmatic. Here, we delve into the biological characteristics of DTPs and explore potential strategies for tracking and targeting them. Recent findings suggest that DTPs exhibit …

Perspectives On Hand Hygiene In Belizean Healthcare Facilities During The Covid-19 Pandemic: A Qualitative Evaluation With Healthcare Workers, Kelsey Mcdavid, Christina Craig, Anh N Ly, Nicholas Bivens, Francis Morey, Russell Manzanero, Gerhaldine Morazan, Ella Hawes, Alexandra Medley, Kristy Murray, Matthew Lozier

Faculty, Staff and Students Publications

The World Health Organization recommends healthcare workers (HCWs) practice hand hygiene (HH) while providing care. Making alcohol-based hand rub (ABHR) available at points of care is recommended during times of high patient volume, such as the COVID-19 pandemic. In low- and middle-income countries, such as Belize, there may be limited access to HH materials within healthcare facilities (HCF). This paper examines the motivators and barriers to HH among HCWs in the 11 largest public healthcare facilities in Belize and HCWs' experiences with an intervention. In 2021, focus group discussions (FGDs) gathered HCWs' HH perceptions and preferences. An intervention was then …

Circulating Tumor Cell Count And Overall Survival In Patients With Metastatic Hormone-Sensitive Prostate Cancer, Amir Goldkorn, Catherine Tangen, Melissa Plets, Daniel Bsteh, Tong Xu, Jacek K Pinski, Sue Ingles, Timothy Junius Triche, Gary R Macvicar, Daniel A Vaena, Anthony W Crispino, David James Mcconkey, Primo N Lara, Maha H A Hussain, David I Quinn, Tanya B Dorff, Seth Paul Lerner, Ian Thompson, Neeraj Agarwal

Faculty, Staff and Students Publications

IMPORTANCE: In metastatic hormone-sensitive prostate cancer (mHSPC), new first-line combination therapies have enhanced overall survival (OS), but clinical outcomes for individual patients vary greatly and are difficult to predict. Peripheral blood circulating tumor cell (CTC) count is the most extensively validated prognostic liquid biomarker in metastatic castration-resistant prostate cancer (mCRPC), and recent studies have suggested that it may also be informative in mHSPC.

OBJECTIVE: To examine the prognostic value of CTC count in men with mHSPC.

DESIGN, SETTING, AND PARTICIPANTS: In this prognostic study, peripheral blood was drawn at registration (baseline) and at progression to mCRPC in the S1216 study …

Galectin 3-Binding Protein (Lgals3bp) Depletion Attenuates Hepatic Fibrosis By Reducing Transforming Growth Factor-Β1 (Tgf-Β1) Availability And Inhibits Hepatocarcinogenesis, Dae-Hwan Kim, Minjeong Sung, Myong-Suk Park, Eun-Gene Sun, Sumin Yoon, Kyung Hyun Yoo, Kamalakannan Radhakrishnan, Sung Yun Jung, Woo-Kyun Bae, Sang-Hee Cho, Ik-Joo Chung

Faculty, Staff and Students Publications

Background: Increased Galectin 3-binding protein (LGALS3BP) serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma (HCC). Considering the crucial role of transforming growth factor-β1 (TGF-β1) in the emergence of these diseases, the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling pathway.

Methods: The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis (MASH) and HCC. Multiple omics techniques, such as RNA-sequencing, transposase-accessible chromatin-sequencing assay, and liquid chromatography-tandem mass spectrometry proteomics, were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 axis. The effects of altered …

Considerations For Reporting Variants In Novel Candidate Genes Identified During Clinical Genomic Testing, Jessica X Chong, Seth I Berger, Samantha Baxter, Erica Smith, Changrui Xiao, Daniel G Calame, Megan H Hawley, E Andres Rivera-Munoz, Stephanie Ditroia, Genomics Research To Elucidate The Genetics Of Rare Diseases (Gregor) Consortium, Michael J Bamshad, Heidi L Rehm

Faculty, Staff and Students Publications

Since the first novel gene discovery for a Mendelian condition was made via exome sequencing, the rapid increase in the number of genes known to underlie Mendelian conditions coupled with the adoption of exome (and more recently, genome) sequencing by diagnostic testing labs has changed the landscape of genomic testing for rare diseases. Specifically, many individuals suspected to have a Mendelian condition are now routinely offered clinical ES. This commonly results in a precise genetic diagnosis but frequently overlooks the identification of novel candidate genes. Such candidates are also less likely to be identified in the absence of large-scale gene …