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Articles 34231 - 34260 of 325145

Full-Text Articles in Medicine and Health Sciences

Achilles Tendon Morphology Adaptations In Chronic Post-Stroke Hemiparesis: A Comparative Analysis With Neurologically Intact Controls, Jing Nong Liang, Greg Bashford, Kornelia Kulig, Kai-Yu Ho Jan 2025

Achilles Tendon Morphology Adaptations In Chronic Post-Stroke Hemiparesis: A Comparative Analysis With Neurologically Intact Controls, Jing Nong Liang, Greg Bashford, Kornelia Kulig, Kai-Yu Ho

Physical Therapy Faculty Research

Introduction: In individuals with chronic post-stroke hemiparesis, slow walking speed is a significant concern related to inadequate propulsion of the paretic limb. However, an overlooked factor is this population's altered morphology of the Achilles tendon, which may compromise the propulsive forces by the paretic limb. This study aimed to explore changes in Achilles tendon morphology, including gross thickness and intra-tendinous collagen fiber bundle organization, following stroke-induced brain lesions.

Methods: Fifteen individuals with chronic post-stroke hemiparesis (at least 6 months post-stroke) and 19 neurologically intact controls participated. Ultrasound imaging was used to evaluate Achilles tendon thickness and collagen organization in the …


Evaluating The Effects Of High-Throughput Structural Neuroimaging Predictors On Whole-Brain Functional Connectome Outcomes Via Network-Based Matrix-On-Vector Regression, Tong Lu, Yuan Zhang, Vince Lyzinski, Chuan Bi, Peter Kochunov, Elliot Hong, Shuo Chen Jan 2025

Evaluating The Effects Of High-Throughput Structural Neuroimaging Predictors On Whole-Brain Functional Connectome Outcomes Via Network-Based Matrix-On-Vector Regression, Tong Lu, Yuan Zhang, Vince Lyzinski, Chuan Bi, Peter Kochunov, Elliot Hong, Shuo Chen

Faculty, Staff and Student Publications

The joint analysis of multimodal neuroimaging data is vital in brain research, revealing complex interactions between brain structures and functions. Our study is motivated by the analysis of a vast dataset of brain functional connectivity (FC) and multimodal structural imaging (SI) features from the UK Biobank. Specifically, we aim to investigate the effects of SI features, such as white matter microstructure integrity (WMMI) and cortical thickness, on the whole-brain functional connectome network. This analysis is inherently challenging due to the extensive structural-functional associations and the intricate network patterns present in multimodal high-dimensional neuroimaging data. To bridge methodological gaps, we developed …


Quantifying Capacity Of Otolaryngology-Head And Neck Surgery In Zimbabwe, Katerina J. Green, Daniel G. Eyassu, Amiti Jain, Priya Arya, Estephania Candelo, Dontre' M. Douse, Naboth N. Matinhira, Clemence Chidziva, Joshua P. Wiedermann Jan 2025

Quantifying Capacity Of Otolaryngology-Head And Neck Surgery In Zimbabwe, Katerina J. Green, Daniel G. Eyassu, Amiti Jain, Priya Arya, Estephania Candelo, Dontre' M. Douse, Naboth N. Matinhira, Clemence Chidziva, Joshua P. Wiedermann

SKMC Student Presentations and Publications

OBJECTIVES: To evaluate the otolaryngology surgical capacity in Harare, Zimbabwe by analyzing procedural volumes across four hospitals, one private and three public, from 2019 to 2022.

METHODS: A retrospective review of hand-written surgical case logs was conducted at Harare Eye, Ear, Nose, and Throat Institute (HEENT), Parirenyatwa Group of Hospitals (PGH), Sally Mugabe Children's Hospital (SMCH), and Sally Mugabe Adult's Hospital (SMAH). Patient age and surgical intervention for all otolaryngology surgeries performed in the operating room from 2019 to 2022 were recorded. Procedures were categorized into six groups: head and neck malignancy, laryngeal surgery, oropharyngeal surgery, otologic surgery, rhinology/sinus surgery, …


Retreatability Of Endosequence® Bcs™ Hiflow Utilizing Both Chloroform And An Aqueous Solution, Dijana Elmejdoubi, Thomas E. Lallier, Masyn Cameron, Albert F. Mcmullen Iii Jan 2025

Retreatability Of Endosequence® Bcs™ Hiflow Utilizing Both Chloroform And An Aqueous Solution, Dijana Elmejdoubi, Thomas E. Lallier, Masyn Cameron, Albert F. Mcmullen Iii

School of Dentistry Faculty Publications

Purpose: When RCT fails, retreatment of the case usually requires removal of the previous root canal fill (RCF). The aim of our research was to evaluate the retreatability of a root canal initially filled with gutta percha and EndoSequence® BCS™ HiFlow utilizing chloroform followed by 18% HCl, 18% HCl alone, chloroform alone or saline solution. Methods: 40 extracted single canal teeth were decoronated and obturated utilizing a single cone gutta percha technique and Endosequence BCS, stored one week in an incubator, and then we attempted to remove the previous RCF. Teeth were divided in 4 different groups (n=10). Canals were …


More Police Spending Is Linked To Higher Opioid Overdose Mortality Rates, Michah W. Rothbart, Zoe Lindenfeld, Amanda I. Mauri, Diana Silver Jan 2025

More Police Spending Is Linked To Higher Opioid Overdose Mortality Rates, Michah W. Rothbart, Zoe Lindenfeld, Amanda I. Mauri, Diana Silver

Population Health Research Brief Series

In the United States, over 100,000 people die from drug overdoses every year. County fiscal policies, particularly police spending and revenue generated from fines and forfeitures, not only shape the resources available for health interventions but may also influence how those resources are used to prevent overdoses. This brief highlights findings from a study that used data from the U.S. Census of Governments to examine how counties use of extractive policing practices (fines and forfeitures) as well as spending on health and policing were related to opioid overdose deaths from 2017 to 2020. Findings show that higher county-level police spending …


Insights Into Rett Syndrome: Social Behavior, Bdnf-Trkb Signaling, And Dendritic Spines, Destynie Medeiros Jan 2025

Insights Into Rett Syndrome: Social Behavior, Bdnf-Trkb Signaling, And Dendritic Spines, Destynie Medeiros

All ETDs from UAB

Rett syndrome (RTT) is a neurodevelopmental disorder primarily affecting females, caused by pathogenic variants in the X-linked MECP2 gene, which encodes the transcriptional modulator Methyl-CpG binding protein 2 (MeCP2). RTT is characterized by motor deficits, loss of speech, autistic features, and intellectual disability. A key gene regulated by MeCP2 is BDNF, encoding the neurotrophin brain-derived neurotrophic factor (BDNF). BDNF levels are lower in multiple brain regions of Mecp2-deficient mice, and experimentally increasing BDNF levels improves several RTT phenotypes in mouse models. Due to BDNF's low blood-brain barrier permeability, we tested LM22A-4, a brain-penetrant small molecule ligand of TrkB receptors, on …


The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco Jan 2025

The C-Terminal Phdvc5hch Tandem Domain Of Nsd2 Is A Combinatorial Reader Of Modified H3k4 And Tri-Methylated H3k27 That Regulates Transcription Of Cell Adhesion Genes In Multiple Myeloma, Andrea Berardi, Charlotte Leonie Kaestner, Michela Ghitti, Giacomo Quilici, Paolo Cocomazzi, Jianping Li, Federico Ballabio, Chiara Zucchelli, Stefan Knapp, Jonathan Licht, Giovanna Musco

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

Histone methyltransferase NSD2 (MMSET) overexpression in multiple myeloma (MM) patients plays an important role in the development of this disease subtype. Through the expansion of transcriptional activating H3K36me2 and the suppression of repressive H3K27me3 marks, NSD2 activates an aberrant set of genes that contribute to myeloma growth, adhesive and invasive activities. NSD2 transcriptional activity also depends on its non-catalytic domains, which facilitate its recruitment to chromatin through histone binding. In this study, using NMR, ITC and molecular dynamics simulations, we show that the tandem PHD domain of NSD2 (PHDVC5HCHNSD2) is a combinatorial reader of unmodified histone H3K4 and tri-methylated H3K27 …


Functional Performance Of Patients With Stroke During Inpatient Rehabilitation: A Cross-Sectional Study Of Home And Access Visits, Melissa J Krauss, Emily Somerville, Callista Poiter, Rebecca M Bollinger, Brianna M Holden, Gabrielle Blenden, Danielle Kretzer, Susan L Stark Jan 2025

Functional Performance Of Patients With Stroke During Inpatient Rehabilitation: A Cross-Sectional Study Of Home And Access Visits, Melissa J Krauss, Emily Somerville, Callista Poiter, Rebecca M Bollinger, Brianna M Holden, Gabrielle Blenden, Danielle Kretzer, Susan L Stark

2020-Current year OA Pubs

BACKGROUND: Home visits prior to inpatient rehabilitation facility (IRF) discharge allow occupational therapists to observe functional abilities among patients with stroke and address barriers that impact daily activities at home. However, home visits prior to IRF discharge are not standard practice due to barriers of time and cost constraints. We explored whether an access visit (visiting the home without the patient) could serve as an alternative to a home visit (with the patient) to anticipate functional abilities at home.

METHODS: We used baseline data from a randomized controlled trial that occurred before and during the COVID-19 pandemic, which caused predischarge …


Advancing De Novo Lipogenesis: Genetic And Metabolic Insights, Sean M Hartig, Mark A Herman Jan 2025

Advancing De Novo Lipogenesis: Genetic And Metabolic Insights, Sean M Hartig, Mark A Herman

Faculty, Staff and Students Publications

De novo lipogenesis (DNL) is the process whereby cells synthesize fatty acids from acetyl-CoA, contributing to steatosis in fatty liver disease. Two new studies, using genetic mouse models, metabolomics, and pharmacology, identified alternative pathways in DNL and unexpected physiological effects when targeting key enzymes in this pathway.


A Caution Against Customized Ai In Healthcare, Kristin M Kostick-Quenet Jan 2025

A Caution Against Customized Ai In Healthcare, Kristin M Kostick-Quenet

Center for Medical Ethics and Health Policy Staff Publications

This article critiques the shift towards personalized AI in healthcare and other high-stakes domains, cautioning that without careful deliberation, customized AI systems can compromise the diversity and reach of human knowledge by restricting exposure to critical information that may conflict with users' preferences and biases. Customized AI should be applied with caution and intention where access to a wide and diverse range of perspectives is essential for impartial, informed decision making.


Modulation Of Stemness And Differentiation Regulators By Valproic Acid In Medulloblastoma Neurospheres, Natália Hogetop Freire, Alice Laschuk Herlinger, Julia Vanini, Matheus Dalmolin, Marcelo A C Fernandes, Carolina Nör, Vijay Ramaswamy, Caroline Brunetto De Farias, André Tesainer Brunetto, Algemir Lunardi Brunetto, Lauro José Gregianin, Mariane Da Cunha Jaeger, Michael D Taylor, Rafael Roesler Jan 2025

Modulation Of Stemness And Differentiation Regulators By Valproic Acid In Medulloblastoma Neurospheres, Natália Hogetop Freire, Alice Laschuk Herlinger, Julia Vanini, Matheus Dalmolin, Marcelo A C Fernandes, Carolina Nör, Vijay Ramaswamy, Caroline Brunetto De Farias, André Tesainer Brunetto, Algemir Lunardi Brunetto, Lauro José Gregianin, Mariane Da Cunha Jaeger, Michael D Taylor, Rafael Roesler

Faculty, Staff and Students Publications

Changes in epigenetic processes such as histone acetylation are proposed as key events influencing cancer cell function and the initiation and progression of pediatric brain tumors. Valproic acid (VPA) is an antiepileptic drug that acts partially by inhibiting histone deacetylases (HDACs) and could be repurposed as an epigenetic anticancer therapy. Here, we show that VPA reduced medulloblastoma (MB) cell viability and led to cell cycle arrest. These effects were accompanied by enhanced H3K9 histone acetylation (H3K9ac) and decreased expression of the MYC oncogene. VPA impaired the expansion of MB neurospheres enriched in stemness markers and reduced MYC while increasing TP53 …


Organizational Readiness For Implementation: A Qualitative Assessment To Explain Survey Responses, Maria Mcclam, Lauren Workman, Timothy J. Walker, Emanuelle M. Dias, Derek W. Craig, Joe R. Padila, Andrea E. Lamont, Abraham Wandersman, Maria E. Fernandez Jan 2025

Organizational Readiness For Implementation: A Qualitative Assessment To Explain Survey Responses, Maria Mcclam, Lauren Workman, Timothy J. Walker, Emanuelle M. Dias, Derek W. Craig, Joe R. Padila, Andrea E. Lamont, Abraham Wandersman, Maria E. Fernandez

Faculty Publications

Background

One factor considered essential to successful implementation is organizational readiness. The purpose of this study was to explore ways to improve the measurement of organizational readiness, and in particular to refine a preliminary measure based on the Readiness = Motivation x innovation Specific Capacity x General Capacity (R = MC2) heuristic. We assessed the experiences of staff in Federally Qualified Health Centers (FQHC) implementing evidence-based interventions (EBIs) designed to increase colorectal cancer screening (CRCS) who previously completed the survey and aimed to understand their perspectives on why our data were positively skewed.

Methods

We conducted a series of qualitative …


Ubr5 In Tumor Biology: Exploring Mechanisms Of Immune Regulation And Possible Therapeutic Implications In Mpnst, Diana Akinyi Odhiambo, Selina Fan, Angela C Hirbe Jan 2025

Ubr5 In Tumor Biology: Exploring Mechanisms Of Immune Regulation And Possible Therapeutic Implications In Mpnst, Diana Akinyi Odhiambo, Selina Fan, Angela C Hirbe

2020-Current year OA Pubs

Malignant peripheral nerve sheath tumor (MPNST) is a rare but aggressive soft-tissue sarcoma characterized by poor response to therapy. The primary treatment remains surgical resection with negative margins. Nonetheless, in the setting of neurofibromatosis type 1 (NF1), the five-year survival rate is at 20-50%, with recurrence occurring in up to 50% of individuals. For patients with metastatic and unresectable disease, current treatment options include cytotoxic chemotherapy, which offers minimal benefit, and most patients die within five years of diagnosis. Despite advances in targeted therapy focusing on inhibiting Ras signaling and its downstream effectors, clinical trials report minimal clinical benefit, highlighting …


Toward Personalized Digital Experiences To Promote Diabetes Self-Management: Mixed Methods Social Computing Approach, Tavleen Singh, Kirk Roberts, Kayo Fujimoto, Jing Wang, Constance Johnson, Sahiti Myneni Jan 2025

Toward Personalized Digital Experiences To Promote Diabetes Self-Management: Mixed Methods Social Computing Approach, Tavleen Singh, Kirk Roberts, Kayo Fujimoto, Jing Wang, Constance Johnson, Sahiti Myneni

Faculty, Staff and Student Publications

BACKGROUND: Type 2 diabetes affects nearly 34.2 million adults and is the seventh leading cause of death in the United States. Digital health communities have emerged as avenues to provide social support to individuals engaging in diabetes self-management (DSM). The analysis of digital peer interactions and social connections can improve our understanding of the factors underlying behavior change, which can inform the development of personalized DSM interventions.

OBJECTIVE: Our objective is to apply our methodology using a mixed methods approach to (1) characterize the role of context-specific social influence patterns in DSM and (2) derive interventional targets that enhance individual …


Organizational Readiness For Implementation: A Qualitative Assessment To Explain Survey Responses, Maria Mcclam, Lauren Workman, Timothy J Walker, Emanuelle M Dias, Derek W Craig, Joe R Padilla, Andrea E Lamont, Abraham Wandersman, Maria E Fernandez Jan 2025

Organizational Readiness For Implementation: A Qualitative Assessment To Explain Survey Responses, Maria Mcclam, Lauren Workman, Timothy J Walker, Emanuelle M Dias, Derek W Craig, Joe R Padilla, Andrea E Lamont, Abraham Wandersman, Maria E Fernandez

Faculty, Staff and Student Publications

BACKGROUND: One factor considered essential to successful implementation is organizational readiness. The purpose of this study was to explore ways to improve the measurement of organizational readiness, and in particular to refine a preliminary measure based on the Readiness = Motivation x innovation Specific Capacity x General Capacity (R = MC2) heuristic. We assessed the experiences of staff in Federally Qualified Health Centers (FQHC) implementing evidence-based interventions (EBIs) designed to increase colorectal cancer screening (CRCS) who previously completed the survey and aimed to understand their perspectives on why our data were positively skewed.

METHODS: We conducted a series of qualitative …


Neural Mechanisms Of Proactive And Reactive Cognitive Control In Humans, Anas Khan Jan 2025

Neural Mechanisms Of Proactive And Reactive Cognitive Control In Humans, Anas Khan

All ETDs from UAB

Cognitive control enables flexible, goal-directed behavior by dynamically adjusting our actions in response to changing task demands. This dissertation investigates the neural mechanisms underlying proactive and reactive cognitive control, particularly focusing on the dorsolateral prefrontal cortex (dlPFC) and the dorsal anterior cingulate cortex (dACC) during tasks that require response inhibition and conflict processing. Using intracranial electroencephalography (iEEG) recordings from human participants, this research examines the distinct roles of oscillatory activity in these regions in both short-term reactive adjustments and long-term proactive control strategies. Chapter 2 explores the role of low-frequency oscillations in the mid-rostral dlPFC during motor inhibition, revealing that …


Molecular Mechanism Of Congenital Cataract Caused By G91 Deletion In Cryβa1, Akosua Konadu Boateng Jan 2025

Molecular Mechanism Of Congenital Cataract Caused By G91 Deletion In Cryβa1, Akosua Konadu Boateng

All ETDs from UAB

The Deletion of Glycine 91 is a mutational hotspot in the CRYβA1 gene (mutant named βA3ΔG91), which causes autosomal dominant congenital nuclear cataracts in several ethnically diverse populations worldwide. Previous in-vitro studies of recombinant βA3ΔG91 protein revealed that this mutation results in defective protein folding, reduced solubility, and oligomerization with other crystallins. While βA3/A1-crystallin is primarily known as a structural protein in the lens, it also plays a role in autophagy regulation in the retinal pigment epithelium (RPE) by controlling endolysosomal acidification through the V-ATPase proton pump. This study employs a novel βA3ΔG91 knock-in mouse model to investigate the pathogenic …


The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop Jan 2025

The Dopaminergic Cell-Intrinsic Clock And Bidirectional Relationships Of Circadian Disruption And Synucleinopathy, Ananya Swaroop

All ETDs from UAB

Circadian rhythms are crucial endogenous cycles with period of ~24 hours that evolved to adapt to light – dark driven changes in environmental conditions. At a molecular level, circadian rhythms are generated by the actions of clock genes that form a transcriptional- translational feedback loop and regulate the rhythmic expression of downstream clock-controlled genes. Cumulatively, the actions of these molecular clocks regulate rhythmicity of physiological and behavioral processes and are extensively characterized within the central circadian pacemaker, the suprachiasmatic nucleus (SCN). Like SCN neurons, dopaminergic neurons of the SN are intrinsically pacemaking, though it is unknown if this intrinsic firing …


Climate Change Will Impact Childhood Cancer Risks, Care And Outcomes., Hannah M. Thompson, Perry Sheffield, Omar Shakeel, Nicole Wood, Mark D. Miller Jan 2025

Climate Change Will Impact Childhood Cancer Risks, Care And Outcomes., Hannah M. Thompson, Perry Sheffield, Omar Shakeel, Nicole Wood, Mark D. Miller

Manuscripts, Articles, Book Chapters and Other Papers

No abstract provided.


A Survey On Food Ingredient Substitutions, Hyunwook Kim, Revathy Venkataramanan, Amit P. Sheth Jan 2025

A Survey On Food Ingredient Substitutions, Hyunwook Kim, Revathy Venkataramanan, Amit P. Sheth

Publications

Diet plays a crucial role in managing chronic conditions and overall well-being. As people become more selective about their food choices, finding recipes that meet dietary needs is important. Ingredient substitution is key to adapting recipes for dietary restrictions, allergies, and availability constraints. However, identifying suitable substitutions is challenging as it requires analyzing the flavor, functionality, and health suitability of ingredients. With the advancement of AI, researchers have explored computational approaches to address ingredient substitution. This survey paper provides a comprehensive overview of the research in this area, focusing on five key aspects: (i) datasets and data sources used to …


Yap Overcomes Mechanical Barriers To Induce Mitotic Rounding And Adult Cardiomyocyte Division, Yuka Morikawa, Jong H Kim, Rich Gang Li, Lin Liu, Shijie Liu, Vaibhav Deshmukh, Matthew C Hill, James F Martin Jan 2025

Yap Overcomes Mechanical Barriers To Induce Mitotic Rounding And Adult Cardiomyocyte Division, Yuka Morikawa, Jong H Kim, Rich Gang Li, Lin Liu, Shijie Liu, Vaibhav Deshmukh, Matthew C Hill, James F Martin

Faculty, Staff and Students Publications

Background: Many specialized cells in adult organs acquire a state of cell cycle arrest and quiescence through unknown mechanisms. Our limited understanding of mammalian cell cycle arrest is derived primarily from cell culture models. Adult mammalian cardiomyocytes, a classic example of cell cycle arrested cells, exit the cell cycle postnatally and remain in an arrested state for the life of the organism. Cardiomyocytes can be induced to re-enter the cell cycle by YAP5SA, an active form of the Hippo signaling pathway effector YAP.

Methods: We performed clonal analyses to determine the cell cycle kinetics of YAP5SA cardiomyocytes. We also performed …


Microtubules Sequester Acetylated Yap In The Cytoplasm And Inhibit Heart Regeneration, Shijie Liu, Vaibhav Deshmukh, Fansen Meng, Yidan Wang, Yuka Morikawa, Jeffrey D Steimle, Rich Gang Li, Jun Wang, James F Martin Jan 2025

Microtubules Sequester Acetylated Yap In The Cytoplasm And Inhibit Heart Regeneration, Shijie Liu, Vaibhav Deshmukh, Fansen Meng, Yidan Wang, Yuka Morikawa, Jeffrey D Steimle, Rich Gang Li, Jun Wang, James F Martin

Faculty, Staff and Students Publications

Background: The Hippo pathway effector YAP (Yes-associated protein) plays an essential role in cardiomyocyte proliferation and heart regeneration. In response to physiological changes, YAP moves in and out of the nucleus. The pathophysiological mechanisms regulating YAP subcellular localization after myocardial infarction remain poorly defined.

Methods: We identified YAP acetylation at site K265 by in vitro acetylation followed by mass spectrometry analysis. We used adeno-associated virus to express YAP-containing mutations that either abolished acetylation (YAP-K265R) or mimicked acetylation (YAP-K265Q) and studied how acetylation regulates YAP subcellular localization in mouse hearts. We generated a cell line with YAP-K265R mutation and investigated the …


The Gip Receptor Activates Futile Calcium Cycling In White Adipose Tissue To Increase Energy Expenditure And Drive Weight Loss In Mice, Xinxin Yu, Shiuhwei Chen, Jan-Bernd Funcke, Leon G Straub, Valentina Pirro, Margo P Emont, Brian A Droz, Kyla Ai Collins, Chanmin Joung, Mackenzie J Pearson, Corey M James, Gopal J Babu, Vissarion Efthymiou, Ashley Vernon, Mary Elizabeth Patti, Yu A An, Evan D Rosen, Matthew P Coghlan, Ricardo J Samms, Philipp E Scherer, Christine M Kusminski Jan 2025

The Gip Receptor Activates Futile Calcium Cycling In White Adipose Tissue To Increase Energy Expenditure And Drive Weight Loss In Mice, Xinxin Yu, Shiuhwei Chen, Jan-Bernd Funcke, Leon G Straub, Valentina Pirro, Margo P Emont, Brian A Droz, Kyla Ai Collins, Chanmin Joung, Mackenzie J Pearson, Corey M James, Gopal J Babu, Vissarion Efthymiou, Ashley Vernon, Mary Elizabeth Patti, Yu A An, Evan D Rosen, Matthew P Coghlan, Ricardo J Samms, Philipp E Scherer, Christine M Kusminski

Faculty, Staff and Student Publications

Obesity is a chronic disease that contributes to the development of insulin resistance, type 2 diabetes (T2D), and cardiovascular risk. Glucose-dependent insulinotropic polypeptide (GIP) receptor (GIPR) and glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) co-agonism provide an improved therapeutic profile in individuals with T2D and obesity when compared with selective GLP-1R agonism. Although the metabolic benefits of GLP-1R agonism are established, whether GIPR activation impacts weight loss through peripheral mechanisms is yet to be fully defined. Here, we generated a mouse model of GIPR induction exclusively in the adipocyte. We show that GIPR induction in the fat cell protects mice from diet-induced …


Rpa And Rad27 Limit Templated And Inverted Insertions At Dna Breaks, Yang Yu, Xin Wang, Jordan Fox, Qian Li, Yang Yu, P J Hastings, Kaifu Chen, Grzegorz Ira Jan 2025

Rpa And Rad27 Limit Templated And Inverted Insertions At Dna Breaks, Yang Yu, Xin Wang, Jordan Fox, Qian Li, Yang Yu, P J Hastings, Kaifu Chen, Grzegorz Ira

Faculty, Staff and Students Publications

Formation of templated insertions at DNA double-strand breaks (DSBs) is very common in cancer cells. The mechanisms and enzymes regulating these events are largely unknown. Here, we investigated templated insertions in yeast at DSBs using amplicon sequencing across a repaired locus. We document very short (most ∼5-34 bp), templated inverted duplications at DSBs. They are generated through a foldback mechanism that utilizes microhomologies adjacent to the DSB. Enzymatic requirements suggest a hybrid mechanism wherein one end requires Polδ-mediated synthesis while the other end is captured by nonhomologous end joining (NHEJ) or by alternative end joining (Alt-EJ). This process is exacerbated …


Cell Cycle Progression Of Under-Replicated Cells, Min Huang, Chang Yang, Litong Nie, Huimin Zhang, Dandan Zhu, Chao Wang, Jeong-Min Park, Mrinal Srivastava, Elina Mosa, Siting Li, Mengfan Tang, Xu Feng, Sarah J Keast, Fabio Stossi, Junjie Chen Jan 2025

Cell Cycle Progression Of Under-Replicated Cells, Min Huang, Chang Yang, Litong Nie, Huimin Zhang, Dandan Zhu, Chao Wang, Jeong-Min Park, Mrinal Srivastava, Elina Mosa, Siting Li, Mengfan Tang, Xu Feng, Sarah J Keast, Fabio Stossi, Junjie Chen

Faculty, Staff and Student Publications

Cell cycle checkpoints are the regulatory mechanisms that secure the strict order of cellular events for cell division that ensure genome integrity. It has been proposed that mitosis initiation depends on the completion of DNA replication, which must be tightly controlled to guarantee genome duplication. Contrary to these conventional hypotheses, we showed here that cells were able to enter mitosis without completion of DNA replication. Although DNA replication was not completed in cells upon depletion of MCM2, CDC45 or GINS4, these under-replicated cells progressed into mitosis, which led to cell death. These unexpected results challenge current model and suggest the …


A Regularized Bayesian Dirichlet-Multinomial Regression Model For Integrating Single-Cell-Level Omics And Patient-Level Clinical Study Data, Yanghong Guo, Lei Yu, Lei Guo, Lin Xu, Qiwei Li Jan 2025

A Regularized Bayesian Dirichlet-Multinomial Regression Model For Integrating Single-Cell-Level Omics And Patient-Level Clinical Study Data, Yanghong Guo, Lei Yu, Lei Guo, Lin Xu, Qiwei Li

Faculty, Staff and Student Publications

The abundance of various cell types can vary significantly among patients with varying phenotypes and even those with the same phenotype. Recent scientific advancements provide mounting evidence that other clinical variables, such as age, gender, and lifestyle habits, can also influence the abundance of certain cell types. However, current methods for integrating single-cell-level omics data with clinical variables are inadequate. In this study, we propose a regularized Bayesian Dirichlet-multinomial regression framework to investigate the relationship between single-cell RNA sequencing data and patient-level clinical data. Additionally, the model employs a novel hierarchical tree structure to identify such relationships at different cell-type …


Causal Models And Prediction In Cell Line Perturbation Experiments, James P Long, Yumeng Yang, Shohei Shimizu, Thong Pham, Kim-Anh Do Jan 2025

Causal Models And Prediction In Cell Line Perturbation Experiments, James P Long, Yumeng Yang, Shohei Shimizu, Thong Pham, Kim-Anh Do

Faculty, Staff and Student Publications

In cell line perturbation experiments, a collection of cells is perturbed with external agents and responses such as protein expression measured. Due to cost constraints, only a small fraction of all possible perturbations can be tested in vitro. This has led to the development of computational models that can predict cellular responses to perturbations in silico. A central challenge for these models is to predict the effect of new, previously untested perturbations that were not used in the training data. Here we propose causal structural equations for modeling how perturbations effect cells. From this model, we derive two estimators for …


Genetics And Biology Of Pancreatic Ductal Adenocarcinoma, Haoqiang Ying, Alec C Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A Depinho Jan 2025

Genetics And Biology Of Pancreatic Ductal Adenocarcinoma, Haoqiang Ying, Alec C Kimmelman, Nabeel Bardeesy, Raghu Kalluri, Anirban Maitra, Ronald A Depinho

Faculty, Staff and Student Publications

Pancreatic ductal adenocarcinoma (PDAC) poses a grim prognosis for patients. Recent multidisciplinary research efforts have provided critical insights into its genetics and tumor biology, creating the foundation for rational development of targeted and immune therapies. Here, we review the PDAC genomic landscape and the role of specific oncogenic events in tumor initiation and progression, as well as their contributions to shaping its tumor biology. We further summarize and synthesize breakthroughs in single-cell and metabolic profiling technologies that have illuminated the complex cellular composition and heterotypic interactions of the PDAC tumor microenvironment, with an emphasis on metabolic cross-talk across cancer and …


Sstr2-Targeted Theranostics In Hepatocellular Carcinoma, Majid Momeny, Solmaz Aghaamiri, Servando Hernandez Vargas, Belkacem Acidi, Sukhen C Ghosh, Tyler M Bateman, Jack T Adams, Vahid Khalaj, Ahmed O Kaseb, Hop S Tran Cao, Ali Azhdarinia Jan 2025

Sstr2-Targeted Theranostics In Hepatocellular Carcinoma, Majid Momeny, Solmaz Aghaamiri, Servando Hernandez Vargas, Belkacem Acidi, Sukhen C Ghosh, Tyler M Bateman, Jack T Adams, Vahid Khalaj, Ahmed O Kaseb, Hop S Tran Cao, Ali Azhdarinia

Faculty, Staff and Student Publications

Background: While the clinical use of radiolabeled somatostatin analogs is well established in neuroendocrine tumors, there is growing interest in expanding their application to other somatostatin receptor 2 (SSTR2)-expressing cancers. This study investigates the potential utility of SSTR2-targeted theranostics in hepatocellular carcinoma (HCC).

Methods: SSTR2 expression in HCC cell lines and clinical samples was evaluated using qRT-PCR, Western blot analysis, and a public dataset. 67Ga-DOTATATE uptake was measured, 177Lu-DOTATATE cytotoxicity was assessed, and 68Ga-DOTATATE tumor targeting was evaluated in HCC animal models and a patient via PET/CT imaging.

Results: SSTR2 expression was confirmed in HCC cell lines and clinical samples. …


Targeted Inhibition Of Aurora Kinase A Promotes Immune Checkpoint Inhibition Efficacy In Human Papillomavirus-Driven Cancers, Soma Ghosh, Madison P O'Hara, Pragya Sinha, Tuhina Mazumdar, Lacin Yapindi, Jagannadha K Sastry, Faye M Johnson Jan 2025

Targeted Inhibition Of Aurora Kinase A Promotes Immune Checkpoint Inhibition Efficacy In Human Papillomavirus-Driven Cancers, Soma Ghosh, Madison P O'Hara, Pragya Sinha, Tuhina Mazumdar, Lacin Yapindi, Jagannadha K Sastry, Faye M Johnson

Faculty, Staff and Student Publications

Background: Human papillomavirus (HPV)-driven cancers include head and neck squamous cell carcinoma and cervical cancer and represent approximately 5% of all cancer cases worldwide. Standard-of-care chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICIs) are associated with adverse effects and limited responses in patients with HPV-driven cancers. The integration of targeted therapies with ICIs may improve outcomes. In a previous study, we demonstrated that Aurora kinase A (AURKA, Aurora A) inhibitors lead to apoptosis of human HPV-positive cancer cells in vitro and in vivo. Here, we explored the potential of Aurora A inhibition to enhance response to ICIs in immune-competent …