Digital Commons Network^™

Predicting Radiotherapy Patient Outcomes With Real-Time Clinical Data Using Mathematical Modelling, Alexander P Browning, Thomas D Lewin, Ruth E Baker, Philip K Maini, Eduardo G Moros, Jimmy Caudell, Helen M Byrne, Heiko Enderling

Faculty, Staff and Student Publications

Longitudinal tumour volume data from head-and-neck cancer patients show that tumours of comparable pre-treatment size and stage may respond very differently to the same radiotherapy fractionation protocol. Mathematical models are often proposed to predict treatment outcome in this context, and have the potential to guide clinical decision-making and inform personalised fractionation protocols. Hindering effective use of models in this context is the sparsity of clinical measurements juxtaposed with the model complexity required to produce the full range of possible patient responses. In this work, we present a compartment model of tumour volume and tumour composition, which, despite relative simplicity, is …

Long-Term Open-Label Vebicorvir For Chronic Hbv Infection: Safety And Off-Treatment Responses, Man-Fung Yuen, Scott Fung, Xiaoli Ma, Tuan Nguyen, Tarek Hassanein, Hie-Won Hann, Magdy Elkhashab, Ronald Nahass, James Park, Ira Jacobson, Walid Ayoub, Steven-Huy Han, Edward Gane, Katie Zomorodi, Ran Yan, Julie Ma, Steven Knox, Luisa Stamm, Maurizio Bonacini, Frank Weilert, Alnoor Ramji, Michael Bennett, Natarajan Ravendhran, Sing Chan, Douglas Dieterich, Paul Yien Kwo, Eugene Schiff, Ho Bae, Jacob Lalezari, Kosh Agarwal, Mark Sulkowski

Department of Medicine Faculty Papers

BACKGROUND & AIMS: The investigational first-generation core inhibitor vebicorvir (VBR) demonstrated safety and antiviral activity over 24 weeks in two phase IIa studies in patients with chronic HBV infection. In this long-term extension study, patients received open-label VBR with nucleos(t)ide reverse transcriptase inhibitors (NrtIs).

METHODS: Patients in this study (NCT03780543) previously received VBR + NrtI or placebo + NrtI in parent studies 201 (NCT03576066) or 202 (NCT03577171). After receiving VBR + NrtI for ≥52 weeks, stopping criteria (based on the treatment history and hepatitis B e antigen status in the parent studies) were applied, and patients either discontinued both VBR …

Short Peripheral Blood Leukocyte Telomere Length In Rheumatoid Arthritis-Interstitial Lung Disease, Tracy J Doyle, Pierre-Antoine Juge, Anna L Peljto, Seoyeon Lee, Avram D Walts, Anthony Joseph Esposito, Sergio Poli, Ritu Gill, Hiroto Hatabu, Mizuki Nishino, Paul F Dellaripa, Michael E Weinblatt, Nancy A Shadick, M Kristen Demoruelle, Jeffrey A Sparks, Ivan O Rosas, Benjamin Granger, Kevin D Deane, Bruno Crestani, Paul J Wolters, Philippe Dieudé, Joyce S Lee

Faculty, Staff and Students Publications

Shortened telomere lengths (TLs) can be caused by single nucleotide polymorphisms and loss-of-function mutations in telomere-related genes (TRG), as well as ageing and lifestyle factors such as smoking. Our objective was to determine if shortened TL is associated with interstitial lung disease (ILD) in individuals with rheumatoid arthritis (RA). This is the largest study to demonstrate and replicate that shortened peripheral blood leukocytes-TL is associated with ILD in patients with RA compared with RA without ILD in a multinational cohort, and short PBL-TL was associated with baseline disease severity in RA-ILD as measured by forced vital capacity percent predicted.

Avaren-Fc, A Novel Immunotherapeutic, Recruits Nk Cells In B16f10 Melanoma Tumor Tissue, Sreevatsa Vemuri, Katarina Mayer, Nobuyuki Matoba

Posters-at-the-Capitol

Melanoma is the fifth most common cancer in the US, with limited effective immunotherapeutic options available for patients. Avaren-Fc (AvFc) is a novel experimental immunotherapeutic agent with a unique “lectibody” property. It is capable of targeting cancer cells through the selective recognition of high mannose glycans, which are aberrantly overrepresented on the surface of malignant cells. AvFc can interact with circulating effector immune cells equipped with Fc receptors, such as natural killer (NK) cells to induce antibody-dependent cell-mediated cytotoxicity (ADCC) and kill cancer cells. Previous work has shown that AvFc effectively induces ADCC activity against B16F10 cancer cells in vitro …

Standardized Pre-Clinical Surgical Animal Model Protocol To Investigate The Cellular And Molecular Mechanisms Of Ischemic Flap Healing, Edita Aksamitiene, Ryan Heffelfinger, Jan Hoek, Edmund Pribitkin

Department of Otolaryngology - Head and Neck Surgery Faculty Papers

BACKGROUND: Some of the most complex surgical interventions to treat trauma and cancer include the use of locoregional pedicled and free autologous tissue transfer flaps. While the techniques used for these reconstructive surgery procedures have improved over time, flap complications and even failure remain a significant clinical challenge. Animal models are useful in studying the pathophysiology of ischemic flaps, but when repeatability is a primary focus of a study, conventional in-vivo designs, where one randomized subset of animals serves as a treatment group while a second subset serves as a control, are at a disadvantage instigated by greater subject-to-subject variability. …

Molecular Mechanisms In Pathophysiology Of Mucopolysaccharidosis And Prospects For Innovative Therapy, Yasuhiko Ago, Estera Rintz, Krishna Sai Musini, Zhengyu Ma, Shunji Tomatsu

Department of Pediatrics Faculty Papers

Mucopolysaccharidoses (MPSs) are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down molecules called glycosaminoglycans (GAGs). These GAGs accumulate over time in various tissues and disrupt multiple biological systems, including catabolism of other substances, autophagy, and mitochondrial function. These pathological changes ultimately increase oxidative stress and activate innate immunity and inflammation. We have described the pathophysiology of MPS and activated inflammation in this paper, starting with accumulating the primary storage materials, GAGs. At the initial stage of GAG accumulation, affected tissues/cells are reversibly affected but progress irreversibly to: (1) …

Comparison Of Three Rapid Diagnostic Tests For Bloodstream Infections Using Benefit-Risk Evaluation Framework (Bed-Frame), Richard D Smith, Min Zhan, Shanshan Zhang, Surbhi Leekha, Anthony Harris, Yohei Doi, Scott Evans, J Kristie Johnson, Robert K Ernst

Faculty, Staff and Student Publications

Rapid diagnostic tests (RDTs) for bloodstream infections have the potential to reduce time to appropriate antimicrobial therapy and improve patient outcomes. Previously, an in-house, lipid-based, matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) method, Fast Lipid Analysis Technique (FLAT MS), has shown promise as a rapid pathogen identification method. In this study, FLAT MS for direct from blood culture identification was evaluated and compared to FDA-cleared identification methods using the Benefit-risk Evaluation Framework (BED-FRAME) analysis. FLAT MS was evaluated and compared to Bruker Sepsityper and bioMérieux BioFire FilmArray BCID2 using results from a previous study. For this study, 301 …

Pressing Need Of Precision Care In Her2-Positive Colorectal Cancer: The Elephant In The Room, Kanwal P S Raghav, Jonathan M Loree, Scott Kopetz

Faculty, Staff and Student Publications

Although dual HER2 inhibition has shown promising clinical activity in patients with RAS wild-type HER2-positive metastatic colorectal cancer, predictive biomarkers of response/resistance are less well characterized. Activating HER2/RTK/MAPK genomic alterations appears to blunt the clinical benefit of dual anti-HER2 therapy and may hold a potential albeit partial role in patient selection. See related article by Randon et al., p. 436.

Cdk4/6 Inhibition Sensitizes Intracranial Tumors To Pd-1 Blockade In Preclinical Models Of Brain Metastasis, Naema Nayyar, Magali A De Sauvage, Jane Chuprin, Emily M Sullivan, Mohini Singh, Consuelo Torrini, Britney S Zhang, Sushobhana Bandyopadhyay, Keith A Daniels, Christopher Alvarez-Breckenridge, Ashish Dahal, Michael A Brehm, Priscilla K Brastianos

Faculty, Staff and Student Publications

PURPOSE: Brain metastases are associated with high morbidity and are often resistant to immune checkpoint inhibitors. We evaluated whether CDK4/6 inhibitor (CDKi) abemaciclib can sensitize intracranial tumors to programmed cell death protein 1 (PD-1) inhibition in mouse models of melanoma and breast cancer brain metastasis.

EXPERIMENTAL DESIGN: Treatment response was evaluated in vivo using immunocompetent mouse models of brain metastasis bearing concurrent intracranial and extracranial tumors. Treatment effect on intracranial and extracranial tumor-immune microenvironments (TIME) was evaluated using immunofluorescence, multiplex immunoassays, high-parameter flow cytometry, and T-cell receptor profiling. Mice with humanized immune systems were evaluated using flow cytometry to study …

Disruption Of The Arabidopsis Acyl-Activating Enzyme 3 Impairs Seed Coat Mucilage Accumulation And Seed Germination, Ninghui Cheng, Paul A Nakata

Faculty, Staff and Students Publications

The Acyl-activating enzyme (AAE) 3 gene encodes an oxalyl-CoA synthetase that catalyzes the conversion of oxalate to oxalyl-CoA as the first step in the CoA-dependent pathway of oxalate catabolism. Although the role of this enzyme in oxalate catabolism has been established, its biological roles in plant growth and development are less understood. As a step toward gaining a better understanding of these biological roles, we report here a characterization of the Arabidopsis thaliana aae3 (Ataae3) seed mucilage phenotype. Ruthidium red (RR) staining of Ataae3 and wild type (WT) seeds suggested that the observed reduction in Ataae3 …

Sod1 Is A Synthetic Lethal Target In Ppm1d-Mutant Leukemia Cells, Linda Zhang, Joanne I Hsu, Etienne D Braekeleer, Chun-Wei Chen, Tajhal D Patel, Alejandra G Martell, Anna G Guzman, Katharina Wohlan, Sarah M Waldvogel, Hidetaka Urya, Ayala Tovy, Elsa Callen, Rebecca Murdaugh, Rosemary Richard, Sandra Jansen, Lisenka Vissers, Bert B A De Vries, Andre Nussenzweig, Shixia Huang, Cristian Coarfa, Jamie N Anastas, Koichi Takahashi, George Vassiliou, Margaret A Goodell

Faculty, Staff and Students Publications

The DNA damage response is critical for maintaining genome integrity and is commonly disrupted in the development of cancer. PPM1D (protein phosphatase, Mg2+/Mn2+ dependent 1D) is a master negative regulator of the response; gain-of-function mutations and amplifications of PPM1D are found across several human cancers making it a relevant pharmacologic target. Here, we used CRISPR/Cas9 screening to identify synthetic-lethal dependencies of PPM1D, uncovering superoxide dismutase-1 (SOD1) as a potential target for PPM1D-mutant cells. We revealed a dysregulated redox landscape characterized by elevated levels of reactive oxygen species and a compromised response to oxidative stress in PPM1D-mutant cells. Altogether, our …

Classification Of Colorectal Cancer Using Resnet And Efficientnet Models, Abhishek Ranjan, Priyanshu Srivastva, B Prabadevi, R Sivakumar, Rahul Soangra, Shamala K. Subramaniam

Physical Therapy Faculty Articles and Research

Introduction:

Cancer is one of the most prevalent diseases from children to elderly adults. This will be deadly if not detected at an earlier stage of the cancerous cell formation, thereby increasing the mortality rate. One such cancer is colorectal cancer, caused due to abnormal growth in the rectum or colon. Early screening of colorectal cancer helps to identify these abnormal growth and can exterminate them before they turn into cancerous cells.

Aim:

Therefore, this study aims to develop a robust and efficient classification system for colorectal cancer through Convolutional Neural Networks (CNNs) on histological images.

Methods:

Despite challenges in …

Hidradenitis Suppurativa Disease Severity And Outcomes Among Black Patients From Low-Income Neighborhoods At A Tertiary Care Hospital: A Retrospective Review, Anna M. Catinis, Olivia A. Gioe, Caroline Savoie, Erika Rosen, Deborah Hilton

School of Medicine Faculty Publications

Hidradenitis suppurativa (HS) is a debilitating, inflammatory condition of apocrine sweat glands. Black patients are disproportionately affected, a finding largely attributed to lower socioeconomic status (SES) in the literature; yet, most HS studies include majority White cohorts. We present, to our knowledge, the first retrospective review of an entirely Black patient population living in low-income neighborhoods diagnosed with hidradenitis suppurativa (HS) to identify potentially modifiable factors related to disease severity and outcomes. We reviewed charts of Black patients with an encounter for HS from 2010-2020 in the New Orleans University Medical Center database. Hurley stage III (HSt III) disease was …

The Respiratory Enzyme Complex Rnf Is Vital For Metabolic Adaptation And Virulence In Fusobacterium Nucleatum, Timmie A Britton, Chenggang Wu, Yi-Wei Chen, Dana Franklin, Yimin Chen, Martha I Camacho, Truc T Luong, Asis Das, Hung Ton-That

Faculty, Staff and Student Publications

The Gram-negative oral pathobiont Fusobacterium nucleatum can traverse to extra-oral sites such as placenta and colon, promoting adverse pregnancy outcomes and colorectal cancer, respectively. How this anaerobe sustains many metabolically changing environments enabling its virulence potential remains unclear. Informed by our genome-wide transposon mutagenesis, we report here that the highly conserved Rhodobacter nitrogen-fixation (Rnf) complex, encoded by the rnfCDGEAB gene cluster, is key to fusobacterial metabolic adaptation and virulence. Genetic disruption of the Rnf complex via non-polar, in-frame deletion of rnfC (ΔrnfC) abrogates polymicrobial interaction (or coaggregation) associated with adhesin RadD and biofilm formation. The defect in coaggregation …

Development And Validation Of A Nomogram For Predicting Pulmonary Infection In Patients Receiving Immunosuppressive Drugs, Chuxuan Luo, Yue Zhang, Jiajie Zhang, Chen Jin, Xiaolan Ye, Yan Ren, Huajuan Shen, Maosheng Chen, Yiwen Li, Qiang He, Guangbiao Xu, Lina Shao

Faculty, Staff and Student Publications

Objective: Pulmonary infection (PI), a severe complication of immunosuppressive therapy, affects patients' prognosis. As part of this study, we aimed to construct a pulmonary infection prediction (PIP) model and validate it in patients receiving immunosuppressive drugs (ISDs). Methods: Totally, 7,977 patients being treated with ISDs were randomised 7:3 to the developing (n = 5,583) versus validation datasets (n = 2,394). Our predictive nomogram was established using the least absolute shrinkage and selection operator (LASSO) and multivariate COX regression analyses. With the use of the concordance index (C-index) and calibration curve, the prediction performance of the final model was …

Expanded T Lymphocytes In The Cerebrospinal Fluid Of Multiple Sclerosis Patients Are Specific For Epstein-Barr-Virus-Infected B Cells, Assaf Gottlieb, H Phuong T Pham, Jerome G Saltarrelli, J William Lindsey

Faculty, Staff and Student Publications

Epstein-Barr virus (EBV) infection has long been associated with multiple sclerosis (MS), but the role of EBV in the pathogenesis of MS is not clear. Our hypothesis is that a major fraction of the expanded clones of T lymphocytes in the cerebrospinal fluid (CSF) are specific for autologous EBV-infected B cells. We obtained blood and CSF samples from eight relapsing-remitting patients in the process of diagnosis. We stimulated cells from the blood with autologous EBV-infected lymphoblastoid cell lines (LCL), EBV, varicella zoster virus, influenza, and candida and sorted the responding cells with flow cytometry after 6 d. We sequenced the …

In-Patient Evolution Of A High-Persister Escherichia Coli Strain With Reduced In Vivo Antibiotic Susceptibility, Joshua B Parsons, Ashelyn E Sidders, Amanda Z Velez, Blake M Hanson, Michelle Angeles-Solano, Felicia Ruffin, Sarah E Rowe, Cesar A Arias, Vance G Fowler, Joshua T Thaden, Brian P Conlon

Faculty, Staff and Student Publications

Gram-negative bacterial bloodstream infections (GNB-BSI) are common and frequently lethal. Despite appropriate antibiotic treatment, relapse of GNB-BSI with the same bacterial strain is common and associated with poor clinical outcomes and high healthcare costs. The role of persister cells, which are sub-populations of bacteria that survive for prolonged periods in the presence of bactericidal antibiotics, in relapse of GNB-BSI is unclear. Using a cohort of patients with relapsed GNB-BSI, we aimed to determine how the pathogen evolves within the patient between the initial and subsequent episodes of GNB-BSI and how these changes impact persistence. Using

Novel Pan-Err Agonists Ameliorate Heart Failure Through Enhancing Cardiac Fatty Acid Metabolism And Mitochondrial Function, Weiyi Xu, Cyrielle Billon, Hui Li, Andrea Wilderman, Lei Qi, Andrea Graves, Jernie Rae Dela Cruz Rideb, Yuanbiao Zhao, Matthew Hayes, Keyang Yu, Mckenna Losby, Carissa S Hampton, Christiana M Adeyemi, Seok Jae Hong, Eleni Nasiotis, Chen Fu, Tae Gyu Oh, Weiwei Fan, Michael Downes, Ryan D Welch, Ronald M Evans, Aleksandar Milosavljevic, John K Walker, Brian C Jensen, Liming Pei, Thomas Burris, Lilei Zhang

Faculty, Staff and Students Publications

BACKGROUND: Cardiac metabolic dysfunction is a hallmark of heart failure (HF). Estrogen-related receptors ERRα and ERRγ are essential regulators of cardiac metabolism. Therefore, activation of ERR could be a potential therapeutic intervention for HF. However, in vivo studies demonstrating the potential usefulness of ERR agonist for HF treatment are lacking, because compounds with pharmacokinetics appropriate for in vivo use have not been available.

METHODS: Using a structure-based design approach, we designed and synthesized 2 structurally distinct pan-ERR agonists, SLU-PP-332 and SLU-PP-915. We investigated the effect of ERR agonist on cardiac function in a pressure overload-induced HF model in vivo. We …

Novel Species Of Triatoma (Hemiptera: Reduviidae) Identified In A Case Of Vectorial Transmission Of Chagas Disease In Northern Belize, Sarah M Gunter, Alisa Nelson, Alexander R Kneubehl, Silvia A Justi, Russell Manzanero, Emily Zielinski-Gutierrez, Claudia Herrera, Julie Thompson, Rajendra Mandage, Hans Desale, Adrianna Maliga, Kim Bautista, Shannon E Ronca, Francis Morey, Rafael Chacon Fuentes, Beatriz Lopez, Eric Dumonteil, Gerhaldine H Morazan, Kristy O Murray

Faculty, Staff and Students Publications

Chagas disease is a leading cause of non-ischemic cardiomyopathy in endemic regions of Central and South America. In Belize, Triatoma dimidiata sensu lato has been identified as the predominate taxon but vectorial transmission of Chagas disease is considered to be rare in the country. We recently identified an acute case of vector-borne Chagas disease in the northern region of Belize. Here we present a subsequent investigation of triatomines collected around the case-patient's home. We identified yet undescribed species, closely related to Triatoma huehuetenanguensis vector by molecular systematics methods occurring in the peridomestic environment. The identification of a T. cruzi-positive, novel …

The Pan-Microbiome Profiling System Taxa4meta Identifies Clinical Dysbiotic Features And Classifies Diarrheal Disease, Qinglong Wu, Shyam Badu, Sik Yu So, Todd J Treangen, Tor C Savidge

Faculty, Staff and Students Publications

Targeted metagenomic sequencing is an emerging strategy to survey disease-specific microbiome biomarkers for clinical diagnosis and prognosis. However, this approach often yields inconsistent or conflicting results owing to inadequate study power and sequencing bias. We introduce Taxa4Meta, a bioinformatics pipeline explicitly designed to compensate for technical and demographic bias. We designed and validated Taxa4Meta for accurate taxonomic profiling of 16S rRNA amplicon data acquired from different sequencing strategies. Taxa4Meta offers significant potential in identifying clinical dysbiotic features that can reliably predict human disease, validated comprehensively via reanalysis of individual patient 16S data sets. We leveraged the power of Taxa4Meta's pan-microbiome …

Kinase Inhibitor Pulldown Assay (Kip) For Clinical Proteomics, Alexander B Saltzman, Doug W Chan, Matthew V Holt, Junkai Wang, Eric J Jaehnig, Meenakshi Anurag, Purba Singh, Anna Malovannaya, Beom-Jun Kim, Matthew J Ellis

Faculty, Staff and Students Publications

Protein kinases are frequently dysregulated and/or mutated in cancer and represent essential targets for therapy. Accurate quantification is essential. For breast cancer treatment, the identification and quantification of the protein kinase ERBB2 is critical for therapeutic decisions. While immunohistochemistry (IHC) is the current clinical diagnostic approach, it is only semiquantitative. Mass spectrometry-based proteomics offers quantitative assays that, unlike IHC, can be used to accurately evaluate hundreds of kinases simultaneously. The enrichment of less abundant kinase targets for quantification, along with depletion of interfering proteins, improves sensitivity and thus promotes more effective downstream analyses. Multiple kinase inhibitors were therefore deployed as …

Metabolomic Rewiring Promotes Endocrine Therapy Resistance In Breast Cancer, Songyeon Ahn, Jun Hyoung Park, Sandra L Grimm, Danthasinghe Waduge Badrajee Piyarathna, Tagari Samanta, Vasanta Putluri, Dereck Mezquita, Suzanne A W Fuqua, Nagireddy Putluri, Cristian Coarfa, Benny Abraham Kaipparettu

Faculty, Staff and Students Publications

Approximately one-third of endocrine-treated women with estrogen receptor-alpha positive (ER+) breast cancers (BC) are at risk of recurrence due to intrinsic or acquired resistance. Thus, it is vital to understand the mechanisms underlying endocrine therapy resistance in ER+ BC to improve patient treatment. Mitochondrial fatty acid β-oxidation (FAO) has been shown to be a major metabolic pathway in triple-negative BC (TNBC) that can activate Src signaling. Here, we found metabolic reprogramming that increases FAO in ER+ BC as a mechanism of resistance to endocrine therapy. A metabolically relevant, integrated gene signature was derived from transcriptomic, metabolomic, and lipidomic analyses in …

Gad65abs Are Not Associated With Beta-Cell Dysfunction In Patients With T2d In The Grade Study, Christiane S Hampe, Ali Shojaie, Barbara Brooks-Worrell, Sepideh Dibay, Kristina Utzschneider, Steven E Kahn, Mary E Larkin, Mary L Johnson, Naji Younes, Neda Rasouli, Cyrus Desouza, Robert M Cohen, Jean Y Park, Hermes J Florez, Willy Marcos Valencia, Robert Stempel, Jerry P Palmer, Ashok Balasubramanyam

Faculty, Staff and Students Publications

CONTEXT: Autoantibodies directed against the 65-kilodalton isoform of glutamic acid decarboxylase (GAD65Abs) are markers of autoimmune type 1 diabetes (T1D) but are also present in patients with Latent Autoimmune Diabetes of Adults and autoimmune neuromuscular diseases, and also in healthy individuals. Phenotypic differences between these conditions are reflected in epitope-specific GAD65Abs and anti-idiotypic antibodies (anti-Id) against GAD65Abs. We previously reported that 7.8% of T2D patients in the GRADE study have GAD65Abs but found that GAD65Ab positivity was not correlated with beta-cell function, glycated hemoglobin (HbA1c), or fasting glucose levels.

CONTEXT: In this study, we aimed to better characterize islet autoantibodies …

Associations Of Galectin-3 Levels With Measures Of Vascular Disease In Patients With Rheumatoid Arthritis, Amanda Nussdorf, Elizabeth Park, Isabelle Amigues, Laura Geraldino-Pardilla, Sabahat Bokhari, Jon T. Giles, Joan M. Bathon

Division of Rheumatology Faculty Papers

OBJECTIVES: Galectin-3 is a beta-galactoside-binding lectin and is a marker of cardiovascular disease (CVD) in the general population. It may also play a role in joint inflammation. We asked whether serum galectin-3 is a useful marker of subclinical vascular disease in patients with rheumatoid arthritis (RA).

METHODS: RA patients without clinical CVD underwent assessment of coronary artery calcium (CAC) score, aortic inflammation (using 18Fluorodeoxyglucose positron emission-computed tomography [FDG PET/CT]), and myocardial flow reserve (MFR). Aorta FDG uptake was measured as standardized uptake values (SUV). Generalized linear models were constructed to explore the associations of galectin-3 levels with CAC score, aortic …

Qiditangshen Granules Alleviates Diabetic Nephropathy Podocyte Injury: A Network Pharmacology Study And Experimental Validation In Vivo And Vitro, Fei Gao, Ying Zhou, Borui Yu, Huidi Xie, Yang Shi, Xianhui Zhang, Hongfang Liu

Faculty, Staff and Student Publications

BACKGROUND: QiDiTangShen granules (QDTS), a traditional Chinese medicine (TCM) compound prescription, have remarkable efficacy in diabetic nephropathy (DN) patients, and their pharmacological mechanism needs further exploration.

METHODS: According to the active ingredients and targets of the QDTS in the TCMSP database, the network pharmacology of QDTS was investigated. The potential active ingredients were chosen based on the oral bioavailability and the drug similarity index. At the same time, targets for DN-related disease were obtained from GeneCards, OMIM, PharmGKB, TTD, and DrugBank. The TCM-component-target network and the protein-protein interaction (PPI) network were constructed with the Cytoscape and STRING platforms, respectively, and …

Small Needle-Knife Versus Extracorporeal Shock Wave Therapy For The Treatment Of Plantar Fasciitis: A Systematic Review And Meta-Analysis, Chaoqun Feng, Junjie Yao, Yizhou Xie, Min Zhao, Youpeng Hu, Ziang Hu, Ruoyan Li, Haoyang Wu, Yuanxin Ge, Fei Yang, Xiaohong Fan

Faculty, Staff and Student Publications

BACKGROUND: Plantar fasciitis (PF) is the most common cause of chronic heel pain among adults. Extracorporeal shock wave therapy (ESWT) is the recommended in the current guidelines, and the small needle-knife yields acceptable clinical effects for musculoskeletal pain.

OBJECTIVE: To systematically compare the efficacy of the small needle-knife versus ESWT for the treatment of PF.

METHODS: The present review was registered in the International Prospective Register of Systematic Reviews (i.e., "PROSPERO", CRD42023448813). Two of the authors searched electronic databases for randomized controlled trials (RCTs) comparing the small needle-knife versus ESWT for the treatment of PF, and collected outcomes including curative …

Armc5 Controls The Degradation Of Most Pol Ii Subunits, And Armc5 Mutation Increases Neural Tube Defect Risks In Mice And Humans, Hongyu Luo, Linjiang Lao, Kit Sing Au, Hope Northrup, Xiao He, Diane Forget, Marie-Soleil Gauthier, Benoit Coulombe, Isabelle Bourdeau, Wei Shi, Lucia Gagliardi, Maria Candida Barisson Villares Fragoso, Junzheng Peng, Jiangping Wu

Faculty, Staff and Student Publications

BACKGROUND: Neural tube defects (NTDs) are caused by genetic and environmental factors. ARMC5 is part of a novel ubiquitin ligase specific for POLR2A, the largest subunit of RNA polymerase II (Pol II).

RESULTS: We find that ARMC5 knockout mice have increased incidence of NTDs, such as spina bifida and exencephaly. Surprisingly, the absence of ARMC5 causes the accumulation of not only POLR2A but also most of the other 11 Pol II subunits, indicating that the degradation of the whole Pol II complex is compromised. The enlarged Pol II pool does not lead to generalized Pol II stalling or a generalized …

Beyond The Global Brain Differences: Intraindividual Variability Differences In 1q211 Distal And 15q112 Bp1-Bp2 Deletion Carriers, Rune Boen, Tobias Kaufmann, Dennis Van Der Meer, Oleksandr Frei, Ingrid Agartz, David Ames, Micael Andersson, Nicola J Armstrong, Eric Artiges, Joshua R Atkins, Jochen Bauer, Francesco Benedetti, Dorret I Boomsma, Henry Brodaty, Katharina Brosch, Randy L Buckner, Murray J Cairns, Vince Calhoun, Svenja Caspers, Sven Cichon, Aiden P Corvin, Benedicto Crespo-Facorro, Udo Dannlowski, Friederike S David, Eco J C De Geus, Greig I De Zubicaray, Sylvane Desrivières, Joanne L Doherty, Gary Donohoe, Stefan Ehrlich, Else Eising, Thomas Espeseth, Simon E Fisher, Andreas J Forstner, Lidia Fortaner-Uyà, Vincent Frouin, Masaki Fukunaga, Tian Ge, David C Glahn, Janik Goltermann, Hans J Grabe, Melissa J Green, Nynke A Groenewold, Dominik Grotegerd, Gøril Rolfseng Grøntvedt, Tim Hahn, Ryota Hashimoto, Jayne Y Hehir-Kwa, Frans A Henskens, Avram J Holmes, Asta K Håberg, Jan Haavik, Sebastien Jacquemont, Andreas Jansen, Christiane Jockwitz, Erik G Jönsson, Masataka Kikuchi, Tilo Kircher, Kuldeep Kumar, Stephanie Le Hellard, Costin Leu, David E Linden, Jingyu Liu, Robert Loughnan, Karen A Mather, Katie L Mcmahon, Allan F Mcrae, Sarah E Medland, Susanne Meinert, Clara A Moreau, Derek W Morris, Bryan J Mowry, Thomas W Mühleisen, Igor Nenadić, Markus M Nöthen, Lars Nyberg, Roel A Ophoff, Michael J Owen, Christos Pantelis, Marco Paolini, Tomas Paus, Zdenka Pausova, Karin Persson, Yann Quidé, Tiago Reis Marques, Perminder S Sachdev, Sigrid B Sando, Ulrich Schall, Rodney J Scott, Geir Selbæk, Elena Shumskaya, Ana I Silva, Sanjay M Sisodiya, Frederike Stein, Dan J Stein, Benjamin Straube, Fabian Streit, Lachlan T Strike, Alexander Teumer, Lea Teutenberg, Anbupalam Thalamuthu, Paul A Tooney, Diana Tordesillas-Gutierrez, Julian N Trollor, Dennis Van 'T Ent, Marianne B M Van Den Bree, Neeltje E M Van Haren, Javier Vázquez-Bourgon, Henry Völzke, Wei Wen, Katharina Wittfeld, Christopher R K Ching, Lars T Westlye, Paul M Thompson, Carrie E Bearden, Kaja K Selmer, Dag Alnæs, Ole A Andreassen, Ida E Sønderby, Enigma-Cnv Working Group

Faculty, Staff and Student Publications

Background: Carriers of the 1q21.1 distal and 15q11.2 BP1-BP2 copy number variants exhibit regional and global brain differences compared with noncarriers. However, interpreting regional differences is challenging if a global difference drives the regional brain differences. Intraindividual variability measures can be used to test for regional differences beyond global differences in brain structure.

Methods: Magnetic resonance imaging data were used to obtain regional brain values for 1q21.1 distal deletion (n = 30) and duplication (n = 27) and 15q11.2 BP1-BP2 deletion (n = 170) and duplication (n = 243) carriers and matched noncarriers (n = 2350). Regional intra-deviation scores, i.e., …

Increased Iron Uptake By Splenic Hematopoietic Stem Cells Promotes Tet2-Dependent Erythroid Regeneration, Yu-Jung Tseng, Yuki Kageyama, Rebecca L Murdaugh, Ayumi Kitano, Jong Hwan Kim, Kevin A Hoegenauer, Jonathan Tiessen, Mackenzie H Smith, Hidetaka Uryu, Koichi Takahashi, James F Martin, Md Abul Hassan Samee, Daisuke Nakada

Faculty, Staff and Student Publications

Hematopoietic stem cells (HSCs) are capable of regenerating the blood system, but the instructive cues that direct HSCs to regenerate particular lineages lost to the injury remain elusive. Here, we show that iron is increasingly taken up by HSCs during anemia and induces erythroid gene expression and regeneration in a Tet2-dependent manner. Lineage tracing of HSCs reveals that HSCs respond to hemolytic anemia by increasing erythroid output. The number of HSCs in the spleen, but not bone marrow, increases upon anemia and these HSCs exhibit enhanced proliferation, erythroid differentiation, iron uptake, and TET2 protein expression. Increased iron in HSCs promotes …

A Novel Erβ High Throughput Microscopy Platform For Testing Endocrine Disrupting Chemicals, Derek A Abbott, Maureen G Mancini, Michael J Bolt, Adam T Szafran, Kaley A Neugebauer, Fabio Stossi, Daniel A Gorelick, Michael A Mancini

Faculty, Staff and Students Publications

In this study we present an inducible biosensor model for the Estrogen Receptor Beta (ERβ), GFP-ERβ:PRL-HeLa, a single-cell-based high throughput (HT) in vitro assay that allows direct visualization and measurement of GFP-tagged ERβ binding to ER-specific DNA response elements (EREs), ERβ-induced chromatin remodeling, and monitor transcriptional alterations via mRNA fluorescence in situ hybridization for a prolactin (PRL)-dsRED2 reporter gene. The model was used to accurately (Z' = 0.58-0.8) differentiate ERβ-selective ligands from ERα ligands when treated with a panel of selective agonists and antagonists. Next, we tested an Environmental Protection Agency (EPA)-provided set of 45 estrogenic reference chemicals with known …