Digital Commons Network^™

Acute Correction Of Acquired Genu Valgum Secondary To Post-Traumatic Growth Arrest At The Time Of Distal Femur Fracture., Josiah Wolf, Nicholas Pelz, Adam Mansour, Christopher Iobst, Allen Kadado

Surgery Articles

A 14-year-old male patient sustained a distal femur fracture after a ground-level fall. His history was notable for severe acquired genu valgum secondary to a childhood lawnmower accident, which had required multiple limb salvage procedures including a Syme amputation and soft-tissue skin grafting. Acute correction of the limb deformity was performed concurrently with fracture fixation using a retrograde intramedullary nail and poller blocking screws. Retrograde intramedullary nailing represents a viable treatment option for simultaneous acute correction of acquired genu valgum and stabilization of distal femur fractures.

Does Dexmedetomidine Affect Opioid Consumption Following Orthognathic Surgery?, Allen F. Champion, Jung-Me Lee, Daniel Taub, Yu Jin Lee

Department of Oral and Maxillofacial Surgery Faculty Papers

BACKGROUND: Despite its purported analgesic effects, controversy exists regarding dexmedetomidine's efficacy as an opioid-sparing anesthetic adjunct.

PURPOSE: The purpose of this study is to measure the association between dexmedetomidine (DEX) administration during orthognathic surgery and postoperative opioid consumption.

STUDY DESIGN, SAMPLE, AND SETTING: A single-blind randomized prospective cohort study was implemented. Patients consenting for orthognathic surgery at Thomas Jefferson University from January 2022 to October 2024 were screened. American Society of Anesthesiologists physical status I to III individuals aged ≥14 years were included. Exclusion criteria were revision surgery, recreational drug use, opioid prescription within 2 years, and chronic pain.

PREDICTOR …

Persistence Of Pet Scan Positivity After Chemoimmunotherapy For Dlbcl, James O. Armitage, Matthew A. Lunning, Julie M. Vose, Dan L. Longo

Journal Articles: Oncology and Hematology

Approximately 80% of patients with diffuse large B-cell lymphoma achieve a complete response after chemoimmunotherapy as defined by positron emission tomography (PET) scan. However, not all patients who fail to achieve a metabolic complete response are destined to relapse. In a number of these patients, the PET scan is falsely positive (ie, 20%-40% in several large series), particularly when the PET scan has a Deauville score of 4. Reflexively intervening with salvage systemic therapy or radiotherapy in these patients is potentially harmful. It seems that very sensitive measurements of circulating tumor DNA might be able to differentiate between patients who …

Efficacy And Safety Of Epcoritamab In Relapsed Or Refractory Large B-Cell Lymphoma: 3-Year Update From The Epcore Nhl-1 Trial, Yasmin H. Karimi, Chan Y. Cheah, Michael Roost Clausen, David Cunningham, Umar Farooq, Tatyana Feldman, Herve Ghesquieres, Wojciech Jurczak, Kim M. Linton, Tycel Phillips, Julie M. Vose, Won Seog Kim, Pegah Jafarinasabian, Barbara D'Angelo Månsson, David Soong, Andrew J. Steele, Zhu Li, Christian W. Eskelund, Martin Hutchings, Catherine Thieblemont

Journal Articles: Oncology and Hematology

Epcoritamab, a CD3xCD20 bispecific antibody, resulted in deep, durable responses with a manageable safety profile in patients with relapsed/refractory large B-cell lymphoma (LBCL) in EPCORE^® NHL-1 (NCT03625037). We report results from a 3-year follow-up. Adults with relapsed/refractory LBCL received epcoritamab until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Median age was 64.0 years, 39% of patients received prior CAR T-cell treatment, and 75% were refractory to ≥ 2 consecutive lines of treatment. As of May 3, 2024 (median follow-up 37.1 months [range, 0.3-45.5]), ORR was 59% and complete response (CR) rate …

Psycinfo Platforms: A Tale Of Two Interfaces (Ovid Vs Ebsco), Sandra Yvette Desjardins, Jamie Quinn

Library Staff Publications

PsycInfo is a foundational database for evidence-based behavioral health literature, which makes it an essential tool for health sciences librarians. This column provides a comprehensive comparison of PsycInfo on Ovid and EBSCO platforms. It offers a foundational overview for new librarians, guiding them through essential functionalities and navigation. The article also helps librarians evaluate potential database acquisitions by highlighting the distinct features and search capabilities of each interface. This comparison aims to equip health sciences librarians with the knowledge to optimize search strategies and inform strategic purchasing decisions.

Behavioral And Psychological Financial Hardship Among Caregivers Of Pediatric Cancer Patients, Josiane Kabayundo, Cheng Zheng, Edward S. Peters, Don W. Coulter, Shinobu Watanabe-Galloway

Journal Articles: Epidemiology

BACKGROUND: Financial hardship encompasses material, behavioral, and psychological domains; however, most research among caregivers of pediatric cancer patients has focused on material hardship. This study examined factors associated with behavioral and psychological financial hardship among caregivers of pediatric cancer patients in Nebraska.

METHODS: We conducted a cross-sectional survey of caregivers of children diagnosed within the past 5 years and treated at two pediatric oncology specialty clinics. Behavioral hardship was defined as delaying medical or mental healthcare due to cost, while psychological hardship was measured by worry about ability to pay medical bills. Descriptive statistics and poisson regression with robust variance …

Differences In Biologic Clinical Trials For Chronic Rhinosinusitis With Nasal Polyps—Are We Comparing Apples With Oranges?, Marjolein Cornet, Peter W. Hellings, Martin Desrosiers, Martin Wagenmann, Richard Follows, Laura Walrave, Luz Adriana Jimenez, Lee Tombs, Dawn Edwards, Peter Howarth, Joseph K. Han

Department of Otolaryngology (ENT) Faculty Publications

In recent years, several biologics targeting Type 2 inflammation have been developed for treating chronic rhinosinusitis with nasal polyps (CRSwNP). These have been studied in registrational randomized controlled trials (RCTs), which vary in their patient populations, trial design, endpoints, geography, timing, or data-handling processes. While (in)direct treatment comparisons and meta-analyses have been carried out to compare efficacy results from RCTs, often these fail to properly account for these between-study differences. Here, we summarize the key between-study differences that can influence trial outcomes and highlight the resulting challenges faced when comparing outcomes from different Phase III RCTs of biologics in CRSwNP.

Nanofibrous Materials And Nanoparticles For Combating Antimicrobial Resistance: Synthesis, Integration, And Translational Perspectives, Rewati Raman Ujjwal, Ashish Dilip Sutar, Rahul Shukla, Gymama Slaughter

Center for Bioelectronics Publications

Antimicrobial resistance (AMR) is a major global health challenge driven by mechanisms such as biofilm formation, efflux pumps, and genetic mutations. Nanoparticulate and fibrous materials have emerged as promising strategies to overcome these limitations through multimodal antimicrobial action and controlled drug delivery. This review highlights recent advances in electrospun nanofibrous systems, including natural and synthetic polymer-based scaffolds, stimuli-responsive nanofibers, and functionalized patches. Nanoparticle-loaded nanofiber systems demonstrate enhanced performance, including bacterial eradication, sustained drug release, and significant biofilm disruption. Multifunctional systems combining antimicrobial, antioxidant, and immunomodulatory properties further show synergism. Emerging innovations, such as piezoelectric and smart sensing systems, enable self-powered …

An Anti-Adhesive Compound Modulating The Production Of Staphylococcus Aureus Cell Wall-Anchored Proteins, Allison C. Leonard, Ruina Bao, Cindy Menjivar, Megan J. Myers, Telmo O. Paiva, Zhiyong Zheng, Kirsten A. Berry, Kenneth W. Bayles, Ronald S. Flannagan, Yves F. Dufrêne, Jeffrey L. Bose, David E. Heinrichs, Georgina Cox

Journal Articles: Pathology and Microbiology

As one of the leading global causes of death associated with antimicrobial resistance, Staphylococcus aureus frequently colonizes the human nasal cavity and adheres to keratinized skin, establishing reservoirs that drive subsequent infections and emphasize the need for new decolonization strategies. Using a high-throughput, whole-cell screening platform, here we identify geranylgeranoic acid (GGA), a naturally occurring polyunsaturated, branched-chain fatty acid, as having dual activity against methicillin-resistant S. aureus (MRSA). At elevated concentrations, GGA exhibits microbicidal effects, whereas at sub‑microbicidal doses, it effectively inhibits MRSA adhesion to keratin, fibronectin, fibrinogen, and immunoglobulins. GGA possesses anti-adhesive activity against a panel of multidrug-resistant S. …

“The True Me”: Unravelling The Dual Narrative Of Borderline Personality Disorder And Autistic Spectrum Disorder, Robin Iliffe-Lewis, Alison Bacon

School of Psychology

Objectives: There is growing recognition that some individuals who receive a diagnosis of Borderline Personality Disorder (BPD) are later diagnosed with autism. However, existing literature on this topic remains limited. This study aimed to explore the experiences of individuals diagnosed with BPD prior to autism, how they made sense of these diagnoses, navigated clinical systems, and learnt to manage the complex challenges associated with this diagnostic sequence.Methods: Thirteen (6 male, 6 female, 1 non-binary) adult participants took part in semi-structured interviews exploring their diagnostic journeys. Reflexive thematic analysis was used to develop a nuanced understanding of their experiences.Results: Three themes …

Clinical Subtypes Of Co-Morbid Insomnia And Obstructive Sleep Apnea (Comisa): Results Of A Cluster Analysis, Yuan Shi, Xujun Feng, Fengyi Hao, Yuru Nie, Yihui Zhang, Zhaohua Chen, Siqi Guan, Larry D. Sanford, Michael V. Vitiello, Xiangdong Tang

Department of Pathology & Anatomy Faculty Publications

Background

Variations in the bidirectional relationship between obstructive sleep apnea (OSA) and insomnia in co-morbid insomnia and OSA (COMISA) may form distinct subtypes of COMISA, which have not been previously characterized. This study aims to identify and characterize subtypes of COMISA.

Methods

From a community-recruited COMISA cohort 256 individuals who met diagnosis for COMISA were used to identify subtypes using a two-step clustering methodology. Demographics and multidimension clinical characteristics were collected and compared among obtained subtypes. Logistic models were used to evaluate whether these subtypes were associated with cardiometabolic and mental disorders. A clinical cohort of 1816 COMISA patients was …

Biological Dental Hygiene: Principles, Educational Pathways, And Clinical Practice Considerations, Tara Newcomb

Dental Hygiene Faculty Publications

Dental hygiene practice is rapidly evolving in response to emerging evidence on the oral–systemic health connection, advances in preventive technologies, and increased emphasis on individualized, minimally invasive care. A commitment to lifelong learning and continuing professional development is essential for maintaining clinical competence and integrating new scientific knowledge into practice. Biological dental hygiene has emerged as a complementary framework that emphasizes whole-body health, biocompatibility, reduction of toxic exposures, and prevention-centered care. This approach expands traditional dental hygiene practice by incorporating enhanced risk assessment, salivary diagnostics, targeted preventive strategies, as well as patient education focused on nutrition, inflammation reduction, and systemic …

Eeg And Imu Gait Signal Processing: A Comparative Assessment Of The "Reza" Exponential Filter And Classic Filters, Reza Pousti, Daniel M. Russell, Derek C. Monroe, Christopher K. Rhea

Rehabilitation Sciences Faculty Publications

Noise degrades both EEG and gait signals, and classical IIR filters (Butterworth, Chebyshev, elliptic) involve trade-offs between passband flatness, ripple, and roll-off. This study compared a novel exponential "Reza" filter with these designs for neural and locomotor data. We analyzed an open-source mobile brain-body imaging dataset with EEG and gait data from 49 healthy adults (EEG: 256-channel, 512 Hz; IMUs: six APDM Opals, 128 Hz). EEG channels were grand-averaged and band-pass filtered at 0.5-50 Hz, while IMU axes were averaged and band-pass filtered at 0.5-5 Hz. The outcomes were signal-to-noise ratio SNR (dB) and band-integrated Welch PSD (EEG:0.5-50 Hz; IMU:0.5-5 …

The Prevalence Of Diabetic Retinopathy In American Indians Or Alaska Natives And Non-Indigenous Americans: A Systematic Review And Meta-Analysis., Caberry W. Yu, Keean Nanji, Anubhav Garg, Michele Zaman, Jane Jomy, Abdullah El-Sayes, Catherine Sun, Shreyas Bhat, Mark Phillips, Dena Zeraatkar, Jinhui Ma, Enrico Borrelli, Sunir J Garg, David H. Steel, Tien Yin Wong, Sobha Sivaprasad, Charles C. Wykoff, Varun Chaudhary

Wills Eye Hospital Papers

TOPIC: To estimate the prevalence of diabetic retinopathy (DR) in adult American Indian or Alaska Native (AIAN) and non-AIAN patients with diabetes.

CLINICAL RELEVANCE: Although diabetes mellitus is more prevalent among AIAN patients compared with non-AIAN patients, the evidence is inconsistent regarding whether AIAN patients have a higher prevalence or severity of DR.

METHODS: We searched Ovid MEDLINE, EMBASE, and Web of Science databases from inception through February 23, 2025. We included primary studies evaluating the prevalence of DR in Americans with diabetes. The prevalence of (1) DR, (2) diabetic macular edema (DME), (3) proliferative diabetic retinopathy (PDR), (4) vision-threatening …

Clinical Outcomes With Perioperative Nivolumab By Nodal Status In Patients With Stage Iii Resectable Nsclc: Phase 3 Checkmate 77t Exploratory Analysis, Mariano Provencio, Mark M Awad, Jonathan D Spicer, Annelies Janssens, Fedor Moiseyenko, Yang Gao, Yasutaka Watanabe, Aurelia Alexandru, Florian Guisier, Nikolaj Frost, Fabio Franke, T Jeroen Nicolaas Hiltermann, Jie He, Fumihiro Tanaka, Shun Lu, Cinthya Coronado Erdmann, Padma Sathyanarayana, Phuong Tran, Vipul Devas, Tina Cascone

Faculty, Staff and Student Publications

Individuals with non-small-cell lung cancer (NSCLC) with metastases to the ipsilateral mediastinum or subcarinal lymph nodes (N2 disease) have poor long-term survival. This exploratory analysis from the randomized phase 3 CheckMate 77T study assessed clinical outcomes by nodal status in individuals with stage III NSCLC who received neoadjuvant nivolumab plus chemotherapy followed by surgery and adjuvant nivolumab (nivolumab) versus neoadjuvant chemotherapy followed by surgery and adjuvant placebo (placebo). Here we show that among patients with N2 disease, nivolumab versus placebo improved event-free survival (1-year rate, 70% versus 45%; hazard ratio, 0.46 (95% confidence interval, 0.30–0.70)) and pathological complete response rate …

Frontline Aspiration Versus Stent Retriever Thrombectomy For M2 Occlusions: Insights From The Star Registry, Michael Gaub, Joshua Osbun, Et Al.

2020-Current year OA Pubs

BACKGROUND: Recent trials have furthered uncertainty regarding the endovascular benefit for medium vessel occlusions (MeVO). Stent retrievers (SR) were employed in the first attempt in most interventional arm participants. We sought to compare outcomes in acute MCA M2 occlusions between frontline aspiration and SR, and to delineate procedural and anatomical covariates associated with differential treatment effect.

METHODS: Retrospective analysis of a multicenter stroke thrombectomy cohort identified cases of MT for M2 occlusions. Unmatched and propensity score-matched (PSM) cohorts were generated comparing frontline aspiration to standalone and combined SR. The primary outcome was functional independence (mRS 0-2) at 90 days. Recanalization, …

Mouse Alport Podocytes Are Susceptible To Aav9 Transduction In Vivo, Meei-Hua Lin, Kohei Omachi, Joshua F Begin, Jennifer L Richardson, Jeffrey H Miner

2020-Current year OA Pubs

INTRODUCTION: Alport syndrome features a defective glomerular basement membrane (GBM) due to variants in COL4A3, COL4A4, and COL4A5. The most severe forms, which lack the GBM's collagen α3α4α5(IV) network, progress from hematuria in early childhood to proteinuria, chronic kidney disease, and kidney failure by the age of ∼30. As a monogenic disease without specific treatments, and with podocytes being the only glomerular cells that synthesize collagen α3α4α5(IV), the ability to efficiently deliver genes to Alport podocytes could open up new possibilities for treatment.

METHODS: As a proof-of-concept study, we investigated whether podocytes in X-linked Alport mice were susceptible to transduction …

Excellent Outcomes In Feasibility Study Of Radiation-Free Conditioning And Transplant In Pediatric Severe Aplastic Anemia, Mithra Lakshmi Narasimhan, Irem Eldem, Jeffrey J Bednarski, Ginny L Schulz, Robert J Hayashi, Shalini Shenoy

2020-Current year OA Pubs

Severe aplastic anemia (SAA) is treated with a hematopoietic cell transplant (HCT) in the presence of an HLA-matched sibling donor (MSD) with disease-free survival (DFS) of >90%. In the absence of an MSD, immunosuppressive therapy (IST) can induce remission but concerns for relapsed/refractory disease and clonal hematopoiesis persist. IST failure is an indication for HCT. Modern HCT approaches target barriers such as graft rejection (GR), graft-versus-host disease (GVHD), and transplant-related toxicities. Traditionally, total body irradiation (TBI) inclusive HCT conditioning helps decrease GR, but the use of TBI in children increases concerns for late effects such as malignancies. To describe outcomes …

Comparison Of Breast And Gastric Her2 Immunohistochemistry (Ihc) Scoring Criteria In The Assessment Of Endometrial Carcinoma, Rachel L Furuya, Whitney Grither, Matthew A Powell, Premal H Thaker, Et Al.

2020-Current year OA Pubs

BACKGROUND: Immunohistochemistry (IHC) testing is the primary method to determine HER2 status at many institutions, often with reflex to in situ hybridization (ISH). DNA- and RNA- based platforms are emerging for HER-2 assessment. While approved IHC algorithms exist for HER2 scoring in breast and gastric carcinomas, neither has been validated in endometrial cancer. This study seeks to compare them and evaluate patterns of DNA and RNA expression.

METHODS: 263 endometrioid endometrial adenocarcinoma (EEA), 275 serous endometrial carcinoma (SEC), and 214 uterine carcinosarcoma (UCS) specimens were randomly selected. Previously stained HER2 IHC slides underwent blinded review by two board-certified pathologists and …

Endometriosis From Initiation To Innovation: Immune Microenvironments, Clonal Lesion Biology, And The Emerging Therapeutic Pipeline, Bindu Santhamma, Jessica Chacon, Eva Deemer, Dorota Stary, Shayla A. Hernandez, Ramadevi Subramani, Rajkumar Lakshmanaswamy, Klaus J. Nickisch, Surinder K. Batra, Hareesh B. Nair

Journal Articles: Biochemistry & Molecular Biology

Endometriosis is a chronic, estrogen-dependent inflammatory disease that, despite its benign histology, displays several cancer-relevant features, including clonal expansion, somatic alteration-associated lesion evolution, tissue invasion, apoptosis resistance, immune evasion, angiogenesis, fibrosis, and metabolic adaptation. These features are particularly important in ovarian endometriosis, where recurrent hemorrhage, iron-driven oxidative stress, and chronic inflammatory remodeling may promote malignant transformation. This review examines endometriosis through an oncologic framework by integrating current evidence on disease initiation, clonal lesion evolution, and the peritoneal, ovarian, and deep-infiltrating microenvironments. We discuss how epithelial, stromal, immune, endothelial, mesothelial, and neural components cooperate to support lesion survival, dissemination, vascularization, fibrosis, …

Feeding Mode Is Associated With Infant Night Sleep Trajectories During The First Postnatal Year, Magdalena Olson, Li Liu, Elizabeth Reifsnider, Dean V. Coonrod, Sarada S. Panchanathan, Megan E. Petrov, Corrie M. Whisner

Ellmer School of Nursing Faculty Publications

Background: Short sleep and formula feeding during infancy are associated with increased risk of childhood obesity. Feeding practices and sleep arrangements vary during infancy and may also be dynamic, yet their impact on infant night sleep duration remains unclear. Understanding these relationships is crucial for formulating recommendations to support breastfeeding and address sleep concerns. Objective: We examined the association between feeding mode and parent-reported infant night sleep duration during the first postnatal year, while additionally evaluating night-weaning and bedsharing as contextual sleep-related practices. Methods: Infants in the Phoenix Metropolitan Area (n = 193) were followed up at 3, 8, 13, …

Coordinated Regulation Of Capping Protein By Carmil And V-1/Myotrophin, John A Hammer, John A Cooper

2020-Current year OA Pubs

Capping Protein (CP) plays a central role in controlling actin filament dynamics in almost all eukaryotic cell types by virtue of its ability to block monomer addition and loss at the barbed end of the actin filament. Like other proteins that control actin assembly, CP is subject to regulation. Here we focus on two direct regulators of CP-CARMIL and V-1/Myotrophin. Specifically, we review recent biochemical, structural, imaging, and cell biological data that argue these two proteins cooperate to create a regulatory cycle for CP that controls its availability, activity, and site of action in the cell. Finally, we discuss unresolved …

Mutations In Hsp40 Co-Chaperone Change The Canonical Interdomain Interactions Stimulating Lgmdd1 Myopathy, Ankan K Bhadra, Geetika Aggarwal, Anshuman Jaysingh, Daniel Chen, Jil Daw, Conrad C Weihl, Heather L True

2020-Current year OA Pubs

Limb-girdle muscular dystrophy D1 (LGMDD1) is a rare, dominantly inherited neuromuscular protein-misfolding chaperonopathy caused by mutations in the Hsp40 co-chaperone DNAJB6, primarily in the glycine-phenylalanine (GF) or J-domains. Currently, no treatments are available, and a challenge in understanding the disease is identifying a specific client protein for DNAJB6 in skeletal muscle. DNAJB6 has homology to the yeast DNAJ family member, Sis1. Our previous research indicated that LGMDD1 GF domain mutants in Sis1 exhibit substrate-specific effects, influenced by Hsp70 activity. Herein, we employed functional assays along with advanced molecular simulation studies to understand the regulatory interdomain interactions in disease-causing mutants of …

Mucin 5ac Modulates Cancer-Associated Fibroblast Heterogeneity Through Epigenetic Reprogramming Of Precursor Cells, Rachel J. Kehrberg, Namita Bhyravbhatla, Zahraa Wajih Alsafwani, Xiaoqi Li, Gopalakrishnan Natarajan, Imran Khan, Randall E. Brand, Maneesh Jain, Surinder K. Batra, Sushil Kumar

Journal Articles: Biochemistry & Molecular Biology

Pancreatic cancer (PC) is characterized by extensive desmoplasia, with heterogeneous cancer-associated fibroblasts (CAFs) as a major component. However, the contribution of distinct precursor cells to CAF heterogeneity remains poorly defined. This study investigated the role of Muc5ac in modulating CAF heterogeneity by maturing precursor cells, including adipose-derived mesenchymal stem cells (AD-MSCs), bone marrow-derived MSCs (BM-MSCs), and pancreatic stellate cells (PSCs), into different CAF subsets. RNA sequencing of precursor cells treated with conditioned media from Muc5ac-proficient or -deficient cancer cells revealed distinct transcriptional profiles. Muc5ac significantly modulated the expression of Dnmts and Tets in AD-MSCs, promoting the acquisition of extracellular matrix …

Pancreatic Cancer Detection Consortium Biomarker Bakeoff: A Phase Ii Blinded Biomarker Validation And Panel Discovery Study, Ann L. Oberg, William R. Bamlet, Grant Izmirlian, Seetharaman Balasenthil, Surinder K. Batra, Masataka Hayashi, Daniel S. Herman, Michael A. Hollingsworth, Maneesh Jain, Ann M. Killary, Brianna M. Krusen, Suyu Liu, Shounak Majumder, Gopalakrishnan Natarajan, Subrata Sen, Lynette M. Smith, Sudhir Srivastava, Brian M. Wolpin, Kenneth S. Zaret, Michael G. Goggins

Journal Articles: Biochemistry & Molecular Biology

PURPOSE: The Pancreatic Cancer Detection Consortium (PCDC) performed a blinded Early Detection Research Network-defined phase II biomarker bakeoff study of blood-based biomarker panels. The aims were to evaluate panel performance, to compare the panels' performance with that of cancer antigen 19-9 (CA19-9) alone, and to evaluate the performance of new combinations of the individual biomarkers.

EXPERIMENTAL DESIGN: Ten biomarkers representing eight biomarker panels and CA19-9 were evaluated using plasma, serum, and germline DNA from 140 stage I to IV pancreatic ductal adenocarcinoma (PDAC) cases and 140 controls from three tertiary care institutions, with controls frequency matched to cases on age …

Overcoming Radiation Resistance: Ferroptosis Induction To Sensitize Solid Tumors To Radiation Therapy, Joseph Carmicheal, Caden M. Fritson, Alexandra Seas, Heidi M. Vieira, Surinder K. Batra

Journal Articles: Biochemistry & Molecular Biology

Radiation therapy (RT) is a mainstay of treatment for a myriad of cancers, often utilized for tumors that are unable to be resected, as well as an adjunct to surgery and chemotherapy. Unfortunately, many cancers are resistant to RT-induced damage and subsequent cell death. This has spurred the pursuit of novel radiation sensitizers that could potentiate the effects of this widely used and important treatment modality. Since its discovery as a regulated cell death mechanism in 2012, ferroptosis has been studied for its connection to cancer and other known oxidative pathways. With this, the interplay between RT and ferroptosis in …

Lysine Demethylase 4a Is A Centrosome-Associated Protein Required For Centrosome Integrity And Genomic Stability, Pratim Chowdhury, Xiaoli Wang, Richard I Han, Manga Motrapu, Ashley G Boice, Yuya Nakatani, Sofia Vargas-Hernandez, Julia F Love, Claude Chew, Sandra L Grimm, Dereck Mezquita, Frank M Mason, Elisabeth D Martinez, Cristian Coarfa, Cheryl L Walker, Anna-Karin Gustavsson, Ruhee Dere

Faculty, Staff and Students Publications

Centrosomes play a fundamental role in nucleating and organizing microtubules in the cell and are vital for faithful chromosome segregation and maintenance of genomic stability. Loss of structural or functional integrity of centrosomes causes genomic instability and is a driver of oncogenesis. Here we identify lysine demethylase 4A (KDM4A), an epigenetic 'eraser' of chromatin methyl marks, as a centrosome-localized protein, visualized at the nanometer-scale resolution. We additionally uncovered that KDM4A demethylase enzymatic activity is required to maintain centrosome homeostasis and integrity; a previously unknown functionality unlinked to altered expression of genes regulating centrosome number. We find that KDM4A interacts with …

Astrocytic Sox9 Overexpression In Alzheimer’S Disease Mouse Models Promotes Aβ Plaque Phagocytosis And Preserves Cognitive Function, Dong-Joo Choi, Sanjana Murali, Wookbong Kwon, Junsung Woo, Eun-Ah Christine Song, Yeunjung Ko, Debosmita Sardar, Brittney Lozzi, Yi-Ting Cheng, Michael R Williamson, Teng-Wei Huang, Kaitlyn Sanchez, Joanna Jankowsky, Benjamin Deneen

Faculty, Staff and Students Publications

Astrocytes play essential roles in the brain, and their dysfunction is associated with nearly every form of neurological disease. Despite their ubiquity, knowledge of how astrocytes contribute to disease pathogenesis is incomplete; accordingly, harnessing their biology toward therapeutics remains a major challenge. Here we show that the transcription factor Sox9 plays a context-specific role in maintaining astrocyte function and circuit activity in the aging hippocampus and Alzheimer's disease (AD) models. We found that Sox9 overexpression in astrocytes in AD models clears existing amyloid beta (Aβ) plaques and preserves cognitive function. Mechanistically, Sox9 promotes the phagocytosis of Aβ plaques by astrocytes …

Unraveling Posttranslational Modification Complexity: Advances In Quantitative Histone Proteoform Mass Spectrometry, Karl F Poncha, Alyssa T Paparella, Nicolas L Young

Faculty, Staff and Students Publications

Histone proteins and their posttranslational modifications are central to chromatin structure and function. These modifications often occur in combinations, generating a diverse array of histone proteoforms that contribute to the dynamic regulation of chromatin architecture. Advancements in mass spectrometry-based proteomics, particularly top-down and middle-down approaches, have significantly enhanced our ability to characterize these proteoforms and elucidate PTM crosstalk. This review provides an analysis of the epigenetic machinery involved in the addition, recognition, and removal of histone PTMs, emphasizing the complexity introduced by histone variants and combinatorial PTM patterns. We examine the challenges and limitations of traditional antibody-based methods for PTM …

Survodutide For Treatment Of Obesity: Baseline Characteristics Of Participants In A Randomized, Double-Blind, Placebo-Controlled, Phase 3 Trial (Synchronize™-1), Carel W Le Roux, Sean Wharton, Biykem Bozkurt, Elke Platz, Gabriele Bleckert, Samina Ajaz Hussain, Martina Brueckmann, Elena Startseva, Isabel M Kloer, Lee M Kaplan

Faculty, Staff and Students Publications

Aims: Survodutide, a novel glucagon receptor and glucagon-like peptide-1 (GLP-1) receptor dual agonist, elicited significant weight loss in a phase 2 trial in individuals with obesity without type 2 diabetes (T2D). Two multinational phase 3 trials are investigating survodutide for obesity management in individuals with or without T2D. We report the baseline characteristics of participants in the SYNCHRONIZE-1 trial in adults with obesity without T2D (ClinicalTrials.gov: NCT06066515).

Materials and methods: Participants aged ≥18 years with BMI ≥30 or ≥27 kg/m2 with ≥1 obesity complication without T2D were randomized 1:1:1 to double-blind, once-weekly, subcutaneous injections of survodutide (up-titrated to 3.6 …