Medical Sciences Commons^™

Genetic Study Of Von Willebrand Factor Antigen Levels ≤ 50 Iu/Dl Identifies Variants Associated With Increased Risk Of Vwd And Bleeding, Rachel K. Friedman, Adam S. Heath, Jennifer E. Huffman, James T. Baker, Natalie R. Hasbani, Sarah A. Gagliano Taliun, Ming-Huei Chen, Tom Howard, Joanne E. Curran, John Blangero

School of Medicine Publications

Background: von Willebrand disease (VWD) is a common inherited bleeding disorder caused by low levels or activity of circulating von Willebrand factor (VWF). Genetic susceptibility to VWF antigen (VWF:Ag) below normal (≤50 IU/dL) in the general population is underexplored.

Methods: To identify genetic variants influencing VWF:Ag levels ≤50 IU/dL, we performed a genome-wide association study in 926 cases with VWF:Ag levels ≤50 IU/dL and 12,846 controls from 7 studies from the TOPMed program. We then examined whether genome-wide significant findings were also associated with clinical diagnosis of VWD in 5 biobanks with 708 VWD cases and 1,286,069 controls, and with …

Changing The Perceived Pain Intensity In Populations With Spinal Cord Injury And With Health Disparities (Happiness): Protocol For A Feasibility Study, Ann Van De Winckel, Lin Zhang, Leslie R. Morse, Brianna Woodliff, Gladys Maestre, Kelsey Baker

School of Medicine Publications

Background: Chronic neuropathic pain affects 69% of adults with spinal cord injury (SCI). Medication, as a primary treatment, has insufficient benefits and significant risks for addiction and adverse effects. Of the available mind and body approaches, Qigong is the most accessible for adults with SCI, with evidence for effectiveness in reducing pain. Still, there is insufficient evidence to make recommendations for adults with SCI. Thus, the feasibility of Qigong in SCI needs to be established. We previously demonstrated feasibility in a pilot study, in which 18 non-Hispanic White adults with SCI completed a 12-week remote Qigong program. However, three additional …

Folliculin Depletion Results In Liver Cell Damage And Cholangiocarcinoma Through Mit/Tfe Activation, Bruno Maria Custode, Francesco Annunziata, Felipe Dos Santos Matos, Valentina Schiano, Veronica Maffia, Milena Lillo, Rita Colonna, Rossella De Cegli, Andrea Ballabio, Nunzia Pastore

Duncan NRI Faculty and Staff Publications

Mutations in the tumor suppressor gene Folliculin (FLCN) are responsible for Birt-Hogg-Dube’ (BHD) syndrome, a rare inherited condition that predisposes affected individuals to skin tumors, pulmonary cysts, and kidney tumors. FLCN regulates key cellular pathways, including TFEB, TFE3, and mTORC1, which are critical for maintaining cell homeostasis. Loss of FLCN leads to both hyperactivation of mTORC1 and constitutive activation of TFEB and TFE3, contributing to tumorigenesis. While previous studies showed that Flcn liver-specific conditional knockout (FlcnLiKO) mice are protected from developing liver fibrosis and damage upon high-fat diet exposure, the potential role of FLCN loss in liver carcinogenesis …

Bridging Psychiatry And Rare Genetic Diseases: A Scoping Review Of Therapeutic Strategies And Diagnostic Delay Paired With Healthcare Economic Burden Analysis, Sheldon R Garrison, Isaac J Siegel, Christopher R Takala, Sarah L Vaithilingam, Gene W Yang, Anthony W Zoghbi, Madeline M Hartig, Sreya Vadapalli, Margaret E Anderson

Duncan NRI Faculty and Staff Publications

Rare genetic diseases (RDs) with primary neuropsychiatric symptoms pose unique challenges for diagnosis and management. While the majority of these RDs have neuropsychiatric symptoms that are secondary to the RD, a subset presents with primary neuropsychiatric symptoms directly linked to their underlying pathophysiology. This subset has significant unmet medical need with delayed diagnoses leading to prolonged delays in treatment optimization and the trialing of medications that fail to target the underlying pathophysiology. This comprehensive review identifies 108 RDs with central neuropsychiatric symptoms that have a 7.7-year average diagnostic delay. Optimal management strategies for these RDs typically includes non-psychotropic medications, dietary …

Rapid Dissection And Dissociation Of The Mouse Olfactory Epithelium For Single-Nucleus Suspensions, Benjamin D W Belfort, Anthony M Insalaco, Claude C Chew, Johnathan D Jia, Julia Younis, Benjamin R Arenkiel

Duncan NRI Faculty and Staff Publications

The murine olfactory epithelium is the initial entry point of the olfactory system, housing various cell types that include olfactory sensory neurons, their regenerating progenitors, and support cells. Olfactory sensory neurons transduce chemical odorants into neural signals, yet the mechanisms underlying how these cells develop and turnover, create synapses with the olfactory bulb, and regulate their odorant receptors remain areas of intense study. Located on the dorsal aspect of the nasal cavity, the olfactory epithelium adheres to intricate bony structures known as turbinates. This anatomy poses unique challenges for its extraction and dissociation, especially in the context of preparing viable …

De Novo And Inherited Variants In Ddx39b Cause A Novel Neurodevelopmental Syndrome, Kevin T A Booth, Sharayu V Jangam, Martin M C Chui, Kayla Treat, Lorenzo Graziani, Alessia Soldano, Yao Ruan, Jeffrey Wan-Hei Hui, Kerry White, Celanie K Christensen, Ty Lynnes, Shinya Yamamoto, Oguz Kanca, Mandy H Y Tsang, Sally A Lynch, Sureni V Mullegama, Julia Baptista, Daniela Iancu, Shelagh K Joss, Sandra Y Y Wong, Christopher C Y Mak, Anna K Y Kwong, Hugo J Bellen, Erin Conboy, Remo Sanges, Anskar Yu-Hung Leung, Michael F Wangler, Brian H Y Chung, Francesco Vetrini

Duncan NRI Faculty and Staff Publications

DDX39B is a conserved member of the DEAD-box family of ATP-dependent RNA helicases, critical in mRNA metabolism across eukaryotes. DDX39B is also a core component of the TRanscription-EXport (TREX) super protein complex, and recent studies have highlighted the important role of its subunits in neurodevelopmental disorders. Here, we describe six individuals from five families, four harbouring de novo missense variants in DDX39B and one with an inherited splicing variant, presenting with variable developmental delay, congenital hypotonia, epilepsy, short stature, skeletal abnormalities, dysmorphic features and microcephaly in three patients.

3D molecular modelling predicts these variants would alter protein structure. In vitro …

Resting Quantitative Myocardial Perfusion-Essential Clinical Coronary Pathophysiology For Preventing Non-Beneficial Revascularization In Cardiomyopathy, K Lance Gould, Nils P Johnson

Faculty, Staff and Student Publications

No abstract provided.

A Retrospective Data Analysis Of Factors Contributing To Surgical Patients Not Achieving Normothermia, Joseph P. O'Rourke Jr, Megan Casselberry

Doctor of Nurse Anesthesia Practice (DNAP) Manuscripts

Postoperative hypothermia, defined as a core temperature below 36°C, is a prevalent and underrecognized complication in surgical settings, contributing to increased patient morbidity, prolonged recovery, and higher healthcare costs. This program evaluation project aimed to identify and address factors contributing to intraoperative and postoperative hypothermia by retrospectively analyzing patient records from a local hospital’s EPIC electronic health record system. Guided by the Iowa Model of Evidence-Based Practice and the W.K. Kellogg Foundation Program Evaluation Model, the project systematically reviewed perioperative temperature management protocols and warming interventions across diverse surgical specialties. Data extraction and analysis focused on patient demographics, procedural variables, …

Impact Of Resources And Structure On Scholarly Productivity In Pediatric Critical Care Fellowship, Andrew G Smith, Danny Castro, Caroline Andy, Angela S Czaja, Donald L Boyer, Erika L Abramson, Pnina Weiss, Richard B Mink

Faculty, Staff and Students Publications

Background: Pediatric critical care medicine (PCCM) fellowship structures vary widely among programs and have not been examined since 2006. The development of scholarly knowledge and skills is an important part of fellowship training. However, the optimal PCCM fellowship structure to enable fellows' scholarly productivity is unknown. Objective: We examined PCCM fellowship time structure and resources to better understand their association with scholarly productivity.

Methods: This is a secondary analysis of cross-sectional survey data from PCCM fellowship program directors. We defined highly productive programs as those in which greater than 75% of fellows published papers from their scholarly projects in the …

Respiratory Failure In Patients With Intracerebral Hemorrhage And Intraventricular Hemorrhage Extension: A Retrospective Study, Min Cheol Chang, Michael Y Lee, Sang Gyu Kwak, Ah Young Lee

Faculty, Staff and Students Publications

Background/Objectives: This study aimed to identify the risk factors for respiratory failure in patients with intracerebral hemorrhage (ICH) accompanied by intraventricular hemorrhage (IVH) extension.

Methods: We retrospectively included 208 patients with ICH accompanied by IVH extension. Respiratory failure was defined as carbon dioxide levels > 45 mmHg with a pH < 7.35 in arterial blood gas analysis (ABGA) or the application of a ventilator due to respiratory dysfunction. We measured the severity of IVH extension using the Graeb scale, and ICH volume was assessed for each patient.

Results: Of the 208 included patients, 83 had respiratory failure. There were no significant differences in age, sex ratio, or Graeb scale score between patients with and without respiratory failure (p > 0.05). However, ICH volume was significantly larger in patients with respiratory failure (42.0 ± 42.5 mL) than …

Using Vizient Database For Benchmarking Pulmonary Resection Outcomes, Anuj Shah, Duc T Nguyen, Swetha Mulpur, Sayali Kelkar, Ray K Chihara, Warren Naselsky, Edward A Graviss, Min P Kim

Faculty, Staff and Students Publications

Background: Benchmarking pulmonary resection outcomes is critical for the evaluation of hospital performance and enhancing the quality of patient care. Both the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) and Society of Thoracic Surgeons General Thoracic Surgical Database (GTSD) provide outcomes after lung resection, but each database had its own limitations. We aimed to determine whether the Vizient database can be used to benchmark lung resection outcomes.

Methods: We performed a retrospective cohort analysis of pulmonary resection cases at a single institution using the Vizient dashboard and GTSD. We examined whether all pulmonary resections were captured and …

Total Aortic Arch Replacement Using The Thoraflex Hybrid Device: Evolution From Investigational To Federally Approved Use In The United States, Vicente Orozco-Sevilla, Joseph S Coselli, Susan Y Green, Veronica A Glover, Ricardo De Jesus Avendaño Garnica, Anna H Xue, Lauren K Barron, Marc R Moon

Faculty, Staff and Students Publications

Background: After the US Food and Drug Administration (FDA) approved the Thoraflex Hybrid device in April 2022, hybrid devices to facilitate total arch replacement (TAR) became commercially available in the United States. However, little is known about how the Thoraflex device has been used since then. We present our experience (2016-2025) with this device.

Methods: At our practice, 62 patients [median age, 65 (54-73) years] underwent frozen elephant trunk (FET) TAR with the Thoraflex device: 14 under an investigational device exemption (IDE) (2016-2018) and 48 after FDA approval (2022-2025). Both Ante-Flo (straight) and Plexus (branched) models were used.

Results: Patients …

Biotechnology Research Incubator For Teachers (Brite) Pilot Program: Advancing Technology Research Education For Secondary School Teachers, Zhongcheng Shi, Katherine A Harris, Alana D Newell, Michael Nguyen, Yuan Yao, Joel Sederstrom, Cynthia C Hallmark, Sherita Love, Fred A Pereira, Shixia Huang

Faculty, Staff and Students Publications

Introduction: Advanced technologies have transformed diagnostics and therapeutics, improving disease management. Secondary school educators play a vital role in fostering critical thinking, problem-solving, and inspiring students in science, technology, engineering, math, and medicine (STEMM) innovations. Comprehensive teacher training enhances education delivery and ensures long-term advancements in science education, empowering future generations.

Materials and methods: We launched the Biotechnology Research Incubator for Teachers (BRITE) pilot program to train secondary school teachers. This 3-week program immerses teachers in Advanced Technology Core facilities, providing hands-on experience with cutting-edge technologies, such as protein array technology, next-generation sequencing, and flow cytometry. It also offers collaborative …

The Eleventh Annual Meeting Of The Southeastern Association Of Shared Resources (Seasr) Nashville, Tn, Usa June 12-14, 2024, Jenny C Schafer, Lyra M Griffiths, Tania E Mesa, Deidre Daria, Daniel Kraushaar, Kristen V Massey, Edith M Sampson, Laura Fox-Goharioon, Laxminarayanan Krishnan, Stacie Woolard, Aaron Pitre

Faculty, Staff and Students Publications

No abstract provided.

Role And Use Of Race In Artificial Intelligence And Machine Learning Models Related To Health, Martin C Were, Ang Li, Bradley A Malin, Zhijun Yin, Joseph R Coco, Benjamin X Collins, Ellen Wright Clayton, Laurie L Novak, Rachele Hendricks-Sturrup, Abiodun O Oluyomi, Shilo Anders, Chao Yan

Faculty, Staff and Students Publications

The role and use of race within health-related artificial intelligence (AI) and machine learning (ML) models have sparked increasing attention and controversy. Despite the complexity and breadth of related issues, a robust and holistic framework to guide stakeholders in their examination and resolution remains lacking. This perspective provides a broad-based, systematic, and crosscutting landscape analysis of race-related challenges, structured around the AI and ML life cycle and framed through "points to consider" to support inquiry and decision-making.

Single-Cell Transcriptomics Reveals Biomarker Heterogeneity Linked To Cdk4/6 Inhibitor Resistance In Breast Cancer Cell Lines, Ilenia Migliaccio, Martina Bonechi, Dario Romagnoli, Giulia Boccalini, Francesca Galardi, Cristina Guarducci, Agostina Nardone, Rachel Schiff, Laura Biganzoli, Luca Malorni, Matteo Benelli

Faculty, Staff and Students Publications

Cyclin dependent kinases 4 and 6 inhibitors have brought great improvements in the treatment of luminal breast cancer, but resistance is a major clinical hurdle. Multiple biomarkers of resistance have been proposed, but none is currently utilized in clinical practice. By performing single-cell RNA sequencing of seven palbociclib-naïve luminal breast cancer cell lines and palbociclib-resistant derivatives, we show that established biomarkers and pathways related to CDK4/6i resistance present marked intra- and inter- cell-line heterogeneity. Transcriptional features of resistance could be already observed in naïve cells correlating with levels of sensitivity (IC50) to palbociclib. Resistant derivatives showed transcriptional clusters that significantly …

Prognostic Significance Of Micropapillary Pattern And Risk Factors In Patients With Resected Stage I Lung Adenocarcinoma And Possible Benefit Of Adjuvant Therapy: A Real-World Multicenter Study, Jianjie Li, Yujia Chi, Bo Jia, Qiwen Zheng, Minghan Yuan, Jianjun Zhang, Aishen Zhou, Wei Sun, Yue Yang, Jun Zhao, Tongtong An, Yuyan Wang, Minglei Zhuo, Xue Yang, Hanxiao Chen, Jingjing Wang, Xiaoyu Zhai, Yidi Tai, Yuling He, Lingdong Kong, Xumeng Ji, Yiliang Liu, Nan Wu, Ken Onodera, Paul Van Schil, Mathew Thomas, Fan Yang, Ziping Wang

Faculty, Staff and Student Publications

Background: Micropapillary (MP) pattern has been identified as a negative prognostic factor in patients with lung adenocarcinoma, but it has not been recognized as a high-risk factor for patients with stage IB lung adenocarcinoma treated with adjuvant chemotherapy. This multicenter cohort study aimed to evaluate the prognostic value of histological subtypes for stage I lung adenocarcinoma and to determine the relative survival benefit of adjuvant chemotherapy for subgroups based on MP pattern.

Methods: This retrospective study included 412 patients with stage I lung adenocarcinoma [according the eighth edition of the tumor-node-metastasis (TNM) classification] with MP pattern who underwent complete surgical …

Domains Of Housing Instability And Intimate Partner Violence Risk Among U.S. Tenants, Anairany Zapata, Leila G Wood, Annalynn M Galvin, Wenyaw Chan, Timothy A Thomas, Jack Tsai, Heather K Way, Elizabeth J Mueller, Daphne C Hernandez

Faculty, Staff and Student Publications

While IPV is often studied as a predictor of housing insecurity, few U.S. studies explore how different forms of housing instability may contribute to intimate partner violence (IPV) risk. Using a mixed-methods approach and a cross-sectional design, this study examined the association between four housing instability domains and IPV among a sample of tenants that had either experienced eviction or were at high risk for eviction. Tenants in Harris and Travis counties (Texas, USA) completed an online survey (n = 1085; March–July 2024). Housing instability was assessed across four domains: homelessness, lease violations, utility hardship, and poor housing quality. …

The Glymphatic System And Sleep: Functional Relevance For Brain Homeostasis And Beyond, David Gozal

Marshall Journal of Medicine

It has been less than 15 years since the glymphatic system was identified. The discovery has revolutionized the understanding of the unique functions of cerebrospinal fluid (CSF) and the extracellular fluid within the central nervous system (CNS) and their unique connectivity to the rest of the body. The role of sleep in regulating glymphatic clearance from the brain and the potential reciprocal role of the glymphatic system in modulating regional neuronal activities, including sleep states, is rapidly emerging. It is shedding light on the role of sleep and the glymphatic system as toxic waste clearance facilitators for the brain, revealing …

Ruptured Internal Mammary Artery Perforator After Reduction Mammoplasty: A Case Report, Carol Wright Becker, Abigail Roop, Daniel Sutphin, Roger Tillotson

Marshall Journal of Medicine

A 60-year-old female who was 10 days post-reduction mammoplasty presented to the emergency department due to the sudden onset of swelling and pain in her left breast. A contrast-enhanced CT scan of the chest revealed active arterial bleeding. The patient was emergently taken to the operating room, where she underwent evacuation of a large hematoma as well as ligation of a left internal mammary perforator artery. This case represents a rare occurrence of life-threatening postoperative bleeding into the chest wall/breast after reduction mammoplasty, which developed 10 days postoperatively. The successful outcome and complete recovery were attributed to the timely recognition …

Open Field Two-Texture Preference Testing Is Not Associated With The Neuropathic Pain-Like Phenotype That Occurs Following Mouse Cervical Contusion Spinal Cord Injury, David A. Jaffe, Megan A. Lyttle, Angelo C. Lepore

Farber Institute for Neuroscience Faculty Papers

Development of neuropathic pain (NP) is one of the major complications associated with spinal cord injury (SCI). While well-established methods such as von Frey mechanical and facial grimace testing are often used to assess SCI-induced NP-like behaviors in animal models, these assays have significant limitations, including experimenter bias and long periods of active testing and analysis. To address these challenges, we aimed to develop a novel open field 2-texture preference test (TTPT) to assess NP-like behaviors following unilateral C5 hemicontusion SCI in mice. To do so, we modified the open field apparatus by introducing both a rough and a smooth …

Método Para La Enseñanza Del Cuidado En Enfermería. Competencia En Práctica Basada En La Evidencia, Adriana Hernández Bustos, María Victoria Rojas Martínez

Ciencias de la Salud

Método para la enseñanza del cuidado en enfermería. Competencia en práctica basada en la evidencia es un libro resultado de un proyecto de investigación multicéntrico desarrollado en Colombia, cuyo objetivo fue analizar el nivel de conocimiento, actitudes y habilidades sobre la Práctica Basada en la Evidencia (PBE) en estudiantes de programas de Enfermería de diferentes regiones del país. Esta obra colectiva surge en respuesta a la necesidad de consolidar la formación en competencias PBE desde el pregrado, reconociendo que el ejercicio profesional en enfermería debe estar fundamentado en el uso sistemático y crítico de la evidencia científica, en armonía con …

Unveiling Spatial Heterogeneity In Medulloblastoma: A Multi-Omics Analysis Of Cellular State And Geographical Organization, Jiankang Li, Hailong Liu, Ziwei Wang, Jiao Zhang, Xuan Chen, Craig Daniels, Xiaochong Wu, Olivier Saulnier, Hiromichi Suzuki, Pasqualino De Antonellis, Alexandra Rasnitsyn, Winnie Ong, Evan Y Wang, Liam D Hendrikse, Yu Su, Yu Tian, Dongming Han, Ruohan Wang, Jialin Mo, Fei Liu, Kaiwen Deng, Dongyang Wang, Zhaoyang Feng, Yifei Jiang, Yanong Li, Yuting Ma, Zijia Liu, Meiyu Li, Peiyi Tian, Yanfeng Shi, Yong Jiang, Tao Yang, Shouwei Li, Jianfeng Liang, Jingchuan Wu, Ying Wang, Wanjing Zou, Yina Jiang, Lusheng Wang, Fang Chen, Xin Jin, Shuaicheng Li, Xiaoguang Qiu, Chunde Li, Ya Gao, Yujie Tang, Michael D Taylor, Tao Jiang

Faculty, Staff and Students Publications

Background: Despite numerous studies on medulloblastoma (MB) cell heterogeneity, the spatial characteristics of cellular states remain unclear.

Methods: We analyze single-nucleus and spatial transcriptomes and chromatin accessibility from human MB spanning four subgroups, to identify malignant cell populations and describe the spatial evolutionary trajectories. The spatial copy number variations (CNVs) patterns and niches were analyzed to investigate the cellular interactions.

Results: Three main malignant cell populations were identified, including progenitor-like, cycling, and differentiated populations. Gene signatures of cell populations strongly correlate to clinical outcomes. These tumor cell populations are geographically organized as stem-like and mature regions, highlighting their spatially heterogeneous …

Long-Term Testosterone Pellet Insertion In Women With Low Libido Shows No Evidence Of Erythrocytosis And A Minimal Side Effect Profile, Beatriz S Hernandez, Gal Saffati, Katherine A Lowrey, Amit Reddy, Bridget S Park, Jeffrey J Song, Gabrielle Lyon, Mohit Khera

Faculty, Staff and Students Publications

Background: Testosterone therapy for low libido in women has become increasingly prevalent in recent years. While numerous testosterone formulations exist and have been studied in women, there has been little data assessing the safety and efficacy of subcutaneous testosterone pellet use in this population. The primary objective of this study is to understand the biochemical effects and side effect profile of female patients who underwent testosterone pellet insertion in a clinical practice.

Methods: A retrospective chart review of female patients who underwent testosterone pellet insertion from 2009 to 2022 was undertaken. Women taking 75 and 100 mg testosterone pellets were …

Integrating Circulating Tumor Dna Into Clinical Management Of Colorectal Cancer: Practical Implications And Therapeutic Challenges, Nikhil Vojjala, Viktoriya Gibatova, Raj N Shah, Sakshi Singal, Rishab Prabhu, Geetha Krishnamoorthy, Karen Riggins, Nagaishwarya Moka

Faculty, Staff and Students Publications

The American Cancer Society estimates that over 152,000 new cases of colorectal cancer (CRC) were diagnosed in 2024, with more than 105,000 cases affecting the colon and 46,000 involving the rectum. CRC remains the second leading cause of cancer-related deaths in the United States, with an estimated 53,010 deaths in 2024. In the era of precision medicine, which incorporates molecular and environmental information into clinical decision-making, identifying patients harboring a deficiency in Deoxyribonucleic acid (DNA) repair allowed for targeted immunotherapies and significantly reduced CRC-related mortality. A significant advancement in this domain is the application of liquid biopsy, which has emerged …

Systematic Review Of Parkinsonism In Cerebrotendinous Xanthomatosis, Jennifer Hanson, Penelope E Bonnen

Faculty, Staff and Students Publications

Background: Cerebrotendinous Xanthomatosis (CTX) is a rare, inherited metabolic disease caused by pathogenic variants in CYP27A1. The clinical presentation of this progressive disease includes cognitive deficits, ataxia, peripheral neuropathy, and pyramidal signs, as well as bilateral cataracts and tendon xanthomas. In some cases, CTX also includes parkinsonism. The goals of this study are to develop a data source that provides improved characterization and awareness of parkinsonism in CTX.

Methods: We conducted a systematic review of the literature according to PRISMA guidelines to identify all published individuals diagnosed with CTX and parkinsonism. Clinical signs, imaging findings and treatment response to …

Retrotransposon Methylation Profiles And Survival In Black Women With High-Grade Serous Ovarian Carcinoma, Christelle Colin-Leitzinger, Katherine A Lawson-Michod, Courtney E Johnson, Irma M Vlasac, Sean Yoder, Tania Mesa, Dana Roeber, Chad Huff, Michelle A T Hildebrandt, Kristin Haller, Anthony J Alberg, Elisa V Bandera, Melissa Bondy, Michele L Cote, Theresa Hastert, Edward S Peters, Paul D Terry, Andrew B Lawson, Andrew Berchuck, Brooke L Fridley, Jing-Yi Chern, Jennifer A Doherty, Jeffrey R Marks, Joellen M Schildkraut, Brock C Christensen, Lucas A Salas, Lauren C Peres

Faculty, Staff and Student Publications

Introduction: Retrotransposons (REs) constitute nearly half of the genome and include long terminal repeat (LTR) elements, Long INterspersed Elements (LINE), and Short INterspersed Elements (SINE). REs are typically silenced in somatic tissues via DNA methylation but can be reactivated through DNA hypomethylation, potentially impacting gene regulation. Here, we investigate genome-scale profiles of RE methylation in high-grade serous ovarian carcinoma (HGSOC) and associations with survival among Black women.

Methods: Methylation levels of LTR, LINE-1, and Alu (type of SINE) in 200 HGSOC tumors were predicted using a random forest approach and clustered using multiple consensus algorithms. Associations between RE methylation clusters …

Microneedle-Based Lc-Ms/Ms Profiling Of Dermal Interstitial Fluid Reveals Early Lipid Dysregulation Contributing To Painful Neuropathy In Prediabetic And Type 2 Diabetic Rats, Srinivasa Rao Gadam

Biomedical Sciences ETDs

Painful diabetic neuropathy (PDN), a complication of type 1 and type 2 diabetes, also occurs in obesity and prediabetes, with dyslipidemia as a modifiable risk factor. The distal-to-proximal neuropathy pattern and length-dependent intraepidermal nerve fiber loss suggest peripheral contributions. We hypothesized that elevated neurotoxic lipid intermediates—diacylglycerols (DAG), free fatty acids (FFA), and acylcarnitines (CARs)—in the dermal interstitial fluid (ISF) drive metabolism-associated hyperalgesia in prediabetic and diabetic rats. Using a microneedle array (MIA) with LC-MS/MS, we profiled ISF and serum lipids from high-fat diet (HFD) and HFD + streptozotocin (STZ) rat models alongside Hargreaves testing. ISF lipid changes appeared earlier (weeks …

Treatment With Allogenic Mesenchymal Stromal Cells For Moderate To Severe Acute Respiratory Distress Syndrome: A Double-Blind, Placebo-Controlled, Multi-Center, Phase 2b Clinical Trial (Stat), Michael A Matthay, Hanjing Zhou, Aartik Sarma, Narges Alipanah-Lechner, Carolyn Hendrickson, Lucy Z Kornblith, Martin Schreiber, David Zonies, Akram Khan, Bryce Robinson, Nicholas J Johnson, Lorraine B Ware, Oscar Guillamondegui, Jonathan Casey, Laura Moore, Bela Patel, Lillian Kao, Charles E Wade, Erin Fox, Charles Cox, Farrakh Khawanja, Robier Aguillon Prada, Sami Hossri, Rachael Callcut, Timothy Albertson, Kevin L Delucchi, Melanie Mcmillan, Charles R Langelier, Shibani Pati, David H Mckenna, Carolyn Leroux, Carolyn S Calfee, Kathleen D Liu

Faculty, Staff and Student Publications

Background: Prior clinical trials established the safety, but not the efficacy of bone marrow-derived mesenchymal stromal cells (MSCs) in the acute respiratory distress syndrome (ARDS).

Methods: We conducted a prospective, double-blind, multi-center randomized phase 2b clinical trial of one dose of intravenous MSCs (10 x 106/kg predicted body weight) versus placebo in 120 ventilated patients with ARDS (PaO2/FiO2 < 250 mmHg). The primary endpoint was change in oxygenation index (OI) over 36 hours from baseline.

Findings: Enrollment began in January 2020. Due to the Coronavirus 2019 (COVID-19) pandemic, the majority of subjects (101/120, 84%) developed ARDS from COVID-19. There were no significant baseline differences in severity of illness between patients treated with MSCs and those who received …

Cd45 And Cd148 Are Critically Involved In Neutrophil Recruitment And Function During Inflammatory Arthritis In Mice, Jan-Niklas Heming, Andreas Margraf, Karolina Najder, Giulia Germena, Mathis Richter, Anika Cappenberg, Katharina Henke, Bernadette Bardel, Lena Schemmelmann, Marina Oguama, Pia Lindental, Wida Amini, Jacqueline Sobocik, Georg Schett, Gerhard Krönke, Helena Block, Jan Rossaint, Oliver Soehnlein, Alexander Zarbock

Faculty, Staff and Student Publications

Neutrophils play a key role in autoimmune diseases like rheumatoid arthritis, contributing to tissue damage through rapid recruitment and activation. In this study, we investigated the regulatory properties of two receptor-like tyrosine phosphatases (RPTPs), CD45 and CD148, in inflammatory arthritis. Using an in vivo mouse model of K/BxN serum transfer-induced arthritis, we found that CD45 and CD148 feature distinct regulatory properties during inflammatory arthritis. CD45 is required for neutrophil infiltration, cytokine release, and reactive oxygen species production, whereas CD148 deficiency leads to a delayed onset of arthritis but unaltered overall neutrophil infiltration and reduced ROS production. Furthermore, we could demonstrate …