Medical Specialties Commons^™

Multiple Subcortical And Subcortico-Cortico Dynamic Network Reconfigurations Characterize Focal-To-Bilateral Tonic-Clonic Seizures, Shilpi Modi, A. Ankeeta, Walter Hinds, Michael R. Sperling, Xiaosong He, Joseph I. Tracy

Department of Neurology Faculty Papers

Temporal lobe epilepsy (TLE) is the most common focal epilepsy, with focal to bilateral tonic-clonic seizures (FBTCS+) a more severe form of the disorder. Evidence has underscored the critical role of the thalamus, mesial temporal region, basal ganglia and cerebellum, along with the cortex, in the propagation, termination, and modulation of seizure activity. We examined time variant patterns of interaction within and between 7 cortical and 4 subcortical systems in 55 healthy controls and 56 patients with TLE (n = 40 with FBTCS+ and 15 without), isolating those patterns most distinctive of FBTCS+ utilizing tools from dynamic network neuroscience on …

Childhood Asthma Biomarkers Derived From Plasma And Saliva Exosomal Mirnas, Abdelnaby Khalyfa, Mohit Verma, Meghan M. Alexander, Zhuanhong Qiao, Tammy Rood, Ragini Kapoor, Trupti Joshi, David Gozal, Benjamin D. Francisco

Biomedical Sciences

Asthma, the most common chronic respiratory condition in children, involves airway inflammation, hyper-responsiveness, and frequent exacerbation that worsen the airflow and inflammation. Exosomes, extracellular vesicles carrying microRNAs (miRNAs), play a key role in cell communication alongside other types of communication and are promising markers of asthma severity. This study compares exosomal miRNA and long non-coding RNA (lncRNA) profiles in boys with asthma, focusing on differences between those with normal lung functions and those with severe airflow obstruction. This study enrolled 20 boys aged 9–18 years with asthma, split into two groups based on their lung function. Ten had normal lung …

Variation A Blood Culture Testing For Three Common Infections, Smit Shah, Jennifer Goldman, Matt Hall, Jillian Cotter, Samantha A. House, Matthew J. Molloy, Michelle Polich, Michael J. Steiner, John R. Stephens, Michael J. Tchou, Ronald J. Teufel Ii, Irma Ugalde, Andrew Yu, Jessica Markham

Presentations

Background: Routine blood culture (BC) testing in uncomplicated community-acquired pneumonia (CAP), skin and soft tissue infections (SSTI), and urinary tract infections (UTI) has demonstrated low clinical utility. Objectives: To evaluate hospital-level BC testing trends and their association with clinical outcome differences for children hospitalized with CAP, SSTI, and UTI. Methods: This retrospective cohort study used the Pediatric Health Information System database to identify hospitalizations of children aged 3 months-18 years admitted with CAP, SSTI, or UTI from 2016-2023. We excluded patients with complicated infections, medical complexity, ICU admission, or length of stay (LOS) >7 days. Hospital-level BC testing rates were …

A Late Presentation Of Benign Cephalic Histiocytosis, Madison A. Hackley, Nicholas D. Brownstone, Shayan Waseh, Simo Huang, Jason B. Lee, Sylvia Hsu

Department of Dermatology and Cutaneous Biology Faculty Papers

No abstract provided.

Author Reply: Investment Case For Mental Health, Cyprian Mostert

Population Health, East Africa

No abstract provided.

Clearance Of Acute Bilateral Idiopathic Central Corneal Stromal Haze Likely Due To Topical Losartan, Karen Asfar, Jad F. Assaf, Jeremiah Gendy, Sadeer Hannush, Shady T. Awwad

Wills Eye Hospital Papers

To report the use of topical losartan as a potential treatment of acute bilateral central corneal stromal haze in a patient presenting with a syndrome resembling central toxic keratopathy (CTK).Patient and Clinical Findings:A 51-year-old man presented with clinically significant central corneal stromal haze bilaterally 6 days after a periorbital and facial contact dermatitis secondary to pesticide exposure. Uncorrected and corrected distance visual acuity (UDVA and CDVA) were 20/80 and 20/70 in the right eye, and 20/200- and 20/150+ in the left eye, respectively. After unsuccessful treatment with topical antivirals, antibiotics and corticosteroids, the patient started off-label treatment with topical losartan …

Identification Of A Translatable Animal Model For Dry Eye Disease Using Comparative Analysis Of Tear Proteins Across Species, Mayelín Pérez-Perdomo, Ana González-López, Laura Ortega-Llamas, David Alba-Molina, Mario Blanco-Blanco, María Del Mar Granados, Adrián Guerrero-Moreno, Stephen Carl Pflugfelder, Christoph Ullmer, Sascha Fauser, Yolanda Jiménez-Gómez, Miguel González-Andrades

Faculty, Staff and Students Publications

Purpose: This study aimed to assess the similarity of tear proteins between experimental animals and humans to identify the most translational animal model for dry eye disease (DED).

Methods: Eleven species were selected for a structural and physicochemical comparison of healthy human tear fluid proteins involved in DED. Amino acid sequences were compared using BLAST. Protein primary structure, isoelectric point (pI) and grand average of hydropathicity (GRAVY) were determined using ExPASy and compared with humans.

Results: Among non-primate mammals, the cat (69.7 %) and pig (68.7 %) showed the highest protein sequence similarity to humans. The ruminants and cat showed …

Short-Term Neurologic Outcomes In Pediatric Extracorporeal Membrane Oxygenation Are Proportional To Bleeding Severity Graded By A Novel Bleeding Scale, Katherine Doane, Danielle Guffey, Laura L Loftis, Trung C Nguyen, Matthew A Musick, Amanda Ruth, Ryan D Coleman, Jun Teruya, Christine Allen, Melania M Bembea, Brian Boville, Jamie Furlong-Dillard, Santosh Kaipa, Mara Leimanis, Matthew P Malone, Lindsey K Rasmussen, Ahmed Said, Marie E Steiner, Deanna T Tzanetos, Heather Viamonte, Linda Wallenkamp, Arun Saini

Faculty, Staff and Students Publications

Patients admitted to a pediatric intensive care unit (PICU) need individualized nutrition support that is tailored to their particular disease severity, nutritional status, and therapeutic interventions. We aim to evaluate how calories and proteins are provided during the first seven days of hospitalization for children in critical condition with organ dysfunction (OD). A single-center retrospective cohort study of children aged 2–18 years, mechanically ventilated > 48 h, and admitted > 7 days to a PICU from 2016 to 2017 was carried out. Nutrition support included enteral and parenteral nutrition. We calculated scores for the Pediatric Sequential Organ Failure Assessment (pSOFA) on days …

Identification Of Distinct Biological Groups Of Patients With Cryptogenic Norse Via Inflammatory Profiling, Martin Guillemaud, Mario Chavez, Firas Kobeissy, Annamaria Vezzani, Anthony D Jimenez, Maysaa Merhi Basha, Ayush Batra, Sophie Demeret, Onome Eka, Krista Eschbach, Brandon Foreman, Nicolas Gaspard, Elizabeth E Gerard, Teneille Emma Gofton, Hiba A Haider, Stephen T Hantus, Charles L Howe, Amy Jongeling, Mariel Kalkach-Aparicio, Padmaja Kandula, Karnig Kazazian, Minjee Kim, Yi-Chen Lai, Clémence Marois, Andrew Mellor, Wazim Mohamed, Mikaela Morales, Cederic M Pimentel, Alexandra M Ramirez, Claude Steriade, Aaron F Struck, Olga Taraschenko, Nathan Torcida Sedano, Mark S Wainwright, Ji Yeoun Yoo, Kevin K W Wang, Vincent Navarro, Lawrence J Hirsch, Aurélie Hanin

Faculty, Staff and Students Publications

Background and objectives: Emerging evidence suggests that immune dysregulation plays a pivotal role in triggering cryptogenic new-onset refractory status epilepticus (c-NORSE), prompting a consensus on early initiation of immunotherapy. However, despite similar timing of administration, responses to immunotherapies have been varied and unpredictable, suggesting the presence of heterogeneous underlying mechanisms. The aim of this study was to identify distinct inflammatory response subtypes in patients with c-NORSE by analyzing their cytokine profiles. Insights into underlying mechanisms were sought to understand the pathophysiology and guide personalized therapies to improve patient outcomes.

Methods: Sixty-two patients with c-NORSE were included. A comprehensive panel …

Corrigendum To “Glands Of Moll: History, Current Knowledge And Their Role In Ocular Surface Homeostasis And Disease” [Progr Retin Eye Res 106 (2025) 101362], Michael Stopfer, Ingrid Zahn, Katharina Jüngert, Gerhard Aumüller, Frans L Moll, Martin Schicht, Helen P Makarenkova, Cintia S De Paiva, Friedrich P Paulsen

Faculty, Staff and Students Publications

No abstract provided.

Implementing A Stakeholder-Informed Approach For Standardized Collection Of Sexual Orientation And Gender Identity Data: Lessons Learned At A Matrix Comprehensive Cancer Center, Susan L Parker, Montserrat Ayala-Ramirez, Jane R Montealegre, Michael E Scheurer

Faculty, Staff and Students Publications

This brief report describes takeaways from the implementation of sexual orientation and gender identity (SOGI) data collection within a matrix comprehensive cancer center. Implementation of standardized and parsimonious SOGI data collection practices is a strategy recommended to improve our understanding of the cancer experiences among sexual and gender minority (SGM) populations. However, interventions are rarely sustained in routine practice without an organized program to support their implementation. We used a stakeholder-engaged approach to integrate a SOGI questionnaire in the electronic health record (EHR) at Dan L Duncan Comprehensive Cancer Center (DLDCCC)-affiliated adult oncology clinics and evaluate its feasibility, acceptability, and …

Predictors Of Failure To Rescue After Fenestrated-Branched Endovascular Aortic Repair Of Thoracoabdominal Aortic Aneurysms: Presented At The Thirty-Seventh Annual Meeting Of The European Society Of Vascular Surgery, Belfast, Northern Ireland, September 26-29, 2023, Andrea Vacirca, Thomas Mesnard, Ying Huang, Bernardo C Mendes, Tomasz Jakimowicz, Darren B Schneider, Stéphan Haulon, Jonathan Sobocinski, Adam W Beck, Andres Schanzer, Mark A Farber, Carlos Timaran, Andrea Kahlberg, Tilo Kölbel, Warren J Gasper, Barend M E Mees, Mauro Gargiulo, Nuno V Dias, Anthony Lee Woongchae, Matthew P Sweet, Kevin Mani, Matthew Eagleton, Luis Mendes Pedro, Hence Verhagen, Kak Khee Yeung, Nikolaos Tsilimparis, Timothy Resch, Luca Bertoglio, Emília Ferreira, Manar Khashram, Titia Sulzer, Marina Dias-Neto, Emanuel R Tenorio, Lucas Ruiter Kanamori, Katarzyna Jama, Ezequiel Parodi, Vivian Gomes, Jesus Porras Colon, Roberto Chiesa, Giuseppe Panuccio, Geert Willem Schurink, Charlotte Lemmens, Enrico Gallitto, Gianluca Faggioli, Angelos Karelis, Anders Wanhainen, Mohammed Habib, Ryan Gouveia E Melo, Kaj Olav Kappe, Samira Elize Mariko Van Knippenberg, Bichlan Tran, Sean Crawford, Marco Panagrosso, Andrea Melloni, Stefano Bonardelli, Rita Garcia, Tiago Ribeiro, Sinead Gormley, Steven Maximus, Gustavo S Oderich, International Multicenter Aortic Research Group

Faculty, Staff and Students Publications

No abstract provided.

Crispr-Cas9 Mediated Proteinase 3 Autoantigen Deletion As A Treatment Strategy For Anti-Neutrophil Cytoplasmic Autoantibody-Associated Vasculitis, Uwe Jerke, Claudia Eulenberg-Gustavus, Dimitrios Laurin Wagner, Adrian Schreiber, Ralph Kettritz

Faculty, Staff and Students Publications

Introduction: Proteinase 3 (PR3) is a major autoantigen in patients with anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV). Here, we performed a proof-of-principle study using ex vivo CRISPR-Cas9 guided gene editing to eliminate the PR3 autoantigen as an alternative to suppressing the autoimmune response to PR3.

Methods: A ribonucleoprotein (RNP) complex of Cas9 protein and a PR3-specific single guide-RNA was transfected into human CD34+ hematopoietic stem and progenitor cells (HSPC) by electroporation. Effects on PR3 protein abundance, neutrophil differentiation, and ANCA-dependent and -independent neutrophil responses were assessed.

Results: Gene editing introduced a frame shift in exon 2 of PRTN3. Consequently, PR3 …

Ad-Sge-Dkk3 Gene Therapy Overcomes Resistance To Immune Checkpoint Blockade In Pleural Mesothelioma, Hee-Jin Jang, Meera Patel, Daniel Y Wang, Sung Wook Kang, Jong Min Choi, Claire Lee, Monica Vilchis, Ji Seon Shim, Sonali Mitra, Priyanka Ranchod, Allen Kuncheria, William Hudson, Peter Jindra, Veronica Lenge De Rosen, Maheshwari Ramineni, Ernest Ramsay Camp, Farrah Kheradmand, R Taylor Ripley, Shawn S Groth, Hyun-Sung Lee, Bryan M Burt

Faculty, Staff and Students Publications

Purpose: Immune checkpoint inhibitors (ICI) have limited efficacy in pleural mesothelioma. We investigated the role of Dickkopf WNT signaling pathway inhibitor 3 (DKK3) in overcoming treatment resistance.

Patients and methods: We performed preclinical studies to elucidate DKK3's role in ICI-resistant mouse mesothelioma. Based on these findings, we conducted a single-arm, phase II clinical trial of a combination of Ad-SGE-DKK3 and nivolumab for chemotherapy-refractory epithelioid pleural mesothelioma, with the objective response rate as the primary outcome.

Results: DKK3 was significantly reduced in human epithelioid mesothelioma. Overexpression of DKK3 in cancer cells activated the p53 pathway, enhanced glycolysis, increased surface PD-L1, and …

Integrative Analysis Reveals The Prognostic Effects Of Epigenetic Regulators In Bladder Cancer, Venugopalareddy Mekala, Yupei Lin, Xiang Wang, Naail Chowdhury, Jianrong Li, Chao Cheng

Faculty, Staff and Students Publications

Background: Epigenetic regulatory genes (epiRG) are pivotal in the epigenetic regulation of the human genome, primarily through DNA and histone modifications. These genes are frequently mutated in human cancers, particularly bladder cancer (BC). However, the functional impact of epiRG mutations on patient outcomes remains poorly understood.

Methods: In this study, we developed gene signatures for the most frequent genomic aberrations of epiRG using The Cancer Genome Atlas Bladder Carcinoma (TCGA-BLCA) dataset and validated these signatures with independent tumor expression profiles for prognostic relevance. Furthermore, we evaluated the role of these signature scores in the immune system within the tumor microenvironment …

Figo Position Statement: Gamete Donations, Laurie Henry, Aris Antsaklis, Dov Feldberg, Jaideep Malhotra, Suchitra Pandit, Carlos Salazar, Alex Vidaeff, Rafal Zadykowicz, M Louise Hull, Nikhil Purandare

Faculty, Staff and Students Publications

Gamete donation has become a crucial part of Assisted Reproductive Technologies (ARTs), providing hope to individuals, including those who may have no other option for parenthood. This process comes with a wide range of ethical, medical, and legal challenges that need to be carefully addressed to protect the well-being and rights of all parties involved: donors, recipients, and offspring. Navigating these complexities requires strict ethical standards, robust regulatory frameworks, and international collaboration. By standardizing these, the field of gamete donation can continue to develop while ensuring that all parties are well informed and safeguarded. This paper explores the ethical concerns …

Microbial Biosensor For Sensing And Treatment Of Intestinal Inflammation, Duolong Zhu, Jeffrey Galley, Jason Pizzini, Elena Musteata, Martin V Douglas, Walter J Chazin, Eric P Skaar, Jeffrey J Tabor, Robert A Britton

Faculty, Staff and Students Publications

Synthetic biology has enabled the development of biosensors to detect intestinal inflammation, yet few target the clinically validated biomarker of intestinal inflammation calprotectin with both diagnostic and therapeutic capabilities. Here, an optimized calprotectin biosensor is presented that leverages a zinc uptake regulator (Zur) controlled promoter coupled with a memory circuit to detect and record intestinal inflammation in vivo. The level of biosensor activation strongly correlates with calprotectin levels in the colon of two independent mouse models of colitis. Coupling of the biosensor with the production of the anti-inflammatory cytokine IL10 allowed for the resolution of chemically induced colitis, demonstrating the …

Unfolding The Mystery Of Autoimmunity: The Environmental Determinants Of Diabetes In The Young (Teddy) Study, Marian Rewers, Daniel Agardh, Suzanne Bennett Johnson, Ezio Bonifacio, Helena Elding Larsson, Patricia Gesualdo, William Hagopian, Michael J Haller, Heikki Hyöty, Randi Johnson, Richard Mcindoe, Eoin Mckinney, Jessica Melin, Åke Lernmark, Richard E Lloyd, Kristian F Lynch, Jill M Norris, Stephen S Rich, Roswith Roth, Desmond Schatz, Jorma Toppari, Eric Triplett, Kendra Vehik, Suvi M Virtanen, Anette-G Ziegler, Beena Akolkar, Jeffrey P Krischer, Teddy Study Group

Faculty, Staff and Students Publications

In 2025, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health celebrates 75 years of leadership in diabetes research. The NIDDK serves people of the U.S. affected by or at risk for many chronic diseases, including diabetes and other endocrine, metabolic, and digestive disorders, by funding innovative research to develop better treatment and prevention and a cure for these conditions. Autoimmunity that leads to type 1 diabetes or celiac disease or thyroid autoimmunity affects 1 in 20 children and adolescents in the U.S. While treatments are available, prevention of these common autoimmune …

Clinical Assessment On Days 1-14 For The Characterization Of Traumatic Brain Injury: Recommendations From The 2024 Ninds Traumatic Brain Injury Classification And Nomenclature Initiative Clinical/Symptoms Working Group, David K Menon, Noah D Silverberg, Adam R Ferguson, Thomas J Bayuk, Shubhayu Bhattacharyay, David L Brody, Scott A Cota, Ari Ercole, Anthony Figaji, Guoyi Gao, Christopher C Giza, Fiona Lecky, Rebekah Mannix, Ana Mikolić, Kasey E Moritz, Claudia S Robertson, Abel Torres-Espin, Spyridoula Tsetsou, John K Yue, Hibah O Awad, Kristen Dams-O'Connor, Adele Doperalski, Andrew I R Maas, Michael A Mccrea, Nsini Umoh, Geoffrey T Manley

Faculty, Staff and Students Publications

The current classification of traumatic brain injury (TBI) primarily uses the Glasgow Coma Scale (GCS) to categorize injuries as mild (GCS 13-15), moderate (GCS 9-12), or severe (GCS ≤8). However, this system is unsatisfactory, as it overlooks variations in injury severity, clinical needs, and prognosis. A recent report by the National Academies of Sciences, Engineering, and Medicine (USA) recommended updating the classification system, leading to a workshop in 2024 by the National Institute of Neurological Disorders and Stroke. This resulted in the development of a new clinical, biomarker, imaging, and modifier (CBI-M) framework, with input from six working groups, including …

Definition And Classification Of Dystonia, Alberto Albanese, Kailash P Bhatia, Victor S C Fung, Mark Hallett, Joseph Jankovic, Christine Klein, Joachim K Krauss, Anthony E Lang, Jonathan W Mink, Sanjay Pandey, Jan K Teller, Marina A J Tijssen, Marie Vidailhet, H A Jinnah

Faculty, Staff and Students Publications

Dystonia is a movement disorder with varied clinical features and diverse etiologies. Here we present a revision of the 2013 consensus definition and classification of dystonia in light of subsequent publications and experience with its application during the last decade. A panel of movement disorder specialists with expertise in dystonia reviewed the original document and proposed some revision. There was broad consensus to retain the definition of dystonia with only minor clarifications to the wording. Dystonia is defined as a movement disorder characterized by sustained or intermittent abnormal movements, postures, or both. Dystonic movements and postures are typically patterned and …

Anemia In Inflammatory Bowel Disease: Practice Patterns And Clinical Outcomes In A Large National Veterans Cohort, Jared A Sninsky, Carolyn Brooks, Shubhada Sansgiry, Richa Shukla, Stalin Subramanian, Jason K Hou

Faculty, Staff and Students Publications

Background: Anemia is a common complication of inflammatory bowel disease (IBD), impacting patient quality of life and clinical outcomes. This study examines anemia management practices and clinical outcomes in a national cohort of veterans with IBD.

Methods: A retrospective cohort study of 89 687 veterans with IBD from 2000 to 2017 was conducted using Veterans Health Administration data. We assessed anemia screening, iron store assessments, and iron therapy. Primary outcomes included anemia resolution within 12 months. Secondary outcomes included IBD-related hospitalizations, steroid use, and surgery within five years. Multivariate logistic regression models assessed associations between patient characteristics and clinical outcomes. …

Cytokine Release Syndrome And Neurotoxicity Following Cd19 Car-T In B-Cell Lymphoma, Roni Shouval, Christopher Strouse, Soyoung Kim, Temitope Oloyede, Sairah Ahmed, Farrukh T Awan, Danny Luan, Veronika Bachanova, Talha Badar, Merav Bar, Pere Barba, Amer M Beitinjaneh, Amanda Cashen, Bhagirathbhai Dholaria, Mahmoud Elsawy, Siddhartha Ganguly, Praveen Ramakrishnan Geethakumari, Uri Greenbaum, Hamza Hashmi, Laquisa C Hill, Michael D Jain, Tania Jain, Partow Kebriaei, Adam S Kittai, Frederick L Locke, Premal D Lulla, Elena Mead, Joseph P Mcguirk, Alberto Mussetti, Taiga Nishihori, Amanda L Olson, Martina Pennisi, Miguel-Angel Perales, Peter A Riedell, Wael Saber, Abu-Sayeef Mirza, Margarida Magalhaes-Silverman, Elizabeth J Shpall, Mohamed Sorror, Kitsada Wudhikarn, Cameron J Turtle, Amy Moskop, Marcelo C Pasquini

Faculty, Staff and Students Publications

Chimeric antigen receptor T cell (CAR-T) therapy is an effective treatment for relapsed-refractory large B-cell lymphoma (LBCL). However, toxicities, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), remain significant concerns. Analyze temporal trends, risk factors, and associations between these toxicities and their severity. In this registry study by the Center for International Blood and Marrow Transplant Research, we studied CRS and ICANS in 1916 LBCL patients treated with commercial CAR-T therapies (axicabtagene ciloleucel 74.9%, tisagenlecleucel 25.1%) between 2018 and 2020. Outcomes include development of CRS/ICANS, timing and severity according to ASTC grading, overall survival (OS). Risk …

Performance Of Stool Xpert Mtb/Rif Ultra For Detection Of Mycobacterium Tuberculosis Among Adults Living With Hiv: A Multicentre, Prospective Diagnostic Study, George W Kasule, Sabine Hermans, Sozinho Acacio, Alexander Kay, Joachim Kikoyo Nsubuga, Carlos Fernández-Escobar, Nosisa Shiba, Lucia Carratalá-Castro, Derrick Semugenze, Patricia Mwachan, Shilzia Munguambe, Joanna Ehrlich, Elisa Lopez-Varela, Andrew R Dinardo, Frank Cobelens, Christoph Lange, Moses Joloba, Anna M Mandalakas, Willy Ssengooba, Alberto L García-Basteiro

Faculty, Staff and Students Publications

Background: When people living with HIV develop pulmonary tuberculosis, it often manifests without detectable acid-fast bacilli on sputum microscopy. We aimed to assess the diagnostic accuracy of stool Xpert MTB/RIF Ultra (hereafter, Ultra) for Mycobacterium tuberculosis detection among adults with HIV.

Methods: This multicentre, prospective diagnostic accuracy study was done in outpatient and inpatient health centres in Eswatini, Mozambique, and Uganda. We enrolled adults aged 15 years and older with HIV with presumptive tuberculosis. We evaluated the diagnostic accuracy of stool Ultra using the simple one-step processing method against a composite microbiological reference standard (CMRS) including three WHO-recommended tuberculosis diagnostic …

Military Inhalational Exposures Outside The Theater Of Conflict And Chronic Respiratory Symptoms, Reza Hosseini, Eric Garshick, Martin D Slade, Andrew Timmons, Anna M Korpak, Nicholas L Smith, Karen S Nakayama, Coleen P Baird, Paul Ciminera, Farrah Kheradmand, Vincent S Fan, Jaime E Hart, Petros Koutrakis, Ware Glenn Kuschner, Octavian C Ioachimescu, Michael Jerrett, Philippe R Montgrain, Susan P Proctor, Christine H Wendt, Cherry Wongtrakool, Emily S Wan, Paul D Blanc, Carrie A Redlich

Faculty, Staff and Students Publications

Importance: Deployment to Afghanistan and Southwest Asia has been associated with adverse respiratory health outcomes. However, the impact of inhalational exposures (eg, vapor, dust, gas, fumes), which are known correlates of reduced lung function and future chronic lung disease, during military service time outside this deployment period has not been assessed.

Objective: To assess military inhalational exposures during nonwartime routine activities and their associations with chronic respiratory symptoms.

Design, setting, and participants: This cross-sectional study used data from the US Department of Veterans Affairs Service and Health Among Deployed Veterans study. US veterans who served between October 7, 2001, and …

Decoding Metastatic Microenvironments Through Single-Cell Omics Reveals New Insights Into Niche Dynamics And Tumor Evolution, Fengshuo Liu, Xiang H-F Zhang

Faculty, Staff and Students Publications

Metastasis is the predominant cause of cancer mortality, primarily driven by complex tumor-host interactions within specialized metastatic niches. Recent advances in single-cell technologies have provided unprecedented insights into metastatic niche formation, evolution and function, including how primary tumors precondition distant organs for metastases and how disseminated tumor cells dynamically interact with host cells to modulate their environments. Integrated single-cell studies across multiple cancer types have also revealed divergent and convergent metastatic adaptation strategies. These findings collectively highlight metastasis as a dynamic, cooperative process shaped by intricate tumor-host interactions, and provide a foundation for novel therapeutic strategies targeting components of the …

Association Of Statin Use On Survival Outcomes Of Patients With Early-Stage Her2-Positive Breast Cancer In The Aphinity Trial, Christian Maurer, Elisa Agostinetto, Lieveke Ameye, Matteo Lambertini, Samuel Martel, Noam Ponde, Mariana Brandão, Francesca Poggio, Arlindo Ferreira, Rachel Schiff, Carmine De Angelis, Richard D Gelber, Susan Dent, Christoph Thomssen, Martine Piccart, Evandro De Azambuja

Faculty, Staff and Students Publications

Purpose: There is evidence that statins might improve the outcome of patients with breast cancer. The role of statins in patients with early HER2-positive breast cancer is unknown. Therefore, we explored the association between statin use and survival outcomes in early HER2-positive breast cancer patients in the phase III APHINITY trial (adjuvant pertuzumab/trastuzumab).

Methods: All patients (intent-to-treat population, n = 4804) were included (6.2 years median follow-up database). The primary objective was to investigate the association of statin use on invasive disease-free survival (IDFS), distant relapse-free interval (DRFI), and overall survival (OS). Patients who received statins at baseline, or started …

Deficits In Mitochondrial Dynamics And Iron Balance Result In Templated Insertions, Jordan Fox, Yang Yu, Yang Yu, Pilendra Thakre, Chloe Fox, Qian Li, Yunxia Wang, Adam Hughes, Xin Wang, Kaifu Chen, Grzegorz Ira

Faculty, Staff and Students Publications

Mitochondrial membrane dynamics control the shape, number, and distribution of mitochondria and regulate energy production and cell health. In a screen for yeast mutants with increased levels of templated insertions (~10-1000 bp) in the nuclear genome, we identified mitochondrial fusion deficient mutants (mgm1Δ, ugo1Δ, fzo1Δ). We found that fusion mutants activate the iron regulon, have decreased iron-sulfur clusters (ISCs), and increased DNA damage, suggesting a role of iron homeostasis in preventing insertions. Consistently, a secondary screen found mutants affecting iron-sulfur cluster production (yfh1Δ, grx5Δ), vacuolar iron storage (ccc1Δ) or general iron homeostasis (aft1Δ) to exhibit high insertion levels. Treatment with …

A Hypomorphic Model Of Cps1 Deficiency For Investigating The Effects Of Hyperammonemia On The Developing Nervous System, Stuti Bakshi, Taryn Diep, Brandon J Willis, Rachel Reyes, Grace F Wu, Georgios Makris, Martin Poms, Isabel Day, Qin Sun, Irina Zhuravka, Lindsay Lueptow, Michelle Tang, Gareth A Cromie, Aimée M Dudley, Johannes Häberle, Gerald S Lipshutz

Faculty, Staff and Students Publications

Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a rare metabolic disorder that, in neonatal onset, is typically characterized by severe life-threatening and neurologically injuring hyperammonemic episodes with high unmet patient need. Patients that retain limited enzyme activity may present later in life with less severe hyperammonemia. CPS1 drives the first step in the urea cycle, the pathway terrestrial mammals utilize to metabolize nitrogen. In order to probe the effect of hyperammonemia on the developing nervous system and explore new therapies, a murine Cps1 exon 3-4 mutant was previously generated. However, these mice die within 24 h of birth, limiting study …

Fibroblast-Restricted Inflammasome Activation Promotes Atrial Fibrillation And Heart Failure With Diastolic Dysfunction, Luge Li, Cristian Coarfa, Yue Yuan, Issam Abu-Taha, Xiaolei Wang, Jia Song, Yuying Zeng, Xiaohui Chen, Amrit Koirala, Sandra L Grimm, Markus Kamler, Lisa K Mcclendon, Michelle Tallquist, Stanley Nattel, Dobromir Dobrev, Na Li

Faculty, Staff and Students Publications

Atrial fibrillation (AF) often coexists with heart failure, both involving inflammatory signaling and cardiac fibroblasts. To understand the role of fibroblast NLR family pyrin domain containing 3 (NLRP3) inflammasome in cardiac function, we found that NLRP3 was up-regulated in atrial fibroblasts from AF patients. Fibroblast-specific activation of NLRP3 in mice induced AF-promoting atrial myopathy and heart failure with diastolic dysfunction, accompanied by increased fibrosis, and reduced conduction velocity. Knockdown of NLRP3 prevented the AF-promoting atrial substrate and cardiomyopathy in the context of NLRP3 activation in fibroblasts. We identify the fibroblast NLRP3 inflammasome as a key pathway governing the promotion of …

A Survey Study Of Roadblocks In Translational Science, Fasiha Kanwal, Christopher I Amos, Katherine H Sippel, Claudia Neuhauser, Ariel Harrison, Mary E Dickinson, Charles Minard, Bettina M Beech

Faculty, Staff and Students Publications

Clinical and translational science needs to address roadblocks to the translational processes. We conducted a survey at two institutions, a private medical school and a large public university, to understand the frequency and distribution of barriers and roadblocks to research. We reviewed the literature to compile a pool of barriers and roadblocks and convened a panel of relevant stakeholders to develop a 20-item questionnaire. Survey respondents were asked to select and prioritize the five leading clinical and translational roadblocks, provide information regarding their academic degrees and rank/position, complete open-ended items regarding their areas of research, and optionally add additional remarks …