Medical Specialties Commons^™

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.

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 …

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 …

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 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 …

Cardiac Rhythm Devices In Heart Failure With Reduced Ejection Fraction – Role, Timing, And Optimal Use In Contemporary Practice European Journal Of Heart Failure Expert Consensus Document, Biykem Bozkurt, Wilfried Mullens, Christophe Leclercq, Andrea M Russo, Gianluigi Savarese, Michael Böhm, Loreena Hill, Koichiro Kinugawa, Naoki Sato, William T Abraham, Antoni Bayes-Genis, Alexandre Mebazaa, Giuseppe M C Rosano, Shelley Zieroth, Cecilia Linde, Javed Butler

Faculty, Staff and Students Publications

Guidelines for management of heart failure with reduced ejection fraction (HFrEF) emphasize personalized care, patient engagement, and shared decision-making. Medications and cardiac rhythm management (CRM) devices are recommended with a high level of evidence. However, there are significant disparities: patients who could benefit from devices are frequently referred too late or not at all. Misconceptions about device therapy and the notion that the needs of patients (especially the prevention of sudden cardiac death) can now be met by expanding drug therapies may play a role in these disparities. This state-of-the-art review is produced by members of the DIRECT HF initiative, …

Diagnostic Accuracy Of Screening Tools For Depression And Anxiety In Cervical Dystonia, Davide Martino, Mehrafarin Ramezani, Steven Bellows, Brian D Berman, Florence Ching-Fen Chang, Jeanne Feuerstein, Victor Fung, Gamze Kilic Berkmen, Irene A Malaty, Claire Maciver, Scott A Norris, Kathryn J Peall, Joel S Perlmutter, Sarah Pirio Richardson, Laura J Wright, Zahra Goodarzi, Hyder A Jinnah

Faculty, Staff and Students Publications

Introduction: Despite their high prevalence and impact, depression and anxiety are not routinely screened for, and accuracy of screening procedures is unknown in adult-onset dystonia. We evaluated accuracy parameters of selected self-rated scales for depression and anxiety in patients with idiopathic cervical dystonia (CD).

Methods: Two-hundred-and-ten patients with idiopathic CD were recruited from 10 movement disorders centers from the US, Canada, Australia, and UK. At the end of each botulinum toxin cycle, participants were administered the Adult Standard Mini-International Neuropsychiatric Interview (MINI) as reference standard for depression and anxiety. Participants completed 8 self-administered index instruments (2 for depression, 2 for …

Formation Of An Expanding Memory Representation In The Hippocampus, Sachin P Vaidya, Guanchun Li, Raymond A Chitwood, Yiding Li, Jeffrey C Magee

Faculty, Staff and Students Publications

How brain networks connected by labile synapses store new information without catastrophically overwriting previous memories remains poorly understood. To examine this, we tracked the same population of hippocampal CA1 place cells (PCs) as mice learned a task for 7 days. We found evidence of memory formation as both the number of PCs maintaining a stable place field and the stability of individual PCs progressively increased across the week until most of the representation was composed of long-term stable PCs. The stable PCs disproportionately represented task-related learned information, were retrieved earlier within a behavioral session and showed a strong correlation with …

Immediate Skin-To-Skin Contact And Postpartum Hemorrhagic Morbidity, Rachel L Wiley, Ipsita Ghose, Dana R Canfield, Minhazur R Sarker, Hector Mendez-Figueroa, Suneet Chauhan

Faculty, Staff and Students Publications

Objective: To examine rates of postpartum hemorrhagic (PPH) morbidity among patients who did and did not have immediate skin-to-skin contact (SSC).

Methods: This study was a retrospective cohort of all non-anomalous, term singleton vaginal births at a Level IV center over 2 years. Exclusion criteria included COVID-19. Immediate SSC was defined as at least 60 min of direct contact initiated between parturient and neonate within 10 min of birth. The primary outcome was a composite of maternal morbidity related to PPH compared among those with and without immediate SSC. We used multivariable Poisson regression adjusted for possible confounders with robust …

Role Of Kctd13 In Modulating Ar And Sox9 Expression In Different Penile Cell Populations, Carolina J Jorgez, Ahmed Chahdi, Hunter Flores, Marisol O'Neill, Abhishek Seth

Faculty, Staff and Students Publications

Objective: Micropenis is a condition with significant physical and psychological implications caused mainly by decreased androgen action in penile development. Kctd13-knockout (Kctd13-KO) mice have micropenis, cryptorchidism, and fertility defects because of reduced levels of androgen receptor (AR) and SOX9. We hypothesized that normalizing the levels of AR and SOX9 in the Kctd13-KO penis could help us to understand the mechanism of action of these signaling pathways on penile development.

Methods: We generated transgenic mice lacking Kctd13 and conditionally expressing AR in the urethral mesenchyme after Cre activation with Twist2cre (Kctd13-KO; AR-CMV; Twist2cre; herein called AR+), and Sox9 in the urethral …

Dessicating Stress Triggers And Exacerbates Experimental Ocular Graft-Versus-Host-Disease, Uta Gehlsen, Martina Maass, Daniela Stary, Svenja Wagener-Ryczek, Gwen Musial, Manolis Pasparakis, Cintia S De Paiva, Michael E Stern, Philipp Steven

Faculty, Staff and Students Publications

Introduction: Chronic ocular graft-versus-host disease (oGVHD) is one of the most common complications after allogeneic hematopoietic stem cell transplantation (aHSCT). Recent studies indicate that desiccating stress by air-conditioning in transplantation wards increases the incidence of oGVHD. To test the hypothesis that experimental desiccating stress is a risk factor for oGVHD a mouse model of oGVHD was subjected to experimental desiccating stress.

Materials/methods: A previously established chemo-induced minor-mismatch mouse model of oGVHD was used. One group was challenged with desiccating stress for 18 days and compared to non-desiccated GVHD animals. Clinical phenotyping was performed weekly and ocular tissue and regional lymph …

High Prevalence Of Strongyloides Stercoralis In People Living With Hiv: A Critical Health Challenge In The Peruvian Amazon Basin, Silvia Otero-Rodriguez, Martin Casapia-Morales, Viviana Pinedo-Cancino, Seyer Mego-Campos, Victoria-Ysabel Villacorta-Pezo, Jorge Parráguez-De-La-Cruz, Eva H Clark, Esperanza Merino, Jose-Manuel Ramos-Rincon

Faculty, Staff and Students Publications

Introduction: Strongyloidiasis is an important but underdiagnosed soil-transmitted helminthiasis, particularly in tropical areas and some vulnerable groups.

Objectives: To assess the parasitological prevalence, seroprevalence and sociodemographic factors of Strongyloides stercoralis infection in patients living with human immunodeficiency virus (PLWH) in an endemic area.

Materials and methods: We performed a cross-sectional study of strongyloidiasis in 537 PLWH in two hospitals in Iquitos, Peru, from 20 Oct 2023 to 20 May 2024. We tested patient sera using Strongyloides IgG enzyme-linked immunosorbent assay (ELISA) and stool via the modified Baermann technique and/or charcoal fecal culture as highly sensitive parasitological techniques. We used multivariable …

Inhibition Of Srebp-1c Rescues Hepatic Cyp7b1 Expression And Bile Acid Synthesis In Malnourished Mice, Xiaoyang Wan, Krishnakant G Soni, Jong Min Choi, Sun Yun Jung, Margaret E Conner, Geoffrey A Preidis

Faculty, Staff and Students Publications

Malnutrition decreases intestinal bile acids, resulting in inefficient nutrient absorption and impaired catch-up growth. Mechanisms by which bile acid depletion occurs in malnutrition are unknown. Using a mouse model of early-life malnutrition, we explored bile acid homeostasis, focusing on transcriptional repression of CYP7B1, a rate-limiting enzyme in the alternative pathway of bile acid biosynthesis, by SREBP-1c, a master regulator of lipid metabolism. Mice were maintained on a low-protein low-fat or isocaloric control chow until eight weeks of age when livers were harvested for proteome profiling, western blot, RT-qPCR, and chromatin immunoprecipitation. Cultured hepatocytes and mice were treated with the SREBP-1c …

Functional Assays In Drosophila Facilitate Classification Of Variants Of Uncertain Significance Associated With Rare Diseases, Jung-Wan Mok, Shelley B Gibson, Haley A Dostalik, Shinya Yamamoto

Faculty, Staff and Students Publications

Individuals living with rare diseases often undergo a frustrating and expensive diagnostic odyssey. Clinical geneticists who analyze exome or genome sequencing data from rare disease patients often encounter a list of variants of uncertain significance (VUS) in known disease-causing genes or rare variants in genes of uncertain significance (GUS) that are difficult to interpret, even with the integration of the latest bioinformatic tools. In this Perspective, we review how studies using the fruit fly Drosophila melanogaster have facilitated rare disease diagnosis by uncovering the clinical relevance of GUS and classifying rare variants into specific allelic categories (loss-of-function or gain-of-function, Muller's …

Development And Diversity Of Astrocytes, Michael R Williamson, Sanjana Murali, Benjamin Deneen

Faculty, Staff and Students Publications

Proper development of the central nervous system (CNS) depends on astrocytes, which are the most abundant glial cells in the CNS. Here, we provide an overview of astrocyte ontogeny and morphogenesis, highlighting mechanisms that regulate astrocyte development. In addition, we describe the roles of astrocytes in regulating the development of other CNS cell types, with emphasis on neural circuits and vascular networks. We also discuss evidence for astrocyte diversity and its implications for CNS development. Finally, we pose open questions related to astrocyte development and its intersection with astrocyte diversity.

Metabolomic Data May Support The Development Of Personalized Nutrition Approaches To Type 2 Diabetes Management, Danielle J Lee, Shragvi Balaji, Jerome I Rotter, Alexis C Wood

Faculty, Staff and Students Publications

Diet is a major modifiable risk factor for type 2 diabetes (T2D), and suboptimal diets continue to contribute substantially to the population burden of T2D. Personalized nutrition proponents argue that specializing recommendations to interindividual differences in diet-health relationships will yield reductions in disease risk. However, how to personalize diet, and to whom, to reduce T2D risk remains unclear. Metabolites offer promise in this respect, as they capture (in part) dietary intake after the processes of digestion, processing, and absorption. The incorporation of metabolite data into diet-health studies therefore offers the opportunity to examine how the effects of food on the …

Fgf21 Promotes Longevity In Diet-Induced Obesity Through Metabolic Benefits Independent Of Growth Suppression, Christy M Gliniak, Ruth Gordillo, Yun-Hee Youm, Qian Lin, Clair Crewe, Zhuzhen Zhang, Bianca C Field, Teppei Fujikawa, Megan Virostek, Shangang Zhao, Yi Zhu, Clifford J Rosen, Tamas L Horvath, Vishwa Deep Dixit, Philipp E Scherer

Faculty, Staff and Students Publications

Approximately 35% of US adults over 65 are obese, highlighting the need for therapies targeting age-related metabolic issues. Fibroblast growth factor 21 (FGF21), a hormone mainly produced by the liver, improves metabolism and extends lifespan. To explore its effects without developmental confounders, we generated mice with adipocyte-specific FGF21 overexpression beginning in adulthood. When fed a high-fat diet, these mice lived up to 3.3 years, resisted weight gain, improved insulin sensitivity, and showed reduced liver steatosis. Aged transgenic mice also displayed lower levels of inflammatory immune cells and lipotoxic ceramides in visceral adipose tissue, benefits that occurred even in the absence …

Intracranial Injury Following Nasogastric Tube Placement After Skull Base Surgery: A Case Report And Systematic Review, Gabrielle Wolter, Zain U Naqvi, Ali Jalali, Tran Locke, K Kelly Gallagher, Meha G Fox

Faculty, Staff and Students Publications

Inadvertent intracranial nasogastric tube placement is a recognized risk following skull base fracture, but prior skull base surgery also poses a significant and underrecognized risk for this potentially fatal complication. We report the case of a 75-year-old female admitted with Clostridioides difficile colitis, six months after endoscopic endonasal resection of a pituitary macroadenoma. A systematic review identified 10 prior cases of intracranial tube placement following skull base or sinonasal surgery, including nasotracheal and feeding tube insertions. Literature suggests that using small-bore flexible tubes and preserving anatomical barriers, such as the position of the middle turbinate and intact bony structures like …

Comprehensive Genome Analysis And Variant Detection At Scale Using Dragen, Sairam Behera, Severine Catreux, Massimiliano Rossi, Sean Truong, Zhuoyi Huang, Michael Ruehle, Arun Visvanath, Gavin Parnaby, Cooper Roddey, Vitor Onuchic, Andrea Finocchio, Daniel L Cameron, Adam English, Shyamal Mehtalia, James Han, Rami Mehio, Fritz J Sedlazeck

Faculty, Staff and Students Publications

Research and medical genomics require comprehensive, scalable methods for the discovery of novel disease targets, evolutionary drivers and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size or location. Here we present DRAGEN, which uses multigenome mapping with pangenome references, hardware acceleration and machine learning-based variant detection to provide insights into individual genomes, with ~30 min of computation time from raw reads to variant detection. DRAGEN outperforms current state-of-the-art methods in speed and accuracy across all variant types (single-nucleotide variations, insertions or deletions, short tandem repeats, structural variations and copy …