Medical Sciences Commons^™

Potential Impact Of Parasites In The Transmission Of Chronic Wasting Disease, Paulina Soto, Rodrigo Morales

Faculty, Staff and Student Publications

No abstract provided.

Optimized Ultrasound Imaging Of Phase-Change Nanodroplets, Charles R Dyall, Dmitry Nevozhay, Andy Liu, Trevor M Mitcham, George J Lu, Konstantin V Sokolov, Richard R Bouchard

Faculty, Staff and Student Publications

Phase-change nanodroplets (PCNDs) continue to generate significant research interest due to their potential to extravasate into tissue, to be targeted for molecular imaging and drug delivery, and to undergo an induced phase-change to "activated" microbubbles (MBs) for ultrasound (US) imaging. To accurately quantify molecular markers, however, one assumes a consistent proportion of PCNDs in a region of interest (ROI) are stably activated and imaged. Herein we present a framework for developing a diagnostic sequence that is optimized for PCND activation uniformity, contrast, and acquisition time. To develop this framework, activation was examined at three scales of increasing complexity: single, adjacent, …

Corrigendum To 'Risk Factors For Bronchiolitis Obliterans Syndrome After Initial Detection Of Pulmonary Impairment After Hematopoietic Cell Transplantation' [Transplantation And Cellular Therapy 29/3 (2023) 204-204], Mansour Alkhunaizi, Badar Patel, Luis Bueno, Neel Bhan, Tahreem Ahmed, Muhammad H Arain, Rima Saliba, Gabriela Rondon, Burton F Dickey, Lara Bashoura, David E Ost, Liang Li, Shikun Wang, Elizabeth Shpall, Richard E Champlin, Rohtesh Mehta, Uday R Popat, Chitra Hosing, Amin M Alousi, Ajay Sheshadri

Faculty, Staff and Student Publications

No abstract provided.

Growth Hormone Pathway As A Prognostic And Therapeutic Biomarker In Patients With Unresectable Hepatocellular Carcinoma Treated With Radiation Therapy, Joe R Eid, Safa Kaseb, Lianchun Xiao, Ryan Sun, Mahesh Kumar Kannan, Manal Hassan, Asif Rashid, Hop S Tran Cao, Hesham M Amin, Eugene J Koay

Faculty, Staff and Student Publications

Purpose: Radiation therapy (RT) has emerged as an effective local therapy option for patients with unresectable hepatocellular carcinoma (HCC) and is associated with improved overall survival (OS). However, some patients still have poor outcomes after RT, and biomarkers are needed to stratify prognostic groups. High circulating growth hormone (GH) levels promote HCC proliferation and survival and are associated with aggressive disease. In this study, we evaluated whether pretreatment GH levels are associated with OS and progression-free survival (PFS) in patients who underwent RT for unresectable HCC.

Methods and materials: Patients undergoing RT for HCC during 2017-2023 were identified from a …

Vo: The Vaccine Ontology, Jie Zheng, Asiyah Yu Lin, Anthony Huffman, Anna Maria Masci, Rebecca Racz, Guanming Wu, Kallan Roan, Edison Ong, Sirarat Sarntivijai, Joy Hu, Eliyas Asfaw, Hayleigh Kahn, Xingxian Li, Xumeng Zhang, Joshua Monickaraj, Nilufer Kosar, Jianfu Li, Warren Manuel, Rashmie Abeysinghe, Hasin Rehana, Benu Bansal, Yuanyi Pan, Jinjing Guo, Virginia He, Justin Song, Andrey I Seleznev, Katelyn Hur, Anna He, Alexander Davydov, Qi Yang, Anna Ostropolets, Randi Vita, Bjoern Peters, Alan Ruttenberg, Alexander D Diehl, Charles Tapley Hoyt, Paola Roncaglia, Rachael P Huntley, Richard H Scheuermann, Melanie Courtot, Thomas Todd, Samantha Sayers, Fang Chen, Xinna Li, Feng-Yu Yeh, Zuoshuang Xiang, Arzucan Ozgur, Patricia L Whetzel, Mark A Musen, Christopher J Mungall, Wolfgang W Leitner, Licong Cui, Lesley A Colby, Harry L T Mobley, Brian D Athey, Gilbert S Omenn, Lindsay G Cowell, Cui Tao, Junguk Hur, Barry Smith, Yongqun He

Faculty, Staff and Student Publications

Vaccines are widely used in both research and clinical settings. To facilitate FAIR data practices, we urgently need to standardize vaccine representation, integrate information across diverse vaccine types, and support computer-assisted reasoning. Accordingly, we have since 2007 developed the community-based Vaccine Ontology (VO), which aligns with the Basic Formal Ontology and adheres to OBO Foundry principles. VO ontologically models vaccines, vaccine components, vaccine immune responses, vaccine investigation studies and other vaccine-related topics. VO represents more than 10,000 vaccines targeting 289 infectious pathogens and cancers in humans and over 30 nonhuman animal species. VO provides mappings to external resources such as …

Hyperdynamic Microtubule-Based Structural Changes In Monocyte-Derived-Neuronal-Like Cells From Patients With Schizophrenia, Alfredo Bellon, Alonso Cortez-Resendiz, Lauren N Forrest, Omar Elmarasi, Janani Iyer, Anjali Iyer, Chachrit Khunsriraksakul, Dajiang Liu, L Elliot Hong, Therese M Jay, Marie-Odile Krebs, Anne Hosmalin

Faculty, Staff and Student Publications

A consistent postmortem finding in schizophrenia (SCZ) is reduction in dendrites' size. However, neurons with larger dendritic trees have also been encountered. In vitro experiments with neurons and neuronal-like cells coming directly from patients with SCZ showed similar results, evidencing at times more extensions and at others less arborizations. The process of extending and retracting neuronal outgrowths depends on microtubules polymerization and depolymerization. The possibility that microtubule polymerization/depolymerization is related to defects in the neuronal structure comes from several microtubular anomalies reported in SCZ such as its abnormal distribution in the cytoplasm, irregular shape of microtubules and even absence of …

Admixture-Informed Polygenic Risk Reporting Using The Eprs Framework, Yu-Jyun Huang, Nuzulul Kurniansyah, Matthew O Goodman, Brian W Spitzer, Jiongming Wang, Adrienne Stilp, Cecelia Laurie, Paul S De Vries, Han Chen, Yuan-I Min, Mario Sims, Gina M Peloso, Xiuqing Guo, Joshua C Bis, Jennifer A Brody, Laura M Raffield, Jennifer A Smith, Wei Zhao, Jerome I Rotter, Stephen S Rich, Susan Redline, Myriam Fornage, Robert Kaplan, Nora Franceschini, Daniel Levy, Alanna C Morrison, Eric Boerwinkle, Nicholas L Smith, Charles Kooperberg, Bruce M Psaty, Sebastian Zöllner, Tamar Sofer

Faculty, Staff and Student Publications

Polygenic risk score values vary with genetic ancestry due to differences in population-specific allele frequencies and linkage disequilibrium patterns. We present a framework to calibrate polygenic risk scores based on ancestral makeup. We propose the "expected polygenic risk score" or ePRS, defined as the expected value of a polygenic risk score based on one's global or local admixture patterns. We further define the "residual polygenic risk score" or rPRS as measuring the deviation of the polygenic risk score from the ePRS. The ePRS reflects the baseline ancestry-driven component of genetic risk, whereas the rPRS isolates an ancestry-agnostic measure of genetic …

The Right Time For A Synapse To Change: Windows And Mechanisms Of Multiday Training Trials, Rong-Yu Liu, Yili Zhang, Roberta Calvo, Paul Smolen, John H Byrne

Faculty, Staff and Student Publications

Although learning over multiple days is more effective than a single day of training, the underlying cellular mechanisms of repeated training trials remain poorly understood. With a combination of empirical and computational approaches, we determined a critical time window for a second stimulus block of a multiday training protocol to augment long-term synaptic facilitation (LTF) of the Aplysia sensorimotor synapse and long-term enhancement of neuronal excitability (LTEE), two cellular correlates of learning and memory. A second stimulus block delivered 24 h after the first block significantly enhanced LTF and LTEE, but was without effect at 18 or 32 h. This …

Rosai-Dorfman Disease In A Rare Cardiac Presentation: Left Ventricular Mass Causing Ventricular Tachycardia, Motaz Al Yafi, Swetha Pasala, Valentina Robila, Cory Trankle, Bharadhwaj Kolipakkam, Patricia Nicolato

Faculty, Staff and Student Publications

Background: Rosai-Dorfman disease (RDD) is a rare, benign histiocytic disorder that most often presents with nodal involvement. Cardiac involvement is exceedingly uncommon and poses significant diagnostic and therapeutic challenges.

Case summary: A 51-year-old woman presented with shortness of breath and palpitations and was found to have monomorphic ventricular tachycardia. Imaging revealed a left ventricular mass, and biopsy confirmed RDD. The lesion was surgically excised with cryoablation and CorMatrix reinforcement. The patient recovered uneventfully and remains disease free 25 months postoperatively.

Discussion: RDD with cardiac involvement has been reported in only approximately 25 cases, with very few affecting the left ventricle. …

Vestibular Schwannoma Microsurgery In The Era Of Multimodal Treatment: Advances In Technique And Patient Selection, Ibrahem Albalkhi, Basel Musmar, Nimer Adeeb, Hussam Abou-Al-Shaar, Jacques J Morcos

Faculty, Staff and Student Publications

Background: The management of vestibular schwannoma (VS) has traditionally prioritized gross total resection to achieve high tumor control, often at the cost of cranial nerve injuries and quality of life impairment. However, advances in surgical approaches and intraoperative technologies, coupled with active surveillance and/or adjuvant treatment, have shifted the management paradigm towards prioritizing patient-centered outcomes, which are as critical as oncological control.

Content: The authors reviewed the technical advances driving this paradigm shift, including endoscopic assistance in the different microsurgical approaches (retrosigmoid, translabyrinthine, and middle cranial fossa approaches) of VS resection and advanced neuromonitoring (facial nerve electromyography and cochlear/auditory evoked …

Breathing-Controlled Electrical Stimulation (Breestim) Selectively Modulates Affective And Cognitive Components Of Pain-An Eeg Study, Ahmad Z Rao, Michael Houston, Hao Meng, Shengai Li, Yingchun Zhang, Sheng Li

Faculty, Staff and Student Publications

Breathing-controlled electrical stimulation (BreEStim) is an innovative neuromodulation intervention that synchronizes deep voluntary breathing with peripheral electrical stimulation. Prior studies have shown its analgesic effects in healthy adults and spinal cord injury patients with neuropathic pain. The present study used EEG to examine BreEStim's neural effects on sensory, affective, and cognitive components of pain. Fourteen healthy participants (7 M, 7 F) completed 30 min of BreEStim and conventional electrical stimulation (EStim) interventions in a randomized, crossover within-subject design. Electrical pain thresholds (EPT) and EEG were recorded pre- and post-intervention. Event-related potentials (ERPs) at pre-EPT-level stimuli before and immediately after each …

Modeling Early Human Heart Development Using An Ipsc-Based 3d Bioprinted Model Of Embryonic Heart Tube, Linqi Jin, Christian Park, Sunder Neelakantan, Shweta Karnik, Arnab Dey, Sarah Fineman, Roshni Nandwani, Carmen J Gil, Boeun Hwang, Melissa A Cadena, Vani Sridhar, Jing Wang, Yuxiao Wu, Connor J Evans, Lan Li, Sarah Rezapourdamanab, Mehdi Salar Amoli, Martin L Tomov, Ryan K Roeder, Reza Avazmohammadi, Lakshmi Prasad Dasi, Hanjoong Jo, Eric Weeks, Holly D Bauser-Heaton, Sean M Wu, Vahid Serpooshan

Faculty, Staff and Student Publications

Human heart development depends on tightly coordinated genetic programs and biomechanical cues, yet the underlying cell-microenvironment interactions remain poorly understood because the developing heart is difficult to study in utero and accurate experimental models are lacking. Recent advances in stem cell biology and three-dimensional (3D) bioprinting now allow the construction of human tissue analogues with defined structure and function. Here we show a perfusable 3D bioprinted model of the human embryonic heart tube composed of layered myocardium, cardiac jelly, and endocardium. Human induced pluripotent stem cell-derived cardiomyocytes and endothelial cells are cultured under controlled flow conditions, producing constructs with high …

Engineering Function In Lung Biology: Integrating Imaging, Regenerative Constructs, And Functional Biodesign, Rene A Girard, Jamie Tran, Yuqing Cai, Mary C Farach-Carson, Hadi T Nia, Allison M Greaney, Laura E Niklason, Killian Hurley, Elvin Blanco, Sinem Koc-Günel, Harry Karmouty-Quintana

Faculty, Staff and Student Publications

The lung is a uniquely demanding target for regeneration because function depends on the coordinated integration of cellular diversity, three-dimensional architecture, cyclic mechanical forces, vascular perfusion, immune surveillance, and extracellular matrix remodeling. While single-cell and spatial profiling, lineage tracing, and iPSC-derived models have transformed our understanding of lung cell states and developmental potential, these descriptive approaches have also highlighted a central bottleneck: the field still lacks broadly adopted platforms to test whether engineered tissues and regenerative interventions restore function under physiologic load. In this review, we focus on emerging technologies that enable functional biodesign in lung biology by coupling engineered …

A Risk-Based Model For Unplanned Cesarean Delivery Following Induction Of Labor In Term Hypertensive Nulliparas., Avihu Krieger, Michal Axelrod, Baha Sibai, Shalom Mazaki-Tovi, Michal Fishel Bartal

Faculty, Staff and Student Publications

Purpose: To develop a practical risk-stratification framework for unplanned cesarean delivery (CD) among term nulliparous individuals with hypertensive disorders of pregnancy (HDP) undergoing induction of labor (IOL).

Methods: This was a retrospective cohort study at a single tertiary care center (January 2010-March 2025) of nulliparous individuals with singleton gestations diagnosed with HDP undergoing IOL at ≥ 37 + 0 weeks. We excluded multiple gestations, major fetal anomalies, planned CD, or intrauterine fetal death. We included demographic and pregnancy characteristics available prior to induction and evaluated association with unplanned CD. Stepwise backward logistic regression was used to build a model for …

Latent Class Patterns Of Medication Attitudes And Their Correlates Among Older Adults In The United States, Jiaming Liang, Min Ji Kwak, Mona Shirvani, Alexander Testa, Rafael Samper-Ternent, Zhigang Xie, Jack Tsai

Faculty, Staff and Student Publications

No abstract provided.

Development Of A Multiplex Assay For Early Detection Of Pancreatic Cancer In High-Risk Groups, Sheng Pan, Ramesh Karki, Lisa A Lai, Chad J Creighton, Teresa A Brentnall, Randall E Brand, Ru Chen

Faculty, Staff and Student Publications

No abstract provided.

There Is Strength In Numbers: The Case For Another Model Of Cardiometabolic Hfpef, Sadia Ashraf, Hunter A Hidalgo, Romain Harmancey

Faculty, Staff and Student Publications

No abstract provided.

Changes In Internet Search Term Popularity In Elder Mistreatment (2018-2023): Infodemiology Study Of Google Trends Data, Nicholas Sevey, Melvin Livingston, Kristin Lees-Haggerty, Olanike Ojelabi, Randi Campetti, Jason Burnett, Carolyn E Z Pickering, David Hancock, Rachit Sabharwal, Michael Brad Cannell

Faculty, Staff and Student Publications

Background: Elder mistreatment (EM) is a significant public health problem that is frequently underdetected and underreported. Insufficient public recognition and engagement have been hypothesized as one contributor to this underreporting; however, few data sources exist to quantify public awareness or engagement with EM at the population level.

Objective: This study examined relative internet search interest in EM compared with other forms of abuse (child abuse and domestic violence) in the United States using Google Trends data.

Methods: We analyzed Google Trends data to compare the Relative Search Index (RSI) for the terms "elder abuse," "child abuse," and "domestic violence" in …

Stress-Induced Il-6 Response Patterns Amplify The Link Between Daily Negative Affect And Later Depressive Symptoms During Bereavement, E Lydia Wu-Chung, Daniel L Argueta, Robert Suchting, Ryan L Brown, Michelle A Chen, Angie S Leroy, Kyle W Murdock, Cobi J Heijnen, Christopher P Fagundes

Faculty, Staff and Student Publications

Depressive symptoms frequently follow exposure to major life stressors, such as spousal bereavement. However, long-term mental well-being varies considerably. Previously, daily negative affect significantly predicted future depressive symptoms. Higher daily negative affect may signify worse long-term mental health for individuals who also show enhanced inflammatory responses to acute stress, as heightened physiological reactivity to acute stress has been linked with increased susceptibility to depression. Among widow(er)s, we examined whether stress-induced inflammatory responses altered the magnitude of the association between daily negative affect and future depressive symptoms. In exploratory analyses, we examined whether these patterns differed between bereaved and nonbereaved adults. …

Diagnostic Potential For Igm Antibody Detection By The Dpp Syphilis Tnt Assay In Neonates At Risk For Congenital Syphilis, Irene A Stafford, Lierni Ugartemendia Ugalde, Laura M Goetzl, Analuisa Mosqueda, Sabrina Dacosta, Dhammika Gunasekera, Mark Rivieccio, Javan Esfandiari, Konstantin P Lyashchenko

Faculty, Staff and Student Publications

Neonatal IgM antibodies reflect an in utero immune response to Treponema pallidum and may offer added diagnostic value. This study evaluated the test performance of treponemal IgM levels measured by the research-use-only (RUO) Dual Path Platform (DPP) Syphilis TnT point-of-care (POC) assay for congenital syphilis (CS) risk stratification. Conducted from May 2023 to May 2025, this study tested neonatal serum samples from infants born to mothers with syphilis using the DPP Syphilis TnT RUO POC assay, which reports treponemal and nontreponemal IgM levels as relative light units (RLU). Neonates were classified as confirmed proven or highly probable CS, possible …

Genome-Wide Association Study Of Copy Number Variations In Parkinson’S Disease, Zied Landoulsi, Ashwin Ashok Kumar Sreelatha, Nicole Kuznetsov, Claudia Schulte, Dheeraj Reddy Bobbili, Ludovica Montanucci, Costin Leu, Lisa-Marie Niestroj, Emadeldin Hassanin, Cloé Domenighetti, Pierre-Emmanuel Sugier, Milena Radivojkov-Blagojevic, Peter Lichtner, Berta Portugal, Connor Edsall, Jens Krüger, Dena G Hernandez, Cornelis Blauwendraat, George D Mellick, Alexander Zimprich, Walter Pirker, Manuela Tan, Ekaterina Rogaeva, Anthony Lang, Sulev Koks, Pille Taba, Suzanne Lesage, Alexis Brice, Jean-Christophe Corvol, Marie-Christine Chartier-Harlin, Eugenie Mutez, Kathrin Brockmann, Angela B Deutschländer, Georges M Hadjigeorgiou, Efthimos Dardiotis, Leonidas Stefanis, Athina Maria Simitsi, Enza Maria Valente, Simona Petrucci, Letizia Straniero, Anna Zecchinelli, Gianni Pezzoli, Laura Brighina, Carlo Ferrarese, Grazia Annesi, Andrea Quattrone, Monica Gagliardi, Lena F Burbulla, Hirotaka Matsuo, Akiyoshi Nakayama, Nobutaka Hattori, Kenya Nishioka, Sun Ju Chung, Yun Joong Kim, Lukas Pavelka, Pierre Kolber, Bart Pc Van De Warrenburg, Bastiaan R Bloem, Andrew B Singleton, Dan Vitale, Mathias Toft, Lasse Pihlstrom, Leonor Correia Guedes, Joaquim J Ferreira, Soraya Bardien, Jonathan Carr, Eduardo Tolosa, Mario Ezquerra, Pau Pastor, Karin Wirdefeldt, Nancy L Pedersen, Caroline Ran, Andrea C Belin, Andreas Puschmann, Carl E Clarke, Karen E Morrison, Dimitri Krainc, Matt J Farrer, Dennis Lal, Alexis Elbaz, Thomas Gasser, Rejko Krüger, Manu Sharma, Patrick May

Faculty, Staff and Student Publications

We investigated the role of copy number variations (CNVs) in Parkinson's disease (PD) using genotyping data from 10,815 patients (2731 early-onset PD, EOPD) and 8901 controls from the COURAGE-PD consortium. CNVs were analyzed using a sliding window genome-wide association and burden approach. No genome-wide significant CNVs were detected in the overall cohort, but a robust deletion spanning exons 2-6 of PRKN was identified in EOPD cases, validated by MLPA, and replicated in the GP2 dataset (23,089 cases, 18,824 controls). CNV burden was significantly enriched in PD-related genes, primarily driven by PRKN, with the strongest effect observed in EOPD. PRKN CNV …

Predicting Clinically Significant Prostate Cancer With Or Without Digital Rectal Exam And Mri Data Using Claritydx Prostate Models, Robert J Paproski, Adam Kinnaird, M Eric Hyndman, Adrian Fairey, Leonard Marks, Christian P Pavlovich, Sean A Fletcher, Roman Zachoval, Vanda Adamcova, Jiri Stejskal, Armen Aprikian, Christopher J D Wallis, Desmond Pink, Catalina Vasquez, Perrin H Beatty, John D Lewis

Faculty, Staff and Student Publications

This prognostic study created optimized ensembles of calibrated random forest models to predict clinically significant prostate cancer (csPCa, grade group ≥2 PCa) using total prostate-specific antigen (PSA), free PSA, negative biopsy status, and age, with or without DRE and MRI data. Observational data were aggregated from cohorts in six organizations in Canada, the USA, and Czechia. Prostate biopsies were performed between 2009 and 2024. Risk models (ClarityDX Prostate + DRE, ClarityDX Prostate + MRI, and ClarityDX Prostate + MRI + DRE) were derived (training cohorts n = 1626 to 2191) and validated (validation cohorts n = 378 to 1318) from …

Evaluating The Impact Of Vosoritide On Complications Of Achondroplasia, Ravi Savarirayan, Jacqueline T Hecht, Kala Jayaram, Sheetal Ingole, Anne Dee, Julie Hoover-Fong

Faculty, Staff and Student Publications

Purpose: Impaired endochondral bone growth in people with achondroplasia causes complications that impair function, cause pain, require surgery, and contribute to mortality. Rates of complications in participants with achondroplasia enrolled in clinical trials of vosoritide, a targeted treatment, were analyzed and compared with published natural history (NH) rates.

Methods: Prevalence (medical history + new events post-treatment initiation) and incidence (new/worsening events posttreatment initiation) were calculated for complications across 6 clinical trials (2.5-30 μg/kg/day vosoritide) in children with achondroplasia, stratified by age at treatment initiation (< 5 years/≥5 years). Complication-related procedures and mortality rates were examined.

Results: By August 2024, 230 participants received vosoritide (68 aged < 5 years at treatment initiation [exposure, 289.1 person-years]; 162 aged ≥5 years at treatment initiation [exposure, 834.5 person-years]). Prevalence for most complications was consistent with or lower than NH rates. Incidence of leg malalignment; foramen magnum stenosis; spinal stenosis; kyphosis; lordosis; hydrocephalus; ear, nose, and throat complications; and pain was generally lower than NH rates. Foramen magnum decompression frequency was 3.0% overall (5.9% in participants who initiated treatment aged < 2 years). Crude mortality was lower than NH rates.

Conclusion: Vosoritide was not associated …

Prmt5 Inhibition Impairs Fanconi Anemia Pathway-Mediated Homologous Recombination And Enhances The Antitumor Efficacy Of Temozolomide In Glioblastoma, Shumpei Onishi, Sridharan Jayamohan, Ashis Chowdhury, Sarah Rivas, Yoshihiro Otani, Celine Ertekin, Jean-Paul Bryant, Sara A Murphy, Kimberly A Rivera-Caraballo, Stuart Walbridge, Bayu Sisay, Dragan Maric, Abdel Elkahloun, Kory Johnson, Desmond A Brown, John D Heiss, Ashish H Shah, Tae Jin Lee, Sangamesh G Kumbar, Ji Young Yoo, Andrew J Brenner, Balveen Kaur, Gangadhara R Sareddy, Yeshavanth Kumar Banasavadi-Siddegowda

Faculty, Staff and Student Publications

Despite multimodal therapy of surgical resection, radiation, and chemotherapy, glioblastoma patients show a dismal prognosis. Protein Arginine Methyltransferase 5 (PRMT5) is overexpressed in glioblastoma, and its inhibition imparts an anti-tumor effect. Tumor cells invariably develop resistance to Temozolomide (TMZ), the standard chemotherapeutic agent for glioblastoma. However, the mechanistic role of PRMT5 in treatment-resistant glioblastoma is unknown. Patient-derived glioma stem-like cells (GSCs), treated with PRMT5 inhibitor (LLY-283) or transfected with PRMT5-target-specific siRNA, were treated with TMZ and subjected to in vitro functional and mechanistic studies. The intracranial mouse xenograft model was used to test the in vivo antitumor efficacy of combination …

Ftsz Forms Biomolecular Condensates In A Polar-Growing Alphaproteobacterium, Todd A Cameron, Miguel Ángel Robles-Ramos, Lorenzo Suigo, Silvia Zorrilla, William Margolin

Faculty, Staff and Student Publications

The conserved tubulin homolog FtsZ assembles into GTP-dependent protofilaments that organize the bacterial cell division machinery. Purified Escherichia coli FtsZ (FtsZEc) can form biomolecular condensates in the absence of GTP in macromolecular crowding conditions, but FtsZ condensates have not yet been confirmed in vivo. FtsZ from the Alphaproteobacterium Agrobacterium tumefaciens (FtsZAt) localizes to distinct polar foci during growth and contains an intrinsically disordered region much longer than FtsZEc, suggesting a greater tendency to form condensates. Here, we show that purified FtsZAt readily formed dynamic condensates in vitro under molecular crowding conditions, and the addition of GTP induced the formation …

Single-Nucleus Brain Transcriptomics Reveals Microglia Dysfunction In Multiple System Atrophy, Rasmus Rydbirk, Frederik Nørby Friis Sørensen, Jonas Folke, Henriette Haukedal, Andrea Asenjo Martinez, Irene Lisa Vargas, Simone Mcgarry, Oline Chantell Hollmann, Camila Gherardelli, Sofia Sepulveda, Adam T Szafran, Michael A Mancini, Sanne Simone Kaalund, Tomasz Brudek, Lisette Salvesen, Sara Bech, Justyna Okarmus, Peter Kharchenko, Morten Meyer, Claudio Soto, Kristine Freude, Abhisek Mukherjee, Susana Aznar, Konstantin Khodosevich

Faculty, Staff and Student Publications

Multiple system atrophy (MSA) is a rare, age-related neurodegenerative disease that shares clinical and pathological features with Parkinson's disease (PD) but presents a more devastating disease course. To elucidate the distinct cellular pathophysiology, we performed single-nucleus RNA sequencing on postmortem striatal brain tissue from 7 MSA and 12 PD patients, and 10 non-neurological cases. Here, we show significant compositional differences in astroglia and microglia subtypes, while oligodendroglia and neurons are comparable. PD brains show abundant microglia expressing MHC class II HLA haplotypes, indicative of a proinflammatory state, alongside more homeostatic astrocytes. In contrast, MSA lack activated microglia but has more …

Sex-Specific Autosomal Susceptibility Loci In Systemic Sclerosis: A Genome-Wide Association Study, Inmaculada Rodriguez-Martin, Martin Kerick, Carlos Rangel-Peláez, Carlos Rosa-Baez, Gonzalo Borrego-Yaniz, Lourdes Ortiz-Fernández, Alfredo Guillen-Del-Castillo, Carmen P Simeón-Aznar, José Luis Callejas, Oliver Distler, Susanna M Proudman, Mandana Nikpour, Nicolas Hunzelmann, Jeska K De Vries-Bouwstra, Ariane L Herrick, Yannick Allanore, Marta E Alarcón-Riquelme, Lorenzo Beretta, Shervin Assassi, Christopher P Denton, Maureen D Mayes, Javier Martin, Marialbert Acosta-Herrera

Faculty, Staff and Student Publications

Background: Systemic sclerosis is an immune-mediated inflammatory disease with marked sex differences in prevalence and severity. Although genome-wide association studies (GWAS) have advanced the understanding of systemic sclerosis genetics, sex-aware approaches remain scarce. We aimed to address this gap by examining autosomal sex-specific genetic factors in systemic sclerosis.

Methods: Based on a chromosomal definition of sex, we conducted a sex-stratified autosomal meta-analysis of GWAS in systemic sclerosis. We retrieved patient-level and control data from a previous GWAS for systemic sclerosis and newly recruited participants from an international multicentre collaboration (data cutoff June 1, 2024). Adult patients (aged ≥18 years) were …

Engineering Of Genetically Encoded Programmable Calcium Channel Inhibitory Binders, Xiaoxuan Liu, Sher Ali, Tien-Hung Lan, Decheng Wang, Brendan Mckee, Tatsuki Nonomura, Siyao Liu, Feng Zhao, Michael X Zhu, Yun Huang, Qing Deng, Guolin Ma, Yubin Zhou

Faculty, Staff and Student Publications

Store-operated Ca2+ release-activated Ca2+ (CRAC) channels, composed of STIM and ORAI, are essential for immune and developmental processes, and their dysregulation underlies channelopathies such as Stormorken syndrome. Here, we report the engineering of genetically encoded CRAC channel inhibitory binders (CRABs) derived from the ORAI C-terminal tail. Guided by deep mutational scanning, we optimize a membrane-anchored CRAB variant that potently inhibits Ca2+ influx and NFAT signaling, and rescues thrombocytopenia-like phenotypes in a zebrafish model of Stormorken syndrome. To enable tunable inhibition, we further design oligomeric, optogenetic (Opto-CRAB), and chemogenetic (Chemo-CRAB) variants, providing graded and real-time control of CRAC activity. Chemo-CRAB further …

A Rare Case Of Cutaneous Extramedullary Hematopoiesis In Chronic Myeloid Leukemia, Bennett Christie-Nguyen, Hanadi El Achi, Levani Iashvili, Amer Wahed, Brenda Mai, Jacob Armstrong

Faculty, Staff and Student Publications

Cutaneous extramedullary hematopoiesis (CEH) is a rare manifestation of extramedullary hematopoiesis (EMH), a process typically associated with fetal development or myeloproliferative neoplasms. EMH most commonly involves the spleen, liver, and lymph nodes, with CEH being exceedingly rare in chronic myeloid leukemia (CML). Here, we present a 34-year-old Hispanic male with multiple bilateral lower extremity lesions, right buttock and leg pain, fatigue, and splenomegaly, who was found to have chronic-phase CML. Punch biopsy of one of the skin lesions demonstrated dermal infiltration by maturing hematopoietic elements, including granulocytes, megakaryocytes, and erythroid precursors, with fluorescence in situ hybridization (FISH) testing confirming a …

Therapeutic Potential Of Glp-1 Receptor Agonists For Smoking Cessation, Christian S Hendershot, W Kyle Simmons, Manish K Jha, Sherry A Mckee, Luba Yammine

Faculty, Staff and Student Publications

Glucagon-like peptide-1 (GLP-1) therapies are under investigation for a growing number of neuropsychiatric conditions, including substance use disorders. Cigarette smoking accounts for the largest proportion of substance use-related morbidity and mortality, in part reflecting increased risk for cardiometabolic disease among people who smoke. Given modest quit rates with approved smoking cessation therapies, medications with novel mechanisms of action are needed to expand the available monotherapy and combination treatment options. Treatments that prevent post-cessation weight gain could further reduce relapse and cardiometabolic risks following smoking cessation. Preclinical findings show that GLP-1 receptor agonists (GLP-1RA) modulate nicotine reward, reduce nicotine self-administration, and …