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Are Drains After Trauma Splenectomy Associated With Organ Space Surgical Site Infections?, Stephanie Martinez Ugarte, Mokunfayo O Fajemisin, Seokhun Kim, William D Rieger, Renee W Green, Gabrielle E Hatton, Lillian S Kao

Faculty, Staff and Student Publications

Introduction: Left upper quadrant (LUQ) drain use after trauma splenectomy varies, with minimal existing data to guide practice. We aimed to investigate the association of LUQ drains with organ space surgical site infection (OS-SSI) after splenectomy. We hypothesized that LUQ drains after trauma splenectomy are associated with increased odds of OS-SSI.

Patients and methods: A retrospective study of adult blunt trauma patients who underwent splenectomy from 7/2018 to 6/2024 was performed. We excluded patients who survived < 5 days after operation, and those with an intraoperatively identified pancreatic injury. Demographics, surgical details, and drain information were abstracted from the medical record. Inverse probability of treatment weighting (IPTW) was used to balance variables between patients who did and did not receive an LUQ drain after splenectomy. Multivariable logistic regression with IPTW was performed to estimate the association of LUQ drains with OS-SSI.

Results: Of 179 patients, 68% (n = 121) were male, the median age was 38 years (interquartile range 28, 55), and 27% (n = …

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

Faculty, Staff and Student Publications

No abstract provided.

Computational Modeling Meets 3d Bioprinting: Emerging Synergies In Cardiovascular Disease Modeling, Tanmay Mukherjee, Mehdi Salar Amoli, Sarah Rezapourdamanab, Lama Rita El Shammas, Martin L Tomov, Emilio A Mendiola, Vahid Serpooshan, Reza Avazmohammadi

Faculty, Staff and Student Publications

Cardiovascular diseases (CVDs) remain the leading cause of death worldwide, underscoring the need for improved strategies in diagnosis, treatment, and disease modeling. Traditional in vitro models often fall short in replicating human CV physiology, prompting efforts to advance cardiac tissue engineering and computational modeling. Among these, three-dimensional (3D) bioprinting has emerged as a transformative tool, enabling the creation of biomimetic CV constructs that more faithfully replicate native tissue structure and function. However, challenges persist in achieving appropriate mechanical properties and long-term performance of engineered CV constructs. Computational modeling offers powerful solutions to assist with these challenges, providing predictive insights into …

Intravenous Buprenorphine Reversed Opioid-Induced Respiratory Depression Without Precipitating Withdrawal In Emergency Department Patients, Anthony Spadaro, Nicholas Imperato, Jaclyn Scalgione, Cynthia Santos

Faculty, Staff and Student Publications

Objective: Buprenorphine is a high-affinity partial agonist that can displace full opioid agonists and could be used to reverse opioid-induced respiratory depression. There is scant evidence to support the use of buprenorphine in an acute opioid overdose to reverse respiratory depression in the era of high fentanyl prevalence in the drug supply. This is a case series of four patients with signs and symptoms of an opioid overdose who showed clinical improvement after receiving intravenous buprenorphine.

Method: A case series of adult emergency department patients treated at a single urban academic medical center was reviewed by the authors, who determined …

Estrogen As A Therapeutic Agent: Targeting Endotheliopathy And Coagulopathy In Trauma, Niruktha Raghavan, Mira Patel, Bryan A Cotton, Julia Coleman, Donald Jenkins

Faculty, Staff and Student Publications

Background: Traumatic injury remains a leading cause of death, often due to uncontrolled hemorrhage and trauma-induced coagulopathy (TIC). TIC is critically triggered by the endotheliopathy of trauma, involving endothelial cell injury and glycocalyx degradation. Despite conventional advances, the stable casualty rate underscores the urgent need for new precision resuscitation strategies that acknowledge factors like biological sex.

Design: The central hypothesis is that estrogen confers a survival advantage in hormonally active females through a dual action: endothelial cell stabilization (halting glycocalyx shedding) and its inherent procoagulant effect. The analysis assesses the therapeutic potential of both exogenous estrogen and female-derived blood products …

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 …

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 …

Cross-Sectional Associations Of Metabolically Healthy Obesity, Lifestyle Factors, And Steatotic Liver Disease In Adults From The Fels Longitudinal Study, Ariana L Garza, Audrey C Choh, John Blangero, Cici X Bauer, Stefan A Czerwinski, Miryoung Lee

Faculty, Staff and Student Publications

Objective: To examine the associations of metabolic health and obesity phenotypes with liver fat accumulation and hepatic steatosis in adults.

Methods: We analyzed 676 non-Hispanic white adults (18-95 years; 55.8% female) from the Fels Longitudinal Study using a cross-sectional design. Participants were classified into metabolically healthy normal weight (MHNW), metabolically healthy obesity (MHO), metabolically unhealthy normal weight (MUNW), and metabolically unhealthy obesity (MUO) phenotypes. Metabolically unhealthy status was defined as the presence of ≥1 metabolic dysfunction, consistent with prior epidemiological definitions; secondary analyses using ≥2 were also performed. Obesity was defined using DXA-derived body fat percentage. Liver fat (%) was …

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 …

Neuropathological Hallmarks During The Chronic Phase Of Ischemic Stroke In Mice And Humans, Romeesa Khan, Gary Guzman, Trang Do, Patrick Devlin, John Ahn, Chunfeng Tan, Venugopal Reddy Venna, Sean P Marrelli, Haniyeh Koochak, Claudia M Di Gesù, Anthony Flores, Louise D Mccullough, Rodney M Ritzel

Faculty, Staff and Student Publications

Background: Advances in acute stroke care, including endovascular thrombectomy and improved neurocritical management, have increased survival after ischemic stroke. However, stroke remains a leading cause of long-term disability, with many survivors experiencing persistent neurological and cognitive impairments. The chronic neurological consequences of stroke, particularly its potential to accelerate brain aging, remain poorly understood.

Methods: We examined chronic neurobehavioral changes at 2 and 6 months after middle cerebral artery occlusion in male C57Bl/6 mice. Behavioral assessments included the open field test (OFT), novel object recognition test (NORT), fear conditioning (FC), nesting activity, and tail suspension testing. Transcriptomic profiling was performed using …

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 …

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 …

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 …

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 Multidomain Peptide Hydrogel-Liposome Composite For Controlled Release Of A Cyclic Dinucleotide In Oral Cancer, Joseph W R Swain, Andrea H Molina, Gemalene M Sunga, Danielle Chew-Martinez, Neeraja Dharmaraj, Alejandra Cobos Perez, Arghadip Dey, Ephraim J Vázquez-Rosado, Simon Young, Jeffrey D Hartgerink

Faculty, Staff and Student Publications

While immunotherapy is a promising treatment strategy for cancer, the majority of head and neck squamous cell carcinoma (HNSCC) patients treated with single-agent immunotherapy do not respond. Therefore, researchers are investigating combination treatments with immunostimulatory molecules that can maximize anti-tumor responses. Cyclic dinucleotides (CDNs) are STING agonists that hold promise in combination approaches, but they require frequent intratumoral administration when used in both preclinical models of HNSCC and clinical trials. To reduce administration frequency, we have created a peptide hydrogel–liposome composite system, K2-Lip(CDN), for local and prolonged availability of CDN. We investigated the loading limits of cationic liposomes in both …

The Effects Of Orexin Receptor Antagonism During Early Withdrawal In Stimulant Use Disorder: Protocol For A Proof-Of-Concept Study, Heather Webber, Nikky Tran, Rita Blake, Sarah Goldman, Trevor George, Bill Bailey, Robert Suchting, Jin Yoon, Jessica Vincent, Michael Weaver, Joy Schmitz, Scott Lane

Faculty, Staff and Student Publications

Background: Stimulant use disorders (StimUDs), including cocaine and methamphetamine use disorders, remain a major public health concern in the United States with no US Food and Drug Administration (FDA)-approved pharmacological treatments. The early recovery period following stimulant use is marked by sleep disturbances, heightened stress reactivity, and dysregulated reward processing, contributing to high rates of resumption of use. Evidence from animal and human studies supports the orexin neuropeptide system as a promising therapeutic target for minimizing these disruptive mechanisms. Suvorexant, an FDA-approved dual orexin receptor antagonist for insomnia, has previously been shown to improve sleep, reduce stress, and attenuate craving …

Translationally-Relevant Tumor Resection Model For Murine Preclinical Models Of Oral Squamous Cell Carcinoma, Gemalene M Sunga, Alejandra Cobos Perez, Andrea H Molina, Nourhan Hussein, Neeraja Dharmaraj, Andrew Sikora, Simon Young

Faculty, Staff and Student Publications

Currently, the first-line treatment for the most common form of head and neck squamous cell carcinoma (HNSCC), oral cavity squamous cell carcinoma (OSCC), is surgical resection, followed by risk-adapted treatments, such as chemoradiotherapy. However, with the current standard of care and even the emergence of new treatments, such as checkpoint blockade, the overall survival for advanced, recurrent disease remains high, and the prevalence of head and neck cancer is projected to continue to increase in the coming years. Thus, deeper investigation into current standard-of-care modalities, in addition to novel therapeutics, is necessary to translate potential and promising treatment options to …

Comparative Effectiveness Of Radiofrequency Or Microwave Ablation And Chemotherapy For The Treatment Of Large (>5 Cm) Hepatocellular Carcinoma Tumors, Artem Boyev, Nirav Thosani, Putao Cen, Jennifer M Bailey-Lundberg, Julie Rowe, Curtis J Wray

Faculty, Staff and Student Publications

Background and objectives

Treatment of hepatocellular carcinoma (HCC) >5 cm is problematic, as patients are often outside transplantation criteria, and cirrhosis compromises curative resection. The purpose of this study was to evaluate survival following treatment with ablation compared to chemotherapy in large HCC.

Methods

This was a retrospective cohort study of the National Cancer Database (NCDB) Participant User File from 2004 to 2017. Patients with HCC >5 cm in diameter treated with ablation versus chemotherapy alone were compared. Inverse probability-weighted propensity scores were used to model treatment assignments in the Cox proportional hazards model.

Results

A total of 14,783 HCC …

Fatigue Survival And Biomechanical Behavior Of Two-Piece Titanium And Zirconia Dental Implants, Jefferson David Melo De Matos, Guilherme Da Rocha Scalzer Lopes, Nathália De Carvalho Ramos, Mário Alexandre Coelho Sinhoreti, Alexandre Luiz Souto Borges, Daher Antonio Queiroz, Marco Antonio Bottino

Faculty, Staff and Student Publications

Background: Titanium implants are considered the gold standard for oral rehabilitation; however, zirconia implants have emerged as a metal-free alternative with promising esthetic and biological properties. Despite these advantages, limited evidence is available regarding their long-term fatigue behavior and fracture resistance.

Material and methods: In this in vitro experimental study conducted at São Paulo State University (UNESP), Brazil, forty implants were divided into two groups (n = 20): zirconia implants (ZZ) and titanium implants (TZ) (4.1 × 10 mm). Implants were embedded in polyurethane blocks according to ISO 14801:2016 specifications. Monolithic zirconia crowns were fabricated using CAD/CAM technology and cemented …

Nuclear Receptor Subfamily 4 Group A Member 2 Induces A Warburg-Like Effect And Promotes Phospholipids Synthesis In The Mouse Heart, Sadia Ashraf, Dorcas Odogwu, David D Mcpherson, Romain Harmancey

Faculty, Staff and Student Publications

Myocardial metabolic flexibility is critical to ensuring the heart's capacity to maintain contraction and cellular functions under rapidly evolving environmental conditions. Although it is a tightly regulated process, loss of metabolic flexibility is often regarded as a contributing factor to heart failure. This study aims to determine the effects of the early response transcription factor nuclear receptor subfamily 4 group A member 2 (NR4A2) on cardiac metabolism and the resulting impact on left ventricular function. A multiomics approach combining the analysis of global ventricular gene expression, genome-wide NR4A2 binding, and untargeted metabolomics was used to track the molecular effects of …

Multiparametric Mri To Predict Response To Irreversible Electroporation Plus Anti-Pd-1 Immunotherapy In Pancreatic Ductal Adenocarcinoma, Qizhen Cao, Mark D Pagel, Charles V Kingsley, Jingfei Ma, James P Long, Xiaoxia Wen, Seth T Gammon, Jorge Delacerda, Sanaz Javadi, Chun Li

Faculty, Staff and Student Publications

Purpose: To investigate contrast-enhanced T1-weighted MRI and diffusion-weighted magnetic resonance imaging (DWI) for early prediction of tumor response to combined irreversible electroporation (IRE) and anti-PD-1 immunotherapy.

Methods: Murine pancreatic ductal adenocarcinoma (PDAC) cells KRAS* were inoculated into the pancreas of C57BL/6 mice. IRE was performed when tumors became palpable. After IRE, mice received six intraperitoneal injections of anti-PD-1 over 2 weeks. T2-weighted MRI, T1-weighted MRI with macromolecular contrast agent poly(L-glutamic acid)-conjugated gadolinium (PG-Gd), and DWI were performed before and after IRE. Survival was analyzed using Kaplan-Meier curves. Mice surviving at least 100 days without recurrence after IRE were considered complete …

Neutrophil-Microglia Interaction Drives Motor Dysfunction In A Neuromyelitis Optica Model Induced By Subarachnoid Aqp4-Igg, Fangfang Qi, Vanda A Lennon, Shunyi Zhao, Yong Guo, Husheng Ding, Caiyun Liu, Whitney M Bartley, Tingjun Chen, Claudia F Lucchinetti, Long-Jun Wu

Faculty, Staff and Student Publications

Neutrophils and neutrophil extracellular traps (NETs) contribute to early neuromyelitis optica (NMO) histopathology initiated by IgG targeting astrocytic aquaporin-4 (AQP4) water channels. Yet, the mechanisms underlying neutrophil recruitment and their pathogenic roles in disease progression remain unclear. To investigate molecular-cellular events preceding classical complement cascade activation in a mouse NMO model, we continuously infused, via spinal subarachnoid route, a non-complement-activating mouse monoclonal AQP4-IgG. Parenchymal infiltration of netting neutrophils containing C5a ensued with microglial activation and motor impairment but no blood-brain barrier leakage. Motor impairment and neuronal dysfunction both reversed when AQP4-IgG infusion stopped. Two-photon microscopy and electron microscopy-based reconstructions revealed …

Gompertz Growth With A Shared Carrying Capacity Optimally Simulates Primary And Metastatic Tumor Growth Dynamics, Pirmin Schlicke, Preethi Korangath, Xiaoxi Pan, Caner Ercan, Kathleen Gabrielson, Lyndsey Werhane, Yinyin Yuan, Sébastien Benzekry, Robert Ivkov, Heiko Enderling

Faculty, Staff and Student Publications

Background: Cancer is a systemic disease with most deaths attributed to metastatic burden. Primary and metastatic tumors, albeit at different anatomic locations, are interconnected through multiple biological processes. Pre-clinical and clinical observations of growth acceleration of metastases after surgery, or abscopal effects outside the radiation field are widely reported, yet reliably triggering favorable and avoiding unfavorable systemic responses remains an unmet clinical need. Understanding local and systemic tumor interaction dynamics will help guide future treatments.

Methods: We analyze the data of multiple in vivo tumor models. We formalize the systemic interplay of tumors as mathematical differential equation and calibrate parameters …

Structural-Functional Analyses Of The Huntingtin/Hap40 Complex In Drosophila And Humans, Stephen M Farmer, Amanda Solbach, Shiyu Xu, Beatriz Rios, Xin Ye, Amy Gao, Daniela Covarrubias, Yue Yu, Lili Ye, Vicky Chuong, Erin Furr Stimming, Haiqing Zhao, Sheng Zhang

Faculty, Staff and Student Publications

Huntington's disease (HD) is a neurodegenerative disorder caused by an abnormal CAG expansion in the Huntingtin (HTT) gene. Given its simple genetic cause but complex pathogenic mechanisms, interest in targeting HTT for HD treatment is growing, necessitating a clear understanding of HTT regulation. HTT protein primarily exists in a core complex with HAP40, forming a highly ordered structure with two large globular domains connected by a bridge. We previously demonstrated that HAP40 is conserved in

Platelets Cause Microvascular Occlusion And Delayed Neurological Deficits After Subarachnoid Hemorrhage In Mice., Ari Dienel, Sung-Ha Hong, Kiara Torres, Kanako Matsumura, Jose Guzman, Peeyush Thankamani Pandit, Bibek Samal, Harveen Kaur, Samitha Nemirajaiah, Angelica Bernal, H Alex Choi, Louise D Mccullough, Spiros L Blackburn, Jaroslaw Aronowski, Devin W Mcbride

Faculty, Staff and Student Publications

After subarachnoid hemorrhage (SAH), some patients develop delayed neurological deficits (DND). Microthrombi are considered a contributing factor to DND, but clinical trials of antiplatelets had mixed results. Existing research suggests that platelets play a role in the etiology of DND, but no comprehensive study has tested causality between platelets and DND after SAH. Here we hypothesize that after SAH, platelet activation promotes microthrombi formation, occlusion of the brain microvasculature and contributes to DND, and that inhibiting platelet aggregation is a therapeutic strategy. Mice experiencing SAH were administered various interventions. The animals were subjected to stimulation of platelets, platelet depletion, or …

Breast Cancer-Derived Extracellular Vesicle Mir-425-5p (Mir-425) Promotes Brain Metastasis Via Activating Astrocytes Through The Novel Mir-425-Znf24-Ccl8 Signaling Axis, Grace L Wong, Munazza S Khan, Sara Manore, Shivani Bindal, Ravi Singh, Hui-Wen Lo

Faculty, Staff and Student Publications

Mechanisms underlying breast cancer brain metastasis (BCBM) are still not well understood. Here, we identified that BCBM patient serum contained extracellular vesicles (EVs) with high levels of microRNAs (miRNAs)-107 and -425. Levels of miR-107 and miR-425 were elevated in brain metastases, and the elevation was associated with poor patient prognoses. Ectopic expression of miR-107 and miR-425 promoted mammospheres; however, the inhibition of miR-425, but not miR-107, suppressed breast cancer mammosphere formation. We further observed that EVs from miR-425-overexpressing breast cancer cells strongly activated astrocytes whereas their inhibitors abrogated the effect. Conditioned media from miR-425-activated astrocytes promoted mammospheres. To elucidate how …

Associations Between Caregiver-Provider Communication Quality And Unmet Care Needs Among Older Adults, Jiaming Liang, Rafael Samper-Ternent, Brian Downer, Zhigang Xie

Faculty, Staff and Student Publications

BACKGROUND: Unmet care needs (lack of assistance with daily activities) among older adults are common and linked to adverse health outcomes, greater healthcare utilization, and caregiver burden. While effective patient-provider communication is known to improve care quality, less is understood about the role of caregiver-provider communication, particularly across sociodemographic, health, and caregiving contexts. METHODS: We conducted a cross-sectional secondary analysis of pooled 2021–2023 National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC) data, restricted to community-dwelling older adults (65 + years) who received assistance from caregivers due to difficulty with daily activities, and had at least …

Functional And Structural Basis Of A Hypermorphic Trpc3 Variant, Briar Bell, Angela M Jaramillo-Granada, Luis O Romero, Irene A Gutierrez, Venkata K P S Mallampalli, Guizhen Fan, Sameer Varma, Matthew L Baker, Irina I Serysheva, Valeria Vásquez, Julio F Cordero-Morales

Faculty, Staff and Student Publications

Cerebellar ataxias are characterized by impaired motor coordination resulting from neuronal dysfunction within the cerebellum. The mechanisms underlying this pathology and its cerebellar-specific neurodegeneration remain unknown. We uncover how a gain-of-function canonical transient receptor potential member 3 (TRPC3) mutation, coupled with a cerebellum-specific isoform, stabilizes the channel’s open state, resists the leading inhibitor Pyr3, and drives calcium-dependent cell death. Restoring calcium homeostasis by expressing a Purkinje cell calcium pump improves cell viability. Transgenic expression of the TRPC3 hypermorphic variant in Caenorhabditis elegans induces neurodegeneration, confirming its pathogenicity across species. Cryo–electron microscopy and molecular simulations reveal the structural basis for the …