Digital Commons Network^™

Lurasidone For Pediatric Bipolar Disorder: A Systematic Review, Alexia Koukopoulos, Claudia Calderoni, Georgios D Kotzalidis, Tommaso Callovini, Lorenzo Moccia, Silvia Montanari, Gianna Autullo, Alessio Simonetti, Mario Pinto, Giovanni Camardese, Gabriele Sani, Delfina Janiri

Faculty, Staff and Students Publications

Background/Objectives: Lurasidone ((3aR,4S,7R,7aS)-2-{(1R,2R)-2-[4-(1,2-benzisothiazol-3-yl)piperazin-1-ylmethyl]cyclohexylmethyl}hexahydro-4,7-methano-2H-isoindole-1,3-dione) is a second-generation antipsychotic approved for schizophrenia and mood disorders. Adolescents and children with bipolar disorder receive treatments that expose them to weight gain and metabolic syndrome. Lurasidone is relatively free from such side effects, so it may constitute a useful alternative for the treatment of these patients. We focused on the use of lurasidone in children and adolescents with bipolar disorder.

Methods: On 11 June 2025, we used the following strategy on PubMed: lurasidone AND ("bipolar disorder" OR "bipolar depression" OR mania OR manic). We filtered for humans and ages 0-18 years and included …

Mis-Splicing-Derived Neoantigens And Cognate Tcrs In Splicing Factor Mutant Leukemias, Won Jun Kim, Edie I Crosse, Emma De Neef, Inaki Etxeberria, Erich Y Sabio, Eric Wang, Jan Philipp Bewersdorf, Kuan-Ting Lin, Sydney X Lu, Andrea Belleville, Nina Fox, Cynthia Castro, Pu Zhang, Takeshi Fujino, Jennifer Lewis, Jahan Rahman, Beatrice Zhang, Jacob H Winick, Alexander M Lewis, Robert F Stanley, Susan Dewolf, Brigita Meškauskaitė Urben, Meril Takizawa, Tobias Krause, Henrik Molina, Ronan Chaligne, Priya Koppikar, Jeffrey Molldrem, Mathieu Gigoux, Taha Merghoub, Anthony Daniyan, Smita S Chandran, Benjamin D Greenbaum, Christopher A Klebanoff, Robert K Bradley, Omar Abdel-Wahab

Faculty, Staff and Student Publications

Mutations in RNA splicing factors are prevalent across cancers and generate recurrently mis-spliced mRNA isoforms. Here we identified a series of bona fide neoantigens translated from highly stereotyped splicing alterations promoted by neomorphic, leukemia-associated somatic splicing machinery mutations. We utilized feature-barcoded peptide-MHC dextramers to isolate neoantigen-reactive T cell receptors (TCRs) from healthy donors, patients with active myeloid malignancy, and following curative allogeneic stem cell transplant. Neoantigen-reactive CD8+ T cells were present in the blood of patients with active cancer and had a distinct phenotype from virus-reactive T cells with evidence of impaired cytotoxic function. T cells engineered with TCRs recognizing …

Anti-Transforming Growth Factor-Β Treatment Shows Increased Bone Mass And Strength In A Novel Mouse Model For Osteogenesis Imperfecta Type I, Ellen Busschers, Yuqing Chen-Everson, Mary Adeyeye, I-Wen Song, Emily Busse, Alexis Castellon, Oscar Ruiz, Nicole Meyers, Yangjin Bae, Catherine Ambrose, Brendan Lee

Faculty, Staff and Students Publications

Anti-transforming growth factor beta (TGF-β) is a promising approach for the treatment of osteogenesis imperfecta (OI). To date, preclinical and clinical studies for the use of anti-TGF-β therapy have focused on moderate to severe OI caused by qualitative defects in collagen. However, the majority of OI patients are represented by type I OI. Mutations resulting in the haploinsufficiency of type I collagen is the cause of OI type I in the majority of patients. To study the effect of anti-TGF-β therapy in type I OI, we generated a novel mouse model for OI type I. CMV-CRE mice were crossed to …

Cholesterol Metabolism Regulated By Camkk2-Creb Signaling Promotes Castration-Resistant Prostate Cancer, Chenchu Lin, Thomas L Pulliam, Jenny J Han, Jiaqian Xu, Carlos Vera Recio, Sandi R Wilkenfeld, Yan Shi, Manoj Kushwaha, Sarah Bench, Eduardo Ruiz, Sanjanaa Senthilkumar, Jayasurya Dileep, Peter D A Shepherd, Nora M Navone, Albert R Klekers, Elizabeth M Whitley, Michael M Ittmann, Livia S Eberlin, Wenyi Wang, Daniel E Frigo

Faculty, Staff and Student Publications

Castration-resistant prostate cancer (CRPC) remains an incurable disease in need of improved treatments. CAMKK2 is an emerging therapeutic target whose oncogenic effects in prostate cancer have, to date, been largely attributed to its activation of AMP-activated protein kinase (AMPK). Here, we demonstrate that CAMKK2 promotes prostate cancer growth through an alternative downstream pathway involving CAMKI and CREB. Unbiased transcriptomics identify CREB-mediated transcription as a CAMKK2-regulated process, findings that we validate using diverse molecular, genetic, and pharmacological approaches in vitro and in vivo. CAMKK2 promotes CREB phosphorylation/activation through CAMKIα independently of AMPK, CAMKIV, or other CAMKI isoforms. Functionally, the CREB family …

Modeling Reemergence Of Vaccine-Eliminated Infectious Diseases Under Declining Vaccination In The Us, Mathew V Kiang, Kate M Bubar, Yvonne Maldonado, Peter J Hotez, Nathan C Lo

Faculty, Staff and Students Publications

Importance: Widespread childhood vaccination has eliminated many infectious diseases in the US. However, vaccination rates are declining, and there are ongoing policy debates to reduce the childhood vaccine schedule, which may risk reemergence of previously eliminated infectious diseases.

Objective: To estimate the number of cases and complications in the US under scenarios of declining childhood vaccination for measles, rubella, poliomyelitis, and diphtheria.

Design, setting, and participants: A simulation model was used to assess the importation and dynamic spread of vaccine-preventable infectious diseases across 50 US states and the District of Columbia. The model was parameterized with data on area-specific estimates …

Multiscale Modeling Of Drug-Induced Liver Injury From Organ To Lobule, Alon Malka-Markovitz, Stelian Camara Dit Pinto, Mohammed Cherkaoui, Steven M Levine, Sharmila Anandasabapathy, Gagan K Sood, Sadhna Dhingra, Gao Yujia, John M Vierling, Nicolas R Gallo

Center for Medical Ethics and Health Policy Staff Publications

Drug-induced liver injury poses significant challenges in drug development and in clinical care. This study builds on prior work developing a Human Liver Virtual Twin by creating a Multiscale Computational Fluid Dynamics framework that integrates patient-specific anatomical data to predict acetaminophen-induced liver injury as a demonstration of its capability. The model bridges vascular, lobular, and cellular scales to simulate dynamic blood flow, drug transport, and injury mechanisms that accurately reflect clinically observed spatial heterogeneity. Results demonstrate accurate blood flow dynamics, predictions of hepatocellular damage, and a scalable framework for studying spatial heterogeneity applicable to other hepatic pathologies. This work establishes …

Detecting Early Changes In Cartilage Collagen And Proteoglycans Distribution Gradients In Mice Harboring The R992c Collagen Ii Mutant Using 2d Correlation Infrared Spectroscopy, Jolanta Fertala, Andrzej Steplewski, Andrzej Fertala

Department of Orthopaedic Surgery Faculty Papers

Collagen II is a vital structural component in developing bones and mature cartilage. Muta- tions in this protein cause spondyloepiphyseal dysplasia, a disease characterized primarily by altered skeletal growth and manifesting with a range of phenotypes, from lethal to mild. This study examined transgenic mice harboring the R992C (p.R1124C) substitution in colla- gen II. Previous research demonstrated significant growth abnormalities and disorganized growth plate structure in these mice, and histological signs of osteoarthritic changes in the knee joints of 9-month-old mice with the R992C mutation. Our study focuses on detecting early structural changes in the articular cartilage that occur before …

Evaluation And Validation Of 3d-Printed Anatomical Urinary System Model And Virtual Reality Rirs Simulators In Rirs Training: A Comparative Study, Mehmet Ezer, Tahsi̇n Batuhan Aydoğan, Lazaros Tzelves, Andreas Skolarikos, Mehmet Uslu, Kemal Sarica, Emre Huri̇

Turkish Journal of Medical Sciences

Background/aim: This study evaluates the use of a 3D-printed anatomical urinary system model (3D-AUSM) and a Virtual Reality RIRS Simulator (VRRS), for training in RIRS, based on real user feedback.

Materials and methods: The 3D-AUSM was created using cadaver CT and MRI scans, and the data was transferred to a VR environment for simulation. A total of 43 inexperienced urology trainees participated in the theoretical phase of the RIRS training program. Of these, 32 trainees (Group T) who passed a proficiency exam proceeded to the hands-on training phase with the 3D-AUSM and VRRS models. Additionally, 17 experienced surgeons (Group S) …

Protocol For Assessing Mobilization Of Peritoneal B Cells To The Pre-Metastatic Omentum In An Orthotopic Mouse Model Of Ovarian Cancer, Wonjae Lee, Hironari Akasaka, Honami Naora

Faculty, Staff and Student Publications

The omentum is a visceral adipose tissue that undergoes dynamic immunological changes prior to and following metastasis. Here, we present a protocol for assessing the mobilization of peritoneal B cells to the pre-metastatic omentum in a mouse ovarian cancer model. We describe steps for isolation and adoptive transfer of peritoneal donor B cells and their detection in the omentum of recipient mice. This protocol could be utilized to study the mobilization of peritoneal B cells to the omentum in other pathological contexts. For complete details on the use and execution of this protocol, please refer to Lee et al.

Protocol For Establishing Genetically Engineered Murine Lung Organoids Mimicking Cell Plasticity And Regeneration, Bongjun Kim, Jae-Il Park

Faculty, Staff and Student Publications

Lung endothelial cells (LuECs) play crucial roles in lung regeneration and support lung organoids (LOs). However, detailed guidelines for LO culture using LuECs have not been reported yet. Here, we present an efficient protocol for generating and culturing murine LOs that mimic regeneration. We describe steps for the isolation of LuECs and lung epithelial cells, followed by LO culture. We also describe how to establish genetically engineered LOs using viral transduction. For complete details on the use and execution of this protocol, please refer to Kim et al.

Janus Kinase Inhibitors In Localized Scleroderma: A Systematic Literature Review, Seher Şener, Yusuf Zi̇ya Şener, Ezgi̇ Deni̇z Batu, Alper Sari, Ali̇ Akdoğan

Turkish Journal of Medical Sciences

Background/aim: Reports on the use of Janus kinase (JAK) inhibitors in the treatment of localized scleroderma are increasing in the literature. In this review, we examined the published studies regarding the use of JAK inhibitors in patients with localized scleroderma.

Materials and methods: We searched MEDLINE and Scopus for articles on patients with localized scleroderma treated with JAK inhibitors. The search included articles from the inception of these databases through August 1st, 2024.

Results: Our literature search showed 11 articles describing 17 patients with localized scleroderma treated with JAK inhibitors. Generalized morphea (47.1%) was the most common type of localized …

Forensic Identification Using Airdna: A Preliminary Study On The Collection, Isolation, Amplification And Sequencing Of Human Dna From Air Samples, Sitki Tiplamaz, Zehra Ömeroğlu Ulu, Bestami̇ Çolak, Hizir Asliyüksek, Fi̇kretti̇n Şahi̇n

Turkish Journal of Medical Sciences

Background/aim: Humans continually release skin cells and DNA fragments into the air. This DNA can either remain airborne or drop onto surfaces as indoor dust. This study investigates the collection, isolation, amplification, and sequencing of human DNA from air samples, focusing on both nuclear DNA and mitochondrial DNA.

Materials and methods: This study was conducted in a 15 m3 room and a meeting room, where air samples were systematically collected and filtered using a vacuum device equipped with various sterile filters. The rigorous protocols were implemented to prevent contamination throughout the process. Thirteen air samples were processed in this research, …

Administration Of Adipose Tissue-Derived Mesenchymal Stem Cells And Bone Marrow-Derived Mesenchymal Stem Cells In Anosmic Mice, Burak Hazir, Alper Ceylan, Emi̇n Ümi̇t Bağriaçik, Duygu Dayanir, Betül Öğüt, Ni̇han Örüklü, Mücahi̇t Yalçin, Berkay Şi̇mşek, Muammer Meli̇h Şahi̇n

Turkish Journal of Medical Sciences

Background/aim: Anosmia, a serious condition that affects the sense of smell, has no universally agreed-upon treatment. Adult stem cells are considered a potential option for treating anosmia. This study aims to evaluate the efficacy of mesenchymal stem cells derived from different tissues in an anosmic mouse model induced by 3-methylindole (3-MI).

Materials and methods: In our study, 36 mice with 3-MI-induced anosmia were divided into subgroups. Anosmia was confirmed by performing a food-finding test (FFT) in each group. Intranasal phosphate-buffered saline was administered to the first group, adipose tissue-derived mesenchymal stem cells (ADSCs) to the second group, and bone marrow-derived …

Primary Mouse Choroidal Endothelial Cell Culture, Qiuhua Yang, Yongfeng Cai, Qian Ma, Yuqing Huo

Faculty, Staff and Students Publications

The study of choroidal endothelial cells is essential for understanding the pathological mechanisms underlying choroidal neovascularization and other vision-threatening disorders. Traditional methods for isolating and culturing primary endothelial cells often yield mixed populations or require specialized equipment, limiting their widespread use. Here, we present a straightforward protocol for isolating and culturing primary mouse choroidal endothelial cells. This protocol involves enzymatic digestion of choroidal tissue, magnetic-activated cell sorting (MACS) to enrich CD31+ endothelial cells, and optimized culture conditions to promote cell proliferation and maintain endothelial phenotype. The protocol is strategic, reproducible, and requires minimal specialized equipment, making it accessible for researchers …

Mucin4 (Muc4) Antibody Labeled With An Nir Dye Brightly Targets Pancreatic Cancer Liver Metastases And Peritoneal Carcinomatosis, Sunidhi Jaiswal, Siamak Amirfakhri, Javier Bravo, Keita Kobayashi, Abhijit Aithal, Sumbal Talib, Kavita Mallya, Maneesh Jain, Aaron M. Mohs, Robert M. Hoffman, Surinder K. Batra, Michael Bouvet

Journal Articles: Biochemistry & Molecular Biology

BACKGROUND/OBJECTIVES: Pancreatic cancer is the fourth leading cause of deaths related to cancer. It is a highly aggressive malignancy and often metastasizes quickly to other parts of the body and organs. The most effective cure is surgical resection, which also is limited by tumor identification and clear tumor margin visualization. Previously, we used MUC4 antibodies labeled with IRDye800CW (anti-MUC4-IR800) to target primary human pancreatic cancer in orthotopic cell line mouse models.

METHODS: In the present study, we established a pancreatic cancer liver metastasis mouse model by implanting a tumor fragment in the liver and a peritoneal carcinomatosis mouse model by …

Integrating Endocannabinoid Signaling, Cck Interneurons, And Hippocampal Circuit Dynamics In Behaving Animals, Shreya Malhotra, Florian Donneger, Jordan S Farrell, Barna Dudok, Attila Losonczy, Ivan Soltesz

Faculty, Staff and Students Publications

The brain's endocannabinoid signaling system modulates a diverse range of physiological phenomena and is also involved in various psychiatric and neurological disorders. The basic components of the molecular machinery underlying endocannabinoid-mediated synaptic signaling have been known for decades. However, limitations associated with the short-lived nature of endocannabinoid lipid signals had made it challenging to determine the spatiotemporal specificity and dynamics of endocannabinoid signaling in vivo. Here, we discuss how novel technologies have recently enabled unprecedented insights into endocannabinoid signaling taking place at specific synapses in behaving animals. In this review, we primarily focus on cannabinoid-sensitive inhibition in the hippocampus in …

Microglial Phagocytosis In Epilepsy: Mechanisms And Impact, Abhijeet S Barath, Long-Jun Wu

The Brown Foundation: Institute of Molecular Medicine

Microglia are resident immune cells critical in maintaining brain homeostasis via their surveillance and phagocytosis function. Under disease contexts such as seizures and epilepsy, microglial phagocytic signalling is activated in response to both inflammatory and non-inflammatory cell death. This process involves a range of well-characterized 'find me' and 'eat me' signals, phagocytic receptors, and less well-characterized intracellular signalling pathways. In addition, epigenetic and transcriptional regulators orchestrate microglial responses to seizures, including the integration of phagocytic and inflammatory pathways. Interestingly, although inhibiting phagocytosis has been shown to improve neuronal survival and cognitive performance after seizures, it paradoxically increases the risk of …

Btp2 Restricts Tulane Virus And Human Norovirus Replication Independent Of Store-Operated Calcium Entry, Francesca J Scribano, J Thomas Gebert, Kristen A Engevik, Nicole M Hayes, Jorge Villanueva, Son Pham, Soni Kaundal, Janam J Dave, B V Venkataram Prasad, Mary K Estes, Sasirekha Ramani, Joseph M Hyser

Faculty, Staff and Students Publications

Human norovirus is the leading cause of viral gastroenteritis across all age groups. While there is a need for human norovirus antivirals, therapeutic development has been hindered by a lack of cell culture systems and animal models of infection. Surrogate viruses, such as Tulane virus (TV), have provided tractable systems to screen potential antiviral compounds. Our previous work demonstrated that TV encodes a viral ion channel, which dysregulates cytosolic calcium signaling. We set out to investigate whether host pathways triggered by viral ion channel activity, including store-operated calcium entry (SOCE), play a role in virus replication. Using pharmacologic inhibitors and …

An Evaluation Of The Monospot Test To Diagnose Epstein-Barr Virus Associated Infectious Mononucleosis (Ebv-Im), Patrick Naughton

ORBioM (Open Research BioSciences Meeting)

/="/">/="/">

Abstract

Aim

To calculate the performance characteristics of the Clearview^® IM II Monospot [heterophile antibody (HA) test] to determine Infectious Mononucleosis associated with Epstein-Barr Virus (EBV-IM) in clinically suspect patients.

Methods

The laboratory results of 420 patients tested for HAs over a two-year period (2018-2019) in a single testing centre in Ireland were analysed. A novel multivariant test (reference) model was designed to determine true positive and negative EBV-IM cases. A cohort of 50 Monospot results were compared against this reference model and the test’s performance characteristics determined.

Results

The Monospot test proved reasonably specific but insensitive …

Beyond The Genome: The Racialized Exposome, Flourishing, And Stress Biology In African Americans, A Non-Exhaustive Review, Enye Washington

University Honors Theses

Racial health disparities remain an enduring challenge in the United States, disproportionately impacting African American communities through higher rates of chronic disease and premature mortality. This non-exhaustive literature explores how the racialized exposome - a term denoting the totality of social, environmental, and structural stressors rooted in systemic racism - biologically embeds itself via stress-responsive pathways. Specifically, it examines the interaction between racial stress, flourishing, and key biological markers, including allostatic load and telomere length, considering the gut-brain axis. The review highlights robust evidence that chronic exposure to racial discrimination and structural adversity contributes to multisystem dysregulation and accelerated cellular …

The Tumor Suppressor Hnrnpk Induces P53-Dependent Nucleolar Stress To Drive Ribosomopathies, Pedro Aguilar-Garrido, María Velasco-Estévez, Miguel Ángel Navarro-Aguadero, Álvaro Otero-Sobrino, Marta Ibáñez-Navarro, Miguel Ángel Marugal, María Hernández-Sánchez, Prerna Malaney, Ashley Rodriguez, Oscar Benitez, Xiaroui Zhang, Marisa Jl Aitken, Alejandra Ortiz-Ruiz, Diego Megías, Manuel Pérez, Gadea Mata, Jesús Gomez, Miguel Lafarga, Orlando Domínguez, Osvaldo Graña-Castro, Eduardo Caleiras, Pilar Ximénez-Embun, Marta Isasa, Paloma Jimena De Andres, Sandra Rodríguez-Perales, Raúl Torres-Ruiz, Enrique Revilla, Rosa María García-Martín, Daniel Azorín, Josune Zubicaray, Julián Sevilla, Oleksandra Sirozh, Vanesa Lafarga, Joaquín Martínez-López, Sean M Post, Miguel Gallardo

Faculty, Staff and Student Publications

The nucleolus is a membraneless organelle and an excellent stress sensor. Any changes in its architecture or composition lead to nucleolar stress, resulting in cell cycle arrest and interruption of ribosomal activity, critical factors in aging and cancer. In this study, we identified and described the pivotal role of the RNA-binding protein HNRNPK in ribosome and nucleolar dynamics. We developed an in vitro model of endogenous HNRNPK overexpression and an in vivo mouse model of ubiquitous HNRNPK overexpression. These models showed disruptions in translation as the HNRNPK overexpression caused alterations in the nucleolar structure, resulting in p53-dependent nucleolar stress, cell …

Advancing Novel Contrast Agents For Applications In Fluorescence-Guided Neurosurgery Using Fluorescence Cryotomography, Augustino Vittorio Scorzo

Dartmouth College Ph.D Dissertations

Fluorescence guided surgery (FGS) is an emerging surgical technique that aims to help surgeons identify tissue types to assist in surgical decision making - ideally providing “cut-by-color” guidance. A primary application for this approach is the identification of tumor tissue to achieve more accurate and complete tumor removal while simultaneously minimizing damage to surrounding normal tissue. The cornerstone of tumor visualization for FGS is the administration of fluorescent contrast agents, or in some cases metabolic precursors, designed to accumulate specifically in tumor tissue, and a wide range of agents that use different targeting mechanisms are currently under investigation. Although these …

The Impact Of Type 2 Diabetes Mellitus On The Severity Of Alzheimer's Disease In Hispanic Populations In The Rio Grande Valley: A Pilot Retrospective Chart Review, Maria Camila Gonzalez Tovar, Daniel Salinas, Kelsey Baker

School of Medicine Publications

Background: Alzheimer's disease (AD) is becoming more prevalent worldwide, leading to a growing demand to understand the impact of risk factors on disease progression. Notably, type 2 diabetes mellitus (DM) has emerged as a significant risk factor for the development of AD, given the pathophysiological role of insulin resistance in cognitive impairment. In particular, the impact of type 2 DM on AD development and severity may be heightened in Hispanic populations due to the high prevalence of both conditions in this community. Here, we sought to understand the role of type 2 DM in AD severity in a Hispanic population …

Type I Interferon Protects Against Bone Loss In Periodontitis By Mitigating An Interleukin (Il)-17-Neutrophil Axis, Jinmei Zhang, Qiong Ding, Angela X Wang, Maoxuan Lin, Ning Yu, Kevin Moss, Megumi A Williamson, Di Miao, Julie T Marchesan, Erliang Zeng, Wei Shi, Hongli Sun, Yu Leo Lei, Shaoping Zhang

Faculty, Staff and Student Publications

Type I interferons (IFNs-I), a group of pleiotropic cytokines, critically modulate host response in various inflammatory diseases. However, the role of the IFN-I pathway in periodontitis remains largely unknown. In this report, we describe that the IFN-β levels in the gingival crevicular fluid of human subjects were negatively associated with periodontitis and clinical gingival inflammation. Disruption of IFN-I signaling worsened alveolar bone resorption in a ligature-induced periodontitis murine model. Deficiency of the IFN-I pathway resulted in an exaggerated inflammatory response in myeloid cells and drastically increased the interleukin-17 (IL-17)-mediated neutrophil recruitment in the gingiva. We further identified that the myeloid …

Virus Against Cancer: Paradigm-Shifting Biological Concepts, Dong Ho Shin, Marta M Alonso, Candelaria Gomez-Manzano, Juan Fueyo

Faculty, Staff and Student Publications

Purpose of review: Virotherapy has emerged as a promising approach to cancer treatment. Over the past two decades, early-phase clinical trials have demonstrated the safety and promising efficacy of virotherapy in subsets of cancer patients. However, a significant knowledge gap needs to be filled to propel the field further and achieve substantial anti-cancer benefits for more than the current 10-20% of treated patients. This article reviews the most relevant current challenges in cancer virotherapy.

Recent findings: Recent clinical observations suggest that patients who respond to virotherapy experience a shift in their immune response from an initial or concomitant response against …

Enhancing Neuronal Viability: The Protective Role Of 10% Human Cerebrospinal Fluid In Primary Neuronal Cultures, Vineet Arora, Alicia Bernhardt, Alessandro Naopli, Mijail Serruya

Farber Institute for Neuroscience Faculty Papers

Human cerebrospinal fluid (hCSF) is a physiologically rich medium containing neurotrophic factors, signaling molecules, and essential metabolites that support neuronal development, survival, and function. While its neuroprotective properties have been demonstrated in organotypic brain slices and human iPSC-derived models, its application in primary rodent cortical neuron cultures-a foundational system for studying synaptic development and neurodegeneration-remains underexplored. In this study, we systematically evaluated the effects of hCSF supplementation on neuronal viability in primary cortical cultures derived from embryonic day 18 (E18) rat embryos. To determine the optimal concentration, we tested a range of media:hCSF ratios and identified 90:10 (i.e., 10% hCSF) …

Integrated Metabolomics And Spatial Transcriptomics Of Cystic Pancreatic Cancer Precursors Reveals Dysregulated Polyamine Metabolism As A Biomarker Of Progression, Ricardo A León-Letelier, Yihui Chen, Rongzhang Dou, Ehsan Irajizad, Michele T Yip-Schneider, Ranran Wu, Rahmah Ejaz, Hamid K Rudsari, Yaxi Li, Rachelle Spencer, Riccardo Ballarò, Jody Vykoukal, Mark Hurd, Jennifer B Dennison, Kim-Anh Do, Anirban Maitra, Jianjun Zhang, Samir Hanash, C Max Schmidt, Johannes F Fahrmann

Faculty, Staff and Student Publications

Purpose: We conducted metabolomics and spatial cell transcriptomics of intraductal papillary mucinous neoplasms (IPMN), recognized pancreatic cancer precursors, to identify oncometabolites that inform upon risk of malignancy of IPMNs.

Experimental design: Untargeted metabolomic analyses were performed on cystic fluid from 125 patients with low-grade (LG) dysplasia or high-grade (HG) dysplasia with/without concurrent pancreatic ductal adenocarcinoma (PDAC; IPMN/PDAC). Predictive performance of individual metabolites for identifying HG or PDAC/IPMN was determined and compared with CA19-9 performance. Data were intersected with metabolic profiles of resected IPMN tissues and murine Kras;Gnas IPMN cell lines as well as spatial and single-cell transcriptomics of IPMNs.

Results: …

Comparative Effects Of Combustible Cigarette Versus Electronic Cigarette Exposures On Kras Mutant Lung Cancer Promotion, Walter V Velasco, Maria T Grimaldo, Nastaran Karimi, Michael J Clowers, Avantika Krishna, Ranran Wu, Rahmah Ejaz, Bo Yuan, Segundo Del Aguila, Iman Bouchelkia, Javier Eduardo Moreno Barragan, Katherine E Larsen, Yasmina Rezai, Farbod Khalaj, Kyler Mitra, Carlos Reyna Rodriguez, Ricardo Millares, Angelica Baca De Anda, Susana Castro-Pando, Umesh C Karandikar, Joseph F Petrosino, Florencia Mcallister, Humam Kadara, Edwin J Ostrin, Johannes F Fahrmann, Kristi Louise Hoffman, Seyed Javad Moghaddam

Center for Medical Ethics and Health Policy Staff Publications

Despite the emerging public health concern related to the use of electronic cigarette vapors (ECV), its impact on lung cancer is poorly understood. We assessed the effect of ECV on lung tumorigenesis in a mouse model of lung adenocarcinoma. Mice were exposed to either room air, combustible cigarette smoke (CCS), or ECV 2 hours daily for 8 weeks at which lung samples were harvested and studied for different outcomes. We found that CCS, but not ECV, led to a significant increase in tumor burden. Immunophenotyping of both CCS- and ECV-exposed lungs displayed pronounced pro-tumor immunosuppressive phenotypes, characterized by significantly decreased …

Sensing Protein Structural Transitions With Microfluidic Modulation Infrared Spectroscopy, Lathan Lucas, Phoebe S Tsoi, Ananya Nair, Allan Chris M Ferreon, Josephine C Ferreon

Faculty, Staff and Students Publications

Microfluidic modulation spectroscopy-infrared (MMS) offers a label-free, high-sensitivity approach for quantifying changes in protein secondary structures under native solution conditions. MMS subtracts the solvent backgrounds from sample signals by alternately flowing proteins and matched buffers through a microfluidic chamber, yielding clear amide I spectra from microliter volumes. In this study, we validated MMS on canonical globular proteins, bovine serum albumin, mCherry, and lysozyme, demonstrating accurate detection and resolution of α-helix, β-sheet, and mixed-fold structures. Applying MMS to the intrinsically disordered protein Tau, we detected environment-driven shifts in transient conformers: both the acidic (pH 2.5) and alkaline (pH 10) conditions increased …

Preoperative Dialysis Dose And Postoperative Outcomes In Patients Receiving Maintenance Hemodialysis, Vikram Fielding-Singh, Matthew W Vanneman, Arden M Morris, Wolfgang C Winkelmayer, Louise Y Sun, Pavel S Roshanov, Maria Montez-Rath, Glenn M Chertow, Eugene Lin

Faculty, Staff and Students Publications

Background: Little is known about preoperative hemodialysis dosing for patients with end-stage kidney disease. We assessed whether changes in preoperative hemodialysis dose (compared to and controlling for baseline dose) are associated with postoperative mortality in patients receiving maintenance hemodialysis.

Methods: We identified fee-for-service Medicare beneficiaries receiving hemodialysis for end-stage kidney disease who underwent surgical procedures between January 1, 2011, and November 30, 2020. Follow-up ended December 31, 2020. The primary exposure was preoperative change in Kt/Vurea, defined as the difference between the Kt/Vurea in the hemodialysis session proximal to the procedure and the mean Kt/Vurea for the preceding 180 days. …