Biomedical Informatics Commons^™

Outcomes Of Adult Patients With Newly Diagnosed Idh-Mutated Aml Treated With Intensive Chemotherapy And Venetoclax, Jennifer Croden, Wei-Ying Jen, Jennifer Marvin-Peek, Lianchun Xiao, Ian M Bouligny, Sanam Loghavi, Gautam Borthakur, Naval G Daver, Hussein A Abbas, Koichi Takahashi, Koji Sasaki, Naveen Pemmaraju, Nicholas J Short, Danielle Hammond, Elias Jabbour, Lucia Masarova, Kelly S Chien, Ghayas C Issa, Guillermo Montalban-Bravo, Musa Yilmaz, Abhishek Maiti, Yesid Alvarado-Valero, Guillermo Garcia-Manero, Farhad Ravandi, Marina Y Konopleva, Hagop M Kantarjian, Tapan M Kadia, Courtney D Dinardo

Faculty, Staff and Student Publications

No abstract provided.

From Nociception In Aneural Animals To Human Suffering: Toward A Comparative Biology Of Pain, Edgar T Walters

Faculty, Staff and Student Publications

Pain is a core feature of human life, but systematic comparisons of this biological trait across taxa have been rare. A broadly accepted definition based on human experience emphasizes dual features of pain: a sensory (discriminative) component for sensing and monitoring tissue injury, and an affective (emotional) component to motivate avoidance of tissue distress. Conscious pain is coupled to unconscious nociception (detection of incipient or existing injury). This Review considers nociception and pain across phyla within a comparative framework, addressing basic questions about evolutionary origins, mechanisms and functions of pain. The occurrence of adaptive cellular responses to injury in virtually …

Phosphorylation At Serine 214 Correlates With Tau Seeding Activity In An Age-Dependent Manner In Two Mouse Models For Tauopathies And Is Required For Tau Transsynaptic Propagation, Pablo Martinez, Nur Jury-Garfe, Henika Patel, Yanwen You, Abigail Perkins, Yingjian You, Audrey Lee-Gosselin, Ruben Vidal, Cristian A Lasagna-Reeves

Faculty, Staff and Students Publications

Background

Tau aggregation and propagation are hallmark features of Alzheimer's disease and related tauopathies. The molecular identity and post-translational modifications that contribute to tau seeding activity remain incompletely understood.

Objective

To characterize the temporal dynamics of tau seeding activity and identify specific phosphorylated tau species associated with tau propagation in vivo.

Methods

We profiled tau seeding activity using a FRET-based biosensor cell line and correlated it with the abundance of phospho- and conformational tau species in two transgenic mouse models of tauopathy (P301S-1N4R and P301S-0N4R). Immunohistochemistry and subcellular fractionation were used to examine the spatial distribution of tau species. Functional …

Associations Of High Attenuation Area-Related Proteomic Biomarkers With Fibrotic Or Subpleural Interstitial Lung Abnormalities, John S Kim, Catherine L Debban, Daniel E Guzman, Riley T Hannan, Mary Salvatore, Claire Mcgroder, David Zhang, Anna J Podolanczuk, Daniel A Duprez, Shwu-Fan Ma, Yong Huang, Jeffrey M Sturek, Stephen S Rich, Jerome I Rotter, Rajat Deo, Ruth F Dubin, Janelle Vu Pugashetti, Jennifer M Wang, Meilan K Han, Justin M Oldham, Imre Noth, Prescott G Woodruff, Victor E Ortega, Julie C Fanburg-Smith, Edward B Stelow, Christopher A Moskaluk, Eric A Hoffman, Christine Kim Garcia, Russell P Bowler, Peter Ganz, R Graham Barr, Ani Manichaikul

Faculty, Staff and Student Publications

No abstract provided.

Picalm Alzheimer’S Risk Allele Causes Aberrant Lipid Droplets In Microglia, Alena Kozlova, Siwei Zhang, Ari Sudwarts, Hanwen Zhang, Stanislau Smirnou, Seul Kee Byeon, Christina Thapa, Xiaotong Sun, Kimberley Stephenson, Xiaojie Zhao, Brendan Jamison, Moorthi Ponnusamy, Xin He, Julie A Schneider, Akhilesh Pandey, David A Bennett, Zhiping P Pang, Alan R Sanders, Hugo J Bellen, Gopal Thinakaran, Jubao Duan

Faculty, Staff and Students Publications

Despite genome-wide association studies (GWAS) of late-onset Alzheimer’s disease (LOAD) having identified many genetic risk loci1–3, the underlying disease mechanisms remain largely unclear. Determining causal disease variants and their LOAD-relevant cellular phenotypes has been a challenge. Here, using our approach for identifying functional GWAS risk variants showing allele-specific open chromatin, we systematically identified putative causal LOAD-risk variants in human induced pluripotent stem (iPS)-cell-derived neurons, astrocytes and microglia, and linked a PICALM LOAD-risk allele to a microglial-specific role of PICALM in lipid droplet (LD) accumulation. Allele-specific open-chromatin mapping revealed functional risk variants for 26 LOAD-risk loci, mostly …

Systematic Targeting Of Gd2-Positive Neuroblastoma Tumors With A Photooncolytic Phage Nanovector Platform, Suleman Khan Zadran, Nicola Facchinello, Piergiuseppe De Rosa, Roberto Saporetti, Paolo Emidio Costantini, Luca Ulfo, Michela Nigro, Annapaola Petrosino, Lucia Pappagallo, Sara Aloisi, Giorgio Milazzo, Zainul Abe Din, Alberto Rigamonti, Leonardo Flora, Martina Santulli, Leonardo Cimadom, Giampaolo Zuccheri, Mattia Zangoli, Manuele Di Sante, Matteo Di Giosia, Francesca Di Maria, Roberto Bernardoni, Eveline Barbieri, Matteo Calvaresi, Alberto Danielli, Giovanni Perini

Faculty, Staff and Students Publications

Disialoganglioside-GD2 is a key molecular target for Neuroblastoma (NB) immunotherapy based on the employment of GD2-targeting antibodies. However, about 50% of treated patients can experience tumor relapse due to limited immune-mediated cytotoxicity and poor antibody penetration into tumors. To address this problem, a tumor-penetrating photo-oncolytic phage nanovector platform is genetically and chemically developed that selectively targets GD2-expressing NB cells. The phage bioconjugates, functionalized with different photosensitizers, result in specific and selective oncolysis of GD2-positive NB cells upon light irradiation, without affecting GD2-negative ones. The photo-oncolytic phage vectors are shown to deeply penetrate into GD2-positive tumor spheroids in vitro, and to …

Tigit Affects Car Nk-Cell Effector Function In The Solid Tumor Microenvironment By Modulating Immune Synapse Strength, Ishwar Navin, Matthew Dysthe, Prashant S Menon, Corrine Baumgartner, Tim Sauer, Navin Varadarajan, Robin Parihar

Faculty, Staff and Students Publications

Therapies using NK cells that express chimeric antigen receptors (CAR-NK) have been successfully employed against hematologic malignancies. However, solid tumors resist CAR-NKs partly by enriching tumor microenvironments with ligands for NK cell inhibitory receptors. Although the NK inhibitory receptor T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) has been implicated in impaired antitumor activity of endogenous NK cells, the consequences of TIGIT expression on engineered CAR-NKs have not been explored. To address this gap, we compared TIGIT-expressing and TIGIT-deleted human CAR-NKs targeting the GD2 solid tumor antigen in tumor immune microenvironment co-cultures and in vivo tumor immune …

Design And Application Of A Tau Seed Amplification Assay For Screening Inhibitors Of Tau Seeding, Damian Gorski, Haley Evans, Tyler Allison, Carla Barria, Danielle Harrison, Victor Banerjee, Nicolas Mendez, Mohammad Shahnawaz, Sanne Kaalund, Jonas Folke, Susana Aznar, Paul Schultz, Fei Wang, Claudio Soto

Faculty, Staff and Student Publications

Background: Tau protein aggregates are a key pathological hallmark of Alzheimer's disease (AD) and are closely associated with cognitive decline and neurodegeneration. It is proposed that tau aggregates faithfully propagate throughout the brain by self-templating their disease-associated conformation onto natively-folded tau monomers, thereby inducing their aggregation and incorporation into growing fibrils. As such, the inhibition or modulation of tau seeding and aggregation represents a viable therapeutic strategy for AD and other tauopathies.

Methods: We have recently developed seed amplification assays (SAA) for the detection and amplification of small quantities of misfolded protein aggregates in various neurodegenerative diseases. In this article, …

Improving Data-Driven Gated (Ddg) Pet And Ct Registration In Thoracic Lesions: A Comparison Of Ai Registration And Ddg Ct, Tinsu Pan, M Allan Thomas, Yang Lu, Dershan Luo

Faculty, Staff and Student Publications

Purpose: Misregistration between CT and PET can result in mis-localization and inaccurate quantification of the tracer uptake in PET. Data-driven gated (DDG) CT can correct registration and quantification but requires a radiation dose of 1.3 mSv and 1 min of acquisition time. AI registration (AIR) does not require an additional CT and has been validated to improve registration and reduce the 'banana' misregistration artifacts around the diaphragm. We aimed to compare a validated AIR and DDG CT in registration and quantification of avid thoracic lesions misregistered in DDG PET scans.

Methods: Thirty PET/CT patient data (23 with 18F-FDG, 4 with …

Current States In Understanding Oligodendroglia-Mediated Neurological Issues In Neurofibromatosis Type 1 (Nf1), Benjamin E Aghoghovwia, Cheng-En Shen, Sabiha Bano, Nandini Shyamala, Alesandra Echeandia Marrero, Khushboo Irshad, Samer Sharafaldin, Nicole M Brossier, Yuan Pan

Faculty, Staff and Student Publications

Neurofibromatosis type 1 (NF1) is among the most common neurogenetic disorders and is associated with an increased risk of developing tumors in the nervous system. Additionally, up to 80% of patients with NF1 experience neurological complications, including deficits in attention, memory, and executive function. Significant effort has been dedicated to studying how NF1 mutations autonomously dysregulate neuronal function. Increasing evidence indicates that NF1 mutations also dysregulate the oligodendroglial lineage that contributes to neurological issues in NF1. Here, we summarize our current understanding of how NF1 mutations impact the oligodendroglial lineage homeostasis and plasticity. We also discuss gaps in knowledge, potential …

Association Between Therapeutic Alliance And Clinical Outcomes In Virtual Telepsychiatry: A Retrospective Analysis Of Data From Talkiatry, Cheryl Person, Nathaniel David Phillips, Kartik Venkatachalam, Georgia Gaveras

Faculty, Staff and Student Publications

Background: Given the increasing demand for accessible mental health services, fully virtual telepsychiatry has become a vital component of modern health care delivery. Therapeutic alliance, the collaborative and affective bond between patients and therapists, is a well-established predictor of clinical outcomes in traditional face-to-face and teletherapy. However, the relationship between therapeutic alliance and clinical outcomes in an outpatient telepsychiatry setting remains less understood.

Objective: Our primary objective was to evaluate the relationship between therapeutic alliance and clinical outcomes for depression and anxiety in an outpatient telepsychiatry practice.

Methods: This retrospective study analyzed data from treatment-seeking adults receiving services from Talkiatry, …

Aging In Mice Alters Regionally Enriched Striatal Astrocytes, Kay E Linker, Violeta Duran-Laforet, Matthias Ollivier, Xinzhu Yu, Dorothy P Schafer, Baljit S Khakh

Faculty, Staff and Student Publications

Aging affects multiple organs and within the brain drives distinct molecular changes across different cell types. The striatum encodes motor behaviors that decline with age, but our understanding of how cells within the striatum change remains incomplete. Using single-cell RNA sequencing from young and aged mice we identify molecularly distinct astrocyte subtypes. We show that astrocytes change significantly with age, exhibiting downregulation of genes, reduced diversity, and a shift to more homogenous inflammatory transcriptomic profiles. By exploring where striatal astrocyte subtypes are located with single-cell resolution, we map astrocytes enriched in dorsal, medial, and ventral striatum. Age increases inflammatory marker …

Comparison Of Imaging Based Single-Cell Resolution Spatial Transcriptomics Profiling Platforms Using Formalin-Fixed Paraffin-Embedded Tumor Samples, Nejla Ozirmak Lermi, Max Molina Ayala, Sharia Hernandez, Wei Lu, Khaja Khan, Alejandra Serrano, Idania Lubo, Leticia Hamana, Katarzyna Tomczak, Sean Barnes, Jinzhuang Dou, Qingnan Liang, Rti Team, Maria Gabriela Raso, Ximing Tang, Mei Jiang, Beatriz Sanchez-Espiridion, Annikka Weissferdt, John Heymach, Jianjun Zhang, Boris Sepesi, Tina Cascone, Anne Tsao, Mehmet Altan, Reza Mehran, Don Gibbons, Ignacio Wistuba, Cara Haymaker, Ken Chen, Luisa M Solis Soto

Faculty, Staff and Student Publications

Imaging-based spatial transcriptomics (ST) is evolving as a pivotal technology in studying tumor biology and associated microenvironments. However, the strengths of the commercially available ST platforms in studying spatial biology have not been systematically evaluated using rigorously controlled experiments. We use serial 5 μm sections of formalin-fixed, paraffin-embedded surgically resected lung adenocarcinoma and pleural mesothelioma samples in tissue microarrays to compare the performance of the ST platforms (CosMx, MERFISH, and Xenium (uni/multi-modal)) in reference to bulk RNA sequencing, multiplex immunofluorescence, GeoMx, and hematoxylin and eosin staining data. In addition to an objective assessment of automatic cell segmentation and phenotyping, we …

Lysosomes Signal Through The Epigenome To Regulate Longevity Across Generations, Qinghao Zhang, Weiwei Dang, Meng C Wang

Faculty, Staff and Students Publications

The epigenome is sensitive to metabolic inputs and crucial for aging. Lysosomes act as a signaling hub to sense metabolic cues and regulate longevity. We find that lysosomal metabolic pathways signal through the epigenome to regulate transgenerational longevity in Caenorhabditis elegans. Activation of lysosomal lipid signaling and lysosomal adenosine monophosphate-activated protein kinase (AMPK) or reduction of lysosomal mechanistic-target-of-rapamycin (mTOR) signaling increased expression of a histone H3.3 variant and increased its methylation on K79, leading to lifespan extension across multiple generations. This transgenerational pro-longevity effect required intestine-to-germline transportation of histone H3.3 and a germline-specific H3K79 methyltransferase, and was recapitulated by …

Synthesis, Structure-Activity Relationships, And Antitumor Activities Of Quinoxiline-Containing Inhibitors Of The Protein-Protein Interactions Between Transcription Coactivator Af9/Enl And Dot1l/Af4, Chandra Bhushan Mishra, Xin Li, Bala Krishna Moku, Sehun Kwak, Dnyaneshwar N Garad, Yongcheng Song

Faculty, Staff and Students Publications

Mixed lineage leukemia (MLL) gene rearrangements cause ~75% of acute leukemia in infants and 5-10% in children and adults with poor clinical outcomes. Protein-protein interactions (PPI) between frequent MLL fusion partners AF9/ENL and AF4 or histone methyltransferase DOT1L are drug targets for MLL-rearranged (MLL-r) leukemia. Sixty-seven quinoxiline compounds were synthesized and tested for their ability to inhibit such PPIs. Compounds 16, 17, 59 and 63 were found to be potent inhibitors with IC50 values of 0.35-1.5 μM. Structure-activity relationships are discussed. Potent inhibitors can suppress expression of MLL target genes Myc and Meis1 and selectively block proliferation of MLL-r and …

Smarcal1 Is A New Osteosarcoma Predisposition Gene, Maryam Rafati, Lillian M Guenther, Laura E Egolf, D Matthew Gianferante, Jung Kim, Kevin Wang, Bin Zhu, Logan G Spector, Nathan Anderson, Katherine A Janeway, Donald A Barkauskas, Douglas S Hawkins, Ana Patiño-Garcia, Philip J Lupo, Michael E Scheurer, Lindsay Morton, Gregory T Armstrong, Yadav Sapkota, M Monica Gramatges, Massimo Serra, Claudia Hattinger, Katia Scotlandi, Irene L Andrulis, Jay S Wunder, Mandy L Ballinger, David M Thomas, Meredith Yeager, Michael Dean, Douglas R Stewart, Aurelie Vogt, Jia Liu, Belynda D Hicks, Wen-Yi Huang, Maria Teresa Landi, Adriana Lori, W Ryan Diver, Sharon A Savage, Stephen J Chanock, Lisa Mirabello

Faculty, Staff and Students Publications

Osteosarcoma, the most common childhood bone tumor, can occur in rare cancer predisposition syndromes; however, most cases are sporadic with no known predisposing factors. We investigated the frequency of SMARCAL1 putative pathogenic variants in our large ongoing study of 2,119 osteosarcoma cases, their relation to patient characteristics, and the population prevalence. Our analysis uncovered a higher frequency of SMARCAL1 pathogenic variants across three osteosarcoma case sets (1.8%, n = 2,119) than in 2,625 comparably sequenced cancer-free controls (0.3%; P <  .001). Cases with SMARCAL1 pathogenic variants had significantly improved overall survival compared to cases without these variants (hazard ratio 0.36, 95% CI 0.14-0.96, P = .034). In the UK Biobank (469,557 exomes), there was a 33-fold increased risk of osteosarcoma in individuals with SMARCAL1 pathogenic variants. These results identify SMARCAL1 as a new osteosarcoma predisposition gene and thus warrant follow-up to identify the mechanisms by which SMARCAL1 contributes to the etiology of osteosarcoma.

Poziotinib For Egfr Exon 20-Insertion Nsclc: Clinical Efficacy Of The Phase 2 Zenith Trial And Differential Impact Of Egfr Exon 20 Insertion Location On Sensitivity, Xiuning Le, Jacqulyne P Robichaux, Monique Nilsson, R S K Vijayan, Ashwin Ravichandran, Jia Wu, Yasir Y Elamin, Lingzhi Hong, Jun Pei, Jun He, Sonia Patel, Hibiki Udagawa, Sriramvignesh Mani, Chang Woon Jang, Jeffrey M Clarke, Nishan Tchekmedyian, Jonathan W Goldman, Mark Socinski, Gajanan Bhat, Sharon Leu, Veronica Bunn, Zhenqiang Su, Sylvie Vincent, John W Lawson, Jason B Cross, John V Heymach

Faculty, Staff and Student Publications

EGFRex20 insertions (EGFRex20ins) can be classified as near- and far-loop based on the insertion location, however, the impact of location on responses to various EGFR tyrosine kinase inhibitors (TKIs) is poorly understood. In vitro studies show that afatinib, poziotinib, and zipalertinib more potently inhibited near-loop than far-loop insertions, whereas mobocertinib has similar IC50 in both groups. Molecular dynamics simulations reveal that near-loop insertions have multiple conformational states and lower transitional energy than far-loop insertions. ZENITH20 trial cohort 1 (NCT03318939) evaluates poziotinib in EGFRex20 NSCLC patients (n = 115) and demonstrates an objective response rate of 14.8% (95% Confidence …

Deciphering The Mycn-Driven Metabolic Microenvironment Of Neuroblastoma, Amber Wolf, Davide Leardini, Lingzhi Li, Riccardo Masetti, Costas A Lyssiotis, Eveline Barbieri

Faculty, Staff and Students Publications

Oncogenic MYCN drives aggressive disease in many cancers including neuroblastoma (NB). Metabolic reprogramming is essential to support cancer cell homeostasis and survival under nutrient- and oxygen-deprived conditions. MYCN directly reprograms many nodes of tumor-intrinsic metabolism, which have significant repercussions on the cells of the tumor microenvironment (TME), resulting in complex intercellular metabolic circuits that contribute to the immunosuppressive microenvironment of NB. These metabolic circuits are also regulated by the organismal and cellular circadian clock and host diet to further impact the TME and NB oncogenesis. This review discusses the mechanisms by which MYCN regulates the metabolic crosstalk between tumor, TME, …

Next-Gen Tools In Cancer Neuroscience, Vera Thiel, Debpali Sur, Caroline C Picoli, Tamara Mcerlain, Katalina Couto, David J Simon, Yuan Pan, Karen Olivia Dixon, Rajan P Kulkarni, Sebastien Talbot, Alexander Birbrair

Faculty, Staff and Student Publications

The emerging field of cancer neuroscience is rapidly evolving, driven by novel technologies and tools. These include advances in single-cell and spatial transcriptomics; genetic mouse models paired with automated high-throughput; and innovative optical electrophysiological approaches, optogenetics, chemogenetics, engineered viruses, and new methods for visualizing neuronal activity. Collectively, these technologies are revolutionizing how we investigate, manipulate, and characterize distinct components that contribute to the nervous system-cancer interface. In the present review, we discuss the key technologies that are closing the gap between oncology and neuroscience, highlighting the innovations that are propelling the cancer neuroscience field forward.

Rna/Dna-Binding Protein Tdp43 Regulates Dna Mismatch Repair Genes With Implications For Genome Stability, Vincent E Provasek, Albino Bacolla, Suganya Rangaswamy, Manohar Kodavati, Joy Mitra, Issa O Yusuf, Vikas H Malojirao, Velmarini Vasquez, Gavin W Britz, Guo-Min Li, Zuoshang Xu, Sankar Mitra, Ralph M Garruto, John A Tainer, Muralidhar L Hegde

Faculty, Staff and Student Publications

TDP43 is an RNA/DNA-binding protein increasingly recognized for its role in neurodegenerative conditions, including amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). As characterized by its aberrant nuclear export and cytoplasmic aggregation, TDP43 proteinopathy is a hallmark feature in over 95% of ALS/FTD cases, leading to detrimental cytosolic aggregates and a reduction in nuclear functionality in neurons. Building on our prior work linking TDP43 proteinopathy to the accumulation of DNA double-strand breaks (DSBs) in neurons, the present investigation uncovers a novel regulatory relationship between TDP43 and DNA mismatch repair (MMR) gene expression. Here, we show that TDP43 depletion or overexpression …

Robust Detection Of Watermarks For Large Language Models Under Human Edits, Xiang Li, Feng Ruan, Huiyuan Wang, Qi Long, Weijie J Su

Faculty, Staff and Student Publications

Watermarking has offered an effective approach to distinguishing text generated by large language models (LLMs) from human-written text. However, the pervasive presence of human edits on LLM-generated text dilutes watermark signals, thereby significantly degrading detection performance of existing methods. In this paper, by modeling human edits through mixture model detection, we introduce a new method in the form of a truncated goodness-of-fit test for detecting watermarked text under human edits, which we refer to as Tr-GoF. We prove that the Tr-GoF test achieves optimality in robust detection of the Gumbel-max watermark in a certain asymptotic regime of substantial text modifications …

Impacts Of The Conductive Networks On Solid-State Battery Operation, Shimao Deng, Yixian Wang, Tianxiao Sun, Wenlong Li, Mingyuan Ge, Jian Wang, Peter Cloetens, Piero Pianetta, David Mitlin, Yijin Liu

Faculty, Staff and Student Publications

The micromorphology of composite cathodes is known to play a vital role in determining all‐solid‐state battery (ASSB) performance. However, much of our current understanding is derived from empirical observations, lacking a deeper mechanistic foundation. The “rocking chair” concept of battery chemistry requires maintaining charge neutrality, emphasizing the necessity of examining electrode micromorphology from the perspective of conductive networks. This study systematically investigates the microscopic electrochemical impacts of conductive network micromorphology by varying the Li+‐to‐e− channel ratio in cathodes comprising LiNbO3‐coated LiNi0.8Co0.1Mn0.1O2, Li6PS5Cl, and carbon fibers. Utilizing multiscale synchrotron‐based spectro‐microscopy, we unravel that unbalanced Li+ and e− conducting channels intensify charge …

Anticonvulsant Use In Older Age Bipolar Disorder In A Global Sample From The Global Aging And Geriatric Experiments In Bipolar Disorder Project: Utilisation D'Anticonvulsivants Pour Le Traitement Des Troubles Bipolaires Du Sujet Âgé Auprès D'Un Échantillon Mondial Provenant Du Projet Gage-Bd, Katie C Bodenstein, Myriam Lesage, Paola Lavin, Sigfried Schouws, Melis Orhan, Alexandra Beunders, Osvaldo P Almeida, Kursat Altinbas, Vicent Balanzá-Martínez, Izabela G Barbosa, Hilary P Blumberg, Farren B S Briggs, Cynthia V Calkin, Orestes V Forlenza, Brent Forester, Ariel G Gildengers, Benno C M Haarman, Tomas Hajek, Beny Lafer, Paula V Nunes, Benoit Mulsant, Andrew T Olagunju, Regan E Patrick, Joquim Radua, Kaylee Sarna, Christian Simhandl, Jair C Soares, Ashley N Sutherland, Nicole Fiorelli, Antonio L Teixeira, Shangying Tsai, Eduard Vieta, Joy Yala, Lisa Eyler, Annemiek Dols, Martha Sajatovic, Soham Rej

Faculty, Staff and Student Publications

Background:

Anticonvulsants are an essential treatment for bipolar disorder; however, there is relatively little known about their use in older age bipolar disorder (OABD). In this paper, which leverages a large international dataset, we aim to 1) describe the use of anticonvulsants in OABD compared to younger age bipolar disorder (YABD; ages < 50 years old) and 2) explore any demographic/clinical correlates.

Methods:

A secondary analysis was conducted on the international data from the Global Aging and Geriatric Experiments in Bipolar Disorder project. The main objective was to report the prevalence of anticonvulsant use in OABD over 50 years old (mean age = 62.27) and the most prescribed anticonvulsant. Additional …

Human Cerebral Organoids Model Tumor Initiation And Infiltration In An Autologous Astrocyte-Supported Setting, Esther Schickel, Tamara Bender, Leon Kaysan, Simone Hufgard, Margot Mayer, David R Grosshans, Christiane Thielemann, Insa S Schroeder

Faculty, Staff and Student Publications

Efforts to efficiently target brain tumors are constrained by the dearth of appropriate models to study tumor behavior toward treatment approaches as well as potential side effects to the surrounding normal tissue. We established a reproducible cerebral organoid model of brain tumorigenesis in an autologous setting by overexpressing

Metabolic Shifts In Murine Inner Ears Mimicking Erythrocytes And Plasma Reveal Diagnostics And Early Predictors For Age-Related Hearing Loss, Qi Guo, Zhenjiang Li, Cheng Luo, Changhan Chen, Xi Long, Yidan Wang, Qingfen Qiang, Fang Yu, Wuping Liu, Yujin Zhang, Rodney E Kellems, Yang Xia

Faculty, Staff and Student Publications

Age-related hearing loss (ARHL) is a major public health concern, driven by the interplay of multiple factors. Here, we reveal spatiotemporal metabolic shifts in murine inner ears mirroring erythrocytes and plasma. Isotope-labeled glucose tracing demonstrates a metabolic rerouting favoring glycolysis over the pentose phosphate pathway, alongside downregulation of the tricarboxylic acid cycle, indicating impaired energy production and redox homeostasis. Accumulation of medium- and long-chain acylcarnitines further exacerbates lipotoxicity. Notably, age-dependent depletion of arginine, lysine, proline, and glycine disrupts the arginine-polyamine-urea cycle. Translationally, UK Biobank plasma metabolomics links omega-6 fatty acids, linoleic acid, glycine, and albumin to ARHL resilience, while branched-chain …

Connecting Innovation And Trust Through Translational Sciences – A Need For A Community Focus And Effective Education Strategiess, Filipa Godoy-Vitorino, Michelle Borrero, Josué Pérez-Santiago, Rubén García-García, Candelaria Gomez-Manzano

Faculty, Staff and Student Publications

Report of a conference held in Puerto Rico, this article highlights how interdisciplinary translational science-anchored in education, public trust, and equity-can accelerate innovation in cancer therapy while empowering underserved communities through inclusive training, collaboration, and research participation.

Galntl5 Binds Galnac And Is Required For Migration Through The Uterotubal Junction And Sperm-Zona Pellucida Binding, Taichi Noda, Reika Uriu, Daisuke Mashiko, Hina Shinohara, Yongcun Qu, Ayumu Taira, Ryan M Matzuk, Duri Tahala, Motochika Nakano, Kimi Araki, Zhifeng Yu, Ying Zhang, Martin M Matzuk, Masahito Ikawa

Faculty, Staff and Students Publications

More than 20 genes expressed in the male reproductive tract have been identified as essential factors for sperm migration to and through the utero-tubal junction (UTJ), and they are divided into ADAM3-dependent and ADAM3-independent pathways. In parallel, sperm having UTJ migration defects also show impaired binding to the zona pellucida (ZP). Herein, we demonstrate that knockout of Galntl5, encoding a sperm surface protein, causes impaired sperm binding with the UTJ and ZP, and null males have severe infertility. GALNTL5 appreciably disappears in sperm lacking Adam3 or Lypd4, required for ADAM3-dependent and ADAM3-independent pathways, and GALNTL5 binds to N …

Retraction Of Activation Of Rac1 By Src-Dependent Phosphorylation Of Dock180y1811 Mediates Pdgfrα-Stimulated Glioma Tumorigenesis In Mice And Humans, Haizhong Feng, Bo Hu, Kun-Wei Liu, Yanxin Li, Xinghua Lu, Tao Cheng, Jia-Jean Yiin, Songjian Lu, Susan Keezer, Tim Fenton, Frank B Furnari, Ronald L Hamilton, Kristiina Vuori, Jann N Sarkaria, Motoo Nagane, Ryo Nishikawa, Webster K Cavenee, Shi-Yuan Cheng

Faculty, Staff and Student Publications

No abstract provided.

Elevated Nr2f1 Underlies The Persistence Of Invasive Disease After Treatment Of Braf-Mutant Melanoma, Manoela Tiago, Timothy J Purwin, Casey D Stefanski, Renaira Oliveira Da Silva, Mitchell E Fane, Yash Chhabra, Jelan I Haj, Jessica Lf Teh, Rama Kadamb, Weijia Cai, Sheera R Rosenbaum, Vivian Chua, Nir Hacohen, Michael A Davies, Jessie Villanueva, Inna Chervoneva, Ashani T Weeraratna, Dan A Erkes, Claudia Capparelli, Julio A Aguirre-Ghiso, Andrew E Aplin

Faculty, Staff and Student Publications

Despite the success of targeted inhibitors in cutaneous melanoma, therapeutic responses are limited by the aged tumor microenvironment and drug-tolerant residual cells. Given the similarities between drug tolerance and cellular dormancy, we studied the dormancy marker, nuclear receptor subfamily 2 group F member 1 (NR2F1), in response to BRAF-V600E inhibitors (BRAFi) plus MEK inhibitors (MEKi) in BRAF-mutant melanoma models. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased NR2F1. NR2F1 was highly expressed in the drug-tolerant invasive cell state of minimal residual disease in patient-derived and mouse-derived xenografts on BRAFi + MEKi. NR2F1 over-expression was sufficient …

33 Unresolved Questions In Nanoscience And Nanotechnology, Chad A Mirkin, Sarah Hurst Petrosko, Natalie Artzi, Koray Aydin, Austin Biaggne, C Jeffrey Brinker, Katherine E Bujold, Y Charles Cao, Rachel R Chan, Chaojian Chen, Peng-Cheng Chen, Xiaodong Chen, Olivier J G L Chevalier, Chung Hang Jonathan Choi, Richard M Crooks, Vinayak P Dravid, Jingshan S Du, Sasha B Ebrahimi, Hongyou Fan, Omar K Farha, C Adrian Figg, Tanner D Fink, Connor M Forsyth, Harald Fuchs, Franz M Geiger, Nathan C Gianneschi, Kyle J Gibson, David S Ginger, Sishi Guo, Justin S Hanes, Liangliang Hao, Jin Huang, Bryan M Hunter, Fengwei Huo, Jeongmin Hwang, Rongchao Jin, Shana O Kelley, Thomas J Kempa, Youngeun Kim, Sergej Kudruk, Sneha Kumari, Kaitlin M Landy, Ki-Bum Lee, Noel J Leon, Jun Li, Yuanwei Li, Zhiwei Li, Bin Liu, Guoliang Liu, Xiaogang Liu, Luis M Liz-Marzán, Jochen H Lorch, Taokun Luo, Robert J Macfarlane, Jill E Millstone, Milan Mrksich, Catherine J Murphy, Rajesh R Naik, Andre E Nel, Christopher Oetheimer, Jenny K Hedlund Orbeck, So-Jung Park, Benjamin E Partridge, Nicholas A Peppas, Michelle L Personick, Arindam Raj, Namrata Ramani, Michael B Ross, Stacey Barnaby Ross, Edward H Sargent, Tanushri Sengupta, George C Schatz, Dwight S Seferos, Tamar Seideman, Soyoung Eileen Seo, Bo Shen, Wooyoung Shim, Donghoon Shin, Ulrich Simon, Andrew J Sinegra, Peter T Smith, Alexander M Spokoyny, Peter J Stang, Alexander H Stegh, J Fraser Stoddart, Dayne F Swearer, Weihong Tan, Michelle H Teplensky, C Shad Thaxton, David R Walt, Mary X Wang, Zhe Wang, Wei David Wei, Paul S Weiss, Peter H Winegar, Younan Xia, Yi Xie, Xiaoyang Xu, Peidong Yang, Yiming Yang, Zihao Ye, Kuk Ro Yoon, Cuizheng Zhang, Hua Zhang, Ke Zhang, Liangfang Zhang, Xiaoyu Zhang, Ye Zhang, Zijian Zheng, Wenjie Zhou, Shengshuang Zhu, Wei Zhu

Faculty, Staff and Student Publications

Significant advances in science and engineering often emerge at the intersections of disciplines. Nanoscience and nanotechnology are inherently interdisciplinary, uniting researchers from chemistry, physics, biology, medicine, materials science, and engineering. This convergence has fostered novel ways of thinking and enabled the development of materials, tools, and technologies that have transformed both basic and applied research, as well as how we address critical societal challenges. In this Nano Focus, we pose and explore 33 questions whose answers could profoundly impact fields such as energy, electronics, the environment, optics, and medicine. These questions highlight the need for deeper foundational understanding, improved tools …