Medicine and Health Sciences Commons^™

Connexin43 In Mesenchymal Lineage Cells Regulates Body Adiposity And Energy Metabolism In Mice, Seung-Yon Lee, Francesca Fontana, Toshifumi Sugatani, Ignacio Portales Castillo, Giulia Leanza, Ariella Coler-Reilly, Roberto Civitelli

2020-Current year OA Pubs

Connexin43 (Cx43) is the most abundant gap junction protein present in the mesenchymal lineage. In mature adipocytes, Cx43 mediates white adipose tissue (WAT) beiging in response to cold exposure and maintains the mitochondrial integrity of brown adipose tissue (BAT). We found that genetic deletion of Gja1 (Cx43 gene) in cells that give rise to chondro-osteogenic and adipogenic precursors driven by the Dermo1/Twist2 promoter led to lower body adiposity and partial protection against the weight gain and metabolic syndrome induced by a high-fat diet (HFD) in both sexes. These protective effects were related to increased locomotion, fuel utilization, energy expenditure, nonshivering …

Lysosome-Related Organelles Contain An Expansion Compartment That Mediates Delivery Of Zinc Transporters To Promote Homeostasis, Adelita D Mendoza, Nicholas Dietrich, Chieh-Hsiang Tan, Daniel Herrera, Jennysue Kasiah, Zachary Payne, Ciro Cubillas, Daniel L Schneider, Kerry Kornfeld

2020-Current year OA Pubs

Zinc is an essential nutrient-it is stored during periods of excess to promote detoxification and released during periods of deficiency to sustain function. Lysosome-related organelles (LROs) are an evolutionarily conserved site of zinc storage, but mechanisms that control the directional zinc flow necessary for homeostasis are not well understood. In

Predicting Proximal Tubule Failed Repair Drivers Through Regularized Regression Analysis Of Single Cell Multiomic Sequencing, Nicolas Ledru, Parker C Wilson, Yoshiharu Muto, Yasuhiro Yoshimura, Haojia Wu, Dian Li, Amish Asthana, Stefan G Tullius, Sushrut S Waikar, Giuseppe Orlando, Benjamin D Humphreys

2020-Current year OA Pubs

Renal proximal tubule epithelial cells have considerable intrinsic repair capacity following injury. However, a fraction of injured proximal tubule cells fails to undergo normal repair and assumes a proinflammatory and profibrotic phenotype that may promote fibrosis and chronic kidney disease. The healthy to failed repair change is marked by cell state-specific transcriptomic and epigenomic changes. Single nucleus joint RNA- and ATAC-seq sequencing offers an opportunity to study the gene regulatory networks underpinning these changes in order to identify key regulatory drivers. We develop a regularized regression approach to construct genome-wide parametric gene regulatory networks using multiomic datasets. We generate a …

Circuit-Based Intervention Corrects Excessive Dentate Gyrus Output In The Fragile X Mouse Model, Pan-Yue Deng, Ajeet Kumar, Valeria Cavalli, Vitaly A Klyachko

2020-Current year OA Pubs

Abnormal cellular and circuit excitability is believed to drive many core phenotypes in fragile X syndrome (FXS). The dentate gyrus is a brain area performing critical computations essential for learning and memory. However, little is known about dentate circuit defects and their mechanisms in FXS. Understanding dentate circuit dysfunction in FXS has been complicated by the presence of two types of excitatory neurons, the granule cells and mossy cells. Here we report that loss of FMRP markedly decreased excitability of dentate mossy cells, a change opposite to all other known excitability defects in excitatory neurons in FXS. This mossy cell …

Specifying Cross-System Collaboration Strategies For Implementation: A Multi-Site Qualitative Study With Child Welfare And Behavioral Health Organizations, Alicia C Bunger, Emmeline Chuang, Amanda M Girth, Kathryn E Lancaster, Rebecca Smith, Rebecca J Phillips, Jared Martin, Fawn Gadel, Tina Willauer, Marla J Himmeger, Jennifer Millisor, Jen Mcclellan, Byron J Powell, Lisa Saldana, Gregory A Aarons

2020-Current year OA Pubs

BACKGROUND: Cross-system interventions that integrate health, behavioral health, and social services can improve client outcomes and expand community impact. Successful implementation of these interventions depends on the extent to which service partners can align frontline services and organizational operations. However, collaboration strategies linking multiple implementation contexts have received limited empirical attention. This study identifies, describes, and specifies multi-level collaboration strategies used during the implementation of Ohio Sobriety Treatment and Reducing Trauma (Ohio START), a cross-system intervention that integrates services across two systems (child welfare and evidence-based behavioral health services) for families that are affected by co-occurring child maltreatment and parental …

Arid2 Mutations May Relay A Distinct Subset Of Cutaneous Melanoma Patients With Different Outcomes, Favour A Akinjiyan, George Nassief, Jordan Phillipps, Tolulope Adeyelu, Andrew Elliott, Farah Abdulla, Alice Y Zhou, George Souroullas, Kevin B Kim, Ari Vanderwalde, Soo J Park, George Ansstas

2020-Current year OA Pubs

ARID genes encode subunits of SWI/SNF chromatin remodeling complexes and are frequently mutated in human cancers. We investigated the correlation between ARID mutations, molecular features, and clinical outcomes in melanoma patients. Cutaneous melanoma samples (n = 1577) were analyzed by next-generation sequencing. Samples were stratified by pathogenic/likely pathogenic mutation in ARID genes (ARID1A/2/1B/5B). PD-L1 expression was assessed using IHC (SP142; positive (+): ≥ 1%). Tumor mutation burden (TMB)-high was defined as ≥ 10 mutations/Mb. Transcriptomic signatures predictive of response to immune checkpoint inhibitors-interferon gamma and T-cell inflamed score were calculated. Real-world overall survival (OS) information was obtained from insurance claims …

The Effect Of Breastfeeding Practices Of Undernourished Mothers In Rural Sierra Leone On Infant Growth And Mortality, Aminata Shamit Koroma, Kevin B Stephenson, Per O Iversen, Mark J Manary, David Taylor Hendrixson

2020-Current year OA Pubs

Breastfeeding provides optimal infant nutrition; however, <50% of infants are exclusively breastfed (EBF) for 6 months. We aimed to describe breastfeeding practices and their effects on growth and mortality among a high-risk mother-infant cohort in rural Sierra Leone. This was a secondary analysis of data from a randomized nutrition intervention trial among undernourished pregnant women. The study's primary outcomes were infant weight and length gains at 6 weeks of age. We included 1270 singleton infants in the analysis, with 1092 (85.6%) having 24-week outcome data. At 6 weeks, 88% were EBF, but the rate of EBF decreased to 17% at 24 weeks. The EBF infants at 6 weeks had improved length (difference of 0.9 mm/week; 95% CI 0.4 to 1.3;

A Novel Theta-Controlled Vibrotactile Brain-Computer Interface To Treat Chronic Pain: A Pilot Study, Phillip Demarest, Nabi Rustamov, James Swift, Tao Xie, Markus Adamek, Hohyun Cho, Elizabeth Wilson, Zhuangyu Han, Alexander Belsten, Nicholas Luczak, Peter Brunner, Simon Haroutounian, Eric C Leuthardt

2020-Current year OA Pubs

Limitations in chronic pain therapies necessitate novel interventions that are effective, accessible, and safe. Brain-computer interfaces (BCIs) provide a promising modality for targeting neuropathology underlying chronic pain by converting recorded neural activity into perceivable outputs. Recent evidence suggests that increased frontal theta power (4-7 Hz) reflects pain relief from chronic and acute pain. Further studies have suggested that vibrotactile stimulation decreases pain intensity in experimental and clinical models. This longitudinal, non-randomized, open-label pilot study's objective was to reinforce frontal theta activity in six patients with chronic upper extremity pain using a novel vibrotactile neurofeedback BCI system. Patients increased their BCI …

Gain: An Integrative Tool Utilizing Generative Adversarial Neural Networks For Augmented Gene Expression Analysis, Michael R Waters, Matthew Inkman, Kay Jayachandran, Roman M Kowalchuk, Clifford Robinson, Julie K Schwarz, S Joshua Swamidass, Obi L Griffith, Jeffrey J Szymanski, Jin Zhang

2020-Current year OA Pubs

Big genomic data and artificial intelligence (AI) are ushering in an era of precision medicine, providing opportunities to study previously under-represented subtypes and rare diseases rather than categorize them as variances. However, clinical researchers face challenges in accessing such novel technologies as well as reliable methods to study small datasets or subcohorts with unique phenotypes. To address this need, we developed an integrative approach, GAiN, to capture patterns of gene expression from small datasets on the basis of an ensemble of generative adversarial networks (GANs) while leveraging big population data. Where conventional biostatistical methods fail, GAiN reliably discovers differentially expressed …

Srf-Deficient Astrocytes Provide Neuroprotection In Mouse Models Of Excitotoxicity And Neurodegeneration, Surya Chandra Rao Thumu, Monika Jain, Sumitha Soman, Soumen Das, Vijaya Verma, Arnab Nandi, David H Gutmann, Balaji Jayaprakash, Deepak Nair, James P Clement, Swananda Marathe, Narendrakumar Ramanan

2020-Current year OA Pubs

Reactive astrogliosis is a common pathological hallmark of CNS injury, infection, and neurodegeneration, where reactive astrocytes can be protective or detrimental to normal brain functions. Currently, the mechanisms regulating neuroprotective astrocytes and the extent of neuroprotection are poorly understood. Here, we report that conditional deletion of serum response factor (SRF) in adult astrocytes causes reactive-like hypertrophic astrocytes throughout the mouse brain. These

Immunoglobulin Replacement Products Protect Against Sars-Cov-2 Infection In Vivo Despite Poor Neutralizing Activity, Ofer Zimmerman, Alexa Michelle Altman Doss, Baoling Ying, Chieh-Yu Liang, Samantha R. Mackin, Hannah G. Davis-Adams, Lucas J. Adams, Laura A. Vanblargan, Rita E. Chen, Suzanne M. Scheaffer, Pritesh Desai, Saravanan Raju, Tarisa L. Mantia, Caitlin C. O'Shaughnessy, Jennifer Marie Monroy, H. James Wedner, Christopher J. Rigell, Andrew L. Kau, Tiffany Biason Dy, Zhen Ren, Jackson S. Turner, Jane A. O'Halloran, Rachel M. Presti, Peggy L. Kendall, Daved H. Fremont, Ali H. Ellebedy, Michael S Diamond

2020-Current year OA Pubs

Immunoglobulin (IG) replacement products are used routinely in patients with immune deficiency and other immune dysregulation disorders who have poor responses to vaccination and require passive immunity conferred by commercial antibody products. The binding, neutralizing, and protective activity of intravenously administered IG against SARS-CoV-2 emerging variants remains unknown. Here, we tested 198 different IG products manufactured from December 2019 to August 2022. We show that prepandemic IG had no appreciable cross-reactivity or neutralizing activity against SARS-CoV-2. Anti-spike antibody titers and neutralizing activity against SARS-CoV-2 WA1/2020 D614G increased gradually after the pandemic started and reached levels comparable to vaccinated healthy donors …

Eosinophils Restrain Humoral Alloimmunity After Lung Transplantation, Zhongcheng Mei, Yuriko Terada, Yuhei Yokoyama, Andrew E. Gelman, Daniel Kreisel, Et Al.

2020-Current year OA Pubs

While the function of many leukocytes in transplant biology has been well defined, the role of eosinophils is controversial and remains poorly explored. Conflicting data exist regarding eosinophils' role in alloimmunity. Due to their prevalence in the lung, and their defined role in other pulmonary pathologies such as asthma, we set out to explore the role of eosinophils in the long-term maintenance of the lung allograft. We noted that depletion of eosinophils results in the generation of donor-specific antibodies. Eosinophil depletion increased memory B cell, plasma cell, and antibody-secreting cell differentiation and resulted in de novo generation of follicular germinal …

Persistent Mucus Plugs In Proximal Airways Are Consequential For Airflow Limitation In Asthma, Brendan K. Huang, Kaharu Sumino, Et Al.

2020-Current year OA Pubs

BACKGROUNDInformation about the size, airway location, and longitudinal behavior of mucus plugs in asthma is needed to understand their role in mechanisms of airflow obstruction and to rationally design muco-active treatments.METHODSCT lung scans from 57 patients with asthma were analyzed to quantify mucus plug size and airway location, and paired CT scans obtained 3 years apart were analyzed to determine plug behavior over time. Radiologist annotations of mucus plugs were incorporated in an image-processing pipeline to generate size and location information that was related to measures of airflow.RESULTSThe length distribution of 778 annotated mucus plugs was multimodal, and a 12 …

How Sex Hormones Affect Migraine: An Interdisciplinary Preclinical Research Panel Review, Frederick Godley Iii, John Meitzen, Hadas Nahman-Averbuch, Mary Angela O'Neal, David Yeomans, Nanette Santoro, Nina Riggins, Lars Edvinsson

2020-Current year OA Pubs

Sex hormones and migraine are closely interlinked. Women report higher levels of migraine symptoms during periods of sex hormone fluctuation, particularly during puberty, pregnancy, and perimenopause. Ovarian steroids, such as estrogen and progesterone, exert complex effects on the peripheral and central nervous systems, including pain, a variety of special sensory and autonomic functions, and affective processing. A panel of basic scientists, when challenged to explain what was known about how sex hormones affect the nervous system, focused on two hormones: estrogen and oxytocin. Notably, other hormones, such as progesterone, testosterone, and vasopressin, are less well studied but are also highlighted …

Genomemuster Mouse Genetic Variation Service Enables Multitrait, Multipopulation Data Integration And Analysis, Robyn L Ball, Alexander S Hatoum, Arpana Agrawal, Et Al.

2020-Current year OA Pubs

Hundreds of inbred mouse strains and intercross populations have been used to characterize the function of genetic variants that contribute to disease. Thousands of disease-relevant traits have been characterized in mice and made publicly available. New strains and populations including consomics, the collaborative cross, expanded BXD, and inbred wild-derived strains add to existing complex disease mouse models, mapping populations, and sensitized backgrounds for engineered mutations. The genome sequences of inbred strains, along with dense genotypes from others, enable integrated analysis of trait-variant associations across populations, but these analyses are hampered by the sparsity of genotypes available. Moreover, the data are …

Streamlined Identification Of Clinically And Functionally Relevant Genetic Regulators Of Lower-Tract Urogenital Development, Meade Haller, Yan Yin, Gabe Haller, Tian Li, Qiufang Li, Laura E Lamb, Liang Ma

2020-Current year OA Pubs

Congenital anomalies of the lower genitourinary (LGU) tract are frequently comorbid due to genetically linked developmental pathways, and are among the most common yet most socially stigmatized congenital phenotypes. Genes involved in sexual differentiation are prime candidates for developmental anomalies of multiple LGU organs, but insufficient prospective screening tools have prevented the rapid identification of causative genes. Androgen signaling is among the most influential modulators of LGU development. The present study uses SpDamID technology in vivo to generate a comprehensive map of the pathways actively regulated by the androgen receptor (AR) in the genitalia in the presence of the p300 …

Dmhppp1r17 Neurons Regulate Aging And Lifespan In Mice Through Hypothalamic-Adipose Inter-Tissue Communication, Kyohei Tokizane, Cynthia S Brace, Shin-Ichiro Imai

2020-Current year OA Pubs

Recent studies have shown that the hypothalamus functions as a control center of aging in mammals that counteracts age-associated physiological decline through inter-tissue communications. We have identified a key neuronal subpopulation in the dorsomedial hypothalamus (DMH), marked by Ppp1r17 expression (DMH

Utilization Of Augmented Reality Head-Mounted Display For The Surgical Management Of Thoracolumbar Spinal Trauma, Michael Ryan Kann, Miguel A Ruiz-Cardozo, Samuel Brehm, Tim Bui, Karan Joseph, Karma Barot, Gabriel Trevino, Abigail Carey-Ewend, Som P Singh, Matthew De La Paz, Ahmed Hanafy, Michael Olufawo, Rujvee P Patel, Alexander T Yahanda, Alexander Perdomo-Pantoja, Magalie Cadieux, Brenton Pennicooke, Camilo A Molina, Et Al.

2020-Current year OA Pubs

No abstract provided.

A Cre-Dependent Reporter Mouse For Quantitative Real-Time Imaging Of Protein Kinase A Activity Dynamics, Elizabeth I Tilden, Aditi Maduskar, Anna Oldenborg, Bernardo L Sabatini, Yao Chen

2020-Current year OA Pubs

Intracellular signaling dynamics play a crucial role in cell function. Protein kinase A (PKA) is a key signaling molecule that has diverse functions, from regulating metabolism and brain activity to guiding development and cancer progression. We previously developed an optical reporter, FLIM-AKAR, that allows for quantitative imaging of PKA activity via fluorescence lifetime imaging microscopy and photometry. However, using viral infection or electroporation for the delivery of FLIM-AKAR is invasive and results in variable expression. Here, we developed a reporter mouse, FL-AK, which expresses FLIM-AKAR in a Cre-dependent manner from the ROSA26 locus. FL-AK provides robust and consistent expression of …

Chimeric Antigen Receptor Macrophages Target And Resorb Amyloid Plaques, Alexander B. Kim, Qingli Xiao, Ping Yan, Qiuyun Pan, Gaurav Pandey, Susie Grathwohl, Ernesto Gonzales, Isabella Xu, Yoonho Cho, Hans Haecker, Slava Epelman, Abhinav Diwan, Jin-Moo Lee, Carl J Deselm

2020-Current year OA Pubs

Substantial evidence suggests a role for immunotherapy in treating Alzheimer's disease (AD). While the precise pathophysiology of AD is incompletely understood, clinical trials of antibodies targeting aggregated forms of β amyloid (Aβ) have shown that reducing amyloid plaques can mitigate cognitive decline in patients with early-stage AD. Here, we describe what we believe to be a novel approach to target and degrade amyloid plaques by genetically engineering macrophages to express an Aβ-targeting chimeric antigen receptor (CAR-Ms). When injected intrahippocampally, first-generation CAR-Ms have limited persistence and fail to significantly reduce plaque load, which led us to engineer next-generation CAR-Ms that secrete …

A Mouse Model To Distinguish Nlrp6-Mediated Inflammasome-Dependent And -Independent Functions, Runzhi Li, Yang Zan, Decai Wang, Xuequn Chen, Anmin Wang, Haoyuan Tan, Guorong Zhang, Siyuan Ding, Chen Shen, Hao Wu, Shu Zhu

2020-Current year OA Pubs

The NOD-like receptor (NLR) family pyrin domain containing 6 (NLRP6) serves as a sensor for microbial dsRNA or lipoteichoic acid (LTA) in intestinal epithelial cells (IECs), and initiating multiple pathways including inflammasome pathway and type I interferon (IFN) pathway, or regulating nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways. NLRP6 can exert its function in both inflammasome-dependent and inflammasome-independent manners. However, there is no tool to distinguish the contribution of individual NLRP6-mediated pathway to the physiology and pathology in vivo. Here, we validated that Arg39 and Trp50 residues in the pyrin domain (PYD) of murine NLRP6 are required for …

Aducanumab Anti-Amyloid Immunotherapy Induces Sustained Microglial And Immune Alterations, Mika P Cadiz, Katelin A Gibson, Kennedi T Todd, David G Nascari, Nashali Massa, Meredith T Lilley, Kimberly C Olney, Md Mamun Al-Amin, Hong Jiang, David M Holtzman, John D Fryer

2020-Current year OA Pubs

Aducanumab, an anti-amyloid immunotherapy for Alzheimer's disease, efficiently reduces Aβ, though its plaque clearance mechanisms, long-term effects, and effects of discontinuation are not fully understood. We assessed the effect of aducanumab treatment and withdrawal on Aβ, neuritic dystrophy, astrocytes, and microglia in the APP/PS1 amyloid mouse model. We found that reductions in amyloid and neuritic dystrophy during acute treatment were accompanied by microglial and astrocytic activation, and microglial recruitment to plaques and adoption of an aducanumab-specific pro-phagocytic and pro-degradation transcriptomic signature, indicating a role for microglia in aducanumab-mediated Aβ clearance. Reductions in Aβ and dystrophy were sustained 15 but not …

Hiv-Associated Gut Microbial Alterations Are Dependent On Host And Geographic Context, Muntsa Rocafort, Guoyan Zhao, Scott A Handley, Et Al.

2020-Current year OA Pubs

HIV-associated changes in intestinal microbiota are believed to be important drivers of disease progression. However, the majority of studies have focused on populations in high-income countries rather than in developing regions where HIV burden is greatest. To better understand the impact of HIV on fecal microbiota globally, we compare the fecal microbial community of individuals in the U.S., Uganda, and Botswana. We identify significant bacterial taxa alterations with both treated and untreated HIV infection with a high degree of uniqueness in each cohort. HIV-associated taxa alterations are also significantly different between populations that report men who have sex with men …

Viral Dnaemia And Dna Virus Seropositivity And Mortality In Pediatric Sepsis, Stephanie S Cabler, Gregory A Storch, Andrew H Walton, John C Lin, Et Al.

2020-Current year OA Pubs

IMPORTANCE: Sepsis is a leading cause of pediatric mortality. Little attention has been paid to the association between viral DNA and mortality in children and adolescents with sepsis.

OBJECTIVE: To assess the association of the presence of viral DNA with sepsis-related mortality in a large multicenter study.

DESIGN, SETTING, AND PARTICIPANTS: This cohort study compares pediatric patients with and without plasma cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus 1 (HSV-1), human herpesvirus 6 (HHV-6), parvovirus B19 (B19V), BK polyomavirus (BKPyV), human adenovirus (HAdV), and torque teno virus (TTV) DNAemia detected by quantitative real-time polymerase chain reaction or plasma IgG …

Immune Response To Sars-Cov-2 Variants After Immunization With Different Vaccines In Mexico, Erika Garay, Sean P J Whelan, Rebecca M Dubois, Sara M O'Rourke, Angel Eduardo Salgado-Escobar, José Esteban Muñoz-Medina, Carlos F Arias, Susana López

2020-Current year OA Pubs

There is limited information on the antibody responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in subjects from developing countries with populations having a high incidence of co-morbidities. Here, we analysed the immunogenicity of homologous schemes using the ChAdOx1-S, Sputnik V, or BNT162b2 vaccines and the effect of a booster dose with ChAdOx1-S in middle-aged adults who were seropositive or seronegative to the SARS-CoV-2 spike protein before vaccination. The study was conducted post-vaccination with a follow-up of 4 months for antibody titre using enzyme-linked immunosorbent assay (ELISA) and pseudovirus (PV) neutralization assays (PNAs). All three vaccines elicited a superior …

Prenatal Exposure To Maternal Disadvantage-Related Inflammatory Biomarkers: Associations With Neonatal White Matter Microstructure, Ashley F P Sanders, Brian Tirado, Nicole A Seider, Regina L Triplett, Rachel E Lean, Jeffrey J Neil, J Philip Miller, Rebecca Tillman, Tara A Smyser, Deanna M Barch, Joan L Luby, Cynthia E Rogers, Christopher D Smyser, Barbara B Warner, Et Al.

2020-Current year OA Pubs

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal …

Action Planning For Building Public Health Program Sustainability: Results From A Group-Randomized Trial, Sarah Moreland-Russell, Todd Combs, Jessica Gannon, Eliot Jost, Louise Farah Saliba, Kimberly Prewitt, Douglas Luke, Ross C Brownson

2020-Current year OA Pubs

BACKGROUND: Public health programs are charged with implementing evidence-based interventions to support public health improvement; however, to achieve long-term population-based benefits, these interventions must be sustained. Empirical evidence suggests that program sustainability can be improved through training and technical assistance, but few resources are available to support public health programs in building capacity for sustainability.

METHODS: This study sought to build capacity for sustainability among state tobacco control programs through a multiyear, group-randomized trial that developed, tested, and evaluated a novel Program Sustainability Action Planning Model and Training Curricula. Using Kolb's experiential learning theory, we developed this action-oriented training model …

Brain Injury Drives Optic Glioma Formation Through Neuron-Glia Signaling, Jit Chatterjee, Joshua P Koleske, Astoria Chao, Andrew D Sauerbeck, Ji-Kang Chen, Xuanhe Qi, Megan Ouyang, Lucy G Boggs, Rujuta Idate, Lara Isabel Marco Y Marquez, Terrence T Kummer, David H Gutmann

2020-Current year OA Pubs

Tissue injury and tumorigenesis share many cellular and molecular features, including immune cell (T cells, monocytes) infiltration and inflammatory factor (cytokines, chemokines) elaboration. Their common pathobiology raises the intriguing possibility that brain injury could create a tissue microenvironment permissive for tumor formation. Leveraging several murine models of the Neurofibromatosis type 1 (NF1) cancer predisposition syndrome and two experimental methods of brain injury, we demonstrate that both optic nerve crush and diffuse traumatic brain injury induce optic glioma (OPG) formation in mice harboring Nf1-deficient preneoplastic progenitors. We further elucidate the underlying molecular and cellular mechanisms, whereby glutamate released from damaged neurons …

Circulating Tumor Cells Prediction In Hormone Receptor Positive Her2-Negative Advanced Breast Cancer: A Retrospective Analysis Of The Monarch 2 Trial, Lorenzo Gerratana, Masha Kocherginsky, Andrew A Davis, Paolo D'Amico, Carolina Reduzzi, Fabio Puglisi, Massimo Cristofanilli

2020-Current year OA Pubs

BACKGROUND: The MONARCH 2 trial (NCT02107703) showed the efficacy of abemaciclib, a cyclin-dependent kinase 4 & 6 inhibitor (CDK4/6i), in combination with fulvestrant for hormone receptor-positive, HER2-negative metastatic breast cancer (MBC). The aim of this analysis was to explore the prediction of circulating tumor cells (CTCs) stratification using machine learning for hypothesis generation of biomarker-driven clinical trials.

PATIENTS AND METHODS: Predicted CTCs were computed in the MONARCH 2 trial through a K nearest neighbor (KNN) classifier trained on a dataset comprising 2436 patients with MBC. Patients were categorized into predicted Stage IVaggressive (pStage IVaggressive, ≥5 predicted CTCs) or predicted Stage …

A Comparative Biochemical And Pathological Evaluation Of Brain Samples From Knock-In Murine Models Of Gaucher Disease, Makaila L Furderer, Bahafta Berhe, Tiffany C Chen, Stephen Wincovitch, Xuntian Jiang, Nahid Tayebi, Ellen Sidransky, Tae-Un Han

2020-Current year OA Pubs

Gaucher disease (GD) is a lysosomal storage disorder stemming from biallelic mutations in