المؤلفون: Hai Ethan Hoang, Jessica Robinson‐Papp, Lan Mu, Kiran T. Thakur, Jacqueline Sarah Gofshteyn, Carla Kim, Vivian Ssonko, Rachelle Dugue, Eileen Harrigan, Brittany Glassberg, Michael Harmon, Allison Navis, Mu Ji Hwang, Kerry Gao, Helena Yan, Nathalie Jette, Anusha K. Yeshokumar

المصدر: Annals of Clinical and Translational Neurology, Vol 9, Iss 8, Pp 1125-1135 (2022)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571, Neurology. Diseases of the nervous system, RC346-429

الوصف: Abstract Objectives Early presentation and workup for acute infectious (IE) and autoimmune encephalitis (AE) are similar. This study aims to identify routine laboratory markers at presentation that are associated with IE or AE. Methods This was a multi‐center retrospective study at three tertiary care hospitals in New York City analyzing demographic and clinical data from patients diagnosed with definitive encephalitis based on a confirmed pathogen and/or autoantibody and established criteria for clinical syndromes. Results Three hundred and thirty‐three individuals with confirmed acute meningoencephalitis were included. An infectious‐nonbacterial (NB) pathogen was identified in 151/333 (45.40%), bacterial pathogen in 95/333 (28.50%), and autoantibody in 87/333 (26.10%). NB encephalitis was differentiated from AE by the presence of fever (NB 62.25%, AE 24.10%; p 1:40; NB 11.54%, AE 32.73%; p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2328-9503Test

الوصول الحر: https://doaj.org/article/5d8dfcea8af3452793067b26602cd0e4Test

المؤلفون: Shreya Saxena, Ian Kinsella, Simon Musall, Sharon H Kim, Jozsef Meszaros, David N Thibodeaux, Carla Kim, John Cunningham, Elizabeth M C Hillman, Anne Churchland, Liam Paninski

المصدر: PLoS Computational Biology, Vol 16, Iss 4, p e1007791 (2020)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Widefield calcium imaging enables recording of large-scale neural activity across the mouse dorsal cortex. In order to examine the relationship of these neural signals to the resulting behavior, it is critical to demix the recordings into meaningful spatial and temporal components that can be mapped onto well-defined brain regions. However, no current tools satisfactorily extract the activity of the different brain regions in individual mice in a data-driven manner, while taking into account mouse-specific and preparation-specific differences. Here, we introduce Localized semi-Nonnegative Matrix Factorization (LocaNMF), a method that efficiently decomposes widefield video data and allows us to directly compare activity across multiple mice by outputting mouse-specific localized functional regions that are significantly more interpretable than more traditional decomposition techniques. Moreover, it provides a natural subspace to directly compare correlation maps and neural dynamics across different behaviors, mice, and experimental conditions, and enables identification of task- and movement-related brain regions.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1553-734XTest; https://doaj.org/toc/1553-7358Test

الوصول الحر: https://doaj.org/article/24b2e8cf88044459b79b2b924db6c74eTest

المؤلفون: Carla Kim, Jingyun Li, Susanna Dang, Paul Schurmann, Antonella Dost, Aaron Moye, Margherita Paschini, Preetida Bhetariya, Roderick Bronson, Shannan Ho Sui

الوصف: Alveolar type 2 (AT2) cells, the epithelial progenitor cells of the distal lung, are known to be the prominent cell of origin for lung adenocarcinoma. The regulatory programs that control chromatin and gene expression in AT2 cells during the early stages of tumor initiation are not well understood. Here, we dissected the response of AT2 cells to Kras activation and p53 loss (KP) using combined single cell RNA and ATAC sequencing in an established tumor organoid system. Multi-omic analysis showed that KP tumor organoid cells exhibit two major cellular states: one more closely resembling AT2 cells (SPC-high) and another with loss of AT2 identity (hereafter, Hmga2-high). These cell states are characterized by unique transcription factor (TF) networks, with SPC-high states associated with TFs known to regulate AT2 cell fate during development and homeostasis, and distinct TFs associated with the Hmga2-high state. CD44 was identified as a marker of the Hmga2-high state, and was used to separate organoid cultures for functional comparison of these two cell states. Organoid assays and orthotopic transplantation studies indicated that SPC-high cells have higher tumorigenic capacity in the lung microenvironment compared to Hmga2-high cells. These findings highlight the utility of understanding chromatin regulation in the early oncogenic versions of epithelial cells, which may reveal more effective means to intervene the progression of Kras-driven lung cancer.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::f68e4e89ddacbc51cd200e0114450dfbTest
https://doi.org/10.21203/rs.3.rs-2663901/v1Test

المؤلفون: Jyoti V. Ankam, Nicole Luche, Mitashee Das, Carla Kim, Michael Harmon, Don Weiss, Jacqueline S. Gofshteyn, Anusha K. Yeshokumar, Stephen Morse, Emily M. Schorr, Sarah D. Torres, Brittany Glassberg, Kiran T. Thakur

المصدر: Neurohospitalist

مصطلحات موضوعية: Pediatrics, medicine.medical_specialty, business.industry, Medicine, Brief Reports, Retrospective cohort study, Bacterial meningitis, Neurology (clinical), business

الوصف: Community-acquired bacterial meningitis (CABM) morbidity and mortality remains high in those infected. Rapid diagnosis and treatment is paramount to reducing mortality and improving outcome. This retrospective cohort study aims to assess the time from presentation to diagnosis and treatment of vaccine preventable CABM as well as identify possible factors associated with delays in diagnosis and antibiotic administration. A retrospective chart review was conducted of individuals who presented to Columbia University Irving Medical Center (CUIMC), Children’s Hospital of New York (CHONY), Mount Sinai Medical Center, and Weill Cornell Medical Center with BM due to Haemophilus influenzae type B, Streptococcus pneumoniae, and Neisseria meningitidis between January 1, 2012 and December 31, 2017. Diagnosis was delayed by more than 8 hours in 13 patients (36.1%) and 5 individuals (13.9%) had a delay of 4 hours or more from presentation to the administration of antibiotics with appropriate CNS coverage. All of these patients were also initially misdiagnosed at an outpatient clinic, outside hospital, or emergency department. This retrospective study identified febrile and/or viral infections not otherwise specified and otitis media as the most common misdiagnoses underlying delays from presentation to diagnosis and to antibiotic treatment in those with BM.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99231496bc9367b0a683b3543d55ade1Test
https://doi.org/10.1177/19418744211037319Test

المؤلفون: Madison Clague, Carla Kim, Jason Zucker, Daniel A Green, Yifei Sun, Susan Whittier, Kiran T Thakur

المصدر: Open forum infectious diseases. 9(8)

مصطلحات موضوعية: Infectious Diseases, Oncology

الوصف: Background Herpes simplex virus–1 is the most common cause of sporadic encephalitis worldwide and requires prompt antiviral treatment. Traditionally, herpes simplex virus–1 (HSV-1) cerebrospinal fluid (CSF) testing is conducted using standalone polymerase chain reaction (PCR). The BioFire CSF FilmArray Meningitis/Encephalitis Panel (BioFire ME Panel) was introduced in 2015 at our institution, providing an alternative method of HSV-1 CSF testing. This study assesses the impact of the BioFire ME Panel on duration of intravenous acyclovir treatment. Methods A retrospective review of electronic medical records between 2010 and 2019 was performed. Information on intravenous acyclovir treatment and HSV-1 CSF testing was collected and analyzed. Our descriptive analysis included Mann-Whitney tests, 2 proportion Z-tests, and logistic regression. Results Our CSF HSV-1-negative cohort included 524 BioFire patients (125 pediatric, 399 adult) and 287 standalone PCR patients (115 pediatric, 172 adult). Across both pediatric and adult groups, patients who were tested for HSV-1 with the BioFire ME Panel had shorter average (SD) durations of intravenous acyclovir treatment (pediatric: 2.00 [5.71] days; adult: 3.26 [6.59] days) compared with patients tested with standalone PCR (pediatric: 4.83 [8.62] days; adult: 4.93 [8.46] days; P Conclusions The implementation of the BioFire ME Panel shortened CSF HSV-1 PCR result time and intravenous acyclovir duration. The shortened treatment and testing times from the BioFire ME Panel implementation may reduce hospital treatment costs and unnecessary use of antiviral treatments.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae069ec6bc77b96e5ce174b94a060bc7Test
https://pubmed.ncbi.nlm.nih.gov/35937646Test

المؤلفون: Lisa Miorin, Chad E. Mire, Shahin Ranjbar, Adam J. Hume, Jessie Huang, Nicholas A. Crossland, Kris M White, Manon Laporte, Thomas Kehrer, Viraga Haridas, Elena Moreno, Aya Nambu, Sonia Jangra, Anastasija Cupic, Marion Dejosez, Kristine A. Abo, Anna E. Tseng, Rhiannon B. Werder, Raveen Rathnasinghe, Tinaye Mutetwa, Irene Ramos, Julio Sainz de Aja, Carolina Garcia de Alba Rivas, Michael Schotsaert, Ronald B. Corley, James V. Falvo, Ana Fernandez-Sesma, Carla Kim, Jean-François Rossignol, Andrew A. Wilson, Thomas Zwaka, Darrell N. Kotton, Elke Mühlberger, Adolfo García-Sastre, Anne E. Goldfeld

المصدر: bioRxiv

مصطلحات موضوعية: viruses, parasitic diseases, Article

الوصف: A well-tolerated and cost-effective oral drug that blocks SARS-CoV-2 growth and dissemination would be a major advance in the global effort to reduce COVID-19 morbidity and mortality. Here, we show that the oral FDA-approved drug nitazoxanide (NTZ) significantly inhibits SARS-CoV-2 viral replication and infection in different primate and human cell models including stem cell-derived human alveolar epithelial type 2 cells. Furthermore, NTZ synergizes with remdesivir, and it broadly inhibits growth of SARS-CoV-2 variants B.1.351 (beta), P.1 (gamma), and B.1617.2 (delta) and viral syncytia formation driven by their spike proteins. Strikingly, oral NTZ treatment of Syrian hamsters significantly inhibits SARS-CoV-2-driven weight loss, inflammation, and viral dissemination and syncytia formation in the lungs. These studies show that NTZ is a novel host-directed therapeutic that broadly inhibits SARS-CoV-2 dissemination and pathogenesis in human and hamster physiological models, which supports further testing and optimization of NTZ-based therapy for SARS-CoV-2 infection alone and in combination with antiviral drugs. ispartof: bioRxiv ispartof: location:United States status: Published online

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::945ea80f17c5b78795ee125d768d7ff6Test
https://doi.org/10.1101/2022.02.08.479634Test

المؤلفون: Shawon Debnath, Irving L. Weissman, Anthony Oliva, Emmanuelle Passegué, Helen M. Blau, Mark A. Krasnow, Heinrich Jasper, Carla Kim, Jennifer Cable, Sang-Bum Park, Thomas A. Rando, David J. Glass, Elaine Fuchs

المصدر: Annals of the New York Academy of Sciences. 1462:27-36

مصطلحات موضوعية: Adult, Research Report, 0301 basic medicine, Aging, Inflammation, Regenerative Medicine, Regenerative medicine, Article, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, History and Philosophy of Science, Response to injury, Neoplasms, medicine, Animals, Humans, business.industry, General Neuroscience, Mesenchymal stem cell, Cancer, Cell Differentiation, medicine.disease, Adult Stem Cells, 030104 developmental biology, 030220 oncology & carcinogenesis, Cancer research, Tumor Stem Cells, New York City, medicine.symptom, Stem cell, business, Stem Cell Transplantation, Adult stem cell

الوصف: Adult stem cells are rare, undifferentiated cells found in all tissues of the body. Although normally kept in a quiescent, nondividing state, these cells can proliferate and differentiate to replace naturally dying cells within their tissue and to repair its wounds in response to injury. Due to their proliferative nature and ability to regenerate tissue, adult stem cells have the potential to treat a variety of degenerative diseases as well as aging. In addition, since stem cells are often thought to be the source of malignant tumors, understanding the mechanisms that keep their proliferative abilities in check can pave the way for new cancer therapies. While adult stem cells have had limited practical and clinical applications to date, several clinical trials of stem cell-based therapies are underway. This report details recent research presented at the New York Academy of Sciences on March 14, 2019 on understanding the factors that regulate stem cell activity and differentiation, with the hope of translating these findings into the clinic.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9993551267e4cde45af80100b3b9b21bTest
https://doi.org/10.1111/nyas.14243Test

المؤلفون: Sarah H. Park, Hang Yu, Smitha Jagadish, Lei Ding, Wayne N. Frankel, Umrao R. Monani, Yeojin Lee, Maoxue Tang, Carla Kim, Sabrina Petri, Carlos B. Rueda, Fanghua Li, Elizabeth M. C. Hillman, E. Dale Abel, Darryl C. De Vivo

المصدر: JCI Insight, Vol 6, Iss 3 (2021)
JCI Insight

مصطلحات موضوعية: Male, 0301 basic medicine, Angiogenesis, Haploinsufficiency, Mouse models, Mice, 0302 clinical medicine, Neurotrophic factors, Medicine, Mice, Knockout, Neurons, Glucose Transporter Type 1, biology, Brain, General Medicine, Cell biology, Endothelial stem cell, Phenotype, medicine.anatomical_structure, Gene Knockdown Techniques, 030220 oncology & carcinogenesis, Female, hormones, hormone substitutes, and hormone antagonists, Research Article, Carbohydrate Metabolism, Inborn Errors, endocrine system, Mice, 129 Strain, Monosaccharide Transport Proteins, Neovascularization, Physiologic, Monogenic diseases, 03 medical and health sciences, Animals, Neuroinflammation, business.industry, Brain-Derived Neurotrophic Factor, Endothelial Cells, nutritional and metabolic diseases, Transporter, carbohydrates (lipids), Disease Models, Animal, 030104 developmental biology, Animals, Newborn, biology.protein, GLUT1, Neuron, business, Neurological disorders, Neuroscience

الوصف: Paucity of the glucose transporter-1 (Glut1) protein resulting from haploinsufficiency of the SLC2A1 gene arrests cerebral angiogenesis and disrupts brain function to cause Glut1 deficiency syndrome (Glut1 DS). Restoring Glut1 to Glut1 DS model mice prevents disease, but the precise cellular sites of action of the transporter, its temporal requirements, and the mechanisms linking scarcity of the protein to brain cell dysfunction remain poorly understood. Here, we show that Glut1 functions in a cell-autonomous manner in the cerebral microvasculature to affect endothelial tip cells and, thus, brain angiogenesis. Moreover, brain endothelial cell-specific Glut1 depletion not only triggers a severe neuroinflammatory response in the Glut1 DS brain, but also reduces levels of brain-derived neurotrophic factor (BDNF) and causes overt disease. Reduced BDNF correlated with fewer neurons in the Glut1 DS brain. Controlled depletion of the protein demonstrated that brain pathology and disease severity was greatest when Glut1 scarcity was induced neonatally, during brain angiogenesis. Reducing Glut1 at later stages had mild or little effect. Our results suggest that targeting brain endothelial cells during early development is important to ensure proper brain angiogenesis, prevent neuroinflammation, maintain BDNF levels, and preserve neuron numbers. This requirement will be essential for any disease-modifying therapeutic strategy for Glut1 DS.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8c701f7fb2f58a8ac0a221c48aa6e554Test
https://doaj.org/article/1207bc382e6a434aa49d1260aea515b1Test

المؤلفون: Adam, Kroopnick, Dan Tong, Jia, Kathryn, Rimmer, Vivian S, Namale, Carla, Kim, Ugoada, Ofoezie, Kiran T, Thakur

المصدر: Journal of neurovirologyReferences. 27(5)

مصطلحات موضوعية: Central Nervous System, Herpesvirus 3, Human, Adrenal Cortex Hormones, Central Nervous System Viral Diseases, Humans, Steroids, Herpes Zoster

الوصف: The role of adjunctive corticosteroids in reducing morbidity and mortality of viral CNS infections remains poorly defined. Clinicians are often left in a quagmire regarding steroid use in complex and rapidly evolving viral CNS infections. Limited studies have explored the underlying mechanisms behind the potential benefit of steroids. Here, we describe steroid use in three cases of viral CNS disease: varicella zoster virus (VZV), Powassan virus, and influenza A-associated acute necrotizing encephalopathy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::0a72d6c5de1fa93fab6e22b6829f7da5Test
https://pubmed.ncbi.nlm.nih.gov/34596868Test

المؤلفون: Don Weiss, Sarah D. Torres, Jacqueline S. Gofshteyn, Jyoti V. Ankam, Mitashee Das, Kiran T. Thakur, Anusha K. Yeshokumar, Stephen Morse, Carla Kim, Brittany Glassberg, Emily C Schorr, Michael Harmon, Nicole Luche

مصطلحات موضوعية: Pediatrics, medicine.medical_specialty, business.industry, Retrospective analysis, Medicine, Bacterial meningitis, business, Tertiary care

الوصف: Background Outcomes in community-acquired bacterial meningitis (CABM) are significantly impacted by delays in diagnosis and treatment. This retrospective case series aims to describe the sociodemographic, epidemiological, and clinical variables including time to diagnosis and treatment of vaccine preventable CABM in three tertiary care settings in New York City (NYC). Methods A retrospective chart review was conducted of patients at Columbia University Irving Medical Center (CUIMC), Children’s Hospital of New York (CHONY), Mount Sinai Health System, and Weill Cornell Medical Center with CABM due to Haemophilus influenzae type B, Streptococcus pneumoniae, and Neisseria meningitidis between January 1, 2012 and December 31, 2017. A descriptive statistical analysis was performed. Results Our case series consisted of 36 patients, 24 (66.7%) females, and 12 (33.33%) males with a median age of 42 years (IQR 55 years). Median time from presentation to lumbar puncture (LP) was eight hours (IQR 7). The median time from hospital presentation to diagnosis was 12 hours (IQR 9), and the median time from LP to diagnosis was three hours (IQR 5). Delay in diagnosis which is defined by more than 8 hours from hospital presentation, occurred in 13 patients (36.1%) due to initial misdiagnosis, most commonly systemic febrile and/or viral infections and otitis media. Conclusions Despite evidence of the importance of early diagnosis and treatment for CABM, this case series shows the ongoing challenges with early clinical diagnosis. Misdiagnoses were an underlying reason for delays from presentation to LP and to antibiotic treatment in the majority of our patients. This study in NYC identifies ongoing major delays in diagnosis and antimicrobial treatment in CABM, and future studies are needed to identify mechanisms to improve time to antibiotic treatment and LP in CABM.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::8de26e1bfaacdc10204f2b8255ca37f2Test
https://doi.org/10.21203/rs.2.21841/v1Test