18 results match your criteria: "NC (A.J.R.); and Columbia University[Affiliation]"
AI powered quantification of nuclear morphology in cancers enables prediction of genome instability and prognosis.
NPJ Precis Oncol
June 2024
PathAI, Boston, MA, USA.
Article Synopsis
- The study focuses on creating a deep learning digital pathology tool for accurately detecting, segmenting, and classifying nuclei in cancer tissues, addressing challenges in quantifying nuclear morphology in histologic images.
- This tool was trained on nucleus annotations to analyze H&E-stained slides from various cancer cohorts (BRCA, LUAD, PRAD), revealing significant differences in nuclear features like shape and size linked to genomic instability and cancer prognosis.
- Results highlighted that certain nuclear characteristics, particularly in fibroblasts, were associated with patient survival outcomes and gene expression related to tumor biology, paving the way for better understanding of cancer biomarkers.
Genomic and Phylogenetic Characterisation of SARS-CoV-2 Genomes Isolated in Patients from Lambayeque Region, Peru.
Trop Med Infect Dis
February 2024
Faculty of Health Sciences, Universidad Científica del Sur, Lima 15307, Peru.
Objective: this study aims to identify and characterise genomic and phylogenetically isolated SARS-CoV-2 viral isolates in patients from Lambayeque, Peru.
Methods: Nasopharyngeal swabs were taken from patients from the Almanzor Aguinaga Asenjo Hospital, Chiclayo, Lambayeque, Peru, which had been considered mild, moderate, and severe cases of COVID-19. Patients had to have tested positive for COVID-19, using a positive RT-PCR for SARS-CoV-2.
Garetosmab in fibrodysplasia ossificans progressiva: a randomized, double-blind, placebo-controlled phase 2 trial.
Nat Med
October 2023
Departments of Orthopaedics, Medicine and the Center for Research in FOP & Related Disorders, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Article Synopsis
- - Fibrodysplasia ossificans progressiva (FOP) is a rare condition that causes painful heterotopic ossification in connective tissues, leading to disability.
- - In the LUMINA-1 phase 2 trial, adults with FOP were given either garetosmab (an activin A-blocking antibody) or a placebo over two 28-week periods, focusing on safety and effects on HO lesions.
- - Although the primary efficacy endpoint was not met in the first period, garetosmab significantly reduced the development of new HO lesions in the second period compared to placebo, with ongoing investigations into its effectiveness.
Integrated Proteomics Unveils Nuclear PDE3A2 as a Regulator of Cardiac Myocyte Hypertrophy.
Circ Res
March 2023
Department of Physiology, Anatomy and Genetics (G.S., K.S., D.K., A.Z., M.F., Y.-C.C., N.C.S., A.K., J.H., K.C.P., M.Z.), University of Oxford, United Kingdom.
Background: Signaling by cAMP is organized in multiple distinct subcellular nanodomains regulated by cAMP-hydrolyzing PDEs (phosphodiesterases). Cardiac β-adrenergic signaling has served as the prototypical system to elucidate cAMP compartmentalization. Although studies in cardiac myocytes have provided an understanding of the location and properties of a handful of cAMP subcellular compartments, an overall view of the cellular landscape of cAMP nanodomains is missing.
View Article and Find Full Text PDFSingle-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.
N Engl J Med
November 2022
From COMPASS Pathfinder (G.M.G., J.C.B., L.M., S.M., S.C.S., J.T., S.W., E.M.), the Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London (C. Bird, L.A.J., G.K., L.N.M., F.R., J.R., S. Ruffell, M. Seynaeve, A.H.Y.), the National Institute for Health and Care Research Clinical Research Facility, King's College Hospital NHS Foundation Trust (K.C.-C., J.C., A.D.), and South London and Maudsley NHS Foundation Trust, Bethlem Royal Hospital (L.A.J., L.N.M., J.R., A.H.Y.), London, and the Cumbria, Northumberland, Tyne and Wear Foundation Trust and Newcastle University, Newcastle (M.W.) - all in the United Kingdom; the Institute for Advanced Diagnostics and Therapeutics, Sheppard Pratt, Baltimore (S.T.A., M.F., T.L.M., S. Rudow); Sant Joan de Déu Hospital and the Sant Joan de Déu Research Foundation, Barcelona (O.A.); SUNY Downstate College of Medicine (P.C.A.), the New York State Psychiatric Institute (D.J.H., R.E.K., R.K., M.C.M., E.M.N.), and the Department of Psychiatry, Columbia University (D.J.H., R.K., M.C.M., E.M.N.) - all in New York; the Department of Psychiatry, Trinity Centre for Health Sciences, Tallaght University Hospital, Dublin (A.B., C. Brennan, L.B., J.R.K., V.O.); the Department of Psychiatry, University Medical Center (UMC) Utrecht Brain Center, University Medical Center Utrecht, Utrecht (R.E.B., H.M.H., A.I.H., M.H.B.K., S.R.O., M.C.R., A.R., M. Somers, L.V., P.Y.), the Research Department, GGz Centraal Innova, Amersfoort (R.E.B.), and the Department of Psychiatry, UMC Groningen, Groningen (J. Kamphuis, J.M., R.A.S.) - all in the Netherlands; the Department of Psychiatry, University of California San Diego (D.B., J. Kawasaki, S.K.P., D.P., S.S., A.S., S.Z.), and Kadima Neuropsychiatry Institute (D.F., S.K.P., A.M., D.S.), La Jolla, the Weill Institute for Neurosciences, University of California San Francisco, San Francisco (R.C.-H.), and the Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford (C.D., K.E., M.L.) - all in California; the Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta (B.W.D., J.L.M.-K., T.M.-C.); the Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, and the Department of Psychiatry, University of Toronto, Toronto (M.I.H.); the Department of Psychiatry, Aalborg University Hospital, and the Department of Clinical Medicine, Aalborg University, Aalborg, Denmark (R.W.L., R.E.N.); the National Institute of Mental Health, Klecany, Czech Republic (T.P.); Charité-Universitätsmedizin Berlin, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Berlin (D.R.); Duke University School of Medicine, Durham, NC (A.J.R.); and the University of Texas (UT) Harris County Psychiatric Center and the UT Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, UT Houston Medical School, Houston (J.C.S.).
Article Synopsis
- * Participants in the 25 mg group showed a significant reduction in depression scores after 3 weeks, with a mean change of -12.0, compared to -7.9 for 10 mg and -5.4 for the control group.
- * Although the higher dose showed benefits, many participants experienced adverse effects, including headache and nausea, and some reported suicidal thoughts, underscoring the need for further research.
Structure of the PAPP-A complex reveals mechanism of substrate recognition.
Nat Commun
September 2022
Calico Life Sciences LLC, South San Francisco, CA, USA.
Insulin-like growth factor (IGF) signaling is highly conserved and tightly regulated by proteases including Pregnancy-Associated Plasma Protein A (PAPP-A). PAPP-A and its paralog PAPP-A2 are metalloproteases that mediate IGF bioavailability through cleavage of IGF binding proteins (IGFBPs). Here, we present single-particle cryo-EM structures of the catalytically inactive mutant PAPP-A (E483A) in complex with a peptide from its substrate IGFBP5 (PAPP-A) and also in its substrate-free form, by leveraging the power of AlphaFold to generate a high quality predicted model as a starting template.
View Article and Find Full Text PDFPosttranscriptional Regulation of the Human LDL Receptor by the U2-Spliceosome.
Circ Res
January 2022
Institute for Clinical Chemistry, University and University Hospital Zurich, Switzerland (P.Z., G.P., J.R., S.V., M.Y., M.K., S.R., L.R., A.v.E.).
Background: The LDLR (low-density lipoprotein receptor) in the liver is the major determinant of LDL-cholesterol levels in human plasma. The discovery of genes that regulate the activity of LDLR helps to identify pathomechanisms of hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease.
Methods: We performed a genome-wide RNA interference screen for genes limiting the uptake of fluorescent LDL into Huh-7 hepatocarcinoma cells.
A BAFF/APRIL axis regulates obesogenic diet-driven weight gain.
Nat Commun
May 2021
Department of Pediatrics, The University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Article Synopsis
- The study investigates the role of B cell activating factor (BAFF) in regulating weight homeostasis and its effects on obesity resistance in mice.
- Overexpression of BAFF leads to protection against weight gain by promoting lipid metabolism and enhancing energy expenditure in both white and brown adipose tissues.
- Genetic deletion of BAFF and its homolog APRIL results in increased obesity, and these findings are relevant to human adipocytes, with higher levels of BAFF/APRIL linked to reduced BMI post-bariatric surgery.
The 'difficult-to-treat depression' and the 'response paradigm' models: Implications and relevance to patient management.
Aust N Z J Psychiatry
August 2021
Department of Psychological Medicine, South London and Maudsley NHS Foundation Trust, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Alterations in acylcarnitines, amines, and lipids inform about the mechanism of action of citalopram/escitalopram in major depression.
Transl Psychiatry
March 2021
Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, Durham, NC, USA.
Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for major depressive disorder (MDD), yet their mechanisms of action are not fully understood and their therapeutic benefit varies among individuals. We used a targeted metabolomics approach utilizing a panel of 180 metabolites to gain insights into mechanisms of action and response to citalopram/escitalopram. Plasma samples from 136 participants with MDD enrolled into the Mayo Pharmacogenomics Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS) were profiled at baseline and after 8 weeks of treatment.
View Article and Find Full Text PDFBupropion and Naltrexone in Methamphetamine Use Disorder.
N Engl J Med
January 2021
From the Peter O'Donnell Jr. Brain Institute at the University of Texas Southwestern Medical Center (M.H.T.) and the University of Texas Southwestern Medical Center (R.W., A.C., T.C., M.K., K.S.-W., S.W.), Dallas, the University of Texas Health Science Center at Houston, Houston (J.S.), and Texas Tech University, Permian Basin, Odessa (A.J.R.); the University of California, Los Angeles, Los Angeles (W.L., S. Shoptaw); the Emmes Company, Rockville (G.S., A.W.), and the National Institute on Drug Abuse Center for the Clinical Trials Network (U.E.G., S. Sparenborg [retired]), Rockville - both in Maryland; the San Francisco Department of Public Health and the University of California, San Francisco, San Francisco (P.C.); CODA, Portland, OR (K.W.); Hennepin Healthcare, University of Minnesota, Minneapolis (G.B.); Medical University of South Carolina, Charleston (S.C.S.); Duke-National University of Singapore, Singapore (A.J.R.); Duke Medical School, Durham, NC (A.J.R.); and Columbia University, New York (E.V.N.).
Background: The use of naltrexone plus bupropion to treat methamphetamine use disorder has not been well studied.
Methods: We conducted this multisite, double-blind, two-stage, placebo-controlled trial with the use of a sequential parallel comparison design to evaluate the efficacy and safety of extended-release injectable naltrexone (380 mg every 3 weeks) plus oral extended-release bupropion (450 mg per day) in adults with moderate or severe methamphetamine use disorder. In the first stage of the trial, participants were randomly assigned in a 0.
Reliability of the Modified TICI Score among Endovascular Neurosurgeons.
AJNR Am J Neuroradiol
August 2020
From the Department of Neurological Surgery (D.M.H., N.C.P., M.R.R., J.C.S.), Clinical Research Office (A.W.W.), Loyola University Stritch School of Medicine and Loyola University Medical Center, Maywood, Illinois.
Background And Purpose: The modified TICI score is the benchmark for quantifying reperfusion after mechanical thrombectomy. There has been limited investigation into the reliability of this score. We aim to identify intra-rater and inter-rater reliability of the mTICI score among endovascular neurosurgeons.
View Article and Find Full Text PDFMultisystem Inflammatory Syndrome in U.S. Children and Adolescents.
N Engl J Med
July 2020
From the COVID-19 Response, Centers for Disease Control and Prevention (L.R.F., E.B.R., J.P.C., M.W.T., M.M.P.), and the Division of Critical Care Medicine, Department of Pediatrics (K.M.T.), the Department of Pediatrics, Division of Infectious Diseases (P.J.), and the Department of Pediatrics, Division of Cardiology (M.E.O.), Emory University School of Medicine, Atlanta; Public Health Service Commissioned Corps, Rockville (L.R.F., E.B.R., M.M.P.), and the Department of Anesthesiology and Critical Care Medicine, Division of Pediatric Anesthesiology and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore (B.J.R.) - both in Maryland; the Department of Pediatrics, Division of Pediatric Critical Care, Bristol-Myers Squibb Children's Hospital, Robert Wood Johnson Medical School, Rutgers University (S.M. Horwitz), the Department of Pediatrics, Division of Population Health, Quality, and Implementation Sciences (PopQuIS), Rutgers Robert Wood Johnson Medical School (L.C.K.), New Brunswick, the Department of Pediatrics, Division of Pediatric Cardiology, Children's Hospital of New Jersey, Newark Beth Israel, Newark (R.F.W.), the Division of Hospital Medicine, Department of Pediatrics, Hackensack University Medical Center, Hackensack (K.N.C.), and the Division of Pediatric Critical Care, Department of Pediatrics, Saint Barnabas Medical Center, Livingston (S.J.G.) - all in New Jersey; the Department of Anesthesiology, Critical Care and Pain Medicine (M.M.N., A.G.R.), the Division of Immunology (M.B.F.S.), and the Department of Cardiology (J.W.N.), Boston Children's Hospital, and the Departments of Pediatrics (M.B.F.S., J.W.N., A.G.R.) and Anaesthesia (A.G.R.), Harvard Medical School, Boston, and the Department of Pediatrics, Pediatric Critical Care, Baystate Medical Center, Springfield (K.L.M.) - both in Massachusetts; the Department of Pediatrics, Division of Pediatric Critical Care Medicine, Central Michigan University, Detroit (S.M. Heidemann, A.A.M.); the Pediatric Critical Care Division, Maria Fareri Children's Hospital at Westchester Medical Center and New York Medical College, Valhalla (A.R.S., S.L.), Pediatric Critical Care Medicine, Department of Pediatrics, Icahn School of Medicine at the Mount Sinai Kravis Children's Hospital (S.P.Z., J.G.), the Division of Pediatric Infectious Diseases, Departments of Pediatrics and Microbiology, New York University Grossman School of Medicine (A.J.R.), Pediatric Critical Care, New York City Health and Hospitals, Kings County Hospital (M.A.K., H.A.), the Division of Pediatric Critical Care, Department of Pediatrics, SUNY Downstate Health Sciences University (S.D.), and the Department of Pediatrics, Division of Pediatric Critical Care, Maimonides Children's Hospital (A.D.), New York - all in New York; the Division of Critical Care, Department of Anesthesiology and Critical Care, University of Pennsylvania Perelman School of Medicine, Philadelphia (J.C.F.); the Department of Pediatrics, Division of Critical Care, Yale University School of Medicine, New Haven (J.S.G., A.G.), and the Division of Critical Care, Connecticut Children's, Hartford (R.M.P., C.L.C.) - both in Connecticut; the Department of Pediatrics, Section of Critical Care Medicine, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora (A.B.M.); the Division of Pediatric Critical Care Medicine, Department of Pediatrics, Advocate Children's Hospital, Chicago (V.H., S.R.); the Department of Pediatrics, Division of Pediatric Rheumatology, MetroHealth Medical Center, Case Western Reserve University (H.B.), and the Division of Pediatric Hospital Medicine, Rainbow Babies and Children's Hospital (A.L.), Cleveland; the Department of Pediatrics, Division of Cardiology, Louisiana State University Health Sciences Center and Children's Hospital of New Orleans, New Orleans (T.T.B.); the Department of Pediatrics, Division of Pediatric Critical Care Medicine, University of Washington, Seattle (L.S.S.); the Pediatric Critical Care Division, Department of Pediatrics, University of Texas Health Science Center at Houston, Houston (A.C.M.); the Department of Pediatrics, Department of Microbiology, Division of Infectious Diseases, University of Mississippi Medical Center, Jackson (C.V.H.); and the Division of Pediatric Infectious Diseases, Department of Pediatrics, Vanderbilt University Medical Center, Nashville (N.B.H.).
Background: Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.
Methods: We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States. The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month.
Metabolomic signature of exposure and response to citalopram/escitalopram in depressed outpatients.
Transl Psychiatry
July 2019
Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, Durham, NC, USA.
Metabolomics provides valuable tools for the study of drug effects, unraveling the mechanism of action and variation in response due to treatment. In this study we used electrochemistry-based targeted metabolomics to gain insights into the mechanisms of action of escitalopram/citalopram focusing on a set of 31 metabolites from neurotransmitter-related pathways. Overall, 290 unipolar patients with major depressive disorder were profiled at baseline, after 4 and 8 weeks of drug treatment.
View Article and Find Full Text PDFExamining the Roles of H3K4 Methylation States with Systematically Characterized Antibodies.
Mol Cell
October 2018
Department of Molecular Genetics and Cell Biology, The University of Chicago, Chicago, IL 60637, USA; Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL 60637, USA. Electronic address:
Histone post-translational modifications (PTMs) are important genomic regulators often studied by chromatin immunoprecipitation (ChIP), whereby their locations and relative abundance are inferred by antibody capture of nucleosomes and associated DNA. However, the specificity of antibodies within these experiments has not been systematically studied. Here, we use histone peptide arrays and internally calibrated ChIP (ICeChIP) to characterize 52 commercial antibodies purported to distinguish the H3K4 methylforms (me1, me2, and me3, with each ascribed distinct biological functions).
View Article and Find Full Text PDFImpact of short-chain galactooligosaccharides on the gut microbiome of lactose-intolerant individuals.
Proc Natl Acad Sci U S A
January 2017
Department of Food, Bioprocessing and Nutrition Sciences, North Carolina State University, Raleigh, NC 27695
Directed modulation of the colonic bacteria to metabolize lactose effectively is a potentially useful approach to improve lactose digestion and tolerance. A randomized, double-blind, multisite placebo-controlled trial conducted in human subjects demonstrated that administration of a highly purified (>95%) short-chain galactooligosaccharide (GOS), designated "RP-G28," significantly improved clinical outcomes for lactose digestion and tolerance. In these individuals, stool samples were collected pretreatment (day 0), after GOS treatment (day 36), and 30 d after GOS feeding stopped and consumption of dairy products was encouraged (day 66).
View Article and Find Full Text PDFEffect of Exercise Intensity on Glucose Requirements to Maintain Euglycemia During Exercise in Type 1 Diabetes.
J Clin Endocrinol Metab
March 2016
Department of Endocrinology and Diabetes (V.B.S., N.P., M.N.C., E.A.D., T.W.J.), Princess Margaret Hospital for Children, Perth, Western Australia 6840, Australia; and School of Paediatrics and Child Health (V.B.S., E.A.D., T.W.J.), School of Sport Science, Exercise, and Health (P.A.F.), and Telethon Kids Institute, The Centre for Child Health Research (R.J.D., A.J.R., N.P., H.C.R., M.N.C., E.A.D., T.W.J.), The University of Western Australia, Perth, Western Australia 6008, Australia.
Context: No recommendations exist to inform the carbohydrate amount required to prevent hypoglycemia associated with exercise of different intensities in individuals with type 1 diabetes (T1D).
Objective: The relationship between exercise intensity and carbohydrate requirements to maintain stable euglycemia in individuals with T1D remains to be determined. It was predicted that an "inverted-U" relationship exists between exercise intensity and the amount of glucose required to prevent hypoglycemia during exercise at basal insulinemia.