1,126 results match your criteria: "France A.H.; Hospital Clinic de Barcelona[Affiliation]"
Long-Term Depressive Symptom Trajectories and Midlife Cognition: The CARDIA Study.
Neurology
July 2024
From the Univ. Bordeaux (L.G.), Inserm, Bordeaux Population Health Research Center, Team VINTAGE, UMR 1219; Inserm, CIC1401-EC, Bordeaux, France; Department of Epidemiology (A.Z.A.H., F.M., P.L.), Mailman School of Public Health, Columbia University, NY; Division of Medicine (T.E.), Miller School of Medicine, University of Miami, FL; Clinical Research Institute (M.E.), Department of Internal Medicine, American University of Beirut, Lebanon; and Departments of Psychiatry (E.V., K.Y.), Neurology, and Epidemiology and Biostatistics, University of California, San Francisco.
Background And Objectives: The nature of associations between depressive symptoms and cognition early in the life course remains unclear, and racial differences in these associations are not well characterized. The aim of this study was to examine the relationship between trajectories of depressive symptom over 20 years, beginning in young adulthood, and cognitive functions in middle-age among Black and White adults.
Methods: We used prospective data from participants of the Coronary Artery Risk Development in Young Adults Study.
Dynamic label-free analysis of SARS-CoV-2 infection reveals virus-induced subcellular remodeling.
Nat Commun
June 2024
Deep Quantitative Biology Department, Nanolive SA, Tolochenaz, Switzerland.
Assessing the impact of SARS-CoV-2 on organelle dynamics allows a better understanding of the mechanisms of viral replication. We combine label-free holotomographic microscopy with Artificial Intelligence to visualize and quantify the subcellular changes triggered by SARS-CoV-2 infection. We study the dynamics of shape, position and dry mass of nucleoli, nuclei, lipid droplets and mitochondria within hundreds of single cells from early infection to syncytia formation and death.
View Article and Find Full Text PDFTirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis.
N Engl J Med
July 2024
From the Metabolic Dysfunction-Associated Steatotic Liver Disease Research Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of California at San Diego, La Jolla (R.L.), and Pacific Rim Pathology, San Diego (C.B.) - both in California; Eli Lilly (M.L.H., Y.T., B.B., D.A.R., A.N., M.C.B., A.H.), the Division of Gastroenterology and Hepatology, Department of Medicine, Indiana University School of Medicine (R.V.), and the Department of Pathology and Laboratory Medicine, Indiana University (O.W.C.) - all in Indianapolis; the Texas Liver Institute, University of Texas Health, San Antonio (E.J.L.); the Department of Hepato-Gastroenterology and Digestive Oncology, Angers University Hospital, and Hemodynamics, Interaction of Fibrosis and Hepatic Tumor Invasiveness Laboratory, Structure Fédérative de Recherche Interactions Cellulaires et Applications Thérapeutiques 4208, Angers University - both in Angers, France (J.B.); the Division of Gastroenterology, Department of Medical Sciences, University of Turin, Turin, Italy (E.B.); the Department of Gastroenterology and Hepatology, Yokohama City University, Yokohama, Japan (M.Y.); and the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health and Division of Gastroenterology, Hepatology and Nutrition, Virginia Commonwealth University School of Medicine, Richmond (A.J.S.).
Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with liver-related complications and death. The efficacy and safety of tirzepatide, an agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, in patients with MASH and moderate or severe fibrosis is unclear.
Methods: We conducted a phase 2, dose-finding, multicenter, double-blind, randomized, placebo-controlled trial involving participants with biopsy-confirmed MASH and stage F2 or F3 (moderate or severe) fibrosis.
Bulevirtide Combined with Pegylated Interferon for Chronic Hepatitis D.
N Engl J Med
July 2024
From Université de Paris-Cité, Department of Hepatology, Hôpital Beaujon Assistance Publique-Hôpitaux de Paris (AP-HP), Centre de Recherche sur l'Inflammation, INSERM Unité Mixte de Recherche 1149, Clichy (T.A.), Hôpital Saint Joseph, Marseille (M.B.), Sorbonne Université, Hôpital Pitié-Salpêtrière, AP-HP, Pitié-Salpétrière, INSERM Unité Mixte de Recherche S 1138, Centre de Recherche des Cordeliers (V.R.), and Hôpital Cochin, AP-HP, Université Paris-Cité (S.P.), Paris, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble (M.-N.H.), and Hospices Civils de Lyon, Université Claude Bernard Lyon 1, INSERM Unité 1052, Lyon Hepatology Institute, Lyon (F.Z.) - all in France; the Infectious Diseases Department, Sechenov University (V.C.), M.F. Vladimirsky Moscow Regional Research and Clinical Institute (P.B.), the Clinic of Modern Medicine (T.S.), and the Research Institute of Emergency Medicine n.a. N.V. Sklifosovsky (V.S.), Moscow, Medical Company "Hepatolog," Samara (V.M.), and South Ural State Medical University, Chelyabinsk (O.S.) - all in Russia; the Department of Pathophysiology and Transplantation, Division of Gastroenterology and Hepatology, Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico, and CRC "A. M. and A. Migliavacca" Center for Liver Disease, University of Milan - both in Milan (P.L.); Klinik für Gastroenterologie, Hepatologie, und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany (H.W.); Matei Bals National Institute of Infectious Diseases (A.S.-C.), Carol Davila University of Medicine and Pharmacy (A.S.-C., G.S.G.), and Dr. Victor Babes Foundation (G.S.G.), Infectious and Tropical Diseases Hospital (S.L.) - all in Bucharest, Romania; Infectious Clinical Hospital "T. Ciorba" (V.P.) and State University of Medicine and Pharmacy "Nicolae Testemitanu" (G.P.), Chisinau, Moldova; and Gilead Sciences, Foster City, CA (D.M., R.-C.M., L.Y., B.L.D., G.C., A.H.L., A.O.).
Article Synopsis
- A phase 2b trial tested the effectiveness of bulevirtide combined with peginterferon alfa-2a compared to peginterferon alone and bulevirtide alone in treating chronic hepatitis D over 48 weeks, with follow-up for an additional 48 weeks.* -
- Results showed that 46% of patients receiving the 10 mg bulevirtide and peginterferon had undetectable levels of the hepatitis D virus 24 weeks after treatment, compared to only 17% in the peginterferon alone group.* -
- The combination therapy indicated a statistically significant improvement in viral response, suggesting that bulevirtide and peginterferon could be a beneficial treatment strategy
Genome-wide meta-analyses of restless legs syndrome yield insights into genetic architecture, disease biology and risk prediction.
Nat Genet
June 2024
Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Article Synopsis
- Restless legs syndrome (RLS) affects nearly 10% of older adults, but many face delays in diagnosis and treatment.
- A large-scale genetic study identified 164 risk loci for RLS, enhancing our understanding of its genetic basis and showing similarities in genetic predispositions between sexes.
- Findings suggest potential drug targets, a relationship between RLS and diabetes, and highlight the effectiveness of machine learning in predicting RLS risk using genetic and other data.
Risk of Seizure Recurrence Due to Autoimmune Encephalitis With NMDAR, LGI1, CASPR2, and GABAR Antibodies: Implications for Return to Driving.
Neurol Neuroimmunol Neuroinflamm
July 2024
From the Department of Epileptology (Krankenhaus Mara) (A.R., C.G.B., U.S.), Medical School, Bielefeld University, Campus Bielefeld-Bethel; Society for Epilepsy Research (A.H.), Bielefeld, Germany; Department of Neurology (C.A.P., M.B.), Odense University Hospital; Department of Clinical Research (M.B.), University of Southern Denmark, Odense, Denmark; Department of Epileptology (T. Baumgartner, R.S.), University Hospital Bonn, Germany; Department of Immunology and Biotechnology (T. Berki), University of Pécs, Medical School, Hungary; Department of Neurology (J.B., Y.C., M.J.T., J.M.V.), Erasmus Medical Center, Rotterdam, Zuid-Holland, the Netherlands; Division of Epilepsy (J.W.B., K.M.S.), Department of Neurology, Mayo Clinic, Rochester, MN; NYU Comprehensive Epilepsy Center (A.C., C. Steriade), New York; French Reference Center on Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis (N.L.C.-P., A.F., J. Honnorat, S.M.-C.), Hospices Civils de Lyon, Hôpital Neurologique, UMR MELIS Inserm 1314 / CNRS 5284, Université Claude Bernard Lyon1, France; Department of Neurology (M.E., P.M.), Second Faculty of Medicine, Charles University, Motol University Hospital, Prague, Czech Republic; Department of Neurology (A.R.F., J. Hébert), Columbia University Irving Medical Center (CUIMC)/New York Presbyterian Hospital, New York; Department of Neurology (Z. Hayden), Medical School, University of Pécs, Pécs, Hungary; Division of Neurology (J. Hébert), University of Toronto, Ontario, Canada; Epilepsy-Center Berlin-Brandenburg (M.H., M.I.-F.), Department of Neurology, Charité - Universitätsmedizin Berlin, Germany; Department of Neurology (Z. Hong), West China Hospital, Sichuan University, Chengdu, China; Oxford Autoimmune Neurology Group (S.R.I., S.R., C.E.U.), Nuffield Department of Clinical Neurosciences, Oxford, United Kingdom; Department of Neurology and Neurosciences (S.R.I.), Mayo Clinic, Jacksonville, FL; Department of Neurology with Institute of Translational Neurology (S.K., C. Strippel), University Hospital Münster, Germany; Translational Neuroimmunology Group (S.R.), Kids Neuroscience Centre, Children's Hospital at Westmead; Faculty of Medicine and Health, University of Sydney; Department of Neurology, Concord Hospital, Sydney, Australia; Division of Neurology (C.E.U.), Department of Medicine, University of British Columbia, Vancouver, Canada; and Laboratory Krone (C.G.B.), Bad Salzuflen, Germany.
Background And Objectives: Patients with ongoing seizures are usually not allowed to drive. The prognosis for seizure freedom is favorable in patients with autoimmune encephalitis (AIE) with antibodies against NMDA receptor (NMDAR), leucine-rich glioma-inactivated 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and the gamma-aminobutyric-acid B receptor (GABAR). We hypothesized that after a seizure-free period of 3 months, patients with AIE have a seizure recurrence risk of <20% during the subsequent 12 months.
View Article and Find Full Text PDFArticle Synopsis
- Trastuzumab deruxtecan (T-DXd) showed significantly better effectiveness compared to trastuzumab emtansine (T-DM1) for patients with advanced HER2-positive metastatic breast cancer in the DESTINY-Breast03 study, with a follow-up of 41 months.
- The results revealed a median progression-free survival (PFS) of 29.0 months for T-DXd versus 7.2 months for T-DM1, along with improved overall survival (OS) of 52.6 months compared to 42.7 months.
- Safety profiles were consistent with earlier data, and no new severe cases of interstitial lung disease or pneumonitis were observed, indicating that
Asciminib in Newly Diagnosed Chronic Myeloid Leukemia.
N Engl J Med
September 2024
From Klinik für Innere Medizin II, Hematology/Oncology, Universitätsklinikum Jena and Comprehensive Cancer Center Central Germany, Campus Jena, Jena (A.H.), and the Department of Oncology and Hematology, Charité-Universitätsmedizin Berlin, Berlin (P.C.) - both in Germany; State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China (J.W.); Uijeongbu Eulji Medical Center, Geumo-dong, Uijeongbu-si (D.-W.K.), and the Department of Internal Medicine, Seoul National University Hospital, Biomedical Research Institute, Cancer Research Institute, Seoul National University College of Medicine, Seoul (I.K.) - both in South Korea; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto (D.D.H.K.); the Department of Internal Medicine, Hematology and Oncology, University Hospital Brno, and Masaryk University - both in Brno, Czech Republic (J.M.); the Department of Hematology, Singapore General Hospital, Singapore (Y.-T.G.); the Department of Hematology, Akita University, Akita City, Japan (N.T.); the Hematology Department, Institut Bergonié, Bordeaux (G.E.), and Novartis Pharma, Paris (S.I.) - both in France; Rocky Mountain Cancer Centers, Boulder, CO (D.A.); the Department of Leukemia, University of Texas M.D. Anderson Cancer Center, Houston (G.C.I.); the University of Chicago, Chicago (R.A.L.); CML Patients Group, CML Advocates Network, Turin, Italy (F.B.); Novartis Pharmaceuticals, East Hanover, NJ (S.K.); Novartis Pharma, Basel, Switzerland (T.M., K.M., L.Y., M.H.); Georgia Cancer Center at Augusta University, Augusta (J.E.C.); and the South Australian Health and Medical Research Institute and University of Adelaide, Adelaide, SA, Australia (T.P.H.).
Article Synopsis
- * The study included 201 patients receiving asciminib and 204 receiving investigator-selected TKIs, with results showing a higher major molecular response at week 48 for asciminib (67.7%) versus TKIs (49.0%), highlighting its potential advantages.
- * Asciminib also outperformed imatinib specifically, achieving a major molecular response in 69.3% of patients, compared to 40.2% with imatinib, suggesting it may be
Single-Cell Transcriptomic Analyses of Brain Parenchyma in Patients With New-Onset Refractory Status Epilepticus (NORSE).
Neurol Neuroimmunol Neuroinflamm
July 2024
From the Departments of Neurology and Immunobiology (A.H., L.Z., D.A.H.); Comprehensive Epilepsy Center (A.H., L.J.H.), Department of Neurology, Yale University School of Medicine, New Haven, CT; Sorbonne Université (A.H., I.P., B.M., V.N.), Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, APHP; AP-HP (A.H., V.N.), Epilepsy Unit and Clinical Neurophysiology Department, DMU Neurosciences, Hôpital de la Pitié-Salpêtrière, Paris, France; Department of Pathology (A.J.H.), Yale University School of Medicine, New Haven, CT; AP-HP (I.P., F.B.), Department of Neuropathology, DMU Neurosciences; AP-HP (B.M.), Department of Neurosurgery, Hôpital de la Pitié-Salpêtrière; and Center of Reference for Rare Epilepsies (V.N.), EpiCare, Hôpital de la Pitié-Salpêtrière, Paris, France.
Article Synopsis
- NORSE is a serious condition that affects otherwise healthy individuals, leading to prolonged seizures and often poor outcomes, and may be linked to immune system dysfunction.
- Researchers used advanced RNA sequencing to analyze brain samples from patients with NORSE and compared them to those with chronic temporal lobe epilepsy (TLE) and healthy controls, looking for connections between brain activity and immune responses.
- Findings showed that NORSE and TLE patients had more excitatory neurons than controls, and this imbalance, along with signs of active immune responses in the brain, suggests that inflammation may play a significant role in the heightened seizure activity in NORSE.
Seasonal Effects on Health Status and Parasitological Traits of an Invasive Minnow in Iberian Waters.
Animals (Basel)
May 2024
GRECO, Institute of Aquatic Ecology, University of Girona, M. Aurèlia Capmany 69, 17003 Girona, Spain.
Biological invasions are of special conservation concern in the Iberian Peninsula and other regions with high levels of endemism. Environmental variability, such as the seasonal fluctuations of Mediterranean streams, is a key factor that affects the spread of aquatic species in novel habitats. Fish parasites have a great potential to reflect such changes in the habitat features of freshwater ecosystems.
View Article and Find Full Text PDFDupilumab for COPD with Blood Eosinophil Evidence of Type 2 Inflammation.
N Engl J Med
June 2024
From the Division of Pulmonary, Allergy, and Critical Care Medicine, University of Alabama at Birmingham, Birmingham (S.P.B.); LungenClinic Grosshansdorf (member of the German Center for Lung Research [DZL]), Airway Research Center North (ARCN), Grosshansdorf (K.F.R.), Christian-Albrechts University, DZL, ARCN, Kiel (K.F.R.), and the Department of Medicine, Pulmonary and Critical Care Medicine, University of Marburg, DZL, Marburg (C.F.V.) - all in Germany; the Section on Pulmonary and Critical Care Medicine, Baylor College of Medicine, Houston (N.A.H.); King's Centre for Lung Health, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King's College London, London (M.B.), and the Medicines Evaluation Unit, Manchester University NHS Foundation Trust, University of Manchester, Manchester (D.S.) - both in the United Kingdom; the Division of Pulmonary, Critical Care, Allergy, and Sleep Medicine, University of California, San Francisco, San Francisco (S.A.C.); the Respiratory Medicine Unit, University of Ferrara, S. Anna University Hospital, Ferrara, Italy (A.P.); Sanofi, Bridgewater, NJ (E.L., X.L., D.B.); Sanofi, Cambridge, MA (N.P., R.M.A., L.B.R.); and Regeneron Pharmaceuticals, Tarrytown, NY (G.D.Y., B.A., J.M., A.B.).
Background: Dupilumab, a fully human monoclonal antibody that blocks the shared receptor component for interleukin-4 and interleukin-13, key and central drivers of type 2 inflammation, has shown efficacy and safety in a phase 3 trial involving patients with chronic obstructive pulmonary disease (COPD) and type 2 inflammation and an elevated risk of exacerbation. Whether the findings would be confirmed in a second phase 3 trial was unclear.
Methods: In a phase 3, double-blind, randomized trial, we assigned patients with COPD who had a blood eosinophil count of 300 cells per microliter or higher to receive subcutaneous dupilumab (300 mg) or placebo every 2 weeks.
Gene-Gene Interaction Between Factor- and Genes in Cerebral Venous Thrombosis: The BEAST Study.
Neurology
June 2024
From the Institute of Cardiovascular Research Royal Holloway (G.K.-D., P.S.), University of London (ICR2UL), United Kingdom; Fondazione IRCCS Ca'Granda-Ospedale Maggiore Policlinico (I.M., S.M.P., M.A., P.B., E.P.), A. Bianchi Bonomi Hemophilia and Thrombosis Center, Milan, Italy; Moncucco Hospital Group (I.M., E.G.), Lugano, Switzerland; Atherosclerosis and Thrombosis Unit (E.G., G.F., D.C.), I.R.C.C.S. Fondazione "Casa Sollievo della Sofferenza", S. Giovanni Rotondo; Medical and Surgical Department (E.G.), University of Foggia, Italy; Department of Obstetrics (E.G.), Gynaecology and Perinatal Medicine, First Sechenov University, Moscow, Russia; Neurology (S.H., J.P., E.H., T.T.), Helsinki University Hospital and University of Helsinki, Finland; Department of Clinical Neuroscience (E.L., K.J., T.T.), Institute of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg; Department of Neurology (E.L., K.J., T.T.), Sahlgrenska University Hospital, Gothenburg, Sweden; Medical Genetics (M. Margaglione, R.S.), Department of Clinical and Experimental Medicine, University of Foggia, Italy; Normandy University (V.L.C.D.), UNIROUEN, INSERM U1096, Rouen University Hospital, Vascular Hemostasis Unit and INSERM CIC-CRB 1404; Department of Neurology (A.B.T.), Rouen University Hospital, France; Neurology Unit (M.Z.), Stroke Unit, Azienda Unità Sanitaria Locale-IRCCS of Reggio Emilia; Department of Clinical and Experimental Medicine (M. Mancuso), Neurological Institute, University of Pisa, Italy; UMC Utrecht Brain Center (Y.M.R.), Department of Neurology and Neurosurgery, University Medical Center Utrecht, the Netherlands; Department of Neurology (B.B.W.), University of Virginia, Charlottesville, VA; Department of Neurology (J.J.M., A.T.), University of Utah, Salt Lake City; Department of Neurology (S.Z., M.C.B., J.M.C.), Amsterdam University Medical Centers, location AMC, Amsterdam Neuroscience, University of Amsterdam, the Netherlands; Department of Neurosciences (R.L.), Experimental Neurology, KU Leuven-University of Leuven; VIB Center for Brain & Disease Research; Department of Neurology, University Hospitals Leuven, Belgium; Department of Pathophysiology and Transplantation (E.P.), Università degli Studi di Milano, Milan; Department of Clinical and Experimental Sciences (P. Costa), Neurology Clinic; Division of Biology and Genetics (M.C.), Department of Molecular and Translational Medicine, University of Brescia, Italy; Stroke Center (D.A.D.S.), Centro Hospitalar Universitário Lisboa Central; CEEM and Institute of Anatomy (D.A.D.S.), Faculdade de Medicina; Instituto de Medicina Molecular João Lobo Antunes (D.A.D.S., J.M.F.), Universidade de Lisboa; Department of Neurosciences (S.G.R., P. Canhao), Hospital of Santa Maria, University of Lisbon, Portugal; Stroke Clinic (A.A.), National Institute of Neurology and Neurosurgery Manuel Velasco Suarez, Mexico City; Department of Neurology (K.S.), University of Athens School of Medicine, Eginition Hospital, Athens, Greece; McMaster University (A.H., R.D., G.P.), Pathology and Molecular Medicine, Population Health Research Institute and Thrombosis and Atherosclerosis Research Institute, Hamilton Health Sciences, Hamilton, Ontario, Canada; Department of Medicine and Surgery (A.P.), University of Parma, Stroke Care Program, Department of Emergency, Parma University Hospital, Italy; Stroke Division (V.N.T.), Florey Institute of Neuroscience and Mental Health, University of Melbourne, Heidelberg, Victoria, Australia; and Department of Clinical Neuroscience (P.S.), Imperial College Healthcare NHS Trust, London, United Kingdom.
Article Synopsis
- Gene-gene interactions are believed to play a significant role in the development of multifactorial diseases like cerebral venous thrombosis (CVT), highlighting potential causes of unexplained heritability.
- A study involving 882 CVT patients and 1,205 control participants found that specific gene variants significantly increased the likelihood of developing CVT, particularly when individuals had certain blood types.
- The research concluded that the interactions between specific genes could raise the risk of CVT by as much as 14 times, underscoring the importance of understanding these genetic factors in disease etiology.
Regression calibration of self-reported mobile phone use to optimize quantitative risk estimation in the COSMOS study.
Am J Epidemiol
October 2024
Institute for Risk Assessment Sciences, Utrecht University, 3584CM Utrecht, the Netherlands.
The Cohort Study of Mobile Phone Use and Health (COSMOS) has repeatedly collected self-reported and operator-recorded data on mobile phone use. Assessing health effects using self-reported information is prone to measurement error, but operator data were available prospectively for only part of the study population and did not cover past mobile phone use. To optimize the available data and reduce bias, we evaluated different statistical approaches for constructing mobile phone exposure histories within COSMOS.
View Article and Find Full Text PDFClinical practice guidelines for the care of girls and women with Turner syndrome.
Eur J Endocrinol
June 2024
Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio 45229, United States.
Article Synopsis
- Turner syndrome (TS) is a condition that affects about 50 out of every 100,000 females and requires comprehensive care throughout life due to its impact on multiple organs.
- Recent guidelines were developed that incorporate new advances in areas such as diagnosis, estrogen treatment, fertility, and neurocognitive health, following discussions and consensus meetings held in Europe and the U.S. in 2021, culminating in a key meeting in Aarhus, Denmark in June 2023.
- A diverse group of professional societies and advocacy groups collaborated to create these guidelines, which cover crucial aspects of TS care, including growth, puberty, cardiovascular health, and ongoing health monitoring throughout the patient's lifespan.
Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results.
Nat Med
May 2024
Prevail Therapeutics, a wholly owned subsidiary of Eli Lilly and Company, New York, NY, USA.
Article Synopsis
- GRN mutations lead to a condition known as FTD-GRN, which causes frontotemporal dementia; PR006 is a new gene therapy aimed at delivering the granulin gene using an adeno-associated virus.
- In initial studies, PR006 showed effectiveness in improving various pathological conditions related to FTD-GRN in animal models and was generally well tolerated in non-human primates.
- An ongoing human trial has reported that PR006 was safe for administration with some transient increases in progranulin levels in cerebrospinal fluid, although some patients experienced treatment-related adverse events, such as CSF pleocytosis and deep vein thrombosis.
Interaction of Norsecurinine-Type Oligomeric Alkaloids with α-Tubulin: A Molecular Docking Study.
Plants (Basel)
May 2024
CNRS, Inserm, CHU Lille, UMR9020-U1277-CANTHER-Cancer Heterogeneity Plasticity and Resistance to Therapies, OncoLille Institut, University of Lille, 59000 Lille, France.
The medicinal plant (Roxb ex. Willd) Baill., also known as (Roxb.
View Article and Find Full Text PDFEfficacy and Safety Analyses of Recombinant Factor VIIa in Severe Post-Partum Hemorrhage.
J Clin Med
May 2024
Hôpital Antoine Béclère, Assistance Publique-Hôpitaux de Paris, Université Paris Saclay, 92140 Clamart, France.
Article Synopsis
- The study aimed to assess the effectiveness and safety of recombinant activated factor VIIa (rFVIIa) for treating severe postpartum hemorrhage (sPPH) through a multi-center randomized controlled trial and observational studies.
- In the RCT, a significantly lower percentage of women treated with rFVIIa required invasive procedures compared to those who did not receive the treatment, although this was not confirmed in the observational studies.
- Safety analysis revealed no increase in thromboembolic events for rFVIIa-treated women compared to non-treated women, indicating that while the efficacy may vary, the treatment is relatively safe.
Exploiting in silico modelling to enhance translation of liver cell therapies from bench to bedside.
NPJ Regen Med
May 2024
Mathematical Institute, University of Oxford, Oxford, OX2 6GG, UK.
Cell therapies are emerging as promising treatments for a range of liver diseases but translational bottlenecks still remain including: securing and assessing the safe and effective delivery of cells to the disease site; ensuring successful cell engraftment and function; and preventing immunogenic responses. Here we highlight three therapies, each utilising a different cell type, at different stages in their clinical translation journey: transplantation of multipotent mesenchymal stromal/signalling cells, hepatocytes and macrophages. To overcome bottlenecks impeding clinical progression, we advocate for wider use of mechanistic in silico modelling approaches.
View Article and Find Full Text PDFPerformance of an Open-Source Large Language Model in Extracting Information from Free-Text Radiology Reports.
Radiol Artif Intell
July 2024
From the Department of Neuroradiology (B.L.G., A.L., C.B., J.P.P., G.K.), Department of Public Health (B.L.G., P.A., A.H.), and INclude Health Data Warehouse (C.G., L.S.), CHU Lille-Université Lille, Rue Emile Laine, 59000 Lille, France; Department of Radiology, UC Davis Health, Sacramento, Calif (L.H.B.); Université Lille, INSERM, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE - Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement, Lille, France (P.A., A.H.); INSERM, U1172-LilNCog-Lille Neuroscience & Cognition, Université Lille, Lille, France (J.P.P., G.K.); and UAR 2014-US 41-PLBS-Plateformes Lilloises en Biologie & Santé, Université Lille, Lille, France (J.P.P., G.K.).
Purpose To assess the performance of a local open-source large language model (LLM) in various information extraction tasks from real-life emergency brain MRI reports. Materials and Methods All consecutive emergency brain MRI reports written in 2022 from a French quaternary center were retrospectively reviewed. Two radiologists identified MRI scans that were performed in the emergency department for headaches.
View Article and Find Full Text PDFGenome sequence analyses identify novel risk loci for multiple system atrophy.
Neuron
July 2024
Neurodegenerative Diseases Research Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA; Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA. Electronic address:
Article Synopsis
- Multiple system atrophy (MSA) is a neurodegenerative disease that leads to symptoms like parkinsonism and ataxia, but its genetic causes are not well understood and treatment options are limited to supportive care.
- A comprehensive study involving the whole genome sequencing of nearly 900 MSA patients and over 7,000 controls discovered four key genetic risk factors associated with the disease.
- The research identified potential susceptibility genes and provided insights into how genetic variations influence gene expression in brain cells, offering a valuable resource for further studies on similar diseases.
Calcaneum-Achilles Tendon Allograft for Massive Posterosuperior Rotator Cuff Lesion With Bony Deficiency.
Arthrosc Tech
April 2024
Division of Orthopaedics and Trauma Surgery, Hôpital de La Tour, Meyrin, Switzerland.
Dealing with massive and irreparable rotator cuff tears presents intricate challenges. Concerning elder patients, either conservative management or reverse shoulder arthroplasty could be the most appropriate treatment. On the other hand, in younger patients, there is a wide spectrum of solutions, most of them being under evaluation and not completely validated.
View Article and Find Full Text PDFIdentifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers.
Nat Commun
April 2024
External Science and Innovation, Pfizer Worldwide Research, Development and Medical, Stockholm, Sweden.
Article Synopsis
- * Our research uncovered 40 proteins linked to cancer risks, including PLAUR for breast cancer and CTRB1 for pancreatic cancer, while also noting possible negative side effects like hypertension from altering these proteins.
- * We found 18 proteins that are associated with cancer risk and linked to existing drugs, plus 15 proteins not yet being studied for clinical use, enhancing our understanding of cancer causes and the implications of targeting these proteins for prevention.
Subgroup analyses from the phase 3 ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer.
NPJ Breast Cancer
April 2024
Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
In this post hoc analysis of the ASCENT study, we compared outcomes with sacituzumab govitecan (SG) vs single-agent chemotherapy in clinically important subgroups of patients with metastatic triple-negative breast cancer (mTNBC). Patients with mTNBC refractory to/relapsing after ≥2 prior chemotherapies (≥1 in the metastatic setting) were randomized 1:1 to receive SG or treatment of physician's choice (TPC) until unacceptable toxicity/progression. The primary endpoint was progression-free survival (PFS) per RECIST 1.
View Article and Find Full Text PDFDiscovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers.
Nature
May 2024
Novartis BioMedical Research, Basel, Switzerland.
The Werner syndrome RecQ helicase WRN was identified as a synthetic lethal target in cancer cells with microsatellite instability (MSI) by several genetic screens. Despite advances in treatment with immune checkpoint inhibitors, there is an unmet need in the treatment of MSI cancers. Here we report the structural, biochemical, cellular and pharmacological characterization of the clinical-stage WRN helicase inhibitor HRO761, which was identified through an innovative hit-finding and lead-optimization strategy.
View Article and Find Full Text PDFAugmented non-hallucinating large language models as medical information curators.
NPJ Digit Med
April 2024
Department of Computer Science, Universidad de Chile, Santiago, Chile.
Reliably processing and interlinking medical information has been recognized as a critical foundation to the digital transformation of medical workflows, and despite the development of medical ontologies, the optimization of these has been a major bottleneck to digital medicine. The advent of large language models has brought great excitement, and maybe a solution to the medicines’ ‘communication problem’ is in sight, but how can the known weaknesses of these models, such as hallucination and non-determinism, be tempered? Retrieval Augmented Generation, particularly through knowledge graphs, is an automated approach that can deliver structured reasoning and a model of truth alongside LLMs, relevant to information structuring and therefore also to decision support.
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