2,257 results match your criteria: "C.H. - both in California; and the Cleveland Clinic[Affiliation]"
Impact of catastrophic brain injury guidelines on organ donation rates: Results of an EAST multicenter trial.
J Trauma Acute Care Surg
January 2025
From the Department of Surgery (K.D.N., D. Tatum, A.P., J.C.D., A.S.A., E.I., B.M., E.C., S.T.), Tulane University School of Medicine, New Orleans, Louisiana; Department of Surgery (K.D.N.), Harbor-UCLA Medical Center, Torrance, California; Department of Surgery (M.B.P., A.W.M., A.B.P.), Vanderbilt University Medical Center, Nashville, Tennessee; Department of Surgery (J.N., C.A.), University of California-Irvine, Orange, California; Department of Surgery (P.O.U., A. Stiles, C.S.), Wake Med, Raleigh, North Carolina; Department of Surgery (J.D. Stodghill, T.M.), Virginia Tech Carilion School of Medicine, Roanoke, Virginia; Department of Surgery (R.M.B., S.A.Z., B. Shammassian, A.A.S.), Louisiana State University Health, New Orleans, Louisiana;Department of Surgery (T.E., I.A., P.M., J. Metheny), Cooper Medical School of Rowan University, Camden, New Jersey; Department of Surgery (M.S.F., M.D.P.), Lehigh Valley Health Network, Allentown, Pennsylvania; Department of Surgery (O.T.M., P.S.), Valleywise Health Medical Center, Phoenix, Arizona; Department of Surgery (D.T.-W.W., J.S.), Arrowhead Regional Medical Center, Colton, California; Department of Surgery (J.D. Sciarretta, P.K.), Emory University School of Medicine, Atlanta, Georgia; Department of Surgery (R.H., D.G.), Loma Linda University Medical Center, Loma Linda, California; Department of Surgery (J. Murry, K. Meadows), UT Health Tyler, Tyler, Texas; Department of Surgery (L.E.J., J.M.W.), Ascension St. Vincent Hospital, Indianapolis, Indiana; Department of Surgery (A.C.B.), University of Kentucky Healthcare, Lexington, Kentucky;17 DeBusk College of Osteopathic Medicine (B. Smith), Lincoln Memorial University, Harrogate, Tennessee; Department of Surgery (S.L.M., N.P.), Conemaugh Memorial Medical Center, Johnstown, Pennsylvania; Department of Surgery (D. Tabello, E.T.), Inova Health System, Falls Church, Virginia; Department of Surgery (S.M.C., F.A.), King Saud Medical City, Riyadh, Saudi Arabia;Department of Surgery (B.S.M., M.A.W.), University of Minnesota, Minneapolis, Minnesota;22 Department of Surgery (T.H.J., G.D.), Our Lady of the Lake Regional Medical Center, Baton Rouge, Louisiana;23 Department of 'Surgery (J.A.M., D.R.), Thomas Jefferson University Hospital, Philadelphia, Pennsylvania;24 Department of Surgery (J.M.H., K.L.), Ascension Via Christi Hospitals Wichita, Wichita, Kansas;25 Department of Surgery (K. Matsushima, S.P.), Los Angeles General Medical Center, Los Angeles, California; Department of Surgery (A. Santos, K.S.), Texas Tech University Health Science Center; Department of Surgery (C.B.), Covenant Medical Center, Lubbock, Texas; Department of Surgery (R.S., S.V.), Bronson Methodist Hospital, Kalamazoo, Michigan; Department of Surgery (R.J.J., R.C.H.), College of Medicine Chattanooga, University of Tennessee, Chattanooga, Tennessee; Department of Surgery (S.L.), Warren Alpert Medical School at Brown University, Providence, Rhode Island; Department of Surgery (N.B., W.A.), Tufts Medical Center, Boston, Massachusetts; Department of Surgery (M.J.L., H.M.), Research Medical Center, Kansas City, Missouri; Department of Surgery (R.P.D., C.A.F.), University of Texas Southwestern Medical Center, Dallas, Texas; Department of Surgery (C.A.F.), Brody School of Medicine at East Carolina, Greenville, North Carolina; Department of Surgery (W.T.H.T., Y.T.), University of Nebraska Medical Center, Omaha, Nevada; Department of Surgery (V.M., F.M.), U General University Hospital of Patras, Pio, Greece; and Department of Surgery (J.D.B., D.R.M.), Broward Health Medical Center, Fort Lauderdale, Florida.
Article Synopsis
- One third of organ donors experience catastrophic brain injury (CBI), but there’s no standardized management for traumatic CBI among trauma centers, leading to variability in practices.
- A multicenter trial involving 33 trauma centers analyzed 790 CBI patients to investigate whether institutions with CBI guidelines had higher organ donation rates.
- While centers with CBI guidelines showed greater use of certain treatments, the presence of guidelines did not significantly increase organ donation rates; however, hormone therapies were linked to a higher likelihood of donation.
Self-reported hearing loss is associated with faster cognitive and functional decline but not diagnostic conversion in the ADNI cohort.
Alzheimers Dement
November 2024
Alzheimer's Disease Research Unit, Yale University School of Medicine, New Haven, Connecticut, USA.
Introduction: Hearing loss is identified as one of the largest modifiable risk factors for cognitive impairment and dementia. Studies evaluating this relationship have yielded mixed results.
Methods: We investigated the longitudinal relationship between self-reported hearing loss and cognitive/functional performance in 695 cognitively normal (CN) and 941 participants with mild cognitive impairment (MCI) enrolled in the Alzheimer's Disease Neuroimaging Initiative.
Stereoselective Vinylic C-H Addition via Metallaphotoredox Migration.
Angew Chem Int Ed Engl
September 2024
State Key Laboratory of Coordination Chemistry, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210093, China.
Geometrically defined allylic alcohols with SE, SZ, RE and RZ stereoisomers serve as valuable intermediates in synthetic chemistry, attributed to the stereoselective transformations enabled by the alkenyl and hydroxyl functionalities. When an ideal scenario presents itself with four distinct stereoisomers as potential products, the simultaneous control vicinal stereochemistry in a single step would offer a direct pathway to any desired stereoisomer. Here, we unveil a metallaphotoredox migration strategy to access stereodefined allylic alcohols through vinylic C-H activation with aldehydes.
View Article and Find Full Text PDFIdentification of NanoLuciferase Substrates Transported by Human ABCB1 and ABCG2 and Their Zebrafish Homologs at the Blood-Brain Barrier.
Mol Pharmacol
November 2024
Fischell Department of Bioengineering, University of Maryland, College Park, Maryland (J.A.Q., C.T.I., H.-C.H.); Laboratory of Cell Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (J.A.Q., S.S., R.W.R., C.C.L., C.T.I., J.R.T., M.M.G.); and Promega Corporation, San Luis Obispo, California (J.R.W., W.Z.)
ATP-binding cassette (ABC) transporters expressed at the blood-brain barrier (BBB) impede delivery of therapeutic agents to the brain, including agents to treat neurodegenerative diseases and primary and metastatic brain cancers. Two transporters, ABCB1 and ABCG2, are highly expressed at the BBB and are responsible for the efflux of numerous clinically useful chemotherapeutic agents, including irinotecan, paclitaxel, and doxorubicin. Based on a previous mouse model, we have generated transgenic zebrafish in which expression of NanoLuciferase (NanoLuc) is controlled by the promoter of glial fibrillary acidic protein, leading to expression in zebrafish glia.
View Article and Find Full Text PDFGene Therapy with Fidanacogene Elaparvovec in Adults with Hemophilia B.
N Engl J Med
September 2024
From the Departments of Medicine and of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia (A.C.), and Pfizer, Collegeville (J.F., J.R.) - both in Pennsylvania; the Division of Hematology, Department of Pediatrics, Ege University Faculty of Medicine, Izmir, Turkey (K.K.); the Department of Hematology, Hemophilia Care and Research, Necker Hospital, Institut Imagine, Paris (L.F.); the Center for Rare Disease and Hemophilia, Taichung Veterans General Hospital, Taichung, Taiwan (J.-D.W.); the Department of Translational Medicine, Lund University, Lund, and the Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Malmö - both in Sweden (J.A.); Instituto de Hematologia do Estado do Rio de Janeiro, Rio de Janeiro (M.H.C.), and Hemocentro UNICAMP, Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas (M.C.O.) - both in Brazil; the Departments of Health Research Methods, Evidence, and Impact and of Medicine, McMaster University, Hamilton, ON (A. Iorio), and the Division of Hematology, St. Michael's Hospital, University of Toronto, Toronto (J.T.) - both in Canada; the Blood Transfusion Center, National Reference Center for Congenital Bleeding Disorders, Laiko General Hospital, Athens (O.K.-F.); Vivantes Hospital in Friedrichshain, Berlin (R.K.), and the Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, and the Center for Rare Diseases Bonn, University Clinic Bonn, Bonn (J.B.O.) - all in Germany; Indiana Hemophilia and Thrombosis Center, Indianapolis (A.D.S.); the Hemostasis and Thrombosis Unit, Division of Hematology, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels (C.H.); the Division of Hematology, National Center for Child Health and Development, Tokyo (A. Ishiguro); the Departments of Medicine and of Laboratory Medicine, University of California, San Francisco, San Francisco (A.D.L.); the Faculty of Medicine and Health, Central Clinical School, and the Gene and Stem Cell Therapy Program, Centenary Institute, University of Sydney, and the Department of Cell and Molecular Therapies, Royal Prince Alfred Hospital - all in Sydney (J.E.J.R.); Pfizer, New York (A.F.); Pfizer, Groton, CT (J.M.); Pfizer, Rome (F.B.); and Pfizer, Cambridge, MA (P.S.).
Article Synopsis
- Fidanacogene elaparvovec is a genetic therapy for hemophilia B that showed promising results in a phase 1-2a study, maintaining high levels of factor IX activity.* -
- In a phase 3 study involving men aged 18 to 65 with severe hemophilia B, the therapy led to a significant 71% reduction in bleeding episodes over 15 months compared to standard prophylactic treatment.* -
- Despite some participants needing glucocorticoids for side effects, the therapy was generally safe, with no serious adverse infusion events reported.*
Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic.
Cell
September 2024
Institut d'Écologie et des Sciences de l'Environnement (IEES-Paris, UMR 7618), CNRS, Sorbonne Université, UPEC, IRD, INRAE, Paris, France. Electronic address:
Article Synopsis
- Zoonotic viruses, like SARS-CoV-2, can spill over from animals to humans, often linked to animal trade, with COVID-19 traced back to the Huanan Seafood Wholesale Market.
- Analysis of environmental samples from the market in early 2020 shows high genetic diversity of SARS-CoV-2, especially near a wildlife stall that had a variety of wildlife DNA, including potential intermediate hosts.
- The research combines genomic techniques to identify specific animal species and suggest which ones should be prioritized for further research on their role in transmitting the virus.
Expression, purification, and biochemical characterization of micro- and macroalgal kainoid synthases.
Methods Enzymol
September 2024
Department of Chemistry and Biochemistry, University of California, Santa Cruz, CA, United States. Electronic address:
Kainoid natural products are a series of potent ionotropic glutamate receptor agonists produced by a variety of divergent marine micro- and macro-algae. The key biosynthetic step in the construction of the pyrrolidine ring pharmacophore involves a unique branch of non-heme iron α-ketoglutarate dependent dioxygenases (Fe/αKGs) termed the kainoid synthases. These Fe/αKG homologs catalyze a stereoselective C-H abstraction followed by a radical carbon-carbon bond reaction to form the bioactive core on N-prenylated L-glutamic acid substrates.
View Article and Find Full Text PDFIntravenous Thrombolysis in Patients With Cervical Artery Dissection: A Secondary Analysis of the STOP-CAD Study.
Neurology
October 2024
From the Department of Neurology (L.S., F. Akpokiere, D.M.M., K.P., V.D., K.B., T.M.B., N.S.K., F. Khan, C.S., N. Mohammadzadeh, E.D.G., K.F., S. Yaghi), Warren Alpert Medical School of Brown University, Providence, RI; Vancouver Stroke Program (T.S.F., L.Z., P.G.), Division of Neurology, University of British Columbia, Vancouver, Canada; Department of Neurology (C.R.L.G.), Atrium Health, Charlotte, NC; Department of Neurology (J. Muppa, N.H.), University of Massachusetts Chan Medical School, Worcester; Department of Neurology (M. Affan, O.U.H.L.), University of Minnesota, Minneapolis; Department of Neurology (M.R.H., K.A., D.J.S., M. Arnold), Inselspital, University Hospital and University of Bern, Switzerland; Department of Neurology (S.S.O., R. Crandall), University of Colorado, Denver; Department of Neurology (E.L.), Weill Cornell Medicine, New York; ; Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suarez (D.L.-M., A. Arauz), Mexico City, Mexico; Service de neurologie (A.N., M.B., E.T.), Université Caen Normandie, CHU Caen Normandie, France; Department of Neurology (J.A.S., J.S.-F., V.B.), Coimbra University, ; Department of Internal Medicine (P.C.-C., M.T.B.), São João University Hospital, Porto, Portugal; Department of Neurology (M.K., D.M.), Corewell Health, Grand Rapids, MI; Department of Neurology (M.K.), Mayo Clinic, Rochester, MN; Department of Neurology (A.R., O.K.), University of Pennsylvania, Philadelphia; Neurology and Neurorehabilitation (J.E.K., S.T.E., C.T.), University Department of Geriatric Medicine FELIX PLATTER, Department of Clinical Research, University of Basel, and University Hospital Basel, Switzerland; Stroke Center (D.A.d.S.), Centro Hospitalar Universitário Lisboa Central, and Institute of Anatomy, Faculdade de Medicina da Universidade de Lisboa; Department of Neurology (M.D.S.); Department of Neuroradiology (S.B.R.), Centro Hospitalar Universitário Lisboa Central, Lisbon, Portugal; Vancouver Stroke Program (S. Mancini), Division of Neurology, University of British Columbia, Vancouver, Canada; Department of Neurology (I.M., R.R.L.), Hadassah-Hebrew University Medical Center, Jerusalem, Israel; Department of Neurology with Experimental Neurology (R.V.R., C.H.N.), Charite Universitätsmedizin-Berlin and Center for Stroke Research, Berlin, and Berlin Institute of Health, Germany; Department of Neurosciences (R. Choi, J. MacDonald), ChristianaCare, Newark, DE; Department of Neurology (R.B.S.), University of California at San Diego; Department of Neurology (X.G.), Loma Linda University, Loma Linda, CA; Department of Neurology (M. Ghannam, M. Almajali, E.A.S.), University of Iowa, Iowa City; Department of Neurosciences (B.R., F.Z.-E., A.P.), Université de Montréal, Canada; Department of Neurology (A.C.F., M.F.B., D.C.), Hospital de Santa Maria, Centro de Estudos Egas Moniz, Faculdade de Medicina, Universidade de Lisboa, Portugal; Neurology and Stroke Unit (M. Romoli, G.D.M., M.L.), Department of Neuroscience, Bufalini Hospital, Cesena, Italy; Department of Neurology (Z.K., K.J.G.), Mayo Clinic, Rochester, MN; Department of Neurology (L.K., J.A.F.), NYU Langone Health, New York; Department of Neurology (J.Y.A., J.A.G.), Washington University, Saint Louis, MO; Neurology Unit, Stroke Unit (M. Zedde, I.G.), Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia; Neuroradiology Unit (R.P.), Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia; Department of Internal Medicine (H.N.), Centro Hospital Universitario do Algarve, Faro, Portugal; Department of Neurology (D.S.L., A.M.), University of California at Los Angeles; Department of Neurology (A.C., B.M.G., R.W.), Duke University, Durham, NC; Department of Neurology (W.K.), University of North Carolina Health Rex, Raleigh; Department of Neurology (S.A.K., M. Anadani), Medical University of South Carolina, Charleston, SC; Department of Neurosurgery (K.P.K.), Medical University of South Carolina, Charleston, SC; Department of Neurology (A.E., L.C., R.C.R., Y.N.A., E.A.M.), University of Cincinnati Medical Center, OH; Department of Neurology (E.B., T.L.T.), University of Alabama at Birmingham; Department of Neurology (M.R.-G., M. Requena), University Hospital Vall d'Hebron, Barcelona, Spain; Department of Neurology (F.G.S.V., J.O.G.), University of Oklahoma; Department of Neurology (V.M.), Einstein-Jefferson Healthcare Network, Philadelphia, PA; Department of Neurology (A.H.), University of Utah, Salt Lake City; Department of Neurology (A.H.); Department of Neurology (S. Sanchez, A.S.Z., Y.K.C., R.S.), Yale New Haven Hospital, New Haven, CT; Department of Neurology (V.Y.V.), All India Institute of Medical Sciences, New Delhi, India; Department of Neurology (S. Yaddanapudi, L.A., A. Browngoehl), Thomas Jefferson University, Philadelphia, PA; Department of Neurology (T.R., R.D., Z.L.), Wake Forest Medical Center, NC; Department of Neurology (M.P., J.E.S.), Cooper University, Camden, NJ; Department of Neurology (S. Mayer, J.Z.W.), Columbia University Medical Center, New York, NY; Department of Neurology (J.P.M., D.K.), Hospital de Egas Moniz, Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal; Department of Neurology (P.K., T.N.N.), Boston Medical Center, MA; Department of Neurology (S.D.A., Z.S., A. Balabhadra, S.P.), Hartford Hospital, CT; Department of Neurology (T.S.), Hospital Moinhos de Vento; Department of Neurology (S.C.M., G.P.M.), Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil; Department of Neurology (Y.D.K.), Yonsei University, Seoul, South Korea; Department of Neurology (B.K., C.E.), University of Tennessee at Memphis; Department of Neurology (S. Lingam, A.Y.Q.), Kansas University Medical Center, Kansas City; Department of Neurology (S.F., A. Alvarado), Western Ontario University, London, Canada; Department of Neurology (F. Khasiyev, G.L.), Saint Louis University, MO; Department of Neurology and Stroke Unit (M.M., V.T.), AOOR Villa Sofia-V. Cervello, Palermo, Italy; First Department of Neurology (A.T., V.T.-P.), National and Kapodistrian University of Athens, Greece; Department of Neurology (M.M.M.-M., V.C.W.), Centro Médico Nacional Siglo XXI IMSS., México City; Department of Neurology (F.I., S.E.E.J.), The Miriam Hospital, Providence, RI; Department of Neurocritical Care (S. Liu, M. Zhou), The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology, Hefei, China; Department of Neurology (M.M.A., F. Ali, M.S.), West Virginia University, WV; Department of Neurology (R.Z.M., T.K.-H.), University of Chicago, IL; Department of Neurology (F.S., J.Z.), Sir Run Run Shaw Hospital of Zhejiang University Medical School, Hangzhou, China; Department of Neurology (D.S., J.S., N. Mongare), Aga Khan University, Nairobi, Kenya; Department of Neurology (A.N.S., R.G., Shayak Sen), Cedars Sinai Medical Center, Los Angeles, CA; Department of Neurology (M. Ghani, M.E.), University of Louisville, KY; and Department of Economics (H.X.), University of California, Santa Barbara.
Article Synopsis
- Cervical artery dissection (CeAD) is a leading cause of ischemic strokes in young adults, and this study explored the effects of intravenous thrombolysis (IVT) on patients with CeAD and stroke symptoms.
- Analyzed data from the STOP-CAD study, it found that IVT significantly improved functional independence after 90 days in patients without increasing the risk of symptomatic intracranial hemorrhage.
- The results suggest that IVT is a beneficial treatment for eligible patients with CeAD, aligning with current medical guidelines on its use.
Assessing the Performance of Models from the 2022 RSNA Cervical Spine Fracture Detection Competition at a Level I Trauma Center.
Radiol Artif Intell
November 2024
From the Edward S. Rogers Department of Electrical and Computer Engineering (Z.H., W.L., E.S.), Department of Medical Imaging, Faculty of Medicine (M.P., S.M., R.M., E.C.), Faculty of Medicine (M.N., J.W., C.W.), and Division of Neurosurgery, Department of Surgery (J.W., C.W.), University of Toronto, 40 St George St, Toronto, ON, Canada M5S 3G4; Department of Medical Imaging (H.M.L., M.N., S.M., R.M., E.C.) and Li Ka Shing Knowledge Institute (S.M., J.W., C.W., E.C.), St Michael's Hospital, Unity Health Toronto, Toronto, Canada; The Jackson Laboratory, Bar Harbor, Maine (R.L.B.); Standard School of Medicine, Stanford University, Stanford, Calif (K.W.Y.); H2O.ai, Mountain View, Calif (Q.H., P.S., P.P.); School of Computer Science, University of Birmingham, Birmingham, UK (H.C.); DoubleYard, Edulab Group, Boston, Ireland (D.H.); Mapbox, London, UK (S.S.); NVIDIA, Santa Clara, Calif (C.H.); Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass (I.P.); University of London, Goldsmiths, London, UK (H.S.); Department of Radiology, The Ohio State University, Columbus, Ohio (L.M.P.); Department of Radiology, Division of Neuroradiology, Thomas Jefferson University, Philadelphia, Pa (A.E.F.); Universidade Federal de São Paulo (Unifesp), São Paulo, Brazil (F.C.K.); Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, Calif (J.T.); Department of Radiology and Imaging Sciences, University of Utah, Salt Lake City, Utah (T.R.); and North York General Hospital, Toronto, Canada (E.S.).
Purpose To evaluate the performance of the top models from the RSNA 2022 Cervical Spine Fracture Detection challenge on a clinical test dataset of both noncontrast and contrast-enhanced CT scans acquired at a level I trauma center. Materials and Methods Seven top-performing models in the RSNA 2022 Cervical Spine Fracture Detection challenge were retrospectively evaluated on a clinical test set of 1828 CT scans (from 1829 series: 130 positive for fracture, 1699 negative for fracture; 1308 noncontrast, 521 contrast enhanced) from 1779 patients (mean age, 55.8 years ± 22.
View Article and Find Full Text PDFAltered Cell Clusters and Upregulated Aqp1 in Connexin 50 Knockout Lens Epithelium.
Invest Ophthalmol Vis Sci
September 2024
Herbert Wertheim School of Optometry and Vision Science Program, University of California at Berkeley, Berkeley, California, United States.
Purpose: To characterize the heterogeneity and cell clusters of postnatal lens epithelial cells (LECs) and to investigate the downstream targets of connexin 50 (Cx50) in the regulation of lens homeostasis and lens growth. To determine differentially expressed genes (DEGs) in the connexin 50 knockout (Cx50KO) lens epithelial cells that shed light on novel mechanism underlying the cataract and small size of the Cx50KO lenses.
Methods: Single-cell RNA sequencing (scRNA-seq) of lens epithelial cells isolated from one-month-old Cx50KO and wild-type (WT) mice were performed.
Trastuzumab Deruxtecan after Endocrine Therapy in Metastatic Breast Cancer.
N Engl J Med
September 2024
From Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, and Massachusetts General Hospital, Boston, MA (A.B.); the Department of Medical Oncology, Fudan University Shanghai Cancer Center, and the Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (X.H.), and Harbin Medical University Cancer Hospital, Harbin (Q.Z.) - all in China; the Division of Medical Oncology, National Cancer Center Singapore, Singapore (R.D.); National Cancer Center Hospital, Tokyo (K.Y.); the Latin American Cooperative Oncology Group, Porto Alegre, Brazil (C.H.B.); Texas Oncology and US Oncology, Baylor University Medical Center, Dallas (J.A.O.); the Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium (H.W.); the Department of Medical Oncology, Institut Curie and Université Paris Cité, Paris (J.-Y.P.), Centre François Baclesse, Caen (C.L.), and the Department of Medical Oncology, Institut du Cancer de Montpellier, Université de Montpellier, INSERM Unité 1194, Montpellier (W.J.) - all in France; Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Barcelona (C.S.); the Department of Oncology, Santo Stefano Hospital, Azienda Unità Sanitaria Locale Toscana Centro, Prato (L.B.), and the European Institute of Oncology, IRCCS, and the Department of Oncology and Hematology-Oncology, University of Milan, Milan (G.C.) - all in Italy; the Division of Medical Oncology, Yonsei Cancer Center (J.S.), and the Department of Internal Medicine, Seoul National University Hospital (S.-A.I.) - both in Seoul, South Korea; Clinical Development, Late-Stage Development, Oncology Research and Development, AstraZeneca, Cambridge, United Kingdom (N.B., G.P.); and Biometrics Oncology, Late-Stage Development, Oncology Research and Development, AstraZeneca, Waltham, MA (J.K.).
Background: Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy.
Methods: We conducted a phase 3, multicenter, open-label trial involving patients with hormone receptor-positive metastatic breast cancer with low HER2 expression (a score of 1+ or 2+ on immunohistochemical [IHC] analysis and negative results on in situ hybridization) or ultralow HER2 expression (IHC 0 with membrane staining) who had received one or more lines of endocrine-based therapy and no previous chemotherapy for metastatic breast cancer.
Comparison of Results from Two Commercially Available In-House Tissue-Based Comprehensive Genomic Profiling Solutions: Research Use Only AVENIO Tumor Tissue Comprehensive Genomic Profiling Kit and TruSight Oncology 500 Assay.
J Mol Diagn
November 2024
Lab Operations, Foundation Medicine GmbH, Penzberg, Germany. Electronic address:
Article Synopsis
- The rise of personalized medicine has highlighted the importance of comprehensive genomic profiling (CGP), but challenges in assay standardization and understanding bioinformatics hinder uniform implementation.
- Two in-house CGP assays were compared in a research context, revealing both agreements and significant differences in detecting genetic variants and providing clinical recommendations.
- These discrepancies were attributed to varied bioinformatics methods for variant analysis, emphasizing the need for careful consideration in implementing high-quality CGP to ensure consistent and reliable genomic insights.
IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.
Neurol Neuroimmunol Neuroinflamm
November 2024
From the Montreal Neurological Institute and Department of Neurology and Neurosurgery (R.P.), Montréal, McGill University; Center for Advanced Research in Sleep Medicine (R.P., A.P., J.-F.G.), Hôpital du Sacré-Coeur de Montréal; Research Institute of the McGill University Health Centre (R.P., A.P., Z.G.-O.), Montreal, Quebec, Canada; Neurology and Medicine (N.V., L.K.F., J.A.F., O.A.R., W.S., B.F.B., A.M.), Mayo Clinic, Rochester, MN; Division of Neurology (N.V., E.K.S.L.), Department of Medicine, Faculty of Medicine, Khon Kaen University, Thailand; Department of Neurology (M.M.L., J.E.), Oregon Health & Science University; Department of Behavioral Neuroscience (M.M.L.); Department of Pulmonary and Critical Care Medicine; Oregon Institute of Occupational Health Sciences; Mental Illness Research Education and Clinical Center (M.M.L.); Neurology; National Center for Rehabilitative Auditory Research; Research Service (M.M.L., J.E.), VA Portland Health Care System, OR; Département of Psychology (J.-F.G.), Université du Québec à Montréal; Department of Human Genetics (Z.G.-O.), McGill University, Montréal, Québec, Canada; Neurology (D.E.H., D.L.B.), Emory University, Atlanta, GA; Neurology (A.Y.A.), Sleep Disorders Center, University of California, Los Angeles; Minnesota Regional Sleep Disorders Center (M.H., C.H.S.), and Departments of Psychiatry, Hennepin County Medical Center, and University of Minnesota Medical School; Minnesota Regional Sleep Disorders Center (M.H.), Hennepin County Medical Center, Minneapolis, MN; Washington University School of Medicine (J.M., A.A.D., Y.-E.S.J.), Saint Louis, MO; Barrow Neurological Institute (S.R.C.), Phoenix, AZ; Movement Disorders Unit (A.V.), Division of Sleep Medicine, Massachusetts General Hospital; Neurological Clinical Research Institute (A.V.), Harvard Medical School, Boston, MA; Psychiatry and Behavioral Sciences (E.H.D., M.G.M.), Stanford University, Redwood City, CA; Neurology and Neurological Sciences (E.H.D., M.G.M.), Stanford University, Palo Alto, CA; and Neurology (E.H.D.), Mt. Sinai School of Medicine, New York.
Background And Objectives: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This study's objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD.
View Article and Find Full Text PDFAdaptive Deep Brain Stimulation in Parkinson's Disease: A Delphi Consensus Study.
medRxiv
August 2024
"Aldo Ravelli" Center for Neurotechnology and Experimental Brain Therapeutics, Department of Health Sciences, University of Milan, Via Antonio di Rudinì 8, 20142 Milan, Italy.
Article Synopsis
- The evolution of Deep Brain Stimulation (DBS) is shifting from conventional methods to adaptive techniques (aDBS), which are expected to become standard practice in the next decade, similar to past advancements in cardiac pacing.
- Research involving 21 experts highlighted the challenges and potential of aDBS, showing consensus on its safety and effectiveness compared to conventional DBS, particularly for Parkinson's Disease patients with motor fluctuations and dyskinesias.
- Further studies are necessary to refine the algorithms used in aDBS, ensuring its widespread and effective use in clinical settings.
Plasma cell-free RNA signatures of inflammatory syndromes in children.
Proc Natl Acad Sci U S A
September 2024
Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14850.
Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections.
View Article and Find Full Text PDFHeterolytic C-H Activation Routes in Catalytic Dehydrogenation of Light Alkanes on Lewis Acid-Base Pairs at ZrO Surfaces.
J Am Chem Soc
September 2024
Department of Chemical and Biomolecular Engineering, University of California at Berkeley, Berkeley, California 94720, United States.
Alkane dehydrogenation is an enabling route to make alkenes useful as chemical intermediates. This study demonstrates the high reactivity of Lewis acid-base (LAB) site pairs at ZrO powders for dehydrogenation of C-C alkanes and the essential requirement for chemical treatments to remove strongly bound HO and CO titrants to avoid the high temperatures required for their desorption and the concomitant loss of active sites through sintering and annealing of ZrO crystallites. The energies and free energies of bound intermediates and transition states from density functional theory (DFT), taken together with kinetic analysis and isotopic methods, demonstrated the kinetic relevance and heterolytic character of the first C-H activation at terminal C-atoms for all alkanes with a modest activation barrier (84 kJ mol) at essentially bare Zr-O LAB site pairs.
View Article and Find Full Text PDFComputational Design of Ligands for the Ir-Catalyzed C5-Borylation of Indoles through Tuning Dispersion Interactions.
J Am Chem Soc
September 2024
State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China.
The indole moiety is ubiquitous in natural products and pharmaceuticals. C-H borylation of the benzenoid moiety of indoles is a challenging task, especially at the C5 position. We have combined computational and experimental studies to introduce multiple noncovalent interactions, especially dispersion, between the substrate and catalytic ligand to realize C5-borylation of indoles with high reactivity and selectivity.
View Article and Find Full Text PDFThalamic transcranial ultrasound stimulation in treatment resistant depression.
Brain Stimul
August 2024
Department of Neurology, University of California, San Francisco, CA, USA; Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, CA, USA.
RNA interacts with topoisomerase I to adjust DNA topology.
Mol Cell
September 2024
Simpson Querrey Institute for Epigenetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA; Department of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address:
Article Synopsis
- Topoisomerase I (TOP1) is a crucial enzyme that helps relieve DNA tension during transcription, but its regulatory mechanisms are not fully understood.* -
- Recent research identified TOP1 as an RNA-binding protein (RBP) that binds primarily to mRNAs, using advanced techniques like eCLIP and UV-RIP-seq in human colon cancer cells.* -
- The study reveals that RNA negatively affects TOP1's activity during transcription by demonstrating that RNA polymerase II's actions on genes hinder TOP1's function, suggesting a complex relationship between RNA and DNA stress management.*
C3 Selective Hydroxylation of Pyridines via Photochemical Valence Isomerization of Pyridine -Oxides.
J Am Chem Soc
September 2024
Department of Biochemistry, The University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, Texas 75390, United States.
The C-H hydroxylation of the pyridine C3 position is a highly desirable transformation but remains a great challenge due to the inherent electronic properties of this heterocycle core which bring difficulties in chemical reactivity and regioselectivity. Herein we present an efficient method for formal C3 selective hydroxylation of pyridines via photochemical valence isomerization of pyridine -oxides. This metal-free transformation features operational simplicity and compatibility with a diverse array of functional groups, and the resulting hydroxylated products are amenable to further elaboration to synthetically useful building blocks.
View Article and Find Full Text PDFCT1812 biomarker signature from a meta-analysis of CSF proteomic findings from two Phase 2 clinical trials in Alzheimer's disease.
Alzheimers Dement
October 2024
Cognition Therapeutics, Pittsburgh, Pennsylvania, USA.
Introduction: CT1812 is in clinical development for the treatment of Alzheimer's disease (AD). Cerebrospinal fluid (CSF) exploratory proteomics was employed to identify pharmacodynamic biomarkers of CT1812 in mild to moderate AD from two independent clinical trials.
Methods: Unbiased analysis of tandem-mass tag mass spectrometry (TMT-MS) quantitative proteomics, pathway analysis and correlation analyses with volumetric magnetic resonance imaging (vMRI) were performed for the SPARC cohort (NCT03493282).
Blood Pressure, Antihypertensive Use, and Late-Life Alzheimer and Non-Alzheimer Dementia Risk: An Individual Participant Data Meta-Analysis.
Neurology
September 2024
From the Faculty of Medicine and Health (M.J.L., D.M.L., B.C.P.L., J.D.C., P.S.S.), and Centre for Healthy Brain Aging (CHeBA) (M.J.L., D.M.L., B.C.P.L., J.D.C., P.S.S.), Discipline of Psychiatry & Mental Health, School of Clinical Medicine, University of New South Wales, Sydney; School of Psychology and Public Health (B.C.P.L.), La Trobe University, Melbourne; The George Institute for Global Health (A.E.S., R.P.), Barangaroo; School of Biomedical Sciences (R.P.), University of New South Wales, Sydney, Australia; School of Public Health (R.P.), Imperial College London, United Kingdom; School of Population Health (A.E.S.), University of New South Wales, Sydney, Australia; Neuropsychiatric Epidemiology Unit (T.R.-S., J.N., I.S.), Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy, Centre for Ageing and Health (AGECAP) at the University of Gothenburg; Aging Research Center (T.R.-S.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet and Stockholm University; Region Västra Götaland (J.N., I.S.), Sahlgrenska University Hospital, Psychiatry, Cognition and Old Age Psychiatry Clinic, Gothenburg, Sweden; Section Genomics of Neurodegenerative Diseases and Aging (J.N.), Department of Clinical Genetics, Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; Institute of Social Medicine (S.G.R.-H., S.R., A.P.), Occupational Health and Public Health (ISAP), Medical Faculty, University of Leipzig, Germany; School of Psychology (S.R.), Massey University, Albany Campus, Auckland, New Zealand; Global Brain Health Institute (GBHI) (S.R.), Trinity College Dublin, Ireland; Department of Medicine and Psychiatry (A.L., C.D.-l-C.), Universidad de Zaragoza; Instituto de Investigación Sanitaria Aragón (IIS Aragón) (A.L., C.D.-l-C., E.L.), Zaragoza; CIBERSAM (A.L., C.D.-l-C., E.L.), Madrid, Spain; Department of Preventive Medicine and Public Health (E.L.), Universidad de Zaragoza, Spain; Department of Neurology (R.B.L., M.J.K., C.A.D.), and Department of Epidemiology and Population Health (R.B.L., C.A.D.), Albert Einstein College of Medicine, Bronx, NY; Department of Neuropsychiatry (K.W.K., J.W.H.), Seoul National University Bundang Hospital, Seongnam; Department of Psychiatry (K.W.K., J.W.H.), Seoul National University College of Medicine; Department of Brain and Cognitive Sciences (K.W.K.), Seoul National University College of Natural Sciences; Workplace Mental Health Institute (D.J.O.), Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, South Korea; Golgi Cenci Foundation (E.R., A.D., M.R.), Abbiategrasso, Milan; Department of Brain and Behavioural Sciences (E.R.), University of Pavia, Italy; 1st Department of Neurology (N.S.), Aiginition Hospital, National and Kapodistrian University of Athens, Greece; Department of Neurology (N.S.), Columbia University, New York, NY; School of Health Sciences and Education (M.Y.), Department of Nutrition and Dietetics, Harokopio University; Department of Neurology (T.D.), University Hospital of Larissa; Faculty of Medicine (T.D.), School of Health Sciences, University of Thessaly, Larissa, Greece; Department of Psychiatry (H.C.H.), Indiana University School of Medicine; Indiana Alzheimer Disease Research Center (H.C.H., S.G.), Indiana Alzheimer Disease Research Center; Department of Biostatistics and Health Data Science (S.G.), Indiana University School of Medicine, Indianapolis; Institut for Neurosciences of Montpellier INM (I.C., K.R.), University Montpellier, INSERM; Institut du Cerveau Trocadéro (K.R.), Paris, France; School of Psychology (K.J.A.), and Ageing Futures Institute (K.J.A.), University of New South Wales; Neuroscience Research Australia (K.J.A.), Sydney; National Centre for Epidemiology and Population Health (N.C.), Australian National University, Canberra, Australia; Department of Geriatric Psychiatry (S.X., L.Y., W.L.), Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine; Alzheimer's Disease and Related Disorders Center (S.X., L.Y., W.L.), Shanghai Jiao Tong University, China; Inserm U1094 (M.G., P.-M.P., V.A.), IRD UMR270, Univ. Limoges, CHU Limoges, EpiMaCT-Epidemiology of Chronic Diseases in Tropical Zone, Institute of Epidemiology and Tropical Neurology, OmegaHealth, France; Laboratory of Chronic and Neurological Diseases Epidemiology (LEMACEN) (M.G.), Faculty of Health Sciences, University of Abomey-Calavi, Cotonou, Benin; Department of Cardiology (V.A.), Dupuytren 2 University Hospital, Limoges, France; School of Medicine (M.N.H.), University of California, San Francisco; Robert N. Butler Columbia Aging Center (A.A.), Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY; Departamento de Psiquiatria (M.S.), Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Brazil; and Neuropsychiatric Institute (P.S.S.), Prince of Wales Hospital, Sydney, Australia.
Article Synopsis
- Previous studies suggest that using antihypertensive medication in older adults may lower the overall risk of dementia, but the effects on different types of dementia, particularly Alzheimer’s disease (AD), are still uncertain.
- This research analyzed data from over 31,000 participants across multiple countries, focusing on how history of hypertension and blood pressure levels impact the risk of developing AD and non-AD types of dementia.
- The findings indicated that untreated hypertension significantly increases the risk of developing AD and non-AD dementia compared to healthy individuals, while treated hypertension showed a similar risk for non-AD but not a significant difference between treated and untreated groups.
Ligand Oxidation Activates a Ruthenium(II) Precatalyst for C-H Hydroxylation.
J Am Chem Soc
August 2024
Department of Chemistry, Stanford University, 337 Campus Drive, Stanford, California 94305, United States.
A new class of Ru-sulfonamidate precatalysts for sp C-H hydroxylation is described along with a versatile process for assembling unique heteroleptic Ru(II) complexes. The latter has enabled structure-performance studies to identify an optimal precatalyst, , bearing one 4,4'-di--butylbipyridine (dtbpy) and one pyridylsulfonamidate ligand. Single-crystal X-ray analysis confirmed the structure and stereochemistry of this adduct.
View Article and Find Full Text PDFDifferentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.
Ann Intern Med
September 2024
Departments of Pediatrics and Medicine, Case Western Reserve University, and University Hospitals Cleveland Medical Center, Cleveland, Ohio (G.A.M.).
Article Synopsis
- The study aims to identify clinical laboratory markers associated with postacute sequelae of SARS-CoV-2 infection (PASC) due to a lack of validated biomarkers.
- Conducted with 10,094 participants across 83 sites, the research compared laboratory measures between those with and without prior SARS-CoV-2 infection and analyzed the impact of PASC indices on these measures.
- Results showed participants with prior infection had lower platelet counts and higher levels of hemoglobin A and urinary albumin-creatinine ratio, but these differences were minor and not significant among those with PASC.
Amelioration of Photoreceptor Degeneration by Intravitreal Transplantation of Retinal Progenitor Cells in Rats.
Int J Mol Sci
July 2024
Gavin Herbert Eye Institute, Sue & Bill Gross Stem Cell Research Center, University of California, Irvine, CA 92697, USA.
Photoreceptor degeneration is a major cause of untreatable blindness worldwide and has recently been targeted by emerging technologies, including cell- and gene-based therapies. Cell types of neural lineage have shown promise for replacing either photoreceptors or retinal pigment epithelial cells following delivery to the subretinal space, while cells of bone marrow lineage have been tested for retinal trophic effects following delivery to the vitreous cavity. Here we explore an alternate approach in which cells from the immature neural retinal are delivered to the vitreous cavity with the goal of providing trophic support for degenerating photoreceptors.
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