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| http://dx.doi.org/10.1503/cmaj.061172 | DOI Listing |
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TAK-994 Mechanistic Investigation into Drug-Induced Liver Injury.
Toxicol Sci
January 2025
Takeda Development Center Americas, Inc, Cambridge, MA, USA.
The frequency of drug-induced liver injury (DILI) in clinical trials remains a challenge for drug developers despite advances in human hepatotoxicity models and improvements in reducing liver-related attrition in preclinical species. TAK-994, an oral orexin receptor 2 agonist, was withdrawn from phase II clinical trials due to the appearance of severe DILI. Here, we investigate the likely mechanism of TAK-994 DILI in hepatic cell culture systems examined cytotoxicity, mitochondrial toxicity, impact on drug transporter proteins, and covalent binding.
View Article and Find Full Text PDFEnhancing the psychological well-being and sleep quality of healthcare providers with a multimodal psychological support program: a randomized controlled trial.
Front Public Health
January 2025
Department of Anesthesiology, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.
Background: The COVID-19 pandemic significantly challenged the global healthcare system, especially frontline healthcare professionals, such as those working in intensive care units (ICUs). In late 2022, a sudden increase in COVID-19 cases in China led to a large number of ICU admissions, requiring new ICU staff (non-ICU professionals to work in ICUs), exacerbating their stress. This study aimed to develop an effective stress management strategy for new ICU professionals, focusing on reducing the detrimental effects of stress on their psychological state.
View Article and Find Full Text PDFOut-of-distribution generalization for segmentation of lymph node metastasis in breast cancer.
Sci Rep
January 2025
Department of Electrical, Computer, and Biomedical Engineering, Toronto Metropolitan University, Toronto, ON, Canada.
Pathology provides the definitive diagnosis, and Artificial Intelligence (AI) tools are poised to improve accuracy, inter-rater agreement, and turn-around time (TAT) of pathologists, leading to improved quality of care. A high value clinical application is the grading of Lymph Node Metastasis (LNM) which is used for breast cancer staging and guides treatment decisions. A challenge of implementing AI tools widely for LNM classification is domain shift, where Out-of-Distribution (OOD) data has a different distribution than the In-Distribution (ID) data used to train the model, resulting in a drop in performance in OOD data.
View Article and Find Full Text PDFAspirin and Hemocompatibility After LVAD Implantation in Patients With Atherosclerotic Vascular Disease: A Secondary Analysis From the ARIES-HM3 Randomized Clinical Trial.
JAMA Cardiol
January 2025
Brigham and Women's Hospital Heart and Vascular Center, Center for Advanced Heart Disease, Harvard Medical School, Boston, Massachusetts.
Importance: The Aspirin and Hemocompatibility Events With a Left Ventricular Assist Device in Advanced Heart Failure (ARIES-HM3) study demonstrated that aspirin may be safely eliminated from the antithrombotic regimen after HeartMate 3 (HM3 [Abbott Cardiovascular]) left ventricular assist device (LVAD) implantation. This prespecified analysis explored whether conditions requiring aspirin (prior percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], stroke, or peripheral vascular disease [PVD]) would influence outcomes differentially with aspirin avoidance.
Objective: To analyze aspirin avoidance on hemocompatibility-related adverse events (HRAEs) at 1 year after implant in patients with a history of CABG, PCI, stroke, or PVD.
MRI of the Rectum: A Decade into DISTANCE, Moving to DISTANCED.
Radiology
January 2025
From the Department of Radiology, Montpellier Cancer Institute, University of Montpellier, 208 av des Apothicaires, 34090 Montpellier, France (S.N.); PINKCC Laboratory, Montpellier Cancer Research Institute, University of Montpellier, Montpellier, France (S.N.); Jones Radiology, South Australia, Australia (K.G.); The University of Adelaide, South Australia, Australia (K.G.); Department of Radiology, The Netherlands Cancer Institute, Amsterdam, the Netherlands (D.M.J.L.); GROW School for Oncology and Reproduction, University of Maastricht, Maastricht, the Netherlands (D.M.J.L.); Department of Radiology, McGill University, Montreal, Quebec, Canada (C.R.); Department of Radiology, Guy's and St Thomas NHS Foundation Trust, London, United Kingdom (V.G.); School of Biomedical Engineering and Imaging Sciences, King's College London, King's Health Partners, London, United Kingdom (V.G.); Department of Radiology, Oregon Health & Science University, Portland, Ore (E.K.); Bordeaux Colorectal Institute, Bordeaux, France (Q.D.); Department of Radiology, Royal Marsden, London, United Kingdom (G.B.); Department of Radiology, Imperial College London, London, United Kingdom (G.B.).
Over the past decade, advancements in rectal cancer research have reshaped treatment paradigms. Historically, treatment for locally advanced rectal cancer has focused on neoadjuvant long-course chemoradiotherapy, followed by total mesorectal excision. Interest in organ preservation strategies has been strengthened by the introduction of total neoadjuvant therapy with improved rates of complete clinical response.
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