Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) is a rapidly advancing technology for biomedical research. As spatial resolution increases, however, so do acquisition time, file size, and experimental cost, which increases the need to perform precise sampling of targeted tissue regions to optimize the biological information gleaned from an experiment and minimize wasted resources. The ability to define instrument measurement regions based on key tissue features and automatically sample these specific regions of interest (ROIs) addresses this challenge.
View Article and Find Full Text PDFBackground: Molecular analysis of fine-needle aspiration biopsies (FNAB) improves the diagnostic accuracy of cytologically indeterminate thyroid nodules (ITNs). Recently, the use of MPTXv2 has been shown to further improve the accuracy of risk stratification of ITNs.
Methods: A total of 338 patient samples with atypia of undetermined significance (n = 258) or follicular neoplasm (n = 80) cytology diagnosis and corresponding surgical outcomes or clinical follow-up, collected between 2016 and 2020 were included [Correction added on 19 June 2024, after first online publication: In the preceding sentence, the n values 260 and 78 have been changed to 258 and 80, respectively.
Alzheimer's disease (AD) is the most common form of neurological dementia, specified by extracellular β-amyloid plaque deposition, neurofibrillary tangles, and cognitive impairment. AD-associated pathologies like cerebral amyloid angiopathy (CAA) are also affiliated with cognitive impairment and have overlapping molecular drivers, including amyloid buildup. Discerning the complexity of these neurological disorders remains a significant challenge, and the spatiomolecular relationships between pathogenic features of AD and AD-associated pathologies remain poorly understood.
View Article and Find Full Text PDFAldehyde dehydrogenases (ALDHs) are promising cancer drug targets, as certain isoforms are required for the survival of stem-like tumor cells. We have discovered selective inhibitors of ALDH1B1, a mitochondrial enzyme that promotes colorectal and pancreatic cancer. We describe bicyclic imidazoliums and guanidines that target the ALDH1B1 active site with comparable molecular interactions and potencies.
View Article and Find Full Text PDFImmune-mediated necrotising myopathy is a subtype of idiopathic inflammatory myopathy characterised by muscle fibre necrosis without significant inflammatory infiltrate. Anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) myopathy is seen in 6%-10% of idiopathic inflammatory myopathy and is diagnosed in the context of elevated serum creatine kinase levels, proximal muscle weakness and anti-HMGCR autoantibodies. We recently encountered a 61-year-old man with anti-HMGCR myopathy with an atypical skin manifestation, partially responsive to triple therapy with steroids, intravenous immunoglobulin (IVIG) and rituximab.
View Article and Find Full Text PDFMyalgia and mild elevation in muscle enzymes are common side effects of statin therapy. While these symptoms are generally self-limited, in rare cases, statin use is associated with an immune-mediated necrotizing myopathy caused by development of autoantibodies against HMG-CoA reductase. The primary presenting symptom of this condition is progressive symmetric proximal weakness that does not abate or worsens even after cessation of statin therapy and is associated with markedly elevated creatine kinase (CK) levels.
View Article and Find Full Text PDFHerpes simplex virus (HSV) is a disease usually characterized by lesions within the epidermis or mucosa of children and adults. However, this infection can also cause complications to many systems of the body, including the peripheral and central nervous system, respiratory system, and hepatobiliary system. In this case, we present a 43-year-old man with a history of substance abuse, who presented with fever, cough, and headache, and within days, progressed into fulminant hepatitis and hypoxic failure.
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