Mayo Clinic

About: Mayo Clinic is a healthcare organization based out in Rochester, Minnesota, United States. It is known for research contribution in the topics: Population & Cancer. The organization has 63387 authors who have published 169578 publications receiving 8114006 citations.

The neuropathological diagnosis of Alzheimer's disease.

Abstract: Alzheimer’s disease is a progressive neurodegenerative disease most often associated with memory deficits and cognitive decline, although less common clinical presentations are increasingly recognized. The cardinal pathological features of the disease have been known for more than one hundred years, and today the presence of these amyloid plaques and neurofibrillary tangles are still required for a pathological diagnosis. Alzheimer’s disease is the most common cause of dementia globally. There remain no effective treatment options for the great majority of patients, and the primary causes of the disease are unknown except in a small number of familial cases driven by genetic mutations. Confounding efforts to develop effective diagnostic tools and disease-modifying therapies is the realization that Alzheimer’s disease is a mixed proteinopathy (amyloid and tau) frequently associated with other age-related processes such as cerebrovascular disease and Lewy body disease. Defining the relationships between and interdependence of various co-pathologies remains an active area of investigation. This review outlines etiologically-linked pathologic features of Alzheimer’s disease, as well as those that are inevitable findings of uncertain significance, such as granulovacuolar degeneration and Hirano bodies. Other disease processes that are frequent, but not inevitable, are also discussed, including pathologic processes that can clinically mimic Alzheimer’s disease. These include cerebrovascular disease, Lewy body disease, TDP-43 proteinopathies and argyrophilic grain disease. The purpose of this review is to provide an overview of Alzheimer’s disease pathology, its defining pathologic substrates and the related pathologies that can affect diagnosis and treatment.

Task Group 142 report: quality assurance of medical accelerators.

Abstract: The task group (TG) for quality assurance of medical accelerators was constituted by the American Association of Physicists in Medicine's Science Council under the direction of the Radiation Therapy Committee and the Quality Assurance and Outcome Improvement Subcommittee. The task group (TG-142) had two main charges. First to update, as needed, recommendations of Table II of the AAPM TG-40 report on quality assurance and second, to add recommendations for asymmetric jaws, multileaf collimation (MLC), and dynamic/virtual wedges. The TG accomplished the update to TG-40, specifying new test and tolerances, and has added recommendations for not only the new ancillary delivery technologies but also for imaging devices that are part of the linear accelerator. The imaging devices include x-ray imaging, photon portal imaging, and cone-beam CT. The TG report was designed to account for the types of treatments delivered with the particular machine. For example, machines that are used for radiosurgery treatments or intensity-modulated radiotherapy (IMRT) require different tests and/or tolerances. There are specific recommendations for MLC quality assurance for machines performing IMRT. The report also gives recommendations as to action levels for the physicists to implement particular actions, whether they are inspection, scheduled action, or immediate and corrective action. The report is geared to be flexible for the physicist to customize the QA program depending on clinical utility. There are specific tables according to daily, monthly, and annual reviews, along with unique tables for wedge systems, MLC, and imaging checks. The report also gives specific recommendations regarding setup of a QA program by the physicist in regards to building a QA team, establishing procedures, training of personnel, documentation, and end-to-end system checks. The tabulated items of this report have been considerably expanded as compared with the original TG-40 report and the recommended tolerances accommodate differences in the intended use of the machine functionality (non-IMRT, IMRT, and stereotactic delivery).

Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma

Abstract: Background Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous. Gene-expression profiling has identified subgroups of DLBCL (activated B-cell–like [ABC], germinal-center B-cell–like [GCB], and unclassified) according to cell of origin that are associated with a differential response to chemotherapy and targeted agents. We sought to extend these findings by identifying genetic subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic vulnerabilities based on tumor genetics. Methods We studied 574 DLBCL biopsy samples using exome and transcriptome sequencing, array-based DNA copy-number analysis, and targeted amplicon resequencing of 372 genes to identify genes with recurrent aberrations. We developed and implemented an algorithm to discover genetic subtypes based on the co-occurrence of genetic alterations. Results We identified four prominent genetic subtypes in DLBCL, termed MCD (based on the co-occurrence of MYD88L265P and CD79B muta...

The "megaprimer" method of site-directed mutagenesis.

Abstract: We describe a simple and efficient method of mutagenesis which we term the "megaprimer" method. The method utilizes three oligonucleotide primers to perform two rounds of polymerase chain reaction. In the method, the product of the first polymerase chain reaction is used as one of the polymerase chain reaction primers (a "megaprimer") for the second polymerase chain reaction. When a phage promoter and a translational initiation signal are attached to the appropriate oligonucleotide primer, the mutant protein can be generated without any in vivo manipulations. To illustrate the method, two mutations in the catalytic domain of the human factor IX gene have been generated. The substitution of megaprimers for oligonucleotide primers may have utility in other polymerase chain reaction-based methods.