Objective. Identify preferred neurofilament assays, and clinically validate serum NfL and pNfH as prognostic and potential pharmacodynamic biomarkers relevant to ALS therapy development. Methods. Prospective, multi-center, longitudinal observational study of patients with ALS (n=229), primary lateral sclerosis (PLS, n=20) and progressive muscular atrophy (PMA, n=11). Biological specimens were collected, processed and stored according to strict standard operating procedures (SOPs) 1. Neurofilament assays were performed in a blinded manner by independent contract research organizations (CROs). Results....

Background: Somatic CDKN2A and TP53 mutations are recurrent events in melanoma, occurring in 13.3% and 15.1% of cases respectively and are associated with poorer outcomes. It is unclear what effect somatic CDKN2A and TP53 mutations have on the clinical outcomes of patients treated with checkpoint inhibitors. Methods: All patients with cutaneous melanoma or melanoma of unknown primary who received checkpoint inhibitor therapy and underwent genomic profiling with the 50-gene Mayo Clinic solid tumor targeted cancer...

Objective: To examine age and sex differences in burnout, career satisfaction, and well-being in US neurologists. Methods: Quantitative and qualitative analyses of men’s (n = 1,091) and women’s (n = 580) responses to a 2016 survey of US neurologists. Results: Emotional exhaustion in neurologists initially increased with age, then started to decrease as neurologists got older. Depersonalization decreased as neurologists got older. Fatigue and overall quality of life in neurologists initially worsened with age, then...

Since the discovery of CSF1R gene mutations in families with hereditary diffuse leukoencephalopathy with spheroids in 2012, more than 70 different mutations have been identified around the world. Through the analyses of mutation carriers, CSF1R-related leukoencephalopathy has been distinctly characterized clinically, radiologically, and pathologically. Typically, patients present with frontotemporal dementia–like phenotype in their 40s–50s, accompanied by motor symptoms, including pyramidal and extrapyramidal signs. Women tend to develop the clinical symptoms at a younger age than...

The gold standard for a definitive diagnosis of Parkinson’s disease (PD) is the pathologic finding of aggregated alpha-synuclein into Lewy bodies and for Alzheimer’s disease (AD) aggregated amyloid into plaques and hyperphosphorylated tau into tangles. Implicit in this clinico-pathologic-based nosology is the assumption that pathological protein aggregation at autopsy reflect pathogenesis at disease onset. While these aggregates may in exceptional cases be on a causal pathway in humans (e.g., aggregated alpha-synuclein in SNCA gene multiplication...

Objective: To determine whether neuronal and neuroaxonal injury, neuroinflammation, and synaptic dysfunction associate with clinical course and outcomes in antibody-mediated encephalitis (AME), we measured biomarkers of these processes in CSF from patients presenting with AME and cognitively normal individuals. Methods: Biomarkers of neuronal (total tau, VILIP-1) and neuroaxonal damage (neurofilament light chain [NfL]), inflammation (YKL-40), and synaptic function (neurogranin, SNAP-25) were measured in CSF obtained from 45 patients at the time of diagnosis of NMDA...

Objectives: To create test collections for evaluating clinical Information Retrieval (IR) systems and advancing clinical IR research. Materials and Methods: Electronic Health Records (EHR) data, including structured and free text data, from 45,000 patients who are a part of the Mayo Clinic Biobank cohort was retrieved from the clinical data warehouse. The clinical IR system indexed 42 million free-text EHR documents. The search queries consisted of 56 topics developed through a collaboration between Mayo Clinic...