Seven-Signal Proteomic Signature for Detection of Operable Pancreatic Ductal Adenocarcinoma and Their Discrimination from Autoimmune Pancreatitis

There is urgent need for biomarkers that provide early detection of pancreatic ductal adenocarcinoma (PDAC) as well as discrimination of autoimmune pancreatitis, as current clinical approaches are not suitably accurate for precise diagnosis. We used mass spectrometry to analyze protein profiles of more than 300 plasma specimens obtained from PDAC, noncancerous pancreatic diseases including autoimmune pancreatitis patients and healthy subjects. We obtained 1063 proteomic signals from 160 plasma samples in the training cohort. A proteomic signature consisting of 7 mass spectrometry signals was used for construction of a proteomic model for detection of PDAC patients. Using the test cohort, we confirmed that this proteomic model had discrimination power equal to that observed with the training cohort. The overall sensitivity and specificity for detection of cancer patients were 82.6% and 90.9%, respectively. Notably, 62.5% of the stage I and II cases were detected by our proteomic model. We also found that 100% of autoimmune pancreatitis patients were correctly assigned as noncancerous individuals. In the present paper, we developed a proteomic model that was shown able to detect early-stage PDAC patients. In addition, our model appeared capable of discriminating patients with autoimmune pancreatitis from those with PDAC

Genetic and Molecular Analysis of Wild-Derived Arrhythmic Mice

A new circadian variant was isolated by screening the intercross offspring of wild-caught mice (Mus musculus castaneus). This variant was characterized by an initial maintenance of damped oscillations and subsequent loss of rhythmicity after being transferred from light-dark (LD) cycles to constant darkness (DD). To map the genes responsible for the persistence of rhythmicity (circadian ratio) and the length of free-running period (τ), quantitative trait locus (QTL) analysis was performed using F2 mice obtained from an F1 cross between the circadian variant and C57BL/6J mice. As a result, a significant QTL with a main effect for circadian ratio (Arrhythmicity; Arrh-1) was mapped on Chromosome (Chr) 8. For τ, four significant QTLs, Short free-running period (Sfp-1) (Chr 1), Sfp-2 (Chr 6), Sfp-3 (Chr 8), Sfp-4 (Chr 11) were determined. An epistatic interaction was detected between Chr 3 (Arrh-2) and Chr 5 (Arrh-3). An in situ hybridization study of clock genes and mouse Period1::luciferase (mPer1::luc) real-time monitoring analysis in the suprachiasmatic nucleus (SCN) suggested that arrhythmicity in this variant might not be attributed to core circadian mechanisms in the SCN neurons. Our strategy using wild-derived variant mice may provide a novel opportunity to evaluate circadian and its related disorders in human that arise from the interaction between multiple variant genes

Effects of change in walking speed on time-distance parameters in post-stroke hemiplegic gait

OBJECTIVES: In stroke patients, the assessment of gait ability over time is important. For quantitative gait assessment using measuring devices, the walking speed condition for measurement is generally based on the patient’s preferred walking speed or the maximum walking speed at the time of measurement. However, because walking speed often increases during the convalescent stage, understanding the effects of change in walking speed on gait when comparing the course of recovery is necessary. Although several previous studies have reported the effects of change in walking speed on gait in stroke patients, the time-distance parameters described in these reports may not be generalizable because of the small case numbers. Therefore, we measured treadmill gait at the preferred walking speed (PWS) and 1.3 times the PWS (130% PWS) in 43 post-stroke hemiplegic patients and analyzed the effects of change in walking speed on time-distance parameters. METHODS: Forty-three patients with hemiplegia after a first stroke, who were able to walk on a treadmill under supervision, were recruited as subjects. Using a three-dimensional motion analysis system, treadmill gait was assessed under two conditions: PWS and 130% PWS. The primary outcome measures were the time-distance parameters, which were compared between the PWS and 130% PWS conditions. RESULTS: Cadence, stride length, and step length of the affected and unaffected lower limbs increased significantly at 130% PWS compared with at PWS. In terms of actual time, single stance time and initial and terminal double stance time in both affected and unaffected limbs decreased significantly at 130% PWS. In terms of relative time (% of the gait cycle), compared with PWS, relative single stance time increased significantly, whereas relative initial and terminal double stance times decreased significantly at 130% PWS in both the affected and unaffected limbs. CONCLUSIONS: This study on treadmill gait in patients with hemiplegia after a first stroke confirmed the effects of change in walking speed on time-distance parameters. Our results will help in the interpretation of time-distance parameters measured under different walking speed conditions

Best practices for the extraction of genomic DNA from formalin‐fixed paraffin‐embedded tumor tissue for cancer genomic profiling tests

Recently, two cancer genomic profiling tests have been approved in Japan and implemented in routine clinical practice: the FDA‐approved FoundationOne CDx test, and the OncoGuide NCC Oncopanel test. The quality and quantity of DNA significantly affects the sequencing results; therefore, preparing a sufficient amount of high‐quality DNA for clinical cancer genomic profiling tests is important. We examined the best practices for the extraction of cancer genomic DNA from formalin‐fixed paraffin‐embedded (FFPE) tumor tissues of pancreatic, lung and colon cancer specimens. We found that the quality of cancer genomic DNA extracted from 10‐μm‐thick FFPE samples improved significantly, compared with that from 4‐μm‐thick FFPE samples, suggesting that 10‐μm‐thick FFPE samples are preferable for clinical cancer genomic profiling tests. For convenience, we created a quick reference table for calculating the required number of FFPE slides