Association of pathway mutation with survival after recurrence in colorectal cancer patients treated with adjuvant fluoropyrimidine and oxaliplatin chemotherapy

Background Although the prognostic biomarkers associated with colorectal cancer (CRC) survival are well known, there are limited data on the association between the molecular characteristics and survival after recurrence (SAR). The purpose of this study was to assess the association between pathway mutations and SAR. Methods Of the 516 patients with stage III or high risk stage II CRC patients treated with surgery and adjuvant chemotherapy, 87 who had distant recurrence were included in the present study. We analyzed the association between SAR and mutations of 40 genes included in the five critical pathways of CRC (WNT, P53, RTK-RAS, TGF-β, and PI3K). Results Mutation of genes within the WNT, P53, RTK-RAS, TGF-β, and PI3K pathways were shown in 69(79.3%), 60(69.0%), 57(65.5%), 21(24.1%), and 19(21.8%) patients, respectively. Patients with TGF-β pathway mutation were younger and had higher incidence of mucinous adenocarcinoma (MAC) histology and microsatellite instability-high. TGF-β pathway mutation (median SAR of 21.6 vs. 44.4 months, p = 0.021) and MAC (20.0 vs. 44.4 months, p = 0.003) were associated with poor SAR, and receiving curative resection after recurrence was associated with favorable SAR (Not reached vs. 23.6 months, p <  0.001). Mutations in genes within other critical pathways were not associated with SAR. When MAC was excluded as a covariate, multivariate analysis revealed TGF-β pathway mutation and curative resection after distant recurrence as an independent prognostic factor for SAR. The impact of TGF-β pathway mutations were predicted using the PROVEAN, SIFT, and PolyPhen-2. Among 25 mutations, 23(92.0%)-24(96.0%) mutations were predicted to be damaging mutation. Conclusions Mutation in genes within TGF-β pathway may have negative prognostic role for SAR in CRC. Other pathway mutations were not associated with SAR.This research was supported by the Seoul National University Hospital (SNUH) Research Fund (03–2014-0440) and a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C1277 and HI13C2163). The funding bodies had no influence on the design of the study and collection, analysis, and interpretation of data and in writing the manuscript

Integrating MAVLink into LabVIEW

Color poster with text and images.The purpose of this study was to integrate an open-source robotics command and control communication protocol called MAVLink into a simple and widely used graphical programming language known as LabVIEW. MAVLink-based control boards can be incorporated into robotic systems used in research for geographic, geologic, agricultural, search and rescue, and atmospheric scientific investigations.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

Arduino Autonomous Robotics System

Color poster with text, photographs, and images.This project was directed toward developing a MAVLINK (Miniature Air Vehicle Link) based LabVIEW ground control system for an Arduino-based Miniature Aerial Vehicle (MAV) to successfully complete autonomous missions, such as an aerial delivery. The Arduino platforms provide cost effective robotics development and control system with complex sensor arrays. Though there are other ground control software to integrate with the Arduino platform using MAVLINK, the purpose of this study was to integrate LabVIEW instrumentation to further enhance the capability of the robot with LabVIEW control and sensors.University of Wisconsin--Eau Claire Office of Research and Sponsored Programs

Motor Planning Error: Toward Measuring Cognitive Frailty in Older Adults Using Wearables

Practical tools which can be quickly administered are needed for measuring subtle changes in cognitive–motor performance over time. Frailty together with cognitive impairment, or ‘cognitive frailty’, are shown to be strong and independent predictors of cognitive decline over time. We have developed an interactive instrumented trail-making task (iTMT) platform, which allows quantification of motor planning error (MPE) through a series of ankle reaching tasks. In this study, we examined the accuracy of MPE in identifying cognitive frailty in older adults. Thirty-two older adults (age = 77.3 ± 9.1 years, body-mass-index = 25.3 ± 4.7 kg/m2, female = 38%) were recruited. Using either the Mini-Mental State Examination or Montreal Cognitive Assessment (MoCA), 16 subjects were classified as cognitive-intact and 16 were classified as cognitive-impaired. In addition, 12 young-healthy subjects (age = 26.0 ± 5.2 years, body-mass-index = 25.3 ± 3.9 kg/m2, female = 33%) were recruited to establish a healthy benchmark. Subjects completed the iTMT, using an ankle-worn sensor, which transforms ankle motion into navigation of a computer cursor. The iTMT task included reaching five indexed target circles (including numbers 1-to-3 and letters A&amp;B placed in random order) on the computer-screen by moving the ankle-joint while standing. The ankle-sensor quantifies MPE through analysis of the pattern of ankle velocity. MPE was defined as percentage of time deviation between subject’s maximum ankle velocity and the optimal maximum ankle velocity, which is halfway through the reaching pathway. Data from gait tests, including single task and dual task walking, were also collected to determine cognitive–motor performance. The average MPE in young-healthy, elderly cognitive-intact, and elderly cognitive-impaired groups was 11.1 ± 5.7%, 20.3 ± 9.6%, and 34.1 ± 4.2% (p &lt; 0.001), respectively. Large effect sizes (Cohen’s d = 1.17–4.56) were observed for discriminating between groups using MPE. Significant correlations were observed between the MPE and MoCA score (r = −0.670, p &lt; 0.001) as well as between the MPE and dual task stride velocity (r = −0.584, p &lt; 0.001). This study demonstrated feasibility and efficacy of estimating MPE from a practical wearable platform with promising results in identifying cognitive–motor impairment and potential application in assessing cognitive frailty. The proposed platform could be also used as an alternative to dual task walking test, where gait assessment may not be practical. Future studies need to confirm these observations in larger samples

Toward Smart Footwear to Track Frailty Phenotypes—Using Propulsion Performance to Determine Frailty

Frailty assessment is dependent on the availability of trained personnel and it is currently limited to clinic and supervised setting. The growing aging population has made it necessary to find phenotypes of frailty that can be measured in an unsupervised setting for translational application in continuous, remote, and in-place monitoring during daily living activity, such as walking. We analyzed gait performance of 161 older adults using a shin-worn inertial sensor to investigate the feasibility of developing a foot-worn sensor to assess frailty. Sensor-derived gait parameters were extracted and modeled to distinguish different frailty stages, including non-frail, pre-frail, and frail, as determined by Fried Criteria. An artificial neural network model was implemented to evaluate the accuracy of an algorithm using a proposed set of gait parameters in predicting frailty stages. Changes in discriminating power was compared between sensor data extracted from the left and right shin sensor. The aim was to investigate the feasibility of developing a foot-worn sensor to assess frailty. The results yielded a highly accurate model in predicting frailty stages, irrespective of sensor location. The independent predictors of frailty stages were propulsion duration and acceleration, heel-off and toe-off speed, mid stance and mid swing speed, and speed norm. The proposed model enables discriminating different frailty stages with area under curve ranging between 83.2&ndash;95.8%. Furthermore, results from the neural network suggest the potential of developing a single-shin worn sensor that would be ideal for unsupervised application and footwear integration for continuous monitoring during walking

A high-throughput optomechanical retrieval method for sequence-verified clonal DNA from the NGS platform

Writing DNA plays a significant role in the fields of synthetic biology, functional genomics, and bioengineering. DNA clones on next generation sequencing (NGS) platforms have the potential to be a rich and cost-effective source of sequence-verified DNAs as a precursor for DNA writing. However, it is still very challenging to retrieve target clonal DNA from highdensity NGS platforms. Here, we propose an enabling technology called ‘Sniper Cloning’ that enables the precise mapping of target clone features on NGS platforms and non-contact rapid retrieval of targets for full utilization of DNA clones. By merging the three cutting-edge technologies of NGS, DNA microarray, and our pulse laser retrieval system, ‘Sniper Cloning’ is a week-long process by which 5,188 error-free synthetic DNAs can be produced in a single run of NGS with a single microarray DNA pool. We believe that this technology has potential as a universal tool for DNA writing in biological sciences.1981sciescopu

Tuning and Maximizing the Single-Molecule Surface-Enhanced Raman Scattering from DNA-Tethered Nanodumbbells

We extensively, study the relationships between single-molecule surface-enhanced Raman scattering (SMSERS) intensity, enhancement factor (EF) distribution over many particles, Interparticle distance, particle size/shape/composition and excitation laser wavelength using the single-particle AFM-correlated Raman measurement method and theoretical calculations. Two different single-DNA-tethered Au-Ag core-shell nanodumbbell (GSND) designs with an engineerable nanogap were used In this study: the GSND-I with various interparticle nanogaps from similar to 4.8 nm to &lt; 1 nm or with no gap and the GSND-II with the fixed interparticle gap size and varying particle size from a 23-30 nm pair to a 50-60 nm pair. From the GSND-I, we learned that synthesizing a &lt; 1 um gap is a key to obtain strong SMSERS signals with a narrow EF value distribution. Importantly, in the case of the GSND-I with &lt; 1 nm interparticle gap, an EF value of as high as 5.9 x 10(13) (average value = 1.8 x 10(12)) was obtained and the EF values of analyzed particles were narrowly distributed between 19 x 10(12) and 5.9 x 10(13). In the case of the GSND-II probes, a combination of &gt; 50 nm Au cores and 514.5 nm laser wavelength that matches well with Ag shell generated stronger SMSERS signals with a more narrow EF distribution than &lt; 50 nm Au. cores with 514.3 nm laser or the GSND-II structures with 632.8 nm laser. Our results show the usefulness and flexibility of these GSND structures In studying and obtaining SMSERS structures with a narrow distribution of high EF values and that the GSNDs with &lt; 1 nm are promising SERS probes with highly sensitive and quantitative detection capability when optimally designed