The Emergent Landscape of Detecting EGFR Mutations Using Circulating Tumor DNA in Lung Cancer.

The advances in targeted therapies for lung cancer are based on the evaluation of specific gene mutations especially the epidermal growth factor receptor (EGFR). The assays largely depend on the acquisition of tumor tissue via biopsy before the initiation of therapy or after the onset of acquired resistance. However, the limitations of tissue biopsy including tumor heterogeneity and insufficient tissues for molecular testing are impotent clinical obstacles for mutation analysis and lung cancer treatment. Due to the invasive procedure of tissue biopsy and the progressive development of drug-resistant EGFR mutations, the effective initial detection and continuous monitoring of EGFR mutations are still unmet requirements. Circulating tumor DNA (ctDNA) detection is a promising biomarker for noninvasive assessment of cancer burden. Recent advancement of sensitive techniques in detecting EGFR mutations using ctDNA enables a broad range of clinical applications, including early detection of disease, prediction of treatment responses, and disease progression. This review not only introduces the biology and clinical implementations of ctDNA but also includes the updating information of recent advancement of techniques for detecting EGFR mutation using ctDNA in lung cancer

Liquid biopsy genotyping in lung cancer: ready for clinical utility?

Liquid biopsy is a blood test that detects evidence of cancer cells or tumor DNA in the circulation. Despite complicated collection methods and the requirement for technique-dependent platforms, it has generated substantial interest due, in part, to its potential to detect driver oncogenes such as epidermal growth factor receptor (EGFR) mutants in lung cancer. This technology is advancing rapidly and is being incorporated into numerous EGFR tyrosine kinase inhibitor (EGFR-TKI) development programs. It appears ready for integration into clinical care. Recent studies have demonstrated that biological fluids such as saliva and urine can also be used for detecting EGFR mutant DNA through application other user-friendly techniques. This review focuses on the clinical application of liquid biopsies to lung cancer genotyping, including EGFR and other targets of genotype-directed therapy and compares multiple platforms used for liquid biopsy

Nonparetic Knee Extensor Strength Is the Determinant of Exercise Capacity of Community-Dwelling Stroke Survivors

Objective. To investigate the relationship among walking speed, exercise capacity, and leg strength in community dwelling stroke subjects and to evaluate which one was the leading determinant factor of them. Design. This is a descriptive, cross-sectional study. Thirty-five chronic stroke patients who were able to walk independently in their community were enrolled. Walking speed was evaluated by using the 12-meter walking test. A maximal exercise test was used to determine the stroke subjects’ exercise capacity. Knee extensor strength, measured as isokinetic torque, was assessed by isokinetic dynamometer. Results. The main walking speed of our subjects was 0.52 m/s. Peak oxygen uptake (VO2 peak) was 1.21±0.43 L/min. Knee extensor strength, no matter whether paretic or nonparetic side, was significantly correlated to 12-meter walking speed and exercise capacity. Linear regression also showed the strength of the affected knee extensor was the determinant of walking speed and that of the nonparetic knee extensor was the determinant of exercise capacity in community dwelling stroke subjects. Conclusions. Walking speed and peak oxygen uptake were markedly decreased after stroke. Knee extensor strength of nonparetic leg was the most important determinant of exercise capacity of the community-dwelling stroke subjects. Knee extensor strengthening should be emphasized to help stroke patient to achieve optimal community living

THE EFFECTS OF FUNGAL MEDIUM ON HATCHING RATE OF BITING MIDGE

The little black mosquitos, Forcipomyia taiwana, bite human and become one of the most annoying pests in Taiwan. Recently, the population of F. taiwana increases and invades urban and countryside. In order to effectively prevent the harassment of F. taiwana, develop control strategy is urgent and necessary. Our study found that the fungal medium influenced the length and width of the F. taiwana eggs. It also significantly decreased the hatching rate of F. taiwana. Besides, this artificial diet was more non-toxic and environment-friendly than general chemical pesticides. Thus, this study provided critical information to develop potentially useful bait of F. taiwana in the future

Reduction in patient burdens with graphical computerized adaptive testing on the ADL scale: tool development and simulation

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to verify the effectiveness and efficacy of saving time and reducing burden for patients, nurses, and even occupational therapists through computer adaptive testing (CAT).</p> <p>Methods</p> <p>Based on an item bank of the Barthel Index (BI) and the Frenchay Activities Index (FAI) for assessing comprehensive activities of daily living (ADL) function in stroke patients, we developed a visual basic application (VBA)-Excel CAT module, and (1) investigated whether the averaged test length via CAT is shorter than that of the traditional all-item-answered non-adaptive testing (NAT) approach through simulation, (2) illustrated the CAT multimedia on a tablet PC showing data collection and response errors of ADL clinical functional measures in stroke patients, and (3) demonstrated the quality control of endorsing scale with fit statistics to detect responding errors, which will be further immediately reconfirmed by technicians once patient ends the CAT assessment.</p> <p>Results</p> <p>The results show that endorsed items could be shorter on CAT (<it>M </it>= 13.42) than on NAT (<it>M </it>= 23) at 41.64% efficiency in test length. However, averaged ability estimations reveal insignificant differences between CAT and NAT.</p> <p>Conclusion</p> <p>This study found that mobile nursing services, placed at the bedsides of patients could, through the programmed VBA-Excel CAT module, reduce the burden to patients and save time, more so than the traditional NAT paper-and-pencil testing appraisals.</p

RISK OF SLEEP DISORDERS IN PATIENTS WITH DECOMPRESSION SICKNESS: A NATIONWIDE, POPULATION-BASED STUDY IN TAIWAN

Background: Decompression sickness (DCS) primarily manifests musculoskeletal pain, cutaneous manifestations, lymphatic symptoms, and neurological symptoms. DCS might affect the central nervous system and induce the stress in the patients, but few studies about the psychiatric morbidity after DCS have been conducted. This study aimed to investigate the association between DCS and the risk of developing psychiatric disorders. Subjects and methods: This study was a population-based, matched cohort design. A total of 738 enrolled patients, with 123 study subjects who had suffered from DCS, and 615 controls matched for sex and age, from the Longitudinal Health Insurance Databank from 2000-2010 in Taiwan, and selected from the National Health Insurance Research Database. After adjusting for the confounding factors, Cox proportional hazards analysis was used to compare the risk of developing psychiatric disorders during the 10 years of follow-up period. Results: Of the study subjects, 10 (8.13%) developed psychiatric disorders when compared to 35 (5.69%) in the control group. The study subjects were more likely to develop psychiatric disorders (crude hazard ratio [HR]: 2.79 (95% CI=1.37-5.69, P<0.01). After adjusting for sex, age, monthly income, urbanization level, geographic region, and comorbidities, the adjusted HR was 3.83 (95% CI=1.60-9.16, P<0.01). Sleep disorders was associated with DCS with the adjusted HR as 5.74 (95% CI=1.04-31.56, P<0.01). Hyperbaric oxygenation therapy was not associated with a lower risk of psychiatric disorders. Conclusions: Patients who suffered from DCS have a 3.8-fold risk of developing psychiatric disorders, and a 5.7-fold risk of sleep disorders. This finding is a reminder for the clinicians that a regular psychiatric follow-up might well be needed for these patients

Genome-wide gene-based association study

Genome-wide association studies, which analyzes hundreds of thousands of single-nucleotide polymorphisms to identify disease susceptibility genes, are challenging because the work involves intensive computation and complex modeling. We propose a two-stage genome-wide association scanning procedure, consisting of a single-locus association scan for the first stage and a gene-based association scan for the second stage. Marginal effects of single-nucleotide polymorphisms are examined by using the exact Armitage trend test or logistic regression, and gene effects are examined by using a p-value combination method. Compared with some existing single-locus and multilocus methods, the proposed method has the following merits: 1) convenient for definition of biologically meaningful regions, 2) powerful for detection of minor-effect genes, 3) helpful for alleviation of a multiple-testing problem, and 4) convenient for result interpretation. The method was applied to study Genetic Analysis Workshop 16 Problem 1 rheumatoid arthritis data, and strong association signals were found. The results show that the human major histocompatibility complex region is the most important genomic region associated with rheumatoid arthritis. Moreover, previously reported genes including PTPN22, C5, and IL2RB were confirmed; novel genes including HLA-DRA, BTNL2, C6orf10, NOTCH4, TAP2, and TNXB were identified by our analysis