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

Competitive Prizes: When Less Scrutiny Induces More Effort

We consider a principal who is keen to induce his agents to work at their maximal effort levels. To this end, he samples n days at random out of the T days on which they work, and awards a prize of B dollars to the most productive agent. The principal's policy (B,n) induces a strategic game Gamma(B,n) between the agents. We show that to implement maximal effort levels weakly (or, strongly) as a strategic equilibrium (or, as dominant strategies) in Gamma(B,n), at the least cost B to himself, the principal must choose a small sample size n. Thus less scrutiny by the principal induces more effort from the agents. The need for reduced scrutiny becomes more pronounced when agents have information of the history of past plays in the game. There is an inverse relation between information and optimal sample size. As agents acquire more information (about each other), the principal -- so to speak -- must "undo" this by reducing his information (about them) and choosing the sample size n even smaller.Competitive prizes, extensive form games, information patterns, strategic equilibria, optimal sample sizes

Occlusion of acute distal brachial, proximal radial and ulnar arteries in a young thrower

SummaryAcute arterial occlusion, a rare condition in throwers, requires early detection and treatment for avoiding further complications. Thus far, no study has mentioned the occurrence of distal brachial, proximal radial, and ulnar artery occlusion in baseball players. An adolescent baseball pitcher presented with acute occlusion of the distal brachial, proximal radial, or ulnar artery. The patient complained of a cold sensation in the hand, wrist, and distal forearm. On physical examination, decreased surface skin temperature, and no radial pulse in the wrist suggested arterial occlusion. Emergency angiography validated the clinical suspicion, and identified the arteries and sites of vascular occlusion. Surgery was performed to alleviate the occlusions, thereby resolving the preoperative complaints and abnormal findings. Furthermore, postoperative magnetic resonance imaging of the shoulder and elbow joint was conducted to determine the causes of arterial occlusion. The patient resumed pitching 4 months postoperatively, and has remained active and symptom free. Magnetic resonance imaging examination revealed no vascular abnormalities or bony or soft tissue in the shoulder or elbow region. With early detection and treatment, a favorable prognosis can be achieved in baseball pitchers with acute upper extremity arterial occlusion so that their pitching career is not jeopardized

The Effect of Mobile Gamification on Brand Loyalty

The purpose of this study is mainly to use the gamification concept to design a mobile gaming app (application) for contextual marketing, and we will integrate digital game design technologies, such as augmented reality (AR) and global positioning system (GPS). The study will then look at associated consumer value and brand loyalty created by the users after experiencing the mobile game. Accordingly, we define the eight elements of a mobile gamification design, including coping-escape, fantasy, recreation, social, omnipotence, competition, skill development, and location-based. This research model treats “location-based” as a formative second-order construct driven by ubiquitous connectivity and contextual offer. Consumer value and brand loyalty are also a second-order construct. The study will conduct a quasi-experimental research to verify our model. It is hoped that service managers can benefit from the insights discovered from this study and implement more effective management strategies for effective performance

Anticipating Daily Intention using On-Wrist Motion Triggered Sensing

Anticipating human intention by observing one's actions has many applications. For instance, picking up a cellphone, then a charger (actions) implies that one wants to charge the cellphone (intention). By anticipating the intention, an intelligent system can guide the user to the closest power outlet. We propose an on-wrist motion triggered sensing system for anticipating daily intentions, where the on-wrist sensors help us to persistently observe one's actions. The core of the system is a novel Recurrent Neural Network (RNN) and Policy Network (PN), where the RNN encodes visual and motion observation to anticipate intention, and the PN parsimoniously triggers the process of visual observation to reduce computation requirement. We jointly trained the whole network using policy gradient and cross-entropy loss. To evaluate, we collect the first daily "intention" dataset consisting of 2379 videos with 34 intentions and 164 unique action sequences. Our method achieves 92.68%, 90.85%, 97.56% accuracy on three users while processing only 29% of the visual observation on average

A Comparative Study on Spin-Orbit Torque Efficiencies from W/ferromagnetic and W/ferrimagnetic Heterostructures

It has been shown that W in its resistive form possesses the largest spin-Hall ratio among all heavy transition metals, which makes it a good candidate for generating efficient dampinglike spin-orbit torque (DL-SOT) acting upon adjacent ferromagnetic or ferrimagnetic (FM) layer. Here we provide a systematic study on the spin transport properties of W/FM magnetic heterostructures with the FM layer being ferromagnetic Co$_{20}$Fe$_{60}$B$_{20}$ or ferrimagnetic Co$_{63}$Tb$_{37}$ with perpendicular magnetic anisotropy. The DL-SOT efficiency $|\xi_{DL}|$, which is characterized by a current-induced hysteresis loop shift method, is found to be correlated to the microstructure of W buffer layer in both W/Co$_{20}$Fe$_{60}$B$_{20}$ and W/Co$_{63}$Tb$_{37}$ systems. Maximum values of $|\xi_{DL}|\approx 0.144$ and $|\xi_{DL}|\approx 0.116$ are achieved when the W layer is partially amorphous in the W/Co$_{20}$Fe$_{60}$B$_{20}$ and W/Co$_{63}$Tb$_{37}$ heterostructures, respectively. Our results suggest that the spin Hall effect from resistive phase of W can be utilized to effectively control both ferromagnetic and ferrimagnetic layers through a DL-SOT mechanism

Using LC-MS with de novo software to fully characterize the multiple methylations of lysine residues in a recombinant fragment of an outer membrane protein from a virulent strain of Rickettsia prowazekii

The outer membrane protein B (OmpB) of the typhus group rickettsiae is an immunodominant antigen and has been shown to provide protection against typhus in animal models. Consequently, OmpB is currently being considered as a potential rickettsiae vaccine candidate to be used in humans. The OmpB from virulent strains are heavily methylated while the attenuated strains are hypomethylated. Western blot analysis of partially digested OmpB revealed that one of the reactive fragments was located at the N-terminus (fragment A, aa 33–272). Recently, we have over expressed, purified, and chemically methylated the recombinant fragment A from Rickettsia prowazekii (Ap). The methylated Ap was thoroughly characterized by LC/MS/MS on the ProteomeX workstation. The protein sequence of Ap with and without methylation was 87.7% and 100% identified, respectively. This high sequence coverage enabled us to determine the sites and extent of methylation on the lysine residues in Ap. All the lysine residues except the C-terminus lysine were either mono-, di- or tri-methylated. In addition, carbamylation on the N-terminus glycine was identified using a combination of denovo sequencing (DeNovoX) and the pattern recognition (SALSA) program with accurate mass measurement. We demonstrated that the use of peptide identification (SEQUEST) in combination with SALSA and denovo sequencing provided a useful means to characterize the sequence and posttranslational modifications of given proteins

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