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

Ridge detection for nonstationary multicomponent signals with time-varying wave-shape functions and its applications

We introduce a novel ridge detection algorithm for time-frequency (TF) analysis, particularly tailored for intricate nonstationary time series encompassing multiple non-sinusoidal oscillatory components. The algorithm is rooted in the distinctive geometric patterns that emerge in the TF domain due to such non-sinusoidal oscillations. We term this method \textit{shape-adaptive mode decomposition-based multiple harmonic ridge detection} (\textsf{SAMD-MHRD}). A swift implementation is available when supplementary information is at hand. We demonstrate the practical utility of \textsf{SAMD-MHRD} through its application to a real-world challenge. We employ it to devise a cutting-edge walking activity detection algorithm, leveraging accelerometer signals from an inertial measurement unit across diverse body locations of a moving subject

Cerebral hemorrhagic infarction following cranioplasty in a shunted patient with tension pneumocephalus resulting from depressed skull and craniodural defect

SummaryA 34-year-old female sustained a severe traumatic brain injury that was treated with decompressive craniectomy and subsequent cranioplasty, then with ventriculoperitoneal shunt about 10 years previously. However, the skull flap was found to be depressed ever since. She was admitted to our hospital for a headache and left hemiparesis with sudden onset. The computed tomography scan displayed tension pneumocephalus in the right frontoparietal region. First, she underwent emergency burr hole drainage and placement of a subdural drain with external ventricular drainage tube. Then her symptoms improved considerably. Unfortunately, 6 months later she was admitted again to our hospital because of headache and left hemiparesis with sudden onset, and the brain computed tomography showed tension pneumocephalus in the right frontoparietal region. She underwent craniectomy to remove the previous depressed skull and simultaneous cranioplasty with Ti-Mesh. On the day of her operation, generalized seizure occurred and her consciousness deteriorated. The magnetic resonance imaging showed hemorrhagic infarction on both sides of the thalamus and the right parieto-occipital region. We think it probable that a sudden increase of cerebral blood flow in the cerebral hemisphere where the cranioplasty had been performed caused reperfusion injury and resulted in hemorrhagic infarction

A comprehensive functional map of the hepatitis C virus genome provides a resource for probing viral proteins.

UnlabelledPairing high-throughput sequencing technologies with high-throughput mutagenesis enables genome-wide investigations of pathogenic organisms. Knowledge of the specific functions of protein domains encoded by the genome of the hepatitis C virus (HCV), a major human pathogen that contributes to liver disease worldwide, remains limited to insight from small-scale studies. To enhance the capabilities of HCV researchers, we have obtained a high-resolution functional map of the entire viral genome by combining transposon-based insertional mutagenesis with next-generation sequencing. We generated a library of 8,398 mutagenized HCV clones, each containing one 15-nucleotide sequence inserted at a unique genomic position. We passaged this library in hepatic cells, recovered virus pools, and simultaneously assayed the abundance of mutant viruses in each pool by next-generation sequencing. To illustrate the validity of the functional profile, we compared the genetic footprints of viral proteins with previously solved protein structures. Moreover, we show the utility of these genetic footprints in the identification of candidate regions for epitope tag insertion. In a second application, we screened the genetic footprints for phenotypes that reflected defects in later steps of the viral life cycle. We confirmed that viruses with insertions in a region of the nonstructural protein NS4B had a defect in infectivity while maintaining genome replication. Overall, our genome-wide HCV mutant library and the genetic footprints obtained by high-resolution profiling represent valuable new resources for the research community that can direct the attention of investigators toward unidentified roles of individual protein domains.ImportanceOur insertional mutagenesis library provides a resource that illustrates the effects of relatively small insertions on local protein structure and HCV viability. We have also generated complementary resources, including a website (http://hangfei.bol.ucla.edu) and a panel of epitope-tagged mutant viruses that should enhance the research capabilities of investigators studying HCV. Researchers can now detect epitope-tagged viral proteins by established antibodies, which will allow biochemical studies of HCV proteins for which antibodies are not readily available. Furthermore, researchers can now quickly look up genotype-phenotype relationships and base further mechanistic studies on the residue-by-residue information from the functional profile. More broadly, this approach offers a general strategy for the systematic functional characterization of viruses on the genome scale

Establishing operando diffraction capability through the study of Li-ion (de) intercalation in LiFePO4

We have used a laboratory diffractometer to perform operando X-ray diffraction on LiFePO4 during electrochemical cycling in a coin cell fitted with a Kapton window. The results obtained are in good agreement with previous studies, verifying that extraction of Li from LiFePO4 follows dual-phase solid solution behaviour, with neither LiFePO4 nor FePO4 maintaining a static composition during deintercalation

Early detection of neurodegeneration in brain ischemia by manganese-enhanced MRI

This study aims to employ in vivo manganese-enhanced MRI (MEMRI) to detect neurodegenerative changes in two models of brain ischemia, photothrombotic cortical injury (PCI) and transient middle cerebral artery occlusion (MCAO) in rodents. After systemic Mn 2+ injection to both ischemic models, a close pattern of Tl-weighted hyperintensity was observed throughout different brain regions in comparison to the distribution of GFAP, MnSOD and GS immunoreactivities, whereby conventional MRI could hardly detect such. In addition, the infarct volumes in the posterior parts of the brain had significantly reduced after Mn 2+ injection to the MCAO model. It is suggested that exogenous Mn 2+ injection may provide enhanced MEMRI detection of oxidative stress and gliosis early after brain ischemia. Manganese may also mediate infarctions at remote brain regions in transient focal cerebral ischemia before delayed secondary damage takes place. © 2008 IEEE.published_or_final_versionThe 30th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBS) 2008, Vancouver, BC., 20-25 August 2008. in Proceedings of the 30th EMBS, 2008, p. 3884-388

Cytotoxic and Anti-HIV Phenanthroindolizidine Alkaloids from Cryptocarya chinensis

Bioassay-guided fractionation of the cytotoxic ethanol extract of Cryptocarya chinensis has led to the isolation of 11 compounds, including two phenanthroindolizidine alkaloids [(−)-antofine (1) and dehydroantofine (2)], five pavine alkaloids (3–7), and four proaporphine alkaloids (8–11). The structures of the isolated compounds were determined by means of NMR spectroscopic methods, and supported by HRMS and optical rotation data. Compounds 1 and 2 showed cytotoxic activity against four cancer cell lines, L1210, P388, A549, and HCT-8, with 1 being the most potent against A549 and HCT-8 with EC50 values of 0.002 and 0.001 μg/mL, respectively. In addition, 2 is first reported to exhibit significant anti-HIV activity