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

Fabrication of GaN-Based White Light-Emitting Diodes on Yttrium Aluminum Garnet-Polydimethylsiloxane Flexible Substrates

This study concerns the characteristics of white GaN-based light-emitting diode (LED) on flexible substrates. The thin film GaN-based blue LEDs were directly transferred from sapphire onto the flexible polydimethylsiloxane (PDMS) substrates by laser lift-off (LLO) process. The PDMS substrates were incorporated 10–40% cerium doped yttrium aluminum garnet phosphor, YAG:Ce3+, and formed the GaN-based white LEDs. The white LEDs prepared by the GaN-based LEDs on the YAG-PDMS substrates reveal one peak at 470 nm corresponding to the emission of the GaN-based LED and a broadband included five weak peaks caused by YAG:Ce3+ phosphors

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

Association between urinary glyphosate levels and hand grip strength in a representative sample of US adults: NHANES 2013–2014

IntroductionGlyphosate, a widely utilized herbicide globally, has been linked to various health issues, including cancer, birth abnormalities, and reproductive issues. Additionally, there is growing experimental support indicating potential harm to skeletal muscles. Despite this, the impact of glyphosate on human muscle health remains unclear.MethodsWe examined information gathered from the 2013-2014 National Health and Nutrition Examination Survey (NHANES), which included 1466 adults aged 18 or older. Our primary aim was to investigate the relationship between glyphosate exposure and hand grip strength, as well as its influence on lean muscle mass.Results and discussionOur investigation uncovered a detrimental correlation between glyphosate exposure and all measures of grip strength, except for the second test of the first hand. Specifically, we observed a statistically significant adverse association between glyphosate exposure and combined grip strength, which is calculated as the sum of the highest readings from both hands (ß coefficient of −2.000, S.E. = 0.891, p = 0.040). We did not observe a significant correlation between glyphosate levels, lean muscle mass, and the likelihood of reaching maximum grip strength meeting sarcopenia criteria. Additionally, we observed an interaction between age and glyphosate, as well as between body mass index (BMI) and glyphosate, concerning the association with combined grip strength. In this comprehensive analysis of NHANES data, our study reveals a potential association between glyphosate exposure and hand grip strength in the adult population. Our findings suggest the need for deeper exploration into the health effects of glyphosate exposure and its impact on muscle strength, shedding light on possible public health concerns

Experimental and Theoretical Studies on Formability of 22MnB5 at Elevated Temperatures by Gleeble Simulator

AbstractThis paper, which includes an experimental analysis and theoretical predictions, presents a method to investigate the formability of high strength steel sheet 22MnB5 at elevated temperatures. In this method, two designs for tensile test specimens with laser engraving grids are developed and used to obtain the strain paths of a uniaxial tensile state and the plane strain occurring at elevated temperatures using a Gleeble simulator. On the other hand, a modified Cockcroft criterion that takes strain path into consideration is employed to predict the entire forming limit diagram. A forming limit diagram could be established as a result of using the modified Cockcroft criterion together with the limit strains obtained from the tensile tests based on two novel specimen designs. In this paper, forming limit diagrams at three strain rates and forming limit diagrams at temperatures ranging from 650 oC to 850 oC were established

Dynamic Power Index Adjustment Based On Battery Level

This disclosure describes techniques for dynamic adjustment of output power index of a wireless remote controller device based on a detected battery level of the device. The battery voltage level of the device is periodically measured. When the level falls below a predetermined threshold, the output power index is adjusted to ensure that the total transmit power from the controller device lies within a specified range. Dynamic adjustment of transmit power via the power index adjustment enables the controller device to have a transmit power that lies between the power spectral distribution (PSD) target and the PSD limit (maximum) over a range of battery voltage values

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

Dose pre-hospital laryngeal mask airway use has a survival benefit in non-shockable cardiac arrest?

Background. Whether pre-hospital laryngeal mask airway (LMA) use poses a survival benefit and should be approved as routine airway management in non-shockable cardiac arrest is of major concern. The present study examined the effectiveness of LMA, in comparison to other pre-hospital airway management on individuals who have experienced non-shockable cardiac arrest. Methods. Adult patients who experienced non-shockable cardiac arrest with activation of the emergency medical service (EMS) made up our study cohort in Taoyuan, Taiwan. The data were abstracted from EMS records and cardiac arrest registration protocols. Results. Among the 1912 enrolled patients, most received LMA insertion (72.4%), 108 (5.6%) bag-valve-mask (BVM) ventilation, 376 (19.7%) high-flow oxygen non-rebreather facemask, and only 44 (2.3%) received endotracheal tube intubation (ETI). With regard to survival to discharge, no significant differences in prevalence were evident among the groups: 2.8% of oxygen facial mask, 1.1% of BVM, 2.1% of LMA, and 4.5% of the ETI group survived to discharge (p = 0.314). In comparison to oxygen facial mask use, different types of airway management remained unassociated with survival to discharge after adjusting for variables by logistic regression analysis (BVM: 95% confidence interval [CI], 0.079 – 1.639 [p = 0.186]; LMA: 95% CI, 0.220–2.487 [p = 0.627]; ETI: 95% CI, 0.325–17.820 [p = 0.390]). The results of Hosmer-Lemeshow goodness-of-fit test of logistic regression model revealed good calibration. Conclusions. Pre-hospital LMA use was not associated with additional survival to discharge compared with facial oxygen mask, BVM, or ETI following non-shockable cardiac arrest