Prevalence and detection of low-allele-fraction variants in clinical cancer samples

Accurate detection of genomic alterations using high-throughput sequencing is an essential component of precision cancer medicine. We characterize the variant allele fractions (VAFs) of somatic single nucleotide variants and indels across 5095 clinical samples profiled using a custom panel, CancerSCAN. Our results demonstrate that a significant fraction of clinically actionable variants have low VAFs, often due to low tumor purity and treatment-induced mutations. The percentages of mutations under 5% VAF across hotspots in EGFR, KRAS, PIK3CA, and BRAF are 16%, 11%, 12%, and 10%, respectively, with 24% for EGFR T790M and 17% for PIK3CA E545. For clinical relevance, we describe two patients for whom targeted therapy achieved remission despite low VAF mutations. We also characterize the read depths necessary to achieve sensitivity and specificity comparable to current laboratory assays. These results show that capturing low VAF mutations at hotspots by sufficient sequencing coverage and carefully tuned algorithms is imperative for a clinical assay

Programmable RF Built-In Self-Test Circuit for 5GHz Wireless LAN

This paper proposes a new programmable RF Built-In Self-Test (BIST) circuit for 5GHz Wireless LAN. It is fabricated using 0.18-µm SiGe technology. This circuit is useful for testability of GHz-band RF IC devices in a complete RF transceiver environment. The proposed circuit helps it to provide DC output voltages and accurate phase difference. It contains two peak detectors and a phase detector. The proposed circuit showed excellent performance

Inkjet printed electronics using copper nanoparticle ink

Inkjet printing of electrode using copper nanoparticle ink is presented. Electrode was printed on a flexible glass epoxy composite substrate using drop on demand piezoelectric dispenser and was sintered at 200 °C of low temperature in N2 gas condition. The printed electrodes were made with various widths and thickness. In order to control the thickness of the printed electrode, number of printing was varied. Resistivity of printed electrode was calculated from the cross-sectional area measured by a profilometer and resistance measured by a digital multimeter. Surface morphology of electrode was analyzed using scanning electron microscope (SEM) and atomic force microscope (AFM). From the study, it was found that 10 times printed electrode has the most stable grain structure and low resistivity of 36.7 nΩ m

Activation of the Transducers of Unfolded Protein Response in Plants

Maintenance of homeostasis of the endoplasmic reticulum (ER) ensures the balance between loading of nascent proteins and their secretion. Certain developmental conditions or environmental stressors affect protein folding causing ER stress. The resultant ER stress is mitigated by upregulating a set of stress-responsive genes in the nucleus modulating the mechanism of the unfolded protein response (UPR). In plants, the UPR is mediated by two major pathways; by the proteolytic processing of bZIP17/28 and by the IRE1-mediated splicing of bZIP60 mRNA. Recent studies have shown the involvement of plant-specific NAC transcription factors in UPR regulation. The molecular mechanisms activating plant-UPR transducers are only recently being unveiled. This review focuses on important structural features involved in the activation of the UPR transducers like bZIP17/28/60, IRE1, BAG7, and NAC017/062/089/103. Also, we discuss the activation of the UPR pathways, including BAG7-bZIP28 and IRE1-bZIP60, in detail, together with the NAC-TFs, which adds a new paradigm to the plant UPR

Real-time machine learning model to predict in-hospital cardiac arrest using heart rate variability in ICU

Abstract Predicting in-hospital cardiac arrest in patients admitted to an intensive care unit (ICU) allows prompt interventions to improve patient outcomes. We developed and validated a machine learning-based real-time model for in-hospital cardiac arrest predictions using electrocardiogram (ECG)-based heart rate variability (HRV) measures. The HRV measures, including time/frequency domains and nonlinear measures, were calculated from 5 min epochs of ECG signals from ICU patients. A light gradient boosting machine (LGBM) algorithm was used to develop the proposed model for predicting in-hospital cardiac arrest within 0.5–24 h. The LGBM model using 33 HRV measures achieved an area under the receiver operating characteristic curve of 0.881 (95% CI: 0.875–0.887) and an area under the precision-recall curve of 0.104 (95% CI: 0.093–0.116). The most important feature was the baseline width of the triangular interpolation of the RR interval histogram. As our model uses only ECG data, it can be easily applied in clinical practice

Neuritin Attenuates Cognitive Function Impairments in Tg2576 Mouse Model of Alzheimer's Disease

<div><p>Neuritin, also known as CPG15, is a neurotrophic factor that was initially discovered in a screen to identify genes involved in activity-dependent synaptic plasticity. Neuritin plays multiple roles in the process of neural development and synaptic plasticity, although its binding receptor(s) and downstream signaling effectors remain unclear. In this study, we found that the cortical and hippocampal expression of neuritin is reduced in the brains of Alzheimer's disease (AD) patients and demonstrated that viral-mediated expression of neuritin in the dentate gyrus of 13-month-old Tg2576 mice, an AD animal model, attenuated a deficit in learning and memory as assessed by a Morris water maze test. We also found that neuritin restored the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neuron cultures prepared from Tg2576 mice. It was also shown that viral-mediated expression of neuritin in the dentate gyrus of 7-week-old Sprague-Dawley rats increased neurogenesis in the hippocampus. Taken together, our results demonstrate that neuritin restores the reduction in dendritic spine density and the maturity of individual spines in primary hippocampal neurons from Tg2576 neurons, and also attenuates cognitive function deficits in Tg2576 mouse model of AD, suggesting that neuritin possesses a therapeutic potential for AD.</p></div

Veno-Arterial-Venous Extracorporeal Membrane Oxygenation in a Critically Ill Patient with Coronavirus Disease 2019

Patients with cardiopulmonary failure may not be fully supported with typical configurations of extracorporeal membrane oxygenation (ECMO), either veno-arterial (VA) or veno-venous (VV). Veno-arterial-venous (VAV)-ECMO is a technique used to support the cardiopulmonary systems during periods of inadequate gas exchange and perfusion. In the severe case of coronavirus disease 2019 (COVID-19), which simultaneously affects the heart and lung, VAV-ECMO may improve a patient&rsquo;s recovery potential. We report the case of a 72-year-old woman with acute respiratory distress syndrome and circulatory failure following COVID-19, who was treated with VAV-ECMO