A lab-on-a-disc platform enables serial monitoring of individual CTCs associated with tumor progression during EGFR-targeted therapy for patients with NSCLC

Rationale: Unlike traditional biopsy, liquid biopsy, which is a largely non-invasive diagnostic and monitoring tool, can be performed more frequently to better track tumors and mutations over time and to validate the efficiency of a cancer treatment. Circulating tumor cells (CTCs) are considered promising liquid biopsy biomarkers; however, their use in clinical settings is limited by high costs and a low throughput of standard platforms for CTC enumeration and analysis. In this study, we used a label-free, high-throughput method for CTC isolation directly from whole blood of patients using a standalone, clinical setting-friendly platform. Methods: A CTC-based liquid biopsy approach was used to examine the efficacy of therapy and emergent drug resistance via longitudinal monitoring of CTC counts, DNA mutations, and single-cell-level gene expression in a prospective cohort of 40 patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer. Results: The change ratio of the CTC counts was associated with tumor response, detected by CT scan, while the baseline CTC counts did not show association with progression-free survival or overall survival. We achieved a 100% concordance rate for the detection of EGFR mutation, including emergence of T790M, between tumor tissue and CTCs. More importantly, our data revealed the importance of the analysis of the epithelial/mesenchymal signature of individual pretreatment CTCs to predict drug responsiveness in patients. Conclusion: The fluid-assisted separation technology disc platform enables serial monitoring of CTC counts, DNA mutations, as well as unbiased molecular characterization of individual CTCs associated with tumor progression during targeted therapy

Dehydrated aqueous two-phase system micro-domains retain their shape upon rehydration to allow patterned reagent delivery to cells

Aqueous reagent solution micro-domains with sharp boundaries and defined shapes are created over cell monolayers within an immiscible bulk aqueous phase through rehydration of freestanding and portable dried reagent patches of the corresponding shape. This is in contrast to typical dissolution of reagent tablets or lyophilized biopolymer patches in aqueous solutions where no discernible reagent solution patterns are formed upon their full hydration. The key to enable the engineering of such stable reagent solution micro-domains is to formulate the reagent patches with polymers that form an aqueous two-phase system (ATPS) upon hydration by the bulk aqueous phase. This paper demonstrates this concept using dried reagent patches that incorporate dextran (DEX) and a bulk aqueous phase comprised of cell culture medium containing poly(ethylene) glycol (PEG). For reagents that prefer to partition in the DEX phase of the resulting ATPS, this procedure results in micro-patterned localization of reagent solution only to regions of the cell monolayer covered with the rehydrated DEX patch. The types of aqueous reagent solution micro-domain shapes that can be formed by the rehydration of such freestanding DEX-reagent patches are surprisingly broad and can be readily controlled by use of different templates for dehydrating the DEX solutions or even by cutting flat patches. The utility of the method is demonstrated through localized delivery of fluorescent molecules and enzymes for cell detachment. The patterned enzymatic detachment of cells enables convenient wound healing assays where cell monolayers can be wounded in different shapes dictated by the silhouette of the original DEX-reagent patchesclose1

Geometrically Induced Multiple Coulomb Blockade Gaps

We have theoretically investigated the transport properties of a ring-shaped array of small tunnel junctions, which is weakly coupled to the drain electrode. We have found that the long range interaction together with the semi-isolation of the array bring about the formation of stable standing configurations of electrons. The stable configurations break up during each transition from odd to even number of trapped electrons, leading to multiple Coulomb blockade gaps in the the $I-V$ characteristics of the system.Comment: 4 Pages (two-columns), 4 Figures, to be published in Physical Review Letter

Super-lattice, rhombus, square, and hexagonal standing waves in magnetically driven ferrofluid surface

Standing wave patterns that arise on the surface of ferrofluids by (single frequency) parametric forcing with an ac magnetic field are investigated experimentally. Depending on the frequency and amplitude of the forcing, the system exhibits various patterns including a superlattice and subharmonic rhombuses as well as conventional harmonic hexagons and subharmonic squares. The superlattice arises in a bicritical situation where harmonic and subharmonic modes collide. The rhombic pattern arises due to the non-monotonic dispersion relation of a ferrofluid

The Horizon Run 5 Cosmological Hydrodynamic Simulation: Probing Galaxy Formation from Kilo- to Giga-parsec Scales

Horizon Run 5 (HR5) is a cosmological hydrodynamical simulation which captures the properties of the Universe on a Gpc scale while achieving a resolution of 1kpc. Inside the simulation box we zoom-in on a high-resolution cuboid region with a volume of 1049×114×114cMpc3.The sub-grid physics chosen to model galaxy formation includes radiative heating/cooling, UV background, star formation, supernova feedback, chemical evolution tracking the enrichment of oxygen and iron, the growth of supermassive black holes and feedback from active galactic nuclei (AGN) in the form of a dual jet-heating mode. For this simulation we implemented a hybrid MPI-OMP version of RAMSES, specifically targeted for modern many-core many thread parallel architectures. In addition to the traditional simulation snapshots, light-cone data was generated on the fly. For the post-processing, we extended the Friends-of-Friend (FoF) algorithm and developed a new galaxy finder PGalF to analyse the outputs of HR5. The simulation successfully reproduces observations, such as the cosmic star formation history and connectivity of galaxy distribution, We identify cosmological structures at a wide range of scales, from filaments with a length of several cMpc, to voids with a radius of ~100 cMpc. The simulation also indicates that hydrodynamical effects on small scales impact galaxy clustering up to very large scales near and beyond the baryonic acoustic oscillation (BAO) scale. Hence, caution should be taken when using that scale as a cosmic standard ruler: one needs to carefully understand the corresponding biases. The simulation is expected to be an invaluable asset for the interpretation of upcoming deep surveys of the Universe

Far-ultraviolet Observations of the North Ecliptic Pole with SPEAR

We present SPEAR/FIMS far-ultraviolet observations near the North Ecliptic Pole. This area, at b~30 degrees and with intermediate HI column, seems to be a fairly typical line of sight that is representative of general processes in the diffuse ISM. We detect a surprising number of emission lines of many elements at various ionization states representing gas phases from the warm neutral medium (WNM) to the hot ionized medium (HIM). We also detect fluorescence bands of H2, which may be due to the ubiquitous diffuse H2 previously observed in absorption.Comment: 5 pages, 3 figures, Accepted for publication in ApJ Letter

Prescriptions patterns and appropriateness of usage of antibiotics in non-teaching community hospitals in South Korea: a multicentre retrospective study

Abstract Background Although non-teaching community hospitals form the majority of healthcare providers in South Korea, there is limited data on antibiotic usage in them. To evaluate the pattern of antibiotic usage and its appropriateness in hospitals with < 400 beds in South Korea. Methods A multicentre retrospective study was conducted in 10 hospitals (six long-term care hospitals, three acute care hospitals, and one orthopaedic hospital), with < 400 beds in South Korea. We analysed patterns of antibiotic prescription in 2019, and their appropriateness in the participating hospitals. For the evaluation of the appropriateness of the prescription, 25 patients under antibiotic therapy were randomly selected at each hospital, over two separate periods. Due to the heterogeneity of their characteristics, the orthopaedics hospital was excluded from the analysis. Results The most commonly prescribed antibiotics in long-term care hospitals was fluoroquinolone, followed by beta-lactam/beta-lactamase inhibitor (anti-pseudomonal). In acute care hospitals, these were third generation cephalosporin, followed by first generation cephalosporin, and second generation cephalosporin. The major antibiotics that were prescribed in the orthopedics hospital was first generation cephalosporin Only 2.3% of the antibiotics were administered inappropriately. In comparison, 15.3% of patients were prescribed an inappropriate dose. The proportion of inappropriate antibiotic prescriptions was 30.6% of the total antibiotic prescriptions. Conclusions The antibiotic usage patterns vary between non-teaching community hospitals in South Korea. The proportion of inappropriate prescriptions exceeded 30% of the total antibiotic prescriptions

Endothelial Function is Not Changed during Short-Term Withdrawal of Thyroxine in Patients with Differentiated Thyroid Cancer and Low Cardiovascular Risk

PURPOSE: The incidence of differentiated thyroid cancer is increasing in young adults and females in Korea. Some of them experience short-term hypothyroidism in preparation for radioiodine (RAI) therapy, which can have a deleterious effect on the cardiovascular system. However, it is not clear if short-term hypothyroidism induces endothelial dysfunction in patients with low cardiovascular risk. Therefore, the aim of this study was to investigate whether short-term hypothyroidism is associated with endothelial dysfunction in patients with low cardiovascular risk. MATERIALS AND METHODS: To evaluate the effect of short-term hypothyroidism on endothelial function in this group, we recruited fifteen female patients with low cardiovascular risk. We analyzed clinical, biochemical, and cardiovascular parameters at four time points: the last day on levothyroxine (LT4) at their usual thyroid-stimulating hormone (TSH)-suppressive doses (P1), 7 days (P2) and 4 weeks (P3) after withdrawal of LT4, and 8 weeks (P4) after replacement of the previous dose of LT4. A high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperemia, and after sublingual nitroglycerin. RESULTS: During short-term hypothyroidism (P3), serum concentrations of total cholesterol and low-density lipoprotein (LDL)-cholesterol were increased (p < 0.001 for each period). In spite of having worsened lipid states, serum high sensitivity C-reactive protein or flow-mediated vasodilatation, which is one of the surrogate markers of the endothelial function, did not change during short-term hypothyroidism. CONCLUSION: Short-term hypothyroidism induced worsening of metabolic parameters, but not enough to induce the endothelial dysfunction in patients with low cardiovascular riskope