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

Diquarks and the production of charmed baryons

Utilizing a quark model characterized by parameters that effectively replicate the masses of ground state hadrons, we illustrate that $(us)$ or $(ds)$ diquarks exhibit greater compactness in comparison to $(ud)$ diquarks. Concretely, the binding energy of the $(us)$ diquark - defined as the diquark's mass minus the combined masses of its individual quarks - is found to be more attractive than that of the $(ud)$ diquark. This heightened attraction present in $(us)$ diquarks could lead to enhanced production of $\Xi_c/D$ particles in high-energy pp or ultrarelativistic heavy-ion collisions.Comment: 9 pages, 5 figure

Camera for QUasars in EArly uNiverse (CQUEAN)

We describe the overall characteristics and the performance of an optical CCD camera system, Camera for QUasars in EArly uNiverse (CQUEAN), which is being used at the 2.1 m Otto Struve Telescope of the McDonald Observatory since 2010 August. CQUEAN was developed for follow-up imaging observations of red sources such as high redshift quasar candidates (z >= 5), Gamma Ray Bursts, brown dwarfs, and young stellar objects. For efficient observations of the red objects, CQUEAN has a science camera with a deep depletion CCD chip which boasts a higher quantum efficiency at 0.7 - 1.1 um than conventional CCD chips. The camera was developed in a short time scale (~ one year), and has been working reliably. By employing an auto-guiding system and a focal reducer to enhance the field of view on the classical Cassegrain focus, we achieve a stable guiding in 20 minute exposures, an imaging quality with FWHM >= 0.6" over the whole field (4.8' * 4.8'), and a limiting magnitude of z = 23.4 AB mag at 5-sigma with one hour total integration time.Comment: Accepted for publication in PASP. 26 pages including 5 tables and 24 figure

Circulating tumor cells detected by lab-on-adisc: Role in early diagnosis of gastric cancer

[Background] The use of circulating tumor cells (CTCs) as an early diagnostic biomarker and prognostic indicator after surgery or chemotherapy has been suggested for various cancers. This study aimed to evaluate CTCs in patients who underwent gastrectomy for gastric cancer and to explore their clinical usefulness in the early diagnosis of gastric cancer. [Methods] A total of 116 patients with gastric cancer who underwent gastrectomy and 31 healthy volunteers were prospectively included between 2014 and 2015. Peripheral blood samples were collected before gastrectomy, and CTCs were examined using a centrifugal microfluidic system with a new fluid-assisted separation technique. [Results] After creating a receiver operating characteristic curve to identify the discriminative CTC value needed differentiate patients with gastric cancer from healthy volunteers, sensitivity and specificity were nearly optimized at a CTC threshold of 2 per 7.5 mL of blood. Of the 102 persons with a CTC level >= 2 per 7.5 mL of blood, 99 (97.1%) had gastric cancer, and of the 45 persons with a CTC level <2 per 7.5 mL of blood, 28 (62.2%) were healthy controls. Accordingly, the sensitivity and specificity for the differentiation of patients with gastric cancer from healthy controls were 85.3% and 90.3%, respectively. However, the presence of CTCs was not associated with any clinicopathologic features such as staging, histologic type, or mucin phenotype. [Conclusion] Although we could not prove the clinical feasibility of CTCs for gastric cancer staging, our results suggest a potential role of CTCs as an early diagnostic biomarker of gastric cancer

Minimal information for studies of extracellular vesicles (MISEV2023): From basic to advanced approaches

Extracellular vesicles (EVs), through their complex cargo, can reflect the state of their cell of origin and change the functions and phenotypes of other cells. These features indicate strong biomarker and therapeutic potential and have generated broad interest, as evidenced by the steady year-on-year increase in the numbers of scientific publications about EVs. Important advances have been made in EV metrology and in understanding and applying EV biology. However, hurdles remain to realising the potential of EVs in domains ranging from basic biology to clinical applications due to challenges in EV nomenclature, separation from non-vesicular extracellular particles, characterisation and functional studies. To address the challenges and opportunities in this rapidly evolving field, the International Society for Extracellular Vesicles (ISEV) updates its 'Minimal Information for Studies of Extracellular Vesicles', which was first published in 2014 and then in 2018 as MISEV2014 and MISEV2018, respectively. The goal of the current document, MISEV2023, is to provide researchers with an updated snapshot of available approaches and their advantages and limitations for production, separation and characterisation of EVs from multiple sources, including cell culture, body fluids and solid tissues. In addition to presenting the latest state of the art in basic principles of EV research, this document also covers advanced techniques and approaches that are currently expanding the boundaries of the field. MISEV2023 also includes new sections on EV release and uptake and a brief discussion of in vivo approaches to study EVs. Compiling feedback from ISEV expert task forces and more than 1000 researchers, this document conveys the current state of EV research to facilitate robust scientific discoveries and move the field forward even more rapidly

25th annual computational neuroscience meeting: CNS-2016

The same neuron may play different functional roles in the neural circuits to which it belongs. For example, neurons in the Tritonia pedal ganglia may participate in variable phases of the swim motor rhythms [1]. While such neuronal functional variability is likely to play a major role the delivery of the functionality of neural systems, it is difficult to study it in most nervous systems. We work on the pyloric rhythm network of the crustacean stomatogastric ganglion (STG) [2]. Typically network models of the STG treat neurons of the same functional type as a single model neuron (e.g. PD neurons), assuming the same conductance parameters for these neurons and implying their synchronous firing [3, 4]. However, simultaneous recording of PD neurons shows differences between the timings of spikes of these neurons. This may indicate functional variability of these neurons. Here we modelled separately the two PD neurons of the STG in a multi-neuron model of the pyloric network. Our neuron models comply with known correlations between conductance parameters of ionic currents. Our results reproduce the experimental finding of increasing spike time distance between spikes originating from the two model PD neurons during their synchronised burst phase. The PD neuron with the larger calcium conductance generates its spikes before the other PD neuron. Larger potassium conductance values in the follower neuron imply longer delays between spikes, see Fig. 17.Neuromodulators change the conductance parameters of neurons and maintain the ratios of these parameters [5]. Our results show that such changes may shift the individual contribution of two PD neurons to the PD-phase of the pyloric rhythm altering their functionality within this rhythm. Our work paves the way towards an accessible experimental and computational framework for the analysis of the mechanisms and impact of functional variability of neurons within the neural circuits to which they belong

Changes in the Brain in Temporal Lobe Epilepsy with Unilateral Hippocampal Sclerosis: An Initial Case Series

Temporal lobe epilepsy (TLE) is a network disorder of the brain. Network disorders predominately involve dysregulation of hippocampal function caused by neuronal hyperexcitability. However, the relationship between the macro- and microscopic changes in specific brain regions is uncertain. In this study, the pattern of brain atrophy in patients with TLE and hippocampal sclerosis (HS) was investigated using volumetry, and microscopic changes in specific lesions were observed to examine the anatomical correspondence with specific target lesions using diffusion tensor imaging (DTI) with statistical parametric mapping (SPM). This retrospective cross-sectional study enrolled 17 patients with TLE and HS. We manually measured the volumes of the hippocampus (HC), amygdala (AMG), entorhinal cortex, fornix, and thalamus (TH) bilaterally. The mean diffusivity and fractional anisotropy of each patient were then quantified and analyzed by a voxel-based statistical correlation method using SPM8. In right TLE with HS, there was no evidence of any abnormal diffusion properties associated with the volume reduction in specific brain regions. In left TLE with HS, there were significant changes in the volumes of the AMG, HC, and TH. Despite the small sample size, these differences in conditions were considered meaningful. Chronic left TLE with HS might cause structural changes in the AMG, HC, and TH, unlike right TLE with HS

Key Substitution Attacks on Lattice Signature Schemes Based on SIS Problem

The notion of key substitution security on digital signatures in the multiuser setting has been proposed by Menezes and Smart in 2004. Along with the unforgeability of signature, the key substitution security is very important since it is a critical requirement for the nonrepudiation and the authentication of the signature. Lattice-based signature is a promising candidate for post-quantum cryptography, and the unforgeability of each scheme has been relatively well studied. In this paper, we present key substitution attacks on BLISS, Lyubashevsky’s signature scheme, and GPV and thus show that these signature schemes do not provide nonrepudiation. We also suggest how to avoid key substitution attack on these schemes