Probing the Global 21-cm Signal via the Integrated Sachs-Wolfe Effect on the 21-cm Background

We propose a novel method to probe the global 21-cm background. This background experiences the integrated Sachs-Wolfe effect (ISW) as the cosmic microwave background does. The 21-cm ISW is modulated by the spectral shape of the global 21-cm signal, and thus the measure of the 21-cm ISW will be a probe of the evolution of the global signal. With the phase-1 SKA telescope, probing the global 21-cm background would be feasible with 10000-hour observation, enabling consistency checks with existing measures of the global 21-cm signal by EDGES and SARAS that are conflicting with each other.Comment: submitted to PRL; 6 pages, 2 figures + supplemental materia

High precision accelerator for our hybrid model of the redshift space power spectrum

Upcoming Large Scale Structure surveys aim to achieve an unprecedented level of precision in measuring galaxy clustering. However, accurately modeling these statistics may require theoretical templates that go beyond second-order perturbation theory, especially for achieving precision at smaller scales. In our previous work, we introduced a hybrid model for the redshift space power spectrum of galaxies. This model combines second-order templates with N-body simulations to capture the influence of scale-independent parameters on the galaxy power spectrum. However, the impact of scale-dependent parameters was addressed by precomputing a set of input statistics derived from computationally expensive N-body simulations. As a result, exploring the scale-dependent parameter space was not feasible in this approach. To address this challenge, we present an accelerated methodology that utilizes Gaussian processes, a machine learning technique, to emulate these input statistics. Our emulators exhibit remarkable accuracy, achieving reliable results with just 13 N-body simulations for training. We reproduce all necessary input statistics for a set of test simulations with an error of approximately 0.1 per cent in the parameter space within $5\sigma$ of the Planck predictions, specifically for scales around $k > 0.1$ $h$Mpc$^{-1}$. Following the training of our emulators, we can predict all inputs for our hybrid model in approximately 0.2,seconds at a specified redshift. Given that performing 13 N-body simulations is a manageable task, our present methodology enables us to construct efficient and highly accurate models of the galaxy power spectra within a manageable time frame.Comment: 22 pages, 9 figure

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

Circulating Tumor Cell Clusters Are Cloaked with Platelets and Correlate with Poor Prognosis in Unresectable Pancreatic Cancer

Simple Summary: Despite recent advances, some patients with pancreatic cancer are refractory to treatment and the disease rapidly progresses, resulting in early death. The potential prognostic value of circulating tumor cells (CTCs) has been demonstrated in other cancer types, but the clinical validity in pancreatic cancer remains elusive. Here, we show that CTC clusters, which show mesenchymal characteristics and platelet marker expression, are highly correlated with poor prognosis in patients with unresectable pancreatic cancer.Circulating tumor cells (CTCs) are known to be heterogeneous and clustered with tumor-associated cells, such as macrophages, neutrophils, fibroblasts, and platelets. However, their molecular profile and clinical significance remain largely unknown. Thus, we aimed to perform a comprehensive gene expression analysis of single CTCs and CTC clusters in patients with pancreatic cancer and to identify their potential clinical relevance to provide personalized medicine. Epitope-independent, rapid (> 3 mL of whole blood/min) isolation of single CTCs and CTC clusters was achieved from a prospective cohort of 16 patients with unresectable pancreatic cancer using a centrifugal microfluidic device. Forty-eight mRNA expressions of individual CTCs and CTC clusters were analyzed to identify pancreatic CTC phenotype. CTC clusters had a larger proportion of mesenchymal expression than single CTCs (p = 0.0004). The presence of CTC clusters positively correlated with poor prognosis (progression-free survival, p = 0.0159; overall survival, p = 0.0186). Furthermore, we found that most CTCs in these patients (90.7%) were cloaked with platelets and found the presence of a positive correlation between the increase in CTC clusters and rapid disease progression during follow-ups. Efficient CTC cluster isolation and analysis techniques will enhance the understanding of complex tumor metastasis processes and can facilitate personalized disease management

Different degree of cytokinemia and T-cell activation according to serum IL-6 levels in critical COVID-19

IntroductionTocilizumab, a humanized anti-interleukin-6 receptor (IL-6R) antibody, is recommended for the treatment of severe to critical coronavirus diseases 2019 (COVID-19). However, there were conflicting results on the efficacy of tocilizumab. Therefore, we hypothesized that the differences in tocilizumab efficacy may stem from the different immune responses of critical COVID-19 patients. In this study, we described two groups of immunologically distinct COVID-19 patients, based on their IL-6 response.MethodsWe prospectively enrolled critical COVID-19 patients, requiring oxygen support with a high flow nasal cannula or a mechanical ventilator, and analyzed their serial samples. An enzyme-linked immunosorbent assay and flow cytometry were used to evaluate the cytokine kinetics and cellular immune responses, respectively.ResultsA total of nine patients with critical COVID-19 were included. The high (n = 5) and low IL-6 (n = 4) groups were distinguished by their peak serum IL-6 levels, using 400 pg/mL as the cut-off value. Although the difference of flow cytometric data did not reach the level of statistical significance, the levels of pro-inflammatory cytokines and the frequencies of intermediate monocytes (CD14+CD16+), IFN-γ+ CD4+ or CD8+ T cells, and HLA-DR+PD-1+ CD4+ T cells were higher in the high IL-6 group than in the low IL-6 group.ConclusionThere were distinctive two groups of critical COVID-19 according to serum IL-6 levels having different degrees of cytokinemia and T-cell responses. Our results indicate that the use of immune modulators should be more tailored in patients with critical COVID-19