Role of Immunohistochemistry in Fine Needle Aspiration and Core Needle Biopsy of Thyroid Nodules

Objectives Immunohistochemistry (IHC) has been used for the diagnosis of indeterminate results in fine needle aspiration (FNA) of thyroid nodules. However, the role of IHC in core needle biopsy (CNB) is not clear and the efficacy of testing for molecular markers following CNB has not been evaluated. The aim of this study is to compare the role of IHC staining in CNB with that in FNA when examining thyroid nodules and to compare the sensitivity and usefulness of different molecular markers. Methods Consecutive cases of thyroid FNA and CNB accompanied by IHC from 2004 to 2014 were included in this study with retrospective review of medical record. The rate of remaining nondiagnostic result (unsatisfactory, atypia of undetermined significance or follicular lesion of undetermined significance [AUS/FLUS]) and rate of strong expression of each molecular marker according to the diagnosis were evaluated. Results IHC was more frequently performed in CNB with multiple molecular markers compared to FNA (38.1% vs. 2.8%, 3 or 4 markers [Gal-3, HBME-1, CK19, and CD56] vs. 1 marker [Gal-3]). In the CNB group, 11.3% remained as AUS/FLUS after IHC, and the rate remaining nondiagnostic was significantly less than in the FNA group (42.9%). Gal-3 and CK19 showed higher specificity and expressed mainly in conventional type of papillary carcinoma and HBME-1 showed higher sensitivity for the diagnosis of carcinoma with expression in both conventional type and follicular variant papillary thyroid carcinoma. Conclusion With these data, we could conclude that IHC was more effective following CNB than following FNA

Doping-dependent superconducting physical quantities of K-doped BaFe2_2As2_2 obtained through infrared spectroscopy

We investigated four single crystals of K-doped BaFe$_2$As$_2$ (Ba-122), Ba$_{1-x}$K$_x$Fe$_2$As$_2$ with $x$ = 0.29, 0.36, 0.40, and 0.51, using infrared spectroscopy. We explored a wide variety of doping levels, from under- to overdoped. We obtained the superfluid plasma frequencies ($\Omega_{\mathrm{sp}}$) and corresponding London penetration depths ($\lambda_{\mathrm{L}}$) from the measured optical conductivity spectra. We also extracted the electron-boson spectral density (EBSD) functions using a two-parallel charge transport channel approach in the superconducting (SC) state. From the extracted EBSD functions, the maximum SC transition temperatures ($T_c^{\mathrm{Max}}$) were determined using a generalized McMillan formula and the SC coherence lengths ($\xi_{\mathrm{SC}}$) were calculated using the timescales encoded in the EBSD functions and reported Fermi velocities. We identified some similarities and differences in the doping-dependent SC quantities between the K-doped Ba-122 and the hole-doped cuprates. We expect that the various SC quantities obtained across the wide doping range will provide helpful information for establishing the microscopic pairing mechanism in Fe-pnictide superconductors.Comment: 16 pages, 4 figures, 1 tabl

Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma

Background Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC. Methods The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status. Results The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10–3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant. Conclusions Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.This work was supported by the National Research Foundation of Korea funded by the Korean Government (MSIT) (Grant No. NRF-2021R1A2C3005360) (YK) and the Ministry of Health & Welfare, Republic of Korea (Grant No. HI18C1876) (SSY). This study was supported by the Future Medicine 20 × 30 Project of the Samsung Medical Center (Grant No. SMX1230041, SMO1230021) and a Samsung Medical Center Research and Development Grant (Grant No. SMO1230661) (JKP)

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Recent Progress and Challenges of Electron Transport Layers in Organic–Inorganic Perovskite Solar Cells

Organic&ndash;inorganic perovskites are crystalline light absorbers which are gaining great attraction from the photovoltaic community. Surprisingly, the power conversion efficiencies of these perovskite solar cells have rapidly increased by over 25% in 2019, which is comparable to silicon solar cells. Despite the many advances in efficiency, there are still many areas to be improved to increase the efficiency and stability of commercialization. For commercialization and enhancement of applicability, the development of electron transport layer (ETL) and its interface for low temperature processes and efficient charge transfer are very important. In particular, understanding the ETL and its interface is of utmost importance, and when this understanding has been made enough, excellent research results have been published that can improve the efficiency and stability of the device. Here, we review the progress of perovskite solar cells. Especially we discuss recent important development of perovskite deposition method and its engineering as well as the electron transport layer

Dye-Sensitized Solar Cells Employing Doubly or Singly Open-Ended TiO2 Nanotube Arrays: Structural Geometry and Charge Transport

We systematically investigated the charge transport properties of doubly or singly open-ended TiO2 nanotube arrays (DNT and SNT, respectively) for their utility as electrodes in dye-sensitized solar cells (DSCs). The SNT or DNT arrays were transferred in a bottom-up (B-up) or top-up (T-up) configuration onto a fluorine-doped tin oxide (FTO) substrate onto which had been deposited a 2 mu m thick TiO2 nanoparticle (NP) interlayer. This process yielded four types of DSCs prepared with SNTs (B-up or T-up) or DNT (B-up or T-up). The photovoltaic performances of these DSCs were analyzed by measuring the dependence of the charge transport on the DSC geometry. High resolution scanning electron microscopy techniques were used to characterize the electrode cross sections, and electrochemical impedance spectroscopy was used to characterize the electrical connection at the interface between the NT array and the TiO2 NP interlayer. We examined the effects of decorating the DNT or SNT arrays with small NPs (sNP@DNT and sNP@SNT, respectively) in an effort to increase the extent of dye loading. The DNT arrays decorated with small NPs performed better than the decorated SNT arrays, most likely because the Ti(OH)(4) precursor solution flowed freely into the array through the open ends of the NTs in the DNT case but not in the SNT case. The sNP@DNT based DSC exhibited a better PCE (10%) compared to the sNP@SNT-based DSCs (6.8%) because the electrolyte solution flow was not restricted, direct electron transport though the NT arrays was possible the electrical connection at the interface between the NT array and the TiO2 NP interlayer was good, and the array provided efficient light harvesting.X111615sciescopu

Aircraft Mission Analysis Enhancement by Using Data Science and Machine Learning Techniques

As air-traffic demand continues to grow, it is expected that there will be a growing need for optimizing fuel consumption to airlines. To that end, it is prerequisite to estimate fuel consumption as accurate as possible. However, most of the aircraft operation datasets have been elusive due to proprietary purposes. Under these circumstances, a comprehensive software dubbed the Aviation Environmental Design Tool (AEDT) has been prevalently used by many aerospace engineers to calculate the fuel consumption. It is highly hypothesized that, besides, if the AEDT could collaborate with reliable weather information, its modeling fidelity would be enhanced. In this paper, we proposed a novel aircraft mission analysis framework by incorporating data-driven approaches with the AEDT and state-of-the-art machine learning (ML) techniques to improve the accuracy of aircraft mission analysis. As the source of weather information, the world-wide weather dataset called MERRA-2 was regressed by a Support Vector Machine (SVM) along the time and three-dimensional coordinates in the entire US territory. The created SVM model successfully provided continuous behavior of weather, showing a good agreement to the reference data. As the final research, a four dimensional (4-D) flight trajectory of operations in several sampled airports has been retrieved from external public databases and integrated with corresponding weather information extracted from the SVM model. Finally, it was observed that the collaboration of the SVM weather model and the AEDT precisely matched the reference data. The accomplishments of this research recommend that researchers conduct further study on the highly capricious behavior of weather with the power of the data-science and machine learning technology

Inducing swift nucleation morphology control for efficient planar perovskite solar cells by hot-air quenching

We introduce 1 step pin-hole free CH(3)NH(3)PbI(3-x)C(l)x perovskite layers by using heated airflow during the nucleation stage of the perovskite. Upon employing heated air, we stimulate uniformly distributed nuclei growth, resulting in a pin-hole free planar perovskite layer. We find an optimized heated airflow of 100 degrees C as the optimized condition. The resulting planar device employing a conventional TiO2 electron transporting layer exhibits 17.6% average power conversion efficiency with 14.3% maximum powerpoint (MPP) efficiency. In addition, our method gives a very reproducible perovskite layer. Thus, our pin-hole free perovskite layer allows for 14.9% efficiency in a larger area device (0.71 cm(2)) that is generally prone to shunting paths.112113sciescopu