Mainly Adrenal Gland Involving NK/T-Cell Nasal Type Lymphoma Diagnosed with Delay due to Mimicking Adrenal Hemorrhage

A 29-yr-old man, presented with abdominal pain and fever, had an initial computed tomography (CT) scan revealing low attenuation of both adrenal glands. The initial concern was for tuberculous adrenalitis or autoimmune adrenalitis combined with adrenal hemorrhage. The patient started empirical anti-tuberculous medication, but there was no improvement. Enlargement of cervical lymph nodes were developed after that and excisional biopsy of cervical lymph nodes was performed. Pathological finding of excised lymph nodes was compatible to NK/T-cell lymphoma. The patient died due to the progression of the disease even after undergoing therapeutic trials including chemotherapy. Lymphoma mainly involving adrenal gland in the early stage of the disease is rare and the vast majority of cases that have been reported were of B-cell origin. From this case it is suggested that extra-nodal NK/T-cell lymphoma should be considered as a cause of bilateral adrenal masses although it is rare

YH29407 with anti-PD-1 ameliorates anti-tumor effects via increased T cell functionality and antigen presenting machinery in the tumor microenvironment

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8+ T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8+ T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8+ T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1

Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte

Background Current diagnostic tests for hereditary spherocytosis (HS) focus on the detection of hemolysis or indirectly assessing defects of membrane protein, whereas direct methods to detect protein defects are complicated and difficult to implement. In the present study, we investigated the patterns of genetic variation associated with HS among patients clinically diagnosed with HS. Methods Multi-gene targeted sequencing of 43 genes (17 RBC membrane protein-encoding genes, 20 RBC enzyme-encoding genes, and six additional genes for the differential diagnosis) was performed using the Illumina HiSeq platform. Results Among 59 patients with HS, 50 (84.7%) had one or more significant variants in a RBC membrane protein-encoding genes. A total of 54 significant variants including 46 novel mutations were detected in six RBC membrane protein-encoding genes, with the highest number of variants found in SPTB (n = 28), and followed by ANK1 (n = 19), SLC4A1 (n = 3), SPTA1 (n = 2), EPB41 (n = 1), and EPB42 (n = 1). Concurrent mutations of genes encoding RBC enzymes (ALDOB, GAPDH, and GSR) were detected in three patients. UGT1A1 mutations were present in 24 patients (40.7%). Positive rate of osmotic fragility test was 86.8% among patients harboring HS-related gene mutations. Conclusions This constitutes the first large-scaled genetic study of Korean patients with HS. We demonstrated that multi-gene target sequencing is sensitive and feasible that can be used as a powerful tool for diagnosing HS. Considering the discrepancies of clinical and molecular diagnoses of HS, our findings suggest that molecular genetic analysis is required for accurate diagnosis of HS.Support was provided by: the National Research Foundation of Korea (NRF) grant funded by the Korea government(MSIT) (NRF-2017R1A2A1A17069780) http://www.nrf.re.kr/

Thermodynamic characterization and heat generation of fast-charging Wadsley-Roth shear phase materials for battery application

This dissertation reviews and clarifies the fundamental thermodynamic relationships relevant to the interpretation of potentiometric entropy measurements on lithium-ion batteries (LIBs) to gain insight into the physicochemical phenomena occurring during cycling. First, contributions from configurational, vibrational, and electronic excitations to the entropy ofan ideal intercalation compound used as a cathode in a battery system were analyzed. The results of this analysis were used to provide an interpretative guide of open circuit voltage Uocv(x, T) and entropic potential ∂Uocv(x, T)/∂T measurements to identify different mechanisms of intercalation, including (i) lithium intercalation as a homogeneous solid solution, (ii) ion ordering reactions from a homogeneous solid solution, (iii) first-order phase transitions involving a two-phase coexistence, and/or (iv) first-order phase transitions passing through a stable intermediate phase. These interpretations were illustrated with experimental data for different battery electrode materials including TiS2, LiCoO2, Li4/3Ti5/3O4, LiFePO4, and graphite electrodes with metallic lithium as the counter electrode. The systematic interpretation of Uocv(x, T) and ∂Uocv(x, T)/∂T can enhance other structural analysis techniques such as X-ray diffraction, electron energy-loss spectroscopy, and Raman spectroscopy. Thermal signatures associated with electrochemical and transport phenomena occurring in LIB systems were investigated by performing potentiometric entropy measurement and isothermal operando calorimetry on LIB systems. Here, LIB system consisting of electrodes made of TiNb2O7 and PNb9O25 were investigated. The potentiometric entropy measurements of TiNb2O7 and PNb9O25 featured signatures of intralayer ion ordering upon lithiation that could not be observed with in situ X-ray diffraction. Furthermore, entropy measurements also confirmed the semiconductor-to-metal transition taking place at PNb9O25 upon lithiation. Furthermore, isothermal operando calorimetry measurements indicated that the nature of heat generation was dominated by Joule heating, which sensitively changed as the conductivity of the electrode increased with increasing lithiation. The heat generation rate decreased at the TiNb2O7 and PNb9O25 electrode upon lithiation due to the decrease in electrical resistivity caused by the semiconductor-to-metal transition also observed in potentiometric entropy measurements. In addition, the time-averaged irreversible heat generation rate indicated that the electrical resistance of the lithium metal electrode was constant and independent of the state of charge while the electrical resistance of the PNb9O25 changedsignificantly with the state of charge. Moreover, calorimetry measurements have shown that the electrical energy losses were dissipated entirely in the form of heat. Furthermore, the enthalpy of mixing, obtained from operando calorimetry, is found to be small across the different degrees of lithiation, pointing to the high rate of lithium-ion diffusion at the origin of rapid rate performance of TiNb2O7 and PNb9O25. Moreover, the effect of particle size on the electrochemical performance and heat generation in LIB systems were investigated using two LIBs consisting of electrodes made of either(W0.2V0.8)3O7 nanoparticles synthesized by sol-gel method combined with freeze-drying or (W0.2V0.8)3O7 microparticles synthesized by solid-state method. Galvanostatic cycling confirmed that the electrode made of (W0.2V0.8)3O7 nanoparticles featured larger capacity and better retention at high C-rates than that made of the (W0.2V0.8)3O7 microparticles. Entropic potential measurements performed at slow C-rate indicated that both nanoparticles and microparticles underwent a semiconductor to metal transition, and nanoparticles underwent a two-phase coexistence region over a narrower range of composition. Operando calorimetry measurements at high C-rate established that the heat generation rate increased at the (W0.2V0.8)3O7 electrode upon lithiation due to an increase in charge transfer resistance regardless of particle size. Moreover, the time-averaged irreversible heat generation rate was slightly but systematically smaller at the electrode made of nanoparticles. Furthermore, the specific dissipated energy and the contribution from enthalpy of mixing caused by lithium concentration gradient was notably smaller for (W0.2V0.8)3O7 nanoparticles. These observations were attributed to the fact that nanoparticles were less electrically resistive and able to accommodate more lithium while lithium ion intercalation therein was more kinetically favorable