Supplementary Table 9, column 'Edoxaban', row 'eGFR category', '95 mL/min' (page 15). The cell should be coloured green instead of yellow. It should also read "60 mg"instead of "60 mg (use with caution in 'supranormal' renal function)."In the above-indicated cell, a footnote has also been added to state: "Edoxaban should be used in patients with high creatinine clearance only after a careful evaluation of the individual thromboembolic and bleeding risk."Supplementary Table 9, column 'Edoxaban', row 'Dose reduction in selected patients' (page 16). The cell should read "Edoxaban 60 mg reduced to 30 mg once daily if any of the following: creatinine clearance 15-50 mL/min, body weight <60 kg, concomitant use of dronedarone, erythromycin, ciclosporine or ketokonazole"instead of "Edoxaban 60 mg reduced to 30 mg once daily, and edoxaban 30 mg reduced to 15mg once daily, if any of the following: creatinine clearance of 30-50 mL/min, body weight <60 kg, concomitant us of verapamil or quinidine or dronedarone."

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2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS).

Principles and Practice of Sleep Medicine

Since the introduction of the first edition of International Classification of Sleep Disorders: Diagnostic and Coding Manual(ICSD-1)in 1990,national and international meetings were held to openly discuss the ongoing developments of sleep disorders and a new International Classification of Sleep Disorders: Diagnostic and Coding Manual(ICSD-2)was published in 2005.Compared with ICSD-1,the classification of ICSD-2 was developed in a manner compatible with new International Classification of Diseases(ICD-9 and ICD-10)and formed a coordinated system of International Classification of Diseases.The updated version was characterized by the significant improvements of its logicality and clinical practicability,and was more consistent with the International Classification of Disease.The contents of ICSD-2 were introduced in this article.

Brief introduction to second edition of International Classification of Sleep Disorders:Diagnostic and Coding Manual

OX40 (CD134) and its binding partner, OX40L (CD252), are members of the TNFR/TNF superfamily and are expressed on activated CD4 and CD8 T cells as well as a number of other lymphoid and non-lymphoid cells. Costimulatory signals from OX40 to a conventional T cell promote division and survival, augmenting the clonal expansion of effector and memory populations as they are being generated to antigen. OX40 additionally suppresses the differentiation and activity of Treg, further amplifying this process. OX40 and OX40L also regulate cytokine production from T cells, antigen-presenting cells, NK cells, and NKT cells, and modulate cytokine receptor signaling. In line with these important modulatory functions, OX40/OX40L interactions have been found to play a central role in the development of multiple inflammatory and autoimmune diseases, making them attractive candidates for intervention in the clinic. Conversely, stimulating OX40 has shown it to be a candidate for therapeutic immunization strategies for cancer and infectious disease. This review provides a broad overview of the biology of OX40, and the intracellular signals from OX40, that impact many aspects of immune function, and have promoted OX40 as one of the most prominent costimulatory molecules known to control T cells.

The Significance of OX40 and OX40L to T cell Biology and Immune Disease

Second-generation chimeric antigen receptors (CARs) retarget and reprogramme T cells to augment their antitumour efficacy. The combined activating and co-stimulatory domains incorporated in these CARs critically determine the function, differentiation, metabolism and persistence of engineered T cells. CD19-targeted CARs that incorporate CD28 or 4-1BB signalling domains are the best known to date. Both have shown remarkable complete remission rates in patients with refractory B cell malignancies. Recent data indicate that CD28-based CARs direct a brisk proliferative response and boost effector functions, whereas 4-1BB-based CARs induce a more progressive T cell accumulation that may compensate for less immediate potency. These distinct kinetic features can be exploited to further develop CAR-based T cell therapies for a variety of cancers. A new field of immunopharmacology is emerging.

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The pharmacology of second-generation chimeric antigen receptors

Obstructive sleep apnea (OSA) and diabetes has been known to be closely related to each other and both diseases impact highly on the public health. There are many evidence of reports that OSA is associated with diabetes with a bidirectional correlation. A possible causal mechanism of OSA to diabetes is intermittent hypoxemia and diabetes to OSA is microvascular complication. However, OSA and diabetes have a high prevalence rate in public and shares the common overlap characteristic and risk factors such as age, obesity, and metabolic syndrome that make it difficult to establish the exact pathophysiologic mechanism between them. In addition, studies demonstrating that treatment of OSA may help prevent diabetes or improve glycemic control have not shown convincing result but have become a great field of interest research. This review outlines the bidirectional correlation between OSA and diabetes and explore the pathophysiologic mechanisms by approaching their basic etiologies.

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Metabolic Consequences of Obstructive Sleep Apnea Especially Pertaining to Diabetes Mellitus and Insulin Sensitivity

In this study, we investigated the effect of an agonistic mAb (DTA-1) against glucocorticoid-induced TNF receptor (GITR) in a murine model of systemic lupus erythematosus-like chronic graft-vs-host disease (cGVHD). A single dose of DTA-1 inhibited the production of anti-DNA IgG1 autoantibody and the development of glomerulonephritis, typical symptoms of cGVHD. DTA-1-treated mice showed clinical and pathological signs of acute GVHD (aGVHD), such as lymphopenia, loss of body weight, increase of donor cell engraftment, and intestinal damage, indicating that DTA-1 shifted cGVHD toward aGVHD. The conversion of cGVHD to aGVHD occurred because DTA-1 prevented donor CD8 + T cell anergy. Functionally active donor CD8 + T cells produced high levels of IFN-γ and had an elevated CTL activity against host Ags. In in vitro MLR, anergic responder CD8 + T cells were generated, and DTA-1 stimulated the activation of these anergic CD8 + T cells. We further confirmed in vivo that donor CD8 + T cells, but not donor CD4 + T cells, were responsible for the DTA-1-mediated conversion of cGVHD to aGVHD. These results indicate that donor CD8 + T cell anergy is a restriction factor in the development of aGVHD and that in vivo ligation of GITR prevents CD8 + T cell anergy by activating donor CD8 + T cells that otherwise become anergic. In sum, our data suggest GITR as an important costimulatory molecule regulating cGVHD vs aGVHD and as a target for therapeutic intervention in a variety of related diseases.

Conversion of Alloantigen-Specific CD8+ T Cell Anergy to CD8+ T Cell Priming through In Vivo Ligation of Glucocorticoid-Induced TNF Receptor

4-1BB cross-linking enhances the survival and cell cycle progression of CD4 T lymphocytes.

Bone mineral loss and cognitive impairment: The PRESENT project

Background: Although size is one of the strongest predictors, small aneurysms often rupture. We compared the characteristics of small and large ruptured intracran

Hyun Goo Kang

Papers

Metabolic Consequences of Obstructive Sleep Apnea Especially Pertaining to Diabetes Mellitus and Insulin Sensitivity

Conversion of Alloantigen-Specific CD8+ T Cell Anergy to CD8+ T Cell Priming through In Vivo Ligation of Glucocorticoid-Induced TNF Receptor

4-1BB cross-linking enhances the survival and cell cycle progression of CD4 T lymphocytes.

Bone mineral loss and cognitive impairment: The PRESENT project

Small versus Large Ruptured Intracranial Aneurysm: Concerns with the Site of Aneurysm.