Nearly 100% Horizontal Dipole Orientation and Upconversion Efficiency in Blue Thermally Activated Delayed Fluorescent Emitters

The relationship between anisotropic orientation and molecular structure of thermally activated delayed fluorescent (TADF)‐based organic light emitting devices (OLEDs) is studied using TADF emitters with carbazole, biscarbazole, and triscarbazole donor units. The bicarbazole and triscarbazole donors are more effective than the carbazole donor in driving the anisotropic orientation of the TADF molecules. A near‐perfect in‐plane orientation of the TADF dipole moment is demonstrated using the triscarbazole donor. In addition, the triscarbazole donor based OLED shows high photoluminescence quantum yield and an upconversion efficiency close to 100%. As a consequence, an external quantum efficiency >30% is obtained.A systematic study correlating donor structure with horizontal dipole orientation of blue triscarbazole thermally activated delayed fluorescent (TADF) emitters shows an exceptionally high horizontal dipole orientation of 95%. The dipole orientation and high photoluminescence quantum yield result in an external quantum efficiency >30% in organic light‐emitting diodes employing these TADF emitters.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/145231/1/adom201701340.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145231/2/adom201701340_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/145231/3/adom201701340-sup-0001-S1.pd

Airway epithelial cells initiate the allergen response through transglutaminase 2 by inducing IL-33 expression and a subsequent Th2 response

Transglutaminase 2 (TG2) is a post-translational protein-modifying enzyme that catalyzes the transamidation reaction, producing crosslinked or polyaminated proteins. Increased TG2 expression and activity have been reported in various inflammatory conditions, such as rheumatoid arthritis, inflammation-associated pulmonary fibrosis, and autoimmune encephalitis. In particular, TG2 from epithelial cells is important during the initial inflammatory response in the lung. In this study, we evaluated the role of TG2 in the pathogenesis of allergic asthma, particularly whether TG2 affects initial activation signaling leading to Th2 differentiation against antigens. Methods We induced allergic asthma by ovalbumin sensitization and intranasal challenge in wild-type (WT) BALB/c and TG2-deficient mice. Broncheoalveolar lavage fluid cells and intracellular cytokine production were analyzed by flow cytometry. Interleukin (IL)-33 and TG2 expression in lung epithelial cells was detected by confocal microscopy. Results Airway responsiveness was attenuated in TG2-deficient mice compared to that in the WT control. In addition, recruitment of eosinophils and Th2 and Th17 differentiation decreased in TG2-deficient mice. Treatment with cysteamine, a transglutaminase inhibitor, also reduced airway hypersensitivity, inflammatory cell recruitment, and T helper cell differentiation. TG2-deficient mice showed reduced IL-33 expression following induction of allergic asthma compared to those in the WT control. Conclusions We found that pulmonary epithelial cells damaged by allergens triggered TG2-mediated IL-33 expression leading to type 2 responses by recruiting both innate and adaptive arms of the immune system.Peer Reviewe

A randomized, phase II study of gefitinib alone versus nimotuzumab plus gefitinib after platinum-based chemotherapy in advanced non-small cell lung cancer (KCSG LU12-01)

We aimed to evaluate the efficacy of dual inhibition of epidermal growth factor receptor (EGFR) with nimotuzumab (EGFR monoclonal antibody) plus gefitinib (EGFR-tyrosine kinase inhibitor) in advanced non-small cell lung cancer (NSCLC) after platinum-based chemotherapy. An open label, randomized, phase II trial was conducted at 6 centers; 160 patients were randomized (1:1) to either gefitinib alone or nimotuzumab (200 mg, i. v. weekly) plus gefitinib (250 mg p. o. daily) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS) at 3 months. Of the total 160 enrolled patients, 155 (77: gefitinib, 78: nimotuzumab plus gefitinib) received at least one dose and could be evaluated for efficacy and toxicity. The majority had adenocarcinoma (65.2%) and ECOG performance status of 0 to 1 (83.5%). The median follow-up was 22.1 months, and the PFS rate at 3 months was 48.1% in gefitinib and 37.2% in nimotuzumab plus gefitinib (P = not significant, NS). The median PFS and OS were 2.8 and 13.2 months in gefitinib and 2.0 and 14.0 months in nimotuzumab plus gefitinib. Combined treatment was not associated with superior PFS to gefitinib alone in patients with EGFR mutation (13.5 vs. 10.2 months in gefitinib alone, P=NS) or those with wild-type EGFR (0.9 vs. 2.0 months in gefitinib alone, P=NS). Combined treatment did not increase EGFR inhibition-related adverse events with manageable toxicities. The dual inhibition of EGFR with nimotuzumab plus gefitinib was not associated with better outcomes than gefitinib alone as a second-line treatment of advanced NSCLC (NCT01498562).

Establishment of peripheral intravenous catheter for pediatric patients in the emergency department: who and how?

Purpose Peripheral intravenous cannulation (PIC) for children is technically difficult. We aimed to investigate factors associated with the primary success of PIC for children in the emergency department (ED). Methods This prospective observational study was conducted on children younger than 3 years who visited the ED from September 2014 to August 2015. The children undergoing primary success, defined as success at the first attempt, comprised the success group. Using a case report form, information about the children (age, sex, and weight), practitioners’ occupation (doctors, nurses, emergency medical technicians [EMTs]), treatment venue, insertion site of PIC, presence of guardians, and use of auxiliary devices were collected and compared between the success and failure groups. Multivariable logistic regression models were constructed to identify factors associated with the primary success. Results Of 439 children, 271 underwent the primary success (61.7%). The success group showed older age, heavier weight, and higher proportion of EMT. No differences were found in treatment venue, insertion site, and presence of the guardian. We found that patients’ age (odds ratio [OR], 1.03; 95% confidence interval [CI], 1.003-1.1), and practitioners’ occupation (EMT; OR, 3.0; 95% CI, 1.9-4.7, compared with doctors) were the factors associated with the primary success. Conclusion Practitioners’ occupation (EMT) and children’s age (older) may be associated with the primary success of PIC. It may be helpful to have specialized personnel when performing PIC on children in the ED

Anti-Biofouling Features of Eco-Friendly Oleamide-PDMS Copolymers

The biofouling of marine organisms on a surface induces serious economic damage. One of the conventional anti-biofouling strategies is the use of toxic chemicals. In this study, a new eco-friendly oleamide-PDMS copolymer (OPC) is proposed for sustainable anti-biofouling and effective drag reduction. The anti-biofouling characteristics of the OPC are investigated using algal spores and mussels. The proposed OPC is found to inhibit the adhesion of algal spores and mussels. The slippery features of the fabricated OPC surfaces are examined by direct measurement of pressure drops in channel flows. The proposed OPC surface would be utilized in various industrial applications including marine vehicles and biomedical devices. © Copyright © 2020 American Chemical Society.1

Analysis of clinical and genomic profiles of therapy-related myeloid neoplasm in Korea

Background Therapy-related myeloid neoplasm (T-MN) rarely occurs among cancer survivors, and wascharacterized by poor prognosis. T-MN has germline predisposition in a considerable proportion. Here, clinical characteristics and germline/somatic variant profiles in T-MN patients were investigated, and the findings were compared with those of previous studies. Methods A review of medical records, cytogenetic study, targeted sequencing by next-generation sequencing, and survival analysis were performed on 53 patients with T-MN at a single institution in Korea. Results The patients were relatively younger compared to T-MN patients in other studies. Our T-MN patients showed ahigh frequency of complex karyotypes, −5/del(5q), and −7/del(7q), which was similar to the Japanese study group but higher than the Australian study group. The most common primary disease was non-Hodgkin lymphoma, followed by breast cancer. The detailed distributions of primary diseases were different across study groups. Seven patients (13.2%) harbored deleterious presumed/potential germline variants in cancer predisposition genes (CPG) such as BRIP1, CEBPA, DDX41, FANCM, NBN, NF1, and RUNX1. In the somatic variant profile, TP53 was the most frequently mutated gene, which was consistent with the previous studies about T-MN. However, the somatic variant frequency in our study group was lower than in other studies. Adverse factors for overall survival were male sex, older age, history of previous radiotherapy, previous longer cytotoxic therapy, and −5/del(5q). Conclusion The findings of our study corroborate important information about T-MN patients. As well as a considerable predisposition to CPG, the clinical characteristics and somatic variant profile showed distinctive patterns. Germline variant testing should be recommended for T-MN patients. If the T-MN patients harbor pathogenic germline variants, the family members for stem cell donation should be screened for carrier status through germline variant testing to avoid donor-derived myeloid neoplasm. For the prediction of the prognosis in T-MN patients, sex, age, past treatment history, and cytogenetic findings can be considered.This work was supported by the National Research Foundation of Korea (NRF) Grant funded by the Korean government (MSIT) (NRF-2017R1A2A1A17069780 and NRF-2020R1A3B3079653) and a Grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI) funded by the Ministry of Health & Welfare, Republic of Korea (Grant No. HR14C0003)

Hypereosinophilia Presenting as Eosinophilic Vasculitis and Multiple Peripheral Artery Occlusions without Organ Involvement

We report here a case with hypereosinophilia and peripheral artery occlusion. A 32-yr-old Korean woman presented to us with lower extremity swelling and pain. Angiography revealed that multiple lower extremity arteries were occlusive. The biopsy specimen showed perivascular and periadnexal dense eosinophilic infiltration in dermis and subcutaneous adipose tissue. Laboratory investigations revealed a persistent hypereosinophilia. She was prescribed prednisolone 60 mg daily. Her skin lesion and pain were improved and the eosinophil count was dramatically decreased. After discharge, eosinophil count gradually increased again. Cyanosis and pain of her fingers recurred. She had been treated with cyclophosphamide pulse therapy. Her eosinophilia was decreased, but the cyanosis and tingling sense were progressive. The extremity arterial stenoses were slightly progressed. Skin biopsy showed perivascular eosinophilic infiltration in the dermis and CD40 ligand (CD40L) positive eosinophilic infiltration. The serum TNF-α was markedly increased. These results suggest that CD40L (a member of TNF-α superfamily) could play a role in the inflammatory processes when eosinophil infiltration and activation are observed. We prescribed prednisolone, cyclophosphamide, clopidogrel, cilostazol, beraprost and nifedipine, and she was discharged

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