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The present study examined the efficacy of a CogSMART-based program in improving cognitive and emotional functioning in a clinic-based sample of Veterans presenting with cognitive concerns and history of mental health diagnoses.Forty Veterans (Significant improvements on global cognition as well as measures of learning/memory and attention were observed from pre- to post-group (Among individuals with mental health diagnosis but without major neurocognitive disorders, CogSMART-based interventions may be an effective treatment for improving aspects of cognition, depression, and life satisfaction.

S1. CSF-1R is most highly expressed on TAMs in CT26 tumors.

Efficacious antitumor immune responses must overcome multiple suppressive mechanisms in the tumor microenvironment to control cancer progression. In this study, we demonstrate that dual targeting of suppressive myeloid populations by inhibiting CSF-1/CSF-1R signaling and activation of antigen-presenting cells with agonist anti-CD40 treatment confers superior antitumor efficacy and increased survival compared with monotherapy treatment in preclinical tumor models. Concurrent CSF-1R blockade and CD40 agonism lead to profound changes in the composition of immune infiltrates, causing an overall decrease in immunosuppressive cells and a shift toward a more inflammatory milieu. Anti-CD40/anti–CSF-1R–treated tumors contain decreased tumor-associated macrophages and Foxp3+ regulatory T cells. This combination approach increases maturation and differentiation of proinflammatory macrophages and dendritic cells and also drives potent priming of effector T cells in draining lymph nodes. As a result, tumor-infiltrating effector T cells exhibit improved responses to tumor antigen rechallenge. These studies show that combining therapeutic approaches may simultaneously remove inhibitory immune populations and sustain endogenous antitumor immune responses to successfully impair cancer progression. Cancer Immunol Res; 5(12); 1109–21. ©2017 AACR.

S4. The cytokine milieu is more inflammatory in anti-CD40 and combination treated tumors.

S3. Increased frequencies of effector CD8+ T cells in dLN and tumor after combination treatment.

S2. CD45+ Immune infiltrate varies with immunotherapy, while frequencies of CD11b+ myeloid population are not significantly altered.

After destructive natural disasters, it is necessary to quickly grasp the damage situation for the initial response. In recent years, studies on the method of the automatic evaluation of building damages due to disasters using the convolutional neural network (CNN), which is a deep learning methodology for image recognition, were conducted. In these studies, it was clarified that a large number of images are necessary to train the CNN with sufficiently high accuracy. However, the number of images of damaged building is limited. Therefore, in the present study, we used the generative adversarial network (GAN) to automatically generate a large number of imitation images of damaged and undamaged buildings and trained the CNN using imitation images to obtain a higher accuracy rate of the CNN. Then, the validity of the CNN for judgment of “damaged” and “undamaged” using imitation images was confirmed. In addition, photographs of actual buildings were input to the trained CNN as test data.

Kinesin motors mediate the intracellular transport of cargo molecules along microtubule tracks (1). The mechanism that regulates the activation of kinesin motors remains an issue of fundamental importance (2, 3). It has been reported that the full length conventional kinesin, kinesin-1, has very little microtubule-stimulated ATPase activity in solution as compared to its shorter motor domain constructs (4, 5). The intramolecular interactions mediated by the motor and tail domains keep the kinesin-1 in a compactly-folded inhibitory state (6–8). It is well established that the mechanical attachment of the inactive full length motor to a glass surface or latex beads is sufficient to transform the inactive motor to an active state, presumably by disrupting its inhibitory conformation (8, 9). Therefore, it is reasonable to speculate that this mode of self-inhibition of kinesin-1 is the general feature conserved in all kinesin-like proteins to keep their motor activity regulated in vivo. GAKIN/KIF13B (10) belongs to the kinesin-3 family. The family also includes KIF1A/Unc104, which is responsible for the transport of synaptic vesicles (11). Our previous studies have identified two cargo molecules for GAKIN; the membrane-associated guanylate kinase homologue (MAGUK) scaffolding protein hDlg/SAP97 (12) and a PIP3 binding protein termed PIP3BP (13). Both MAGUKs and PIP3 have been implicated in the regulation of cell polarity pathways, and their subcellular localization is considered to be important for their functions in vivo. Recently, we have shown that the transport of PIP3 containing vesicles to the distal ends of neurites by the GAKIN-PIP3BP complex regulates the axon-dendrite polarity determination in the hippocampal neurons (13). Human Dlg is an important component of cell-cell contact sites such as epithelial adherence junctions and neuronal synaptic membranes, where it forms a multi-protein complex containing transmembrane receptors and cytoskeletal proteins (14). The loss of Drosophila Dlg disrupts epithelial apical-basal polarity resulting in the tumor-like overgrowth in imaginal discs (15). MAGUK proteins are also implicated in the transport of multi-protein complexes to specialized sites. For example, SAP97, the rat orthologue of hDlg, regulates the transport of AMPA receptor complex to the synapse (16–18). A scaffolding complex containing Lin-2, another MAGUK, mediates the transport of the NMDA receptor (19). These findings prompted us to investigate the regulatory mechanism of the hDlg-GAKIN cargo-motor complex and its role in the transport phenomenon. Here, we report that a specific segment of hDlg encodes the activation signal for converting an inactive GAKIN to an active motor in vitro. To our knowledge, this is the first demonstration of the regulation of a kinesin motor by direct interaction of its natural cargo using in vitro measurements of purified components.

Excessive vascular endothelial growth factor-A (VEGF-A) signaling induces vascular leakage and angiogenesis in diseases. VEGFR2 trafficking to the cell surface, mediated by kinesin-3 family protein KIF13B, is essential to respond to VEGF-A in inducing angiogenesis. However, the precise mechanism of how KIF13B regulates VEGF-induced signaling and endothelial permeability is unknown. Here we show that KIF13B-mediated recycling of internalized VEGFR2 through Rab11-positive recycling vesicle regulates VE-cadherin phosphorylation and endothelial permeability. Phosphorylated VEGFR2 at the cell-cell junction was internalized and associated with KIF13B in Rab5-positive early endosomes. KIF13B mediated VEGFR2 recycling through Rab11-positive recycling vesicle, and inhibition of this recycling attenuated phosphorylation of VEGFR2 at Y951, Src, and VE-cadherin at Y685, which are necessary for endothelial permeability. Failure of VEGFR2 trafficking to the cell surface induced accumulation and degradation of VEGFR2 in lysosomes. Furthermore, in the animal model of wet age-related macular degeneration (AMD), inhibition of KIF13B-mediated VEGFR2 trafficking also mitigated vascular leakage. Thus, the present results identify the fundamental role of VEGFR2 recycling to the cell surface in mediating vascular permeability, suggesting a promising strategy for mitigating vascular leakage associated with inflammatory diseases.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the effects (benefits and harms) of different interventions aimed at controlling pain associated with panretinal photocoagulation, in people with severe non‐proliferative diabetic retinopathy and proliferative diabetic retinopathy, according to the classification of ETDRS 1991.

Whereas elevated LDL-C is a major risk factor for CAD, the inverse association between HDL-C levels and risk of CAD is well-known. Although insulin resistance and glucose intolerance are associated with low HDL-C levels, it is not clear whether the association of LDL-C with CAD differs depending on glucose status and HDL-C values. We examined associations of LDL-C with new-onset CAD according to HDL-C and glucose status using a nationwide claims database on 600,6individuals during 2008-20with no history of CAD. Cox proportional hazards model identified risks of CAD events among combinations of tertiles of HDL-C and sextiles of LDL-C according to glucose status. During a mean follow-up period of 5.6 years, 2,391 CAD events occurred. CAD risk increased from lower LDL-C levels accompanied by lower HDL-C levels regardless of glucose status (Table) . Compared with the highest tertile of HDL-C and lowest sextile of LDL-C, groups with the highest tertile of HDL-C and highest sextile of LDL-C and the lowest tertile of HDL-C and highest sextile of LDL-C had approximately 4-fold and 9-fold, respectively, increased risks of CAD regardless of glucose status. Despite the necessity of a lower LDL-C target for people with than without diabetes, our results demonstrated that the necessity of modulating the LDL-C target according to HDL-C levels is not affected by concomitant diabetes. Disclosure M.H.Yamada: None.

Elevated serum uric acid reportedly increases the risk of development and progression of diabetic retinopathy with conflicting results. However, whether it also increases the incidence of severe vision-threatening diabetic eye diseases has been scarcely investigated. Also unknown is whether there are sex differences in the incidence of advanced retinopathies. To clarify this, we utilized ICD-and medical treatment codes from a nationwide claims database that finally included 13,721 type 2 diabetes patients (mean age 50 y, HbA1c 7.0%, mean follow-up period 5.8 y, 10,962 men) . During the study period, 388 patients developed vision-threatening treatment-required diabetic eye diseases (4.9/1000 person-years) . Multivariate Cox analysis demonstrated that a serum uric acid ≥7.1 mg/dl was significantly positively associated in men with future occurrence of treatment-required diabetic eye diseases, but not in women. Hazard ratios for those with serum uric acid ≥7.1 mg/dl for incident treatment-required diabetic eye diseases were 1.36 (95% confidence interval, 1.01-1.85) in men and 2. (0.71-6.08) in women, compared with the reference group ( Disclosure M. Yamamoto: None. K. Fujihara: None. H. Ishiguro: None. M. Ishizawa: None. M.H. Yamada: None. T. Osawa: None. M. Kitazawa: None. M. Kaneko: None. M. Iwanaga: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Funding The Japan Society for the Promotion of Science and the Ministry of Health, Labor and Welfare, Japan. (18K17897)

In 2016, to help achieve the goal of avoiding heart failure and preserving cardiac structure and function, the American Heart Association (AHA) designated Life’s Simple 7 as risk factors that can be addressed through lifestyle changes: smoking, weight, physical activity, diet, cholesterol, blood pressure (BP) , and blood glucose. Although most of these factors are also risk factors for the progression of kidney disease, the association between Life’s Simple 7 and risk of dialysis is unknown. We investigated the impact of 6 factors on the initiation of dialysis based on the AHA’s 7 factors using a nationwide claims database involving 294,647 participants during 2008-16. Multivariate Cox regression model identified risks of starting dialysis. Hazard ratios (HRs) were compared among 7 groups who had 0 to 6 of the following risk factors adjusted by age and sex: BMI ≥25, systolic BP (SBP) ≥140 mmHg, LDL-cholesterol ≥140 mg/dl, diabetes mellitus (DM) , no regular exercise, and smoking. Compared with SBP In summary, the risk of dialysis increased with worsening of risk factors derived from AHA’s Life’s Simple 7. These results indicated that factors similar to those used to predict cardiovascular disease might also be useful to predict initiation of dialysis. Use of these approaches might be helpful in clinical practice, especially in patient education. Disclosure T.Osawa: None. K.Fujihara: None. M.H.Yamada: None. Y.Yaguchi: None. T.Sato: None. M.Kitazawa: None. Y.Matsubayashi: None. T.Yamada: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Japan Society for the Promotion of Science (18K17897) .

Although we showed a significant association of poor adherence to OHAs with start of dialysis, this relationship according to the estimated glomerular filtration rate (eGFR) was not clarified. Patients with eGFR Disclosure Y.Yaguchi: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. Y.Matsubayashi: None. T.Yamada: None. M.Iwanaga: None. M.Kitazawa: None. M.Yamamoto: None. S.Kodama: None.

Muscle strength, balance, and flexibility has been associated with the development of type 2 diabetes and atherosclerosis, but little is known whether the physical score (PS) , which integrates these physical fitness indices, can predict future metabolic diseases. We investigated the longitudinal relationship between baseline and changes in PS and future prediabetes and MetS. Analyzed were 5620 men aged 30 to 69 y without MetS who underwent physical fitness tests. Principal component analysis was performed on the correlation matrix of the physical fitness test results according to age. PS was defined as the first principal component score. Associations between PS values at the start of observation (year 0) , change in the PS one year later (year 1) and the onset of prediabetes and MetS at the end of observation (years 4 or 5) were examined by Cox hazard regression analysis. The same analysis was performed for the 3812 men without prediabetes at baseline. No significant difference was found for the development of prediabetes, but a significant difference was found for development of MetS. The hazard ratio for the development of MetS was 1.30 (1.18,1.44) for every 1 decrease in the PS in year 0 and 1.35 (1.13,1.60) for every 1 decrease in the change in PS from year 0 to year 1. PS was a simple and non-invasive indicator to predict MetS. Disclosure T. Sato: None. K. Fujihara: None. M. Yamamoto: None. M. Kitazawa: None. H. Ishiguro: None. T. Osawa: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited.

This study aims to examine the impact of the association between metabolic syndrome (MetS) and metabolic dysfunction-associated fatty liver disease (MAFLD) , which both have insulin resistance and are pathophysiologically similar, on the development of new-onset cardiovascular disease, with and without type 2 diabetes mellitus (T2DM) A total of 570,426 participants without a history of cardiovascular disease who were enrolled in the nationwide claims database from 2008-2016 were included in this study. Participants were classified according to the presence or absence of MetS and/or MAFLD, and the risk of developing coronary artery disease (CAD) and/or cerebrovascular disease (CVD) in each category was analyzed using a multivariate Cox proportional hazard model. The same analysis was performed with stratification by the presence or absence of T2DM. During a median follow-up of 5.2 years, 2,252 CAD and 3,128 CVD events occurred. The hazard ratio (HR) (95% CI) for CAD, compared with the group with neither MAFLD nor MetS, was 1.46 (1.32-1.62) for MAFLD only (without MetS) , 2.02 (1.51-2.70) for MetS only (without MAFLD) , and 2.33 (2.10-2. 58) for MAFLD + MetS. For CVD, The HR was 1.41 (1.28-1.55) for MAFLD only, 1.67 (1.38-2.02) for MetS only, and 1.89 (1.72-2.08) for MAFLD + MetS. These results were similar for non-T2DM participants but different for T2DM participants, with no significant increased risk for CAD in MetS only and a significant increased risk for CVD only when both MAFLD and MetS coexisted. The predictive ability for cardiovascular disease development in patients with MetS and MAFLD differed depending on the presence or absence of T2DM. These results suggest that distinguishing between the diagnosis of MetS and MAFLD, taking into account the presence or absence of T2DM, may lead to more accurate identification of patients at high risk of developing cardiovascular disease. Disclosure K. Fujihara: None. M.H. Yamada: None. M. Yamamoto: None. H. Ishiguro: None. M. Kitazawa: None. M. Iwanaga: None. S. Kodama: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Funding The Japan Society for Promotion of Science (JSPS) KAKENHI Grant Number JP 20K19706)

Since advanced microangiopathy of diabetes severely impairs activities of daily living (ADL) and quality of life (QoL) and macroangiopathy is life-threatening regardless of severity, treatment of diabetes requires appropriate risk management to avoid all such complications. However, current studies have analyzed and reported diabetes complications separately, despite varying incident rates and impacts on ADL/QoL and severity of illness. It is difficult to determine which predictors should be prioritized when extrapolating the results of these studies to the comprehensive care of individual patients. We defined the combined severe diabetic complications as a new life-altering outcome and determined the association of established risk factors with combined severe diabetic complications. We analyzed data from a nationwide database involving 36,994 participants with diabetes mellitus without any prior life-altering complication of diabetes during 2008-19. Combined severe diabetic complications included severe diabetic eye disease, initiating dialysis, coronary artery disease (CAD) , cerebrovascular disease (CVD) , heart failure (HF) , or amputation which were determined according to ICD-codes, medication and medical procedures. During a median follow-up period of 5.0 years, the following events occurred: severe diabetic eye disease, 774; dialysis initiated, 134: CAD, 703; CVD, 535; HF, 161; and amputations, 31. Multivariate Cox regression model showed the HRs per 1SD for combined severe diabetic complications of HbA1c, SBP, current smoking, HDL-C, BMI and LDL- C were 1.54 (1.49-1.59) , 1.37 (1.31-1.42) , 1.35 (1.23-1.48) , 0.83 (0.79-0.88) , 0.85 (0.81-0.90) and 1. (1.06-1.16) , respectively. We found that HbA1c was the most strongly associated with combined severe diabetic complications among established risk factors. Also, our results implied the necessity of revisiting the value of BMI in risk management for combined severe diabetic complications. Disclosure Y.Yaguchi: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. Y.Matsubayashi: None. T.Yamada: None. M.Iwanaga: None. M.Kitazawa: None. M.Yamamoto: None. S.Kodama: None.

The association between screen time (ST) , including that for smartphones, and overweight/obesity (OW/OB) in children was examined separately for boys and girls, considering the influence of lifestyle factors including diet, physical activity, and sleep time. A cross-sectional study was conducted in 2242 Japanese children (1278 girls) aged 10-14 years. OW/OB was defined by the International Obesity Task Force. Logistic regression analysis showed that only for girls, total ST (≥4h) , smartphone ST (≥3h) and non-smartphone ST (≥2h) were all independently and significantly associated with overweight/obesity compared to In Japanese girls, smartphone ST, non-smartphone ST, and total ST were all significantly associated with OW/OB. To avoid OW/OB, it is suggested to keep smartphone ST, non-smartphone ST, and total ST to Disclosure K. Fujihara: None. S.Y. Morikawa: None. H. Ishiguro: None. M.H. Yamada: None. C. Horikawa: None. Y. Ogawa: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited.

Although a linear relationship between SBP and risk of coronary artery disease or cerebrovascular disease was observed regardless of GTS, this association in HF is little known. We analyzed data from a nationwide claims database from 20to 20on 589,621 individuals. A Cox proportional hazards model identified risks of HF among 5 levels of SBP according to GTS [i.e. normal glucose tolerance (NGT) , prediabetes, diabetes (DM) ]. Incidence of HF per 1,000 person-years was 0.for NGT, 0.18 for prediabetes, and 0.80 for DM. Compared with SBP Disclosure K.Fujihara: None. M.H.Yamada: None. M.Yamamoto: None. M.Oe: None. T.Osawa: None. M.Iwanaga: None. T.Yamada: None. S.Kodama: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Funding JSPS (21K11569)

In adults, short sleep duration and late bedtime were associated with hyperglycemia and obesity, but these relationships in children are little known. We evaluated the association of bedtime and sleep duration with overweight/obesity or hyperglycemia in children by sex, considering the effects of diet, physical activity, and screen time. A cross-sectional study was conducted for 1139 Japanese children (553 boys) aged 10-y. Overweight was as defined by the International Obesity Task Force. Cutoff value for hyperglycemia was HbA1c ≥5.6%. Variables associated with hyperglycemia or overweight were based on logistic regression analysis. Multivariate logistic regression analysis showed that compared with an early bedtime (˜21:59) and long sleep duration (weekdays ≥8.67 h, weekends ≥9 h) , short sleep duration (weekdays Disclosure H. Shiozaki: None. K. Fujihara: None. M.H. Yamada: None. T. Osawa: None. M. Kitazawa: None. M. Yamamoto: None. T. Sato: None. T. Yamada: None. H. Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. Funding Patient Centered Outcomes Research Institute

Insulin and its secretagogues are essential for some patients with type 2 diabetes (T2D) to maintain glycemic control (GC) . However, these drugs are inevitably accompanied by hypoglycemia. Avoiding severe hypoglycemia (SH) is essential considering its poor prognosis. This network meta-analysis aimed to find optimal hypoglycemic treatment regimens for T2D in terms of GC and SH. MEDLINE and EMBASE were used to identify trials comparing 2 or more treatments including insulins and/or SU/glinide and included both GC and SH in study outcomes. Treatment hierarchy was summarized as the surface under cumulative ranking probabilities (SUCRA) . There were 137 eligible trials from which 36 treatments were identified. Insulin plus (+) non-insulin drugs except for SU/glinide (others) had a higher SUCRA for changes in hemoglobin A1c (A1C) compared with only insulins (68.2±5.6% vs. 39.9±6.6%; P=0.01) although the difference in the SUCRA for SH was not significant (P=0.59) . Compared with only insulins, SU/glinide + others had a lower SUCRA for SH (42.4±5.8% vs. 58.5±3.4%, P=0.05) and comparable SUCRA for A1C change (P=1.00) . Cluster analysis indicated that premixed insulin + glucagon-like peptide-1 receptor agonist (Mix-ins+GLP1) consistently belonged to the high-efficacy group for A1C change and achievement of A1C Disclosure S.Kodama: None. K.Kato: None. K.Watanabe: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. T.Sato: None. M.H.Yamada: None. M.Yamamoto: None. Y.Matsubayashi: None. H.Ishiguro: None. M.Iwanaga: None. K.Fujihara: None. T.Yamada: None.

Breslow’s Health Practice Index (HPI) includes recommendations for a healthy lifestyle and is composed of 7 simple lifestyle factors (sleep, breakfast, snacks, body mass index (BMI) , physical activity, drinking alcohol, and smoking status) . Cardiovascular health metrics (CVHMs) defined according to the American Heart Association are composed of lifestyle factors and clinical laboratory values (smoking status, BMI, physical activity, diet, systolic blood pressure In summary, not only to follow a healthy lifestyle but to achieve laboratory treatment targets may be essential in people with diabetes. Disclosure T.Iijima: None. T.Yamada: None. S.Kodama: None. H.Sone: Research Support; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Holdings Co., Ltd., Takeda Pharmaceutical Company Limited. K.Fujihara: None. M.H.Yamada: None. M.Yamamoto: None. T.Osawa: None. Y.Matsubayashi: None. T.Sato: None. Y.Yaguchi: None. M.Iwanaga: None.

Cell-penetrating peptides (CPPs) are short peptides with the ability to translocate through the cell membrane to facilitate their cellular uptake. CPPs can be used as drug-delivery systems for molecules that are difficult to uptake. Ocular drug delivery is challenging due to the structural and physiological complexity of the eye. CPPs may be tailored to overcome this challenge, facilitating cellular uptake and delivery to the targeted area. Retinal diseases occur at the posterior pole of the eye; thus, intravitreal injections are needed to deliver drugs at an effective concentration in situ. However, frequent injections have risks of causing vision-threatening complications. Recent investigations have focused on developing long-acting drugs and drug delivery systems to reduce the frequency of injections. In fact, conjugation with CPP could deliver FDA-approved drugs to the back of the eye, as seen by topical application in animal models. This review summarizes recent advances in CPPs, protein/peptide-based drugs for eye diseases, and the use of CPPs for drug delivery based on systematic searches in PubMed and clinical trials. We highlight targeted therapies and explore the potential of CPPs and peptide-based drugs for eye diseases.

Aim To compare the long‐term efficacy of sodium‐glucose co‐transporter‐2 inhibitors and dipeptidyl peptidase‐4 inhibitors as second‐line drugs after metformin for patients not at high risk of atherosclerotic cardiovascular disease (ASCVD). Materials and methods In a 52‐week randomized open‐label trial, we compared ipragliflozin and sitagliptin in Japanese patients diagnosed with type 2 diabetes, without prior ASCVD and treated with metformin. The primary endpoint was a glycated haemoglobin (HbA1c) reduction of ≥0.5% (5.5 mmol/mol) without weight gain at 52 weeks. Results Of a total of 111 patients (mean age 59.2 years, mean body mass index [BMI] 26.6 kg/m2, 61.3% men), 54 patients received ipragliflozin and 57 received sitagliptin. After 52 weeks, achievement of the primary endpoint was not significantly different (37.0% and 40.3%; P = 0.72). HbA1c reduction rate at 24 weeks was greater for sitagliptin (56.1%) than for ipragliflozin (31.5%; P = 0.01). From 24 to 52 weeks, the HbA1c reduction with sitagliptin was attenuated, with no significant difference in HbA1c reduction after 52 weeks between sitagliptin (54.4%) and ipragliflozin (38.9%; P = 0.10). Improvements in BMI, C‐peptide and high‐density lipoprotein cholesterol were greater with ipragliflozin than with sitagliptin. Adverse events occurred in 17 patients with ipragliflozin and in 10 patients with sitagliptin (P = 0.11). Conclusion The HbA1c‐lowering effect at 24 weeks was greater with sitagliptin than with ipragliflozin, but with no difference in efficacy related to HbA1c and body weight at 52 weeks. However, some ASCVD risk factors improved with ipragliflozin.

The success of the sterile insect technique (SIT) relies on the achievement of high levels of sterility and mating success of the factory-reared sterile males and thus their biological quality, which can be enhanced by the reduction of stress factors encountered during rearing, handling, and irradiation procedures. The achievement of consistent sterility levels requires reliable and standard irradiation protocols. Additionally, mosquito adults require immobilization prior to, and during irradiation to increase processing efficiency and to avoid physical damage caused by movement in restricted space. Common methods for immobilization include chilling and anesthetics such as nitrogen. Here we assessed the effects of chilling and exposure to nitrogen on the irradiation dose-response of Aedes mosquitoes, and their downstream effects on some male quality parameters including longevity and flight ability. We found that chilling does not incur damage in the insects in terms of longevity and flight ability when chilling duration and temperature are carefully controlled, and a recovery phase is provided. Irradiation in nitrogen shows high radioprotective effects during irradiation, resulting in reduced induction of sterility. Overall, longevity of males can be improved by irradiating in anoxia, however the exposure to nitrogen itself comes with negative impacts on flight ability. The results reported here will assist in the standardization and optimization of irradiation protocols for the SIT to control mosquito populations of medical relevance.

Early division of the dorsal pancreatic artery (DPA) or its branches to the uncinate process during pancreaticoduodenectomy (PD) in addition to early division of the gastroduodenal artery and inferior pancreaticoduodenal artery should be performed to reduce blood loss by completely avoiding venous congestion. However, the significance of early division of DPA or its branches to the uncinate process has not been reported. The aim of this study was to investigate the anatomy of DPA and its branches to the uncinate process using the currently available high-resolution dynamic computed tomography (CT) as the first step to investigate the significance of DPA in the artery-first approach during PD. Preoperative dynamic thin-slice CT data of 160 consecutive patients who underwent hepato–pancreato–biliary surgery were examined focusing on the anatomy of DPA and its branches to the uncinate process. DPA was recognized in 103 patients (64%); it originated from the celiac axis or its branches in 70 patients and from the superior mesenteric artery or its branches in 34 patients. The branches to the uncinate process were visualized in 82 patients (80% of those with DPA), with diameters of 0.5–1.5 mm in approximately 80% of the 82 patients irrespective of DPA origin. DPA branches to the uncinate process were recognized using high-resolution CT in approximately half of the patients.

Funding Acknowledgements Type of funding sources: None. Background In patients with sludge or severe spontaneous echo contrast (SEC) in the left atrial appendage (LAA), isoproterenol loading transesophageal echocardiography (ISP-TEE) has been reported to check the presence of thrombus in the LAA, as the sludge or severe SEC disappears (Figure 1). Purpose The aim of this study was to assess the safety of ISP-TEE for the identification of LAA thrombus and the hemodynamic changes in the LAA caused by ISP loading. Methods We prospectively enrolled 25 patients with atrial fibrillation (AF) and sludge or SEC in the LAA who underwent ISP-TEE from April 2020 to July 2021. ISP was administered intravenously to achieve the target heart rate (HR) defined as follows: Max HR [beats per minutes: bpm] = 220 – age (years), Target HR [bpm] = Max HR × 0.8. Patients with tachycardia exceeding Max HR before ISP administration, hemodynamic instability, and other contraindications to ISP were excluded from the study. To assess the safety of ISP-TEE, we evaluated patients’ condition, changes in systolic blood pressure (sBP) and HR before and after ISP loading. We also assessed the presence or absence of worsening heart failure, new arrhythmias other than atrial fibrillation, and cerebral infarction or transient ischemic attack during the examination, and after 24 hours. Hemodynamic evaluation was performed using LAA blood flow velocity, LAA tissue Doppler imaging (TDI) velocity, and LAA volume fraction (LAAVF) defined as follows: LAAVF (%) = (Max LAA volume – Min LAA volume) / Max LAA volume × 100. Quantification of LAA volume was performed using the stacked-contour method of a 3-dimensional TEE full-volume acquisition. Results Among 25 patients, 13 patients had sludge or grade3 SEC, 7 patients had grade2 SEC, 5 patients had grade1 SEC. HR after ISP loading was significantly higher than before loading, but sBP did not change significantly before and after ISP loading. No complications due to ISP loading were observed during examination and after 24 hours. After ISP loading, there were 18 patients with grade 1 SEC or no SEC (classified as Group1), 7 patients had residual sludge or grade 2 to 3 SEC (classified as Group2). The differences in LAA blood flow velocity between before and after ISP loading was faster in Group1 than in Group2: 13.0 ± 10.5 vs 2.6 ± 4.2. p = 0.019. The differences in TDI velocity was also faster in Group1 than in Group2: 1.46 ± 1.14 vs 0.19 ± 0.50, p = 0.010. The differences in LAAVF was higher in Group1 than in Group2: 13.7 ± 10.3 vs 2.2 ± 2.0, p = 0.009. Conclusions In our study, no complications were observed in ISP-TEE for the identification of LAA thrombus. Patients with grade 1 SEC or no SEC, the LAA function was increased by ISP loading. These results may provide insights into the mechanisms of ISP loading on SEC in the LAA. Abstract Figure.

Calpains are calcium-regulated cysteine proteases that have been implicated in the regulation of cell death pathways. Here, we used our calpain-1 null mouse model to evaluate the function of calpain-1 in neural degeneration following a rodent model of traumatic brain injury. In vivo, calpain-1 null mice show significantly less neural degeneration and apoptosis and a smaller contusion 3 days post-injury than wild type littermates. Protection from traumatic brain injury corroborated with the resistance of calpain-1 neurons to apoptosis induced by oxidative stress. Biochemical analysis revealed that caspase-3 activation, extracellular calcium entry, mitochondrial membrane permeability, and release of apoptosis-inducing factor from mitochondria are partially blocked in the calpain-1 null neurons. These findings suggest that the calpain-1 knock-out mice may serve as a useful model system for neuronal protection and apoptosis in traumatic brain injury and other neurodegenerative disorders in which oxidative stress plays a role.

The cancer cells secrete VEGF, which induces vascular leakage and metastasis. Inhibition of VEGFR2 trafficking to the cell surface prevents receiving VEGF, vascular leakage, and cancer metastasis., VEGF-A induces vascular leakage and angiogenesis via activating the cell surface localized receptor VEGF receptor 2 (VEGFR2). The amount of available VEGFR2 at the cell surface is however tightly regulated by trafficking of VEGFR2 by kinesin family 13 B (KIF13B), a plus-end kinesin motor, to the plasma membrane of endothelial cells (ECs). Competitive inhibition of interaction between VEGFR2 and KIF13B by a peptide kinesin-derived angiogenesis inhibitor (KAI) prevented pathological angiogenesis in models of cancer and eye disease associated with defective angiogenesis. Here, we show the protective effects of KAI in VEGF-A-induced vascular leakage and cancer metastasis. Using an EC-specific KIF13B knockout (Kif13biECKO) mouse model, we demonstrated the function of EC expressed KIF13B in mediating VEGF-A-induced vascular leakage, angiogenesis, tumor growth, and cancer metastasis. Thus, KIF13B-mediated trafficking of VEGFR2 to the endothelial surface has an essential role in pathological angiogenesis induced by VEGF-A, and is therefore a potential therapeutic target.

Phosphatidylinositol 3,4,5-triphosphate (PIP3) plays a key role in neuronal polarization and axon formation. PIP3-containing vesicles are transported to axon tips by the kinesin KIF13B via an adaptor protein, centaurin α1 (CENTA1). KIF13B interacts with CENTA1 through its forkhead-associated (FHA) domain. We solved the crystal structures of CENTA1 in ligand-free, KIF13B-FHA domain-bound, and PIP3 head group (IP4)-bound conformations, and the CENTA1/KIF13B-FHA/IP4 ternary complex. The first pleckstrin homology (PH) domain of CENTA1 specifically binds to PIP3, while the second binds to both PIP3 and phosphatidylinositol 3,4-biphosphate (PI(3,4)P 2 ). The FHA domain of KIF13B interacts with the PH1 domain of one CENTA1 molecule and the ArfGAP domain of a second CENTA1 molecule in a threonine phosphorylation-independent fashion. We propose that full-length KIF13B and CENTA1 form heterotetramers that can bind four phosphoinositide molecules in the vesicle and transport it along the microtubule.

Purpose Vascular endothelial growth factor (VEGF) and its receptor VEGFR2 are promising therapeutic targets for wet age-related macular degeneration (AMD). As a topically applicable option, we developed the peptide KAI to selectively interfere with VEGFR2 trafficking to the cell surface where it receives VEGF. This study sought to determine the efficacy of KAI in the mouse model of choroidal neovascularization (CNV). Methods The specificity of KAI was tested by surface plasmon resonance. The drug delivery was analyzed by cryosection and the ELISA after treatment of KAI eyedrop to the mouse eyes. For the laser-induced CNV model, mice with laser-induced ruptures in Bruch's membrane received daily treatment of KAI eyedrop or control peptide. The other groups of mice received intravitreal injection of anti-VEGF or IgG control. After two weeks, CNV was quantified and compared. Results First, we showed the specificity and high affinity of KAI to VEGFR2. Next, biodistribution revealed successful delivery of KAI eyedrop to the back of the mouse eyes. KAI significantly reduced the disease progression in laser-induced CNV. The comparison with current therapy suggests that KAI eyedrop is as effective as current therapy to prevent CNV in wet AMD. Moreover, the genetic deletion of a kinesin KIF13B, which mediates VEGFR2 trafficking to the cell surface, confirmed the pivotal role of KIF13B in disease progression of wet AMD and neovascularization from choroidal vessels. Conclusions Taken together, pharmacologic inhibition and genetic deletion complementarily suggest the therapeutic possibility of targeting VEGFR2 trafficking to inhibit pathological angiogenesis in wet AMD.

In this study, Sc concentration dependence of Sc x Al1−x N/AlN/poly-crystalline diamond/Si surface acoustic wave (SAW) characteristics at high Sc from 23.8% to 44.3% was investigated by fabricating one-port SAW resonator at high frequency. 3.8 GHz one-port resonator fabricated on Sc0.43Al0.57N showed an excellent performance of electro-mechanical coupling coefficient (K 2) as high as 6.34% for 2nd mode Sezawa wave, which enables a wide bandwidth in high frequency applications. The temperature coefficient of frequency was approximately −40 to −50 ppm deg−1 for the device fabricated with Sc concentration of 42.9%. This is a smaller value compared to conventional high K2 bulk materials such as LiNbO3. As the result, a high K2 6.34% material system at a higher Sc concentration of ScAlN/AlN/PCD was found to be possible at a high phase velocity of 7000 m s−1. Combined with the extremely high-power durability of diamond based device, high-power durable wideband SAW device at high frequency can be expected.

Made available in DSpace on 2022-04-29T08:40:51Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 This study compared the plasma progesterone concentrations from pregnant and non-pregnant buffaloes to identify non-pregnant females and submit cows earlier to oestrous resynchronization. Forty-four multiparous mix-breed Murrah buffaloes were selected for the study. The cows were subjected to hormonal oestrous synchronization and separated into 4 groups, P12 (pregnant, n = 8) and P18 (n = 8) at 12 and 18 days post-insemination; NP12 (non-pregnant, n = 7) and NP18 (n = 7) at 23 and 29 days after the onset of synchronization, respectively. The embryos and blood were collected, and the plasma was separated for centrifugation and used to determine progesterone concentration. Progesterone concentration was higher in P18 than P12 (p =.02) and NP18 groups (p

GaN-on-Diamond high electron mobility transistors were successfully fabricated by surface-activated room-temperature bonding technique. Various diamond substrates were finely polished and bonded to GaN-HEMTs by surface-activated room-temperature bonding. Fabricated devices showed superior characteristics in thermal dissipation compared to the device with conventional structure.

Although UP is a very important feature of diabetic nephropathy, decreased eGFR without UP has become phenotypic of renal complications of DM in the new definition of DKD. Although both UP and reduced eGFR are strong predictors of kidney disease, only a few studies have examined the association between these two variables and risk of dialysis in the same cohort that included people with and without DM. We analyzed data from a nationwide claims database involving 335,778 participants (DM 20,223, non-DM 315,555) during 2008-16. Multivariate Cox regression model identified risks of starting dialysis. HRs were compared among 8 groups of combinations of DM+/-, UP (-, ≥+) and eGFR ( In summary, both eGFR Disclosure T. Osawa: None. K. Fujihara: None. M. H. Yamada: None. Y. Yaguchi: None. T. Sato: None. M. Kitazawa: None. Y. Matsubayashi: None. T. Yamada: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. Funding Japan Society for the Promotion of Science (18K17897)

Although a history of both CVD and glucose abnormality are risk factors for CVD, few large studies have examined the association between prior CVD and glucose abnormality on subsequent CVD in the same cohort. Thus, we compared the impact of prior CVD, glucose abnormality status and their combinations on subsequent CVD using real-world data. Men aged 18-72 years and followed for ≥3 years between 2008 and 2016 were classified as normoglycemia (n = 210,434), borderline glycemia (n = 119,933) or diabetes (DM) (n = 33,260) defined by fasting plasma glucose, HbA1c, and antidiabetic drug prescription. Prior and subsequent CVD were identified according to claims using ICD-10 codes, medical procedures and questionnaires. Cox regression showed that CVD+ conferred a 5- to 8-fold excess risk for CVD regardless of glucose abnormality status (Table). Borderline glycemia did not influence risk of CVD in both prior CVD+ and CVD- status, whereas DM affected subsequent CVD in CVD-. In CVD-/DM, age, current smoking, SBP, HDL-C and HbA1c were associated with risk of CVD, but only SBP was related to CVD risk in CVD+/DM. Impacts of glucose tolerance and glycemic control on risk of CVD were much less than prior CVD. SBP was more strongly associated with CVD risk than glycemia in DM with prior CVD. Individualized treatment strategies should consider glucose tolerance status and prior CVD. Disclosure M. Oe: Employee; Self; Kowa Company, Ltd. T. Yamada: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. K. Fujihara: None. M. H. Yamada: None. T. Osawa: None. M. Kitazawa: None. Y. Matsubayashi: None. T. Sato: None. Y. Yaguchi: None. M. Iwanaga: None.

We investigated the impact of medication adherence for a one-year period and subsequent glycemic control and their combinations on the risk of micro/macrovascular diseases among Japanese using nationwide claims data. Analyzed were 19,565 patients with diabetes whose medication records for oral hypoglycemic agents (OHAs) were available for at least 1 year without prior treatment-requiring diabetic eye disease (TRDED), initiation of dialysis (dialysis), coronary artery disease (CAD), or cerebrovascular disease (CVD), respectively (mean age 53y, HbA1c 7.2%). Medication adherence was evaluated by the proportion of days covered (PDC), and PDC Disclosure Y. Yaguchi: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. K. Fujihara: None. M. H. Yamada: None. Y. Matsubayashi: None. T. Yamada: None. M. Iwanaga: None. M. Kitazawa: None. M. Yamamoto: None. S. Kodama: None.

Heavy total alcohol consumption was reported to increase the risk of development and progression of diabetic retinopathy. However, differing from total alcohol consumption, whether the quantity of alcohol intake per occasion had harmful or beneficial effects related to severe eye diseases caused by diabetes remains unknown. To clarify this, we utilized ICD-10 and medical treatment codes from a nationwide claims database that finally included 21,392 men with type 2 diabetes (mean age 53 y, HbA1c 7.0%, mean follow-up period 4.3 y). During the study period, 425 patients developed vision-threatening treatment-required diabetic eye diseases (TRDED) (4.6/1000 person-years). Multivariate Cox analysis demonstrated that a large quantity of alcohol per occasion defined as ≥3 drinks per occasion was positively associated with future occurrence of TRDED. One drink was defined as a standard Japanese drink with a volume equivalent to 23 g ethanol. Hazard ratio in patients drinking large amounts of alcohol per occasion for incident TRDED was 4.49 (95% confidence interval, 1.98-10.19) compared with the reference group (≤1 drink per occasion) after adjusting for covariates including total alcohol consumption. This finding demonstrated that a large quantity of alcohol per occasion had a significant association with future vision-threatening retinopathy in men with type 2 diabetes. The mechanism of this finding with regard to severe retinopathy awaits further research. Disclosure M. Yamamoto: None. T. Yamada: None. S. Kodama: None. H. Sone: Research Support; Self; Astellas Pharma Inc., Eisai Co., Ltd., Kyowa Kirin Co., Ltd., Novo Nordisk, Ono Pharmaceutical Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co. K. Fujihara: None. Y. Yaguchi: None. T. Osawa: None. M. Kaneko: None. M. Kitazawa: None. T. Sato: None. M. H. Yamada: None. Y. Matsubayashi: None.

An important method to improve the sensitivity of a nuclear magnetic resonance (NMR) system is to increase the quality factor ( Q ) of the pickup coils. In this paper, we focus on the following three items: 1) effect of the surface resistance ( R s) of the YBa2Cu3O7-δ (YBCO) films on the Q of the NMR pickup coil; 2) relationship between coil line width and current flowing through coil; and 3) effect of Si-ion irradiation to YBCO films on the Q of the NMR pickup coils. In the study of 1), we examined the Q of the NMR pickup coils made by YBCO films with different R s and found that reduction of R s is useful in increasing the Q of the NMR pickup coils. In the study of 2), we simulated the current flowing in the NMR coils by an electromagnetic simulator, and found that wider microstrip lines of the NMR pickup coil increase the current. In the study of 3), we examined Si-ion irradiation effect to reduce R s of YBCO films, and found low irradiation energy and low irradiation density of Si-ion is useful to decrease R s and useful to obtain the high Q NMR pickup coils.

We investigate magnetic properties of mixed crystals of spinel oxides Zn(Cr1−xFex)2O4 and Cd(Cr1−xFex)2O4 to study Cr-site substitution effects on the geometrically-frustrated magnetism of chromite spinels ZnCr2O4 and CdCr2O4. Zn(Cr1−xFex)2O4 and Cd(Cr1−xFex)2O4 with above x ∼ 0.1 exhibit spin-glass-like behavior below ∼10 K which is suppressed by magnetic field H > 1 kOe. Moreover, the Fe concentration x dependence of Weiss temperature ΘW in Zn(Cr1−xFex)2O4 (Cd(Cr1−xFex)2O4) exhibits the sign change of ΘW from negative below x ∼ 0.4 (x ∼ 0.1) to positive above x ∼ 0.4 (x ∼ 0.1). This suggests that, in Zn(Cr1−xFex)2O4 and Cd(Cr1−xFex)2O4, the competition of antiferromagnetic and ferromagnetic interactions (bond frustration) becomes stronger with increasing the Fe concentration x, while the geometrical frustration becomes weaker with increasing x.

Background: Docetaxel, trastuzumab, and pertuzumab (DTP) therapy is established first-line therapy for patients with HER2-positive metastatic breast cancer (HER2 + MBC). However, the poor tolerability of docetaxel impedes its long-term administration. The safety of eribulin, trastuzumab, and pertuzumab (ETP) therapy for HER2 + MBC has been confirmed in Japan. We examined the primary endpoint—overall response rate, the secondary endpoints—time to treatment failure, progression-free survival, and overall survival, as well as adverse events (AEs) of ETP therapy. (University Hospital Medical Information Network identifier:000021585) Methods: Eribulin 1.4 mg/m2/day iv (days 1 and 8), trastuzumab 8 mg/kg iv over 90 min (initial dose) and 6 mg/kg iv over 30 min (second and subsequent doses), and pertuzumab 840 mg/body over 60 min (initial dose) and 420 mg/body over 30 min (second and subsequent doses) were administered. Cycles consisting of 2 doses of eribulin and 1-week drug holiday were repeated. Patients were treated with trastuzumab and pertuzumab when AEs developed that did not allow medication continuation by reducing the dose of eribulin. Antitumor effect was assessed according to RECIST version 1.1. and toxicities to CTCAE Japanese version 4.0. All patients provided written informed consent before enrollment. The study protocol was approved by the Institutional or Central Ethics Committee, and the study was conducted in accordance with the Declaration of Helsinki, Good Clinical Practice, and local ethical and legal regulations. Results: 25 female patients (median age: 57 years [41-75]) were enrolled from April 18, 2016, through November 22, 2017. Twenty-four had performance status (PS) 0, 1 PS 1, 8 stage 4 breast cancer, and 17 metastatic breast cancer. Anthracycline, taxane, and trastuzumab were administered as neoadjuvant and adjuvant pharmacotherapies to 13, 15, and 14 patients, respectively. Primary tumor was positive for estrogen and progesterone receptors in 12 and 6 patients, respectively. Lung, liver, and bone metastases occurred in 9, 9, and 6 patients, respectively. Three (12%), 17 (68%), 1 (4%), 1 (4%), and 2 (8%) patients showed complete response (CR), partial response (PR), long-term stable disease (LSD; stable disease ≥24 weeks), stable disease (SD; stable disease Conclusions: Similar to DTP, ETP showed high response rates and good safety as first-line therapy for HER2 + MBC. Citation Format: Inoue K, Ninomiya J, Okubo K, Nakakuma T, Yamada H, Kimizuka K, Higuchi T, Saito T. Eribulin, trastuzumab, and pertuzumab as first-line therapy for patients with HER2-positive metastatic breast cancer: A multicenter, collaborative, open-label, phase II clinical trial for the SBCCSG-36 investigators [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-14.