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Pulmonic stenosis (PS) is a common congenital heart disease in dogs. It may be associated with an aberrant coronary artery (CA) in brachycephalic breeds. If present, a CA anomaly must be identified before pulmonic valvuloplasty. A 1.7-year-old Boston terrier was referred for a grade V/VI systolic heart murmur and exercise intolerance. Echocardiography revealed combined type B valvular and supravalvular PS; an aberrant CA was also suspected. Non–electrocardiography (ECG)-gated, 160-multislice computed tomographic angiography (CTA) confirmed severe right ventricular wall hypertrophy, a hypoplastic pulmonic valve annulus, and severe supravalvular PS with a marked main pulmonary artery bulge; a single left coronary ostium with an anomalous pre-pulmonic right CA was also identified. Surgical correction with pulmonic valvuloplasty and pulmonary artery patch angioplasty under cardiopulmonary bypass was planned. The patient died intraoperatively due to profound hypotension after weaning from extracorporeal circulation. However, this is the first case report in which type B valvular and supravalvular PS with an aberrant pre-pulmonic right CA was diagnosed by non–ECG-gated, 160-multislice CTA in a Boston terrier, showing a similar level of image quality to ECG-gated CTA. Thus, in PS cases, high-slice CTA may be helpful to determine if CA anomalies are present and to establish a therapeutic plan.

Background CT-P13 subcutaneous (SC) infliximab formulation was developed to provide patients with a convenient option for treatment. Previous studies have shown efficacy and safety of CT-P13 SC comparable to CT-P13 intravenous (IV) in inflammatory bowel disease (IBD)1 and rheumatoid arthritis2. This study aimed to demonstrate superiority of CT-P13 SC over placebo in maintenance therapy after induction therapy of CT-P13 IV in patients with ulcerative colitis (UC). Methods Patients with moderately to severely active UC (modified Mayo score 5 to 9 with endoscopic subscore of ≥ 2 points) were enrolled LIBERTY-UC (NCT04205643) and treated with open label CT-P13 IV 5 mg/kg at Weeks 0, 2 and 6 as induction therapy. At Week 10, patients who had a clinical response, defined as decrease in modified Mayo score from baseline of at least 2 points and at least 30%, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1 point, were randomised in a 2:1 ratio to receive either CT-P13 SC 120 mg (CT-P13 SC) or placebo SC arms every 2 weeks up to Week 54. The primary endpoint was clinical remission at Week 54. The key secondary endpoints of clinical response, endoscopic-histologic mucosal improvement, and corticosteroid-free remission were assessed at Week 54. Safety was evaluated up to Week 54. Results A total of 548 patients were enrolled. Among them, 438 patients (79.9%) responded to CT-P13 IV induction dosing and were randomised (294 in CT-P13 SC arm and 144 in placebo arm, respectively) at Week 10. The rate of clinical remission at Week 54 was significantly greater in CT P13 SC (43.2%) compared to placebo (20.8%) (P The safety profile during maintenance phase was generally comparable between CT-P13 SC and placebo arms (table 2). No deaths were reported. Conclusion CT-P13 SC was more effective than placebo for clinical remission, clinical response, endoscopic histologic mucosal improvement, and corticosteroid-free remission at Week 54 in patients with moderately to severely active UC. No new safety concerns were identified. These results demonstrate that the CT-P13 SC provides both a robust clinical benefit and the convenience of SC administration to patient with moderately to severely active UC. 1 Schreiber et al., 2021. Gastroenterology 2021;160:2340–23 2 Westhovens et al., 2020. Rheumatology 2020;00:1

Objectives High-grade serous ovarian cancer (HGSOC) represents most epithelial ovarian cancers. Whilst initially responding to platinum-based therapy, ~75% of patients develop resistance, conferring poor prognosis. Homologous recombination repair proficiency is associated with platinum resistance and limited response to PARP inhibitors. PI3K pathway inhibition downregulates BRCA expression, abrogating homologous recombination repair proficiency, and may lead to (re)sensitization to PARP inhibitors. As alpelisib (PI3Kα inhibitor) + olaparib (PARP inhibitor) demonstrated preliminary synergism in platinum-resistant/refractory, BRCA-wild-type, recurrent HGSOC in a phase 1b study, the EPIK-O study is further evaluating this combination. Methods EPIK-O/ENGOT-OV61 (NCT04729387) is a phase 3, randomized (1:1), open-label, active-controlled trial evaluating the efficacy and safety of alpelisib + olaparib versus single-agent chemotherapy in patients (N≈358) with no germline BRCA mutation, platinum-resistant/refractory HGSOC. Adult women with platinum-resistant/refractory, histologically confirmed HGSOC, high-grade endometrioid ovarian, fallopian tube, or primary peritoneal cancer, with no germline BRCA1/2 mutation, are included; patients must have received 1–3 prior systemic therapies. In Arm 1, patients receive alpelisib 200 mg orally OD + olaparib 200 mg orally BID; in Arm 2, patients receive paclitaxel 80 mg/m2 IV weekly or pegylated liposomal doxorubicin 40–50 mg/m2 IV Q28D (investigator’s choice). The primary endpoint is progression-free survival per radiologic tumor assessment (RECIST 1.1) by a blinded independent review committee. Key secondary endpoint is overall survival. Other secondary endpoints include overall response rate, clinical benefit rate, safety, and quality of life. Results Enrollment is planned in 28 countries; completion of data collection for the primary endpoint is anticipated in 2023. Conclusions Not applicable.

Eggshell is composed of a very ordered and mineralized structure and is important for egg quality. Eggshell strength is particularly important because of its direct association with economic outcomes and egg safety. Various factors related to laying hens and their environment affects eggshell strength. However, the molecular mechanisms of liver functions related to decreased eggshell strength of aged laying hens are largely unknown. Therefore, this study aimed to identify potential factors affecting eggshell strength in aged laying hens at the hepatic transcriptomic level. A total of five hundred 92-wk-old Hy-line Brown laying hens were screened to select those exhibiting the greatest variation in eggshell strength. Based on the final eggshell strength, 12 hens producing eggs with strong eggshell strength (SES) and weak eggshell strength (WES) were finally selected (n = 6) for liver tissue sampling. The RNA-sequencing was performed to identify differentially expressed genes (DEGs) between the 2 groups. We identified a total of 2,084 DEGs, of which 1,358 genes were upregulated and 726 genes were downregulated in the WES group compared with SES group. According to the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, the DEGs indicated the mammalian target of rapamycin signaling pathway, the Janus kinase-signal transducer and activator of transcription pathway, the mitogen‑activated protein kinase signaling pathway, and the insulin resistance pathways. Genes related to fatty liver disease were upregulated in WES group compared with SES group. In addition, expression of several genes associated with oxidative stress and bone resorption activity was altered in aged laying hens with different eggshell strength. Overall, these findings contribute to the identification of genes involved in different intensity of eggshell strength, enabling more understanding of the hepatic molecular mechanism underlying in decreased eggshell strength of aged laying hens.

Background: There are many factors that might contribute to the delay of surgery in patients with breast cancer. Previous studies investigate the influence of delay of surgery, but they reported inconsistent results. The purpose of this study was to evaluate the impact of time of surgery on prognosis of breast cancer. Methods: We performed a retrospective review of the patients with breast cancer, who received surgery between 1992 and 2009, by using data from Korea Breast Cancer Society Registry. Kaplan-Meier survival analysis and Cox regression model were used to evaluate the impact of time to surgery in breast cancer and subgroup analyses were performed for each disease stage and molecular subtype. Result: A total 14727 patients were included for analysis. Delay of surgery more than 31 days was associated with worse survival for breast cancer [hazard ratio (HR) = 2.16; 95% confidence interval (CI), 1.936-2.408, p Conclusion: Surgical delay of more than 31 days were independent risk factors for worse outcome of breast cancer in each molecular subtype and breast cancer group except stage 0 and I. Although preoperative evaluation is required, surgical delay should be shortened to enhance survival of breast cancer, especially in patients with tumor size more than 2cm or presence of lymph node metastasis. Citation Format: Kim J-M, Choi HJ, Kim I, Ryu JM, Yu J, Lee JE, Kim SW, Nam SJ, Lee SK. The impact of time interval between diagnosis and surgery in each type and stage of breast cancer [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 P2-08-29.

SummaryThe endomembrane reticulum (ER) is largely reorganized by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 ORF3a and membrane (M) protein expression affects ER-derived structures including cubic membrane and double membrane vesicles in coronavirus-infected cells; however, the molecular mechanisms underlying ER remodeling remain unclear. We introduced a “plug and playable” proximity labeling tool (TurboID-GBP) for interactome mapping of GFP-tagged SARS-CoV-2 ORF3a and M proteins. Through mass spectrometric identification of the biotinylated lysine residue (K+226 Da) on the viral proteins using Spot-TurboID workflow, 117 and 191 proteins were robustly determined as ORF3a and M interactomes, respectively, and many, including RNF5 (E3 ubiquitin ligase), overlap with the mitochondrial-associated membrane (MAM) proteome. RNF5 expression was correlated to ORF3a ubiquitination. MAM formation and secreted proteome profiles were largely affected by ORF3a expression. Thus, SARS-CoV-2 may utilize MAM as a viral assembly site, suggesting novel anti-viral treatment strategies for blocking viral replication in host cells.HighlightsSARS-CoV-2 proteins ORF3a and M alter endoplasmic reticulum proteome profileORF3a affects mitochondrial-associated membrane formationSARS-CoV-2 may utilize mitochondrial-associated membrane as viral assembly siteORF3a and M interactome proteins may serve as targets for COVID-19 treatmenteTOC BlurbER remodelling by SARS-CoV-2 ORF3a and M protein

Objective: Two previous individual participant data meta-analyses (IPDMAs) found that different diagnostic interviews classify different proportions of people as having major depression overall or by symptom levels. We compared the odds of major depression classification across diagnostic interviews among studies that administered the Depression subscale of the Hospital Anxiety and Depression Scale (HADS-D). Methods: Data accrued for an IPDMA on HADS-D diagnostic accuracy were analysed. We fit binomial generalized linear mixed models to compare odds of major depression classification for the Structured Clinical Interview for DSM (SCID), Composite International Diagnostic Interview (CIDI), and Mini International Neuropsychiatric Interview (MINI), controlling for HADS-D scores and participant characteristics with and without an interaction term between interview and HADS-D scores. Results: There were 15,856 participants (1942 [12%] with major depression) from 73 studies, including 15,335 (97%) non-psychiatric medical patients, 164 (1%) partners of medical patients, and 357 (2%) healthy adults. The MINI (27 studies, 7345 participants, 1066 major depression cases) classified participants as having major depression more often than the CIDI (10 studies, 3023 participants, 269 cases) (adjusted odds ratio [aOR] = 1.70 (0.84, 3.43)) and the semi-structured SCID (36 studies, 5488 participants, 607 cases) (aOR = 1.52 (1.01, 2.30)). The odds ratio for major depression classification with the CIDI was less likely to increase as HADS-D scores increased than for the SCID (interaction aOR = 0.92 (0.88, 0.96)). Conclusion: Compared to the SCID, the MINI may diagnose more participants as having major depression, and the CIDI may be less responsive to symptom severity. © 2019 Elsevier Inc.

Background: Health-related quality of life (HRQoL) was a secondary end point in AGO-OVAR 16, which randomized 940 patients with EOC after first-line chemotherapy to maintenance pazopanib (PZ) or placebo (P). Additional post hoc analyses were carried out to investigate additional patient-centered end points. Patients and methods: HRQoL was measured with EORTC-QLQ-C30, QLQ-OV28 and EQ-5D-3L. Pre-specified end points included mean differences in HRQoL between treatment arms. Exploratory analyses included quality-adjusted progression-free survival (QAPFS), impact of specific symptoms and progressive disease (PD) on HRQoL and time to second-line chemotherapy. The objective was to provide clinical perspective to the significant median PFS gain of 5.6 months with PZ. Results: There were statistically significant differences between PZ and P in QLQ-C30 global health status [5.5 points; 95% confidence interval (CI), 0.7-10.4, P = 0.024] from baseline to 25 months, but not EQ-5D-3L (0.018 points; 95% CI-0.033 to 0.069, P = 0.485). The impact of diarrhea was captured in QLQ-OV28 Abdominal/GI-Symptoms scale (8.1 points; 95% CI 3.6-12.5, P = 0.001). QAPFS was 386 days (95% CI 366-404 days) with PZ versus 359 days (95% CI 338-379 days) with placebo (P = 0.052). PD was associated with a decline in HRQoL (P

Purpose The 21 gene expression assay, Oncotype DX (ODX) is costly (the current estimated cost is ˜$4000), and were tested in only approximately one-third of breast cancer patients who meet the inclusion criteria in the United States. Recent study of University of Tennessee Medical Center reported a novel nomogram for prediction of ODX recurrence score using clinico-pathologic data, which was based on a large dataset from the National Cancer Data Base (NCDB). The purpose of this study was to confirm that the nomogram could predict ODX score group accurately with Korean data, which is different from the NCDB in terms of ethnicity. Methods A retrospective review was performed with 218 patients who received breast-conserving surgery or mastectomy at Samsung Medical Center and were tested with the ODX from April 2011 to January 2017. An online nomogram calculator, provided by the University of Tennessee Medical Center on their website was used in order to calculate the probability of a low-risk or a high-risk ODX score for each patient. The cut-off value for predictive accuracy of the nomogram was set same as the original study. Results With the cut-off value as 90% for inspection of the commercial ODX score, high-risk group showed 33.3% positive predictive value (PPV) and low-risk group showed 68.7%. With the cut-off value as 86% for TAILORx score, PPV was 66.7% for high-risk group, and 38.9% for low-risk group. The sensitivity of the nomogram for the low-risk group commercial ODX score was 96.8%, and 33.3% for the TAILORx score. For the high-risk group, sensitivity was 20% for the commercial ODX score, and 16.7% for the TAILORx score. Conclusions Although the nomogram for prediction of ODX score was based on a large dataset of NCDB, it could not be generalized to patients in Asia. Further studies based on large data from different ethnicities should be performed to develop the nomogram for patients worldwide. Citation Format: Kim J-M, Ryu JM, Kim I, Choi HJ, Nam SJ, Kim SW, Yu J, Lee SK, Lee JE. The accuracy of nomograms based on large dataset using clinico-pathologic variables for prediction of oncotype DX breast cancer recurrence score [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P5-11-01.

Aluminum alloy A356-T6 and automotive steel sheet SAPH440 were joined using friction stir spot welding and self-piercing riveting. The maximum tensile shear strength values in weld joints were approximately 3.5 kN at a rotation speed of 500 rpm and plunge depth of 1.0 mm. It was confirmed that the intermetallic compound layer of weld joints below 9.23 m did not exceed the permissible thickness 10 m of Al–Fe joints. The self-piercing riveting joints exhibited maximum tensile- shear strength of 7.9 kN, which was higher than that of the weld joints. However, during the riveting process, cracking appeared in the joint on the aluminum side, which was caused by lack of ductility of cast aluminum. In addition, it was observed that the cracks on the aluminum side were getting larger, as the radius of the lower mold increased. Алюминиевый сплав А356-Т6 и автомобильную листовую сталь SAPH440 соединяли с помощью точечной ротационной сварки трением и самопробивной клепки. Максимальный предел прочности на сдвиг при растяжении для сварных соединений составлял примерно 3,5 кН при скорости вращения 500 об/мин и глубине проникновения 1,0 мм. Доказано, что слой интерметаллидов сварных соединений толщиной менее 9,23 мкм не превышал допустимый уровень в 10 мкм для соединений Al–Fe. Клепаные соединения имели предел прочности 7,9 кН в отличие от сварных соединений. Однако при клепке на алюминии появлялись трещины ввиду низкой пластичности литого материала, при этом трещины подрастали по мере увеличения радиуса нижней формы.

The precipitation of AlN particles and grain refinement in the Al(N)-added medium C–Mn steel have been studied using a Gleeble hot-deformation simulator and extraction replica TEM technique. No significant grain refinement occurs during either hot-rolling or hot-deformation/isothermal-holding, which is due to the absence of AlN precipitation; the lack of precipitation is caused by an unusually high-energy barrier for nucleation. Abrupt grain refinement occurs on reheating because of the copious precipitation of AlN during reheating. The copious precipitation of AlN during reheating is possible because thermally unstable Fe-rich sulphides act as precursors for AlN precipitation during reheating.

Breast cancers (BC) in younger, premenopausal patients (YBC) tend to be more aggressive with worse prognosis, higher chance of relapse and poorer response to endocrine therapies compared to breast cancers in older patients. The proportion of YBC (age ≤ 40) among BC in East Asia is estimated to be 16-32%, significantly higher than the 7% reported in Western countries. To characterize the molecular bases of Asian YBC, we have performed whole-exome sequencing (WES) and whole-transcriptome sequencing (WTS) on tumor and matched normal samples from 134 Korean BC patients consisting of 74 YBC cases (age ≤ 40) and 60 OBC cases (age > 40). We then performed comparison analyses and integrative analyses with the TCGA BC cohort consisting of 1,116 tumors from primarily Caucasian patients, also grouped by age into YBC (age ≤ 40), IBC (40 < age ≤ 60) and OBC (age > 60). Somatic mutation prevalence analysis identified 7 significantly mutated genes and the same top three genes – TP53, GATA3 and PIK3CA – were reported by the TCGA BC study. To identify differentially expressed (DE) genes and pathways in YBCs vs. OBCs, we performed logistic regression analyses while controlling for the confounding effects of tumor purity and stage. We were surprised to see a significant overlap in DE pathways between a comparison of adjacent normal tissues in younger vs. older TCGA cohorts and a comparison of YBC vs. OBC tumors, indicating that normal tissue compartment could contribute to observed differences between bulk tumors. To separately examine molecular signatures from tumor, stroma and normal compartments, we used non-negative matrix factorization (NMF) analyses to virtually dissect bulk tumor expression data and identified 14 factors including 3 factors associated with normal tissues, 1 factor associated with stroma and 1 factor associated with tumor infiltrating lymphocytes (TIL). Integrative analyses of tumor associated factors and DE pathways revealed that estrogen response, endocrine therapy resistance, and oxidative phosphorylation pathways are up-regulated in YBCs compared to OBCs while cell cycle and proliferation pathways are up-regulated in Asian OBCs. Interestingly, many immune and inflammation pathways correlated with the TIL factor were significantly upregulated in OBCs vs. YBCs. Using gene expression signatures representing distinct immune cell types, we classified our cohort into four subtypes of varying TIL activities and observed significant enrichment of the TIL-high subtype in OBCs compared to YBCs. These observations were confirmed by IHC analyses of four TIL markers (CD45, CD4, CD8 and CD163) in 120 tumors. To our knowledge, this is the first large-scale multi-omics study of Asian breast cancer and would significantly contribute to the compendium of molecular data available for studying young breast cancers. The major landmarks in the molecular landscape looked similar across BCs of different ethnicities and ages, however, we have identified a number of distinguishing molecular characteristics associated with Asian YBC. The sources for some signatures were further traced to non-tumor intrinsic compartments, indicating that tumor microenvironment may play potentially important roles in driving the carcinogenesis of young breast cancers. Citation Format: Kan Z, Ding Y, Cho S, Lee S-H, Powell E, Jung HH, Chung W, Deng S, Choi Y-l, Kim J, Park W-Y, Vizcarra P, Fernandez-Banet J, Nichols T, Ram S, Lee SK, Kim SW, Lee JE, Ching KA, Kim J-Y, Ahn JS, Im Y-H, Nam SJ, Park YH. Multi-omics and immuno-oncology profiling reveal distinct molecular signatures of young Asian breast cancers [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-05-15.

Anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) with a non-common pattern can be diagnostic challenging. Pathologists can be unavoidably and unintentionally blind to non-descript tumor cells in a lymphohistiocytic- (LH) or small-cell (SC)-pattern. We report a case of primary systemic ALK+ ALCL with a SC pattern that presented as secondary gastric lesions with a mixed LH and SC pattern that was masqueraded as inflammatory lesions.A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered.A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.

Grille opening shape for small passenger car is designed numerically by using parametric study. Key geometric parameters to design a grille opening configuration are represented by vertical height, horizontal width, size, linear deformation, position, and blockage. Numerical study investigates the effects of those key parameters on the aerodynamic drag and the grille inlet flow rate, which are very important to the aerodynamic performance as well as the powertrain cooling performance of the car. Flow simulations are performed at the velocity of 110 km/h inflow condition. The outflow boundary condition is implemented by pressure outlet condition of atmospheric pressure. Moving wall condition of 110 km/h is set on the ground.

Following growing public awareness of the danger from hurricanes and tremendous demands for analysis of loss, many researchers have conducted studies to develop hurricane damage analysis methods. Although researchers have identified the significant indicators, there is currently a shortage of comprehensive research for identifying the relationship among the vulnerabilities, natural disasters, and insured losses associated with individual buildings. To address this lack of research, this study will identify vulnerabilities and hazard indicators, develop metrics to measure the influence of economic losses from hurricanes, and visualize the spatial distribution of vulnerability to evaluate overall hurricane damage. This paper has utilized the Geographic Information System to facilitate collecting and managing data, and has combined vulnerability factors to assess the financial losses suffered by Texas coastal counties. A multiple regression method has been applied to develop hurricane damage prediction models. To reflect the pecuniary loss, insured loss payment was used as the dependent variable to predict the actual financial damage. Exposures, built environment vulnerability indicators, and hazard indicators were all used as independent variables. Accordingly, the models and findings may possibly provide vital references for government agencies and emergency planners to establish the hurricane damage mitigation strategies. In addition, insurance companies could utilize the model to predict hurricane damage.

Patients with type 2 diabetes mellitus (T2DM) are required to perform multiple self-care behaviours to achieve and maintain optimal glycaemic control (HbA1c), which prevents complications and premature mortality. Patients with T2DM and low socioeconomic status (SES) are more likely to have suboptimal HbA1c, often due to being less adherent to recommended self-care activities than their higher-SES counterparts.Although studies support performing certain diabetes self-care behaviours for optimizing glycaemic control, there is limited research on the relative importance of each behaviour for this purpose. Identifying what behaviours are most important for HbA1c among low-SES patients with T2DM would be particularly useful for informing policy and intervention efforts for this high-risk group.In a cross-sectional study of 314 adults with T2DM and low SES, we used the Summary of Diabetes Self-Care Activities to assess self-care behaviours and multivariate models to test which behaviours were associated with lower HbA1c.Only medication adherence was significantly associated with lower HbA1c after adjusting for the other self-care behaviours (β = -0·14, P = 0·028) and further adjusting for demographic and diabetes characteristics (β = -0·16, P = 0·024).Medication adherence may be the most important self-care behaviour for glycaemic control among adults with T2DM and low SES.Focused efforts to improve medication adherence among low-SES patient populations may improve glycaemic control.

Jeju horse (Natural Monument number 347) is a breed of horse that has experienced long-term isolation and domestication in Jeju Island, South Korea. We evaluated genetic features of this breed, including SNP, by whole-genome resequencing using an Illumina HiSeq 2000. A total of 5,986,852 SNP were identified in 4 Jeju horses and were divided into homozygous and heterozygous SNP (2,357,099 and 3,629,753 SNP, respectively). It revealed that 63.8% of these SNP resided in intergenic regions. Immune response genes with nonsynonymous SNP were overrepresented in Jeju horses as evidenced by Gene Ontology clustering. Among these genes, Toll-like receptors (TLR) are highly enriched. Comparing TLR genes between Jeju horses and the Przewalski's horse, and genes showed "possibly damaging" mutations in several regions by analysis with PolyPhen-2. These results provide a framework for further genetic studies in Jeju horse by domestication. Furthermore, research on functions of SNP-associated genes would aid in understanding the molecular genetic variation of horse breeds.

Aim: Homeless people have limited access to medical care despite their higher risk for medical illnesses. The aim of our study was to describe the demographic and clinical features as well as the outcomes of lung cancer in homeless people and to calculate the costs for the treatment. Methods: We retrospectively analyzed 22 homeless patients diagnosed with lung cancer between 2005 and 2013 at a single center in Seoul metropolitan city, South Korea. Costs were calculated referring to health care claims obtained from the Seoul National University Boramae Medical Center. Results: The median age of patients was 62 years and all patients were male. 68% were current or ex-smoker. Histologic diagnoses were as follows: non-small cell lung cancer (n = 16), small cell lung cancer (n = 3) or unknown (n = 3). Most of the patients (78%) had an advanced disease (stage IIIB; n = 2, stage IV; n = 15); five patients (23%) died during their initial hospitalization with a median survival of 1.5 months (0.4-2.4 months); seven (32%) were lost to follow-up after an initial outpatient visit or discharge from initial admission, with a median follow-up duration of 14 days (1-30 days) and only five patients (23%) received an appropriate treatment for their lung cancer (palliative chemotherapy and/or tyrosine kinase inhibitor, n = 3; whole-brain radiation therapy, n = 1; craniotomy and tumor removal, n = 1), with a median follow-up duration of 12.6 months (1.3-19.7 months). In contrast, four of five patients with an early stage of disease (22%, stage I; n = 4, stage IIA; n = 1), received a curative surgery. Their median follow-up duration was 25.9 months (2.5-77.3 months). In total, median follow up duration and days of hospitalization were 30 days and 26 days, respectively. The median treatment costs amounted to e8,922 (based on an exchange rate of Korean Won 1440 = Euro e1), constituting 47.3% of the per capita income in 2013. 98% of the costs were attributed to the inpatient treatment. The National Health Insurance paid 85% of the costs and the remainder was financed by the homeless shelter in which the patient lived or by the Seoul Metropolitan Government if the patient lived on the streets. Conclusions: Among the homeless, lung cancer is associated with a poor prognosis and substantial costs during the relatively short follow-up and survival period. Disclosure: All authors have declared no conflicts of interest.

Cyclization of 2,3-oxidosqualene by different oxidosqualene cyclase (OSC) genes is responsible for sapogenin heterogeneity. The very first phase is the conversion of 2,3-oxidosqualene into β-amyrin by β-amyrin synthase (BAS) gene, a member of OSC family, in soy saponin biosynthesis pathway. This paper reports the identification of a new BAS gene (GmBAS3) and its expression pattern in soybean (Glycine max (L.) Merr.). GmBAS3 gene was identified by PCR/RACE method with an open reading frame of 2286 bp nucleotides encoding a 762 amino acid long protein devouring a characteristic QW motif repeated five times and DCTAE motif. GmBAS3 shared 96 and 92% homology with Glycyrrhiza uralensis BAS and Lotus japonicus putative BAS respectively. Expression of the gene was detected by RT-PCR in regard to seedlings age and tissue type. A spatio-temporal expression of GmBAS3 was found in 21-day-old seedlings in the hypocotyls, young leaves and mature leaves but not observed in stem and root tissues. No expression was perceived in 10-day-old seedling. This study also support the premise that β-amyrin synthesis hang on more than one type of BAS genes with there expression in different plant parts at different times.

There is increasing penetration of renewable generation in buildings and districts. There are challenges in making the effective use of this generation. The objective of the ORIGIN project (Orchestration of Renewable Integrated Generation In Neighborhoods) is to shape loads so that the fraction of energy consumed that is from local renewable generation is maximized, and energy imported from outside sources is minimized. This paper presents the overall approach taken in the ORIGIN project and explores building physics aspects of solar thermal storage system orchestration. The case study districts are briefly introduced and characteristics of their generation, buildings, districts and shiftable loads described. The orchestration approach taken in ORIGIN is then presented. At the core of the ORIGIN system is the orchestration algorithm which generates informational and control outputs to shape future loads to best meet the objectives. The model based approach used to quantify thermal and electrical load shifting opportunities for pre-charging, coasting or avoiding loads, while meeting thermal comfort and other demands, is described using a solar thermal storage system as an example. The future steps for the ORIGIN project; retrofit of the ORIGIN system into existing districts and potential for other future applications is briefly discussed.

Background:Long noncoding RNAs (lncRNAs) have recently emerged as important biological regulators and the aberrant expression of lncRNAs has been reported in various diseases including cancer, cardiovascular disease, and diabetes mellitus. However, the role of lncRNAs in the pathogenesis of rheumatoid arthritis (RA) remains unknown.Objectives:Thus, we studied lncRNAs influenced by IL-1, which is one of the key mediators in the pathogenesis of RA, and also investigated whether regulation of NF-κB activation, which is known to be induced by IL-1, could lead to the changes of expression of those lncRNAs.Methods:Fibroblast-like synoviocytes (FLS) were obtained from the knee joints of the patients with RA. The next-generation sequencing (NGS) data were analyzed to identify differentially expressed lncRNAs between unstimulated RA FLS and IL-1-stimulated RA FLS. The expression levels of the top 5 candidates in NGS data were validated by RT-qPCR using extended number of unstimulated RA FLS and IL-1-stimulated RA FLS. IMD-0560, an inhibitor of IκB kinase (IKK) was used for the regulation of NF-κB activation. Activation and inhibition of NF-κB were confirmed by Western blotting. Changed expressions of the lncRNAs were identified by RT-qPCR.Results:NGS analysis revealed up-regulated 30 lncRNAs and down-regulated 15 lncRNAs in IL-1-treated RA FLS compared with unstimulated RA FLS. Top 5 lncRNAs were selected among 30 lncRNAs up-regulated by IL-1 in RA FLS based on fold-change with P-value cutoff. The up-regulated lncRNAs including NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 were validated by RT-qPCR. IMD-0560 inhibited phosphorylation of IκBα induced by IL-1 in RA FLS. Overexpression of lncRNAs induced by IL-1 was also inhibited by IMD-0560 in RA FLS.Conclusion:Our study revealed that IL-1 increased the expression of NR_046035, NR_027783, NR_033422, NR_003133, and NR_049759 in RA FLS. In addition, the expression of these lncRNAs was regulated by inhibition of NF-κB activation. Thus, our data suggest that the lncRNAs might be involved in the pathogenesis of RA through NF-κB signaling pathway.References:[1]Long noncoding RNAs and human disease. Trends Cell Biol. 2011 Jun;21(6):354-61.[2]A long noncoding RNA mediates both activation and repression of immune response genes. Science. 2013 Aug 16;341(6147):789-92.[3]Long noncoding RNA expression profile in fibroblast-like synoviocytes from patients with rheumatoid arthritis. Arthritis Res Ther. 2016 Oct 6;18(1):227.Disclosure of Interests:None declared

The increasing occurrence of natural disaster events and related damages have led to a growing demand for models that predict financial loss. Although considerable research has studied the financial losses related to natural disaster events, and has found significant predictors, there has not yet been a comprehensive study that addresses the relationship among the vulnerabilities, natural disasters, and economic losses of the individual buildings. This study identified hurricanes and their vulnerability indicators in order to establish a metric to predict the related financial loss. We identify hurricane-prone areas by imaging the spatial distribution of the losses and vulnerabilities. This study utilized a Geographical Information System (GIS) to combine and produce spatial data, as well as a multiple linear regression method, to establish a hurricane damage prediction model. As the dependent variable, we utilized the following ratio to predict the real pecuniary loss: the value of the Texas Windstorm Insurance Association (TWIA) claim payout divided by the appraised values of the buildings. As independent variables, we selected the hurricane indicators and vulnerability indicators of the built environment and the geographical features. The developed statistical model and results can be used as important guidelines by insurance companies, government agencies, and emergency planners for predicting hurricane damage.