Coastal Resilience Decision Making with Machine Learning

Our research aims to understand how social data can be integrated with climate data using machine learning for coastal resilience decisions. Although data analytics techniques have been adapted for decision models, incorporating unstructured data is a challenge. We adapt a design science research approach to develop a coastal resilience decision model that can accommodate various sets of climate criteria and social attributes to help us understand coastal risks in communities vulnerable to coastal hazards. We collected social data from environmental groups and individuals and conducted an exploratory social media data analysis on coastal resilience in the greater Boston, U.S., area. We employ non-negative matrix factorization (NMF), a topic modeling technique, to extract human-interpretable topics from a preliminary dataset of 131 documents from 50 different accounts. The outcomes of this research can help community members and policy makers understand and develop robust sustainability and climate focused decisions

Coastal Resilience with Social Data Analytics: A Design Science Approach

We adapt a design science approach (DSR) for coastal resilience and climate justice using big data analytics. Our big data and machine learning based artifact can accommodate various sets of social attributes to understand coastal risks for vulnerable communities. We analyzed social data from communities vulnerable to coastal hazards by incorporating machine learning (ML) to assess coastal community needs and demands. In addition, we developed a user interface that provides data selection and weighting functionalities. We extend IS literature in design science research and ML techniques to further our understanding of coastal resilience in vulnerable communities. The outcomes of this research can help community members and policy makers understand and develop robust sustainability and climate focused decisions using a coastal resilience decision approach

The A54T polymorphism at the intestinal fatty acid binding protein 2 is associated with insulin resistance in glucose tolerant Caucasians

BACKGROUND: An A54T polymorphism at the fatty acid binding protein 2 (FABP2) locus was found to be associated with insulin resistance in non-diabetic Pima Indians. To see whether this association is present in other populations, we performed a cross sectional study to examine the role of this polymorphism on insulin resistance in 55 healthy and normotensive Caucasian subjects with normal glucose tolerance. Insulin sensitivity (%S) and beta cell function (%B) were assessed using the Homeostasis Model Assessment (HOMA). Their genotypes were determined using a polymerase chain reaction-restriction fragment length polymorphism assay. The relationship between the genotypes and the phenotypes was examined. RESULTS: After genotyping, we identified 24 AA, 27 AT and 4 TT subjects. The TT subjects were combined with the AT subjects during the analysis due to its small sample size. No differences were noted in gender distribution, clinical features, and fasting lipid profile between the two genotypic groups (AA vs. AT/TT). The AT/TT group had a higher fasting plasma insulin concentration and a lower %S than the AA group (p = 0.0444 and p = 0.0461, respectively). However, no differences were noted in plasma glucose concentrations and %B. Univariate analysis revealed that this polymorphism explained 7.3% of the variation in %S. Multivariate analysis revealed that the polymorphism was an independent determinant for %S (p = 0.0434) and with body mass index accounted for 28.7% of the variation in %S. In contrast, this polymorphism had no impact on %B. CONCLUSIONS: The A54T polymorphism at the FABP2 locus is a risk factor for insulin resistance in a Caucasian population

An Improved Animal Model of Multiple Myeloma Bone Disease

Multiple myeloma (MM) is a plasma cell malignancy that causes an accumulation of terminally differentiated monoclonal plasma cells in the bone marrow, accompanied by multiple myeloma bone disease (MMBD). MM animal models have been developed and enable to interrogate the mechanism of MM tumorigenesis. However, these models demonstrate little or no evidence of MMBD. We try to establish the MMBD model with severe bone lesions and easily accessible MM progression. 1 x 10(6) luciferase-expressing 5TGM1 cells were injected into 8-12 week-old NOD SCID gamma mouse (NSG) and C57BL/KaLwRij mouse via the tail vein. Myeloma progression was assessed weekly via in vivo bioluminescence (BL) imaging using IVIS-200. The spine and femur/tibia were extracted and scanned by the micro-computer tomography for bone histo-morphometric analyses at the postmortem. The median survivals were 56 days in NSG while 44.5 days in C57BL/KaLwRij agreed with the BL imaging results. Histomorphic and DEXA analyses demonstrated that NSG mice have severe bone resorption that occurred at the lumbar spine but no significance at the femur compared to C57BL/KaLwRij mice. Based on these, we conclude that the systemic 5TGM1 injected NSG mouse slowly progresses myeloma and develops more severe MMBD than the C57BL/KaLwRij model

Biomarker analyses of clinical outcomes in patients with advanced hepatocellular carcinoma treated with Sorafenib with or without Erlotinib in the SEARCH Trial

Purpose: Sorafenib is the current standard therapy for advanced HCC, but validated biomarkers predicting clinical outcomes are lacking. This study aimed to identify biomarkers predicting prognosis and/or response to sorafenib, with or without erlotinib, in HCC patients from the phase 3 SEARCH trial. Experimental Design: 720 patients were randomized to receive oral sorafenib 400 mg BID plus erlotinib 150 mg QD or placebo. Fifteen growth factors relevant to the treatment regimen and/or to HCC were measured in baseline plasma samples. Results: Baseline plasma biomarkers were measured in 494 (69%) patients (sorafenib plus erlotinib, n=243; sorafenib plus placebo, n=251). Treatment arm–independent analyses showed that elevated HGF (HR, 1.687 [high vs low expression]; endpoint multiplicity adjusted [e-adj] P=0.0001) and elevated plasma VEGF-A (HR, 1.386; e-adj P=0..0377) were significantly associated with poor OS in multivariate analyses, and low plasma KIT (HR, 0.75 [high vs low]; P=0.0233; e-adj P=0.2793) tended to correlate with poorer OS. High plasma VEGF-C independently correlated with longer TTP (HR, 0.633; e-adj P=0.0010) and trended toward associating with improved disease control rate (univariate:OR, 2.047; P=0.030; e-adj P=0.420). In 67% of evaluable patients (339/494), a multimarker signature of HGF, VEGF-A, KIT, epigen, and VEGF-C correlated with improved median OS in multivariate analysis (HR, 0.150; P<0.00001). No biomarker predicted efficacy from erlotinib. Conclusions: Baseline plasma HGF, VEGF-A, KIT, and VEGF-C correlated with clinical outcomes in HCC patients treated with sorafenib with or without erlotinib. These biomarkers plus epigen constituted a multimarker signature for improved OS

Hepatic glucokinase promoter polymorphism is associated with hepatic insulin resistance in Asian Indians.

BACKGROUND: The role of glucokinase (GCK) in the pathogenesis of maturity-onset diabetes of the young is well established. However, its role in the common form of type 2 diabetes is far from convincing. We investigated the role of the G-to-A polymorphism in the hepatic GCK promoter on insulin sensitivity and beta cell function in 63 normotensive Asian Indians with normal glucose tolerance. As proposed by Matsuda and DeFronzo, hepatic insulin sensitivity (ISI(H)) and total body insulin sensitivity (ISI(M)) were estimated from the oral glucose tolerance test. Beta cell function was estimated using %B from the Homeostasis Model Assessment and insulingenic index (dI/dG). RESULT: We identified 38 GG, 24 GA, and one AA subjects. The AA subject was pooled with the GA subjects during the analysis. No difference was noted in the demographic features between the two genotypic groups (GG vs. GA/AA). Compared to the GG group, the GA/AA group had a lower ISI(H) (p=0.002), a lower ISI(M) (p=0.009), a higher %B (p=0.014), and a higher dI/dG (p=0.030). Multivariate analysis revealed that this polymorphism is an independent determinant for ISI(H) (p=0.019) and along with age, waist-hip ratio, gender, and diastolic blood pressure accounted for 51.5% of the variation of ISI(H). However, this polymorphism was a weak, but independent determinant for ISI(M) (p=0.089) and %B (p=0.083). Furthermore, it had no independent effect on dI/dG (p=0.135). CONCLUSIONS: These data suggest that the G-to-A polymorphism in the hepatic GCK promoter is associated with hepatic insulin resistance in Asian Indians

The Effects of Age and Alcohol on Lipid Metabolism in the Liver

Background: Alcohol-associated liver disease (ALD) encompasses the liver manifestation of chronic alcohol abuse, characterized by different stages of liver damage that progresses from fat accumulation to steatohepatitis, fibrosis and eventually cirrhosis. The severity of liver damage is influenced by age, which is also a predictor for ALD-related mortality. Thus, the purpose of this study was to investigate how aging and alcohol affect lipid metabolism in the liver. Methods: Rats aged 4 months, 8 months, 12 months, and 22 months-old were pair-fed Lieber-DeCarli control or ethanol diet for 6 weeks. Serum and liver were collected for analyses when rats were euthanized. Analyses included histopathology, measurements of non-esterified fatty acid content and hepatic triglyceride content, and gene expression.https://digitalcommons.unmc.edu/surp2022/1034/thumbnail.jp

Telomerase and Telomere Length in Pulmonary Fibrosis

In addition to its expression in stem cells and many cancers,telomerase activity is transiently induced inmurine bleomycin (BLM)induced pulmonary fibrosis with increased levels of telomerase transcriptase (TERT) expression, which is essential for fibrosis. To extend these observations to human chronic fibrotic lung disease,we investigated the expression of telomerase activity in lung fibroblasts from patients with interstitial lung diseases (ILDs), including idiopathic pulmonaryfibrosis (IPF).The resultsshowedthat telomerase activity was induced in more than 66% of IPF lung fibroblast samples, in comparison with less than 29% from control samples,some of which were obtained from lung cancer resections. Less than 4%of the humanIPF lung fibroblast samples exhibited shortened telomeres,whereas less than 6% of peripheral blood leukocyte samples from patients with IPF or hypersensitivity pneumonitis demonstrated shortened telomeres. Moreover, shortened telomeres in lategeneration telomerase RNA component knockout mice did not exert a significant effect on BLM-induced pulmonary fibrosis. In contrast, TERT knockout mice exhibited deficient fibrosis that was independent of telomere length. Finally, TERT expression was up-regulated by a histone deacetylase inhibitor, while the induction of TERT in lung fibroblastswasassociatedwiththebindingofacetylatedhistoneH3K9to the TERT promoter region. These findings indicate that significant telomerase inductionwas evident in fibroblasts from fibroticmurine lungs and a majority of IPF lung samples, whereas telomere shortening was not a common finding in the human blood and lung fibroblast samples. Notably, the animal studies indicated that the pathogenesis of pulmonary fibrosis was independent of telomere length