Genetic Influences on Injection Drug Use

BACKGROUND: The goal of this dissertation was to create a risk phenotype which could be used to represent the intensity of injection drug use and to link this phenotype to genetics. In paper 1, a review of the literature suggests that a) injection drug users are at high risk for HIV and are at the highest risk for dependence among drug users, b) substance use disorders are chronic and recurrent, and c) genetic factors influence opioid, and other drug, addiction. In paper 2, I devised a risk phenotype, injection-years. In paper 3, I conducted genome wide analysis using injection years as the risk phenotype. METHODS: Data for paper 2 and paper 3 came from the AIDS Linked to the Intravenous Experience (ALIVE) cohort. Paper 2 deals with the problem of missing data in a longitudinal data set, using three different imputation models and examining the sensitivity. Using the imputed ALIVE GWAS cohort I created the risk phenotype, termed “injection years”. In paper 3, I conducted three analyses: genome wide association analysis, polygenic risk score analysis, and pathway analysis to explore the association between injection years and genetics. RESULTS: Our results concerning injection years are consistent with Genberg’s findings, which used the same ALIVE cohort. This result suggested that injection years could be used as a tool to measure the intensity of injection behavior. In genome wide analysis, no significant single SNP or gene sets were found. The findings suggest that injection years are influenced by polygenes. CONCLUSION: Using the appropriate model, multiple imputation can provide reliable information for longitudinal data. Efforts to identify injection drug users who are most likely to be “persistent users” and to identify related genes could help decrease the public health burden and improve personal health

Vision-Based Reactive Planning and Control of Quadruped Robots in Unstructured Dynamic Environments

Quadruped robots have received increasing attention for the past few years. However, existing works primarily focus on static environments or assume the robot has full observations of the environment. This limits their practical applications since real-world environments are often dynamic and partially observable. To tackle these issues, vision-based reactive planning and control (V-RPC) is developed in this work. The V-RPC comprises two modules: offline pre-planning and online reactive planning. The pre-planning phase generates a reference trajectory over continuous workspace via sampling-based methods using prior environmental knowledge, given an LTL specification. The online reactive module dynamically adjusts the reference trajectory and control based on the robot's real-time visual perception to adapt to environmental changes

Radiomics nomogram for prediction of glypican-3 positive hepatocellular carcinoma based on hepatobiliary phase imaging

IntroductionThe hepatobiliary-specific phase can help in early detection of changes in lesion tissue density, internal structure, and microcirculatory perfusion at the microscopic level and has important clinical value in hepatocellular carcinoma (HCC). Therefore, this study aimed to construct a preoperative nomogram for predicting the positive expression of glypican-3 (GPC3) based on gadoxetic acid-enhanced (Gd-EOB-DTPA) MRI hepatobiliary phase (HBP) radiomics, imaging and clinical feature.MethodsWe retrospectively included 137 patients with HCC who underwent Gd-EOB-DTPA-enhanced MRI and subsequent liver resection or puncture biopsy at our hospital from January 2017 to December 2021 as training cohort. Subsequently collected from January 2022 to June 2023 as a validation cohort of 49 patients, Radiomic features were extracted from the entire tumor region during the HBP using 3D Slicer software and screened using a t-test and least absolute shrinkage selection operator algorithm (LASSO). Then, these features were used to construct a radiomics score (Radscore) for each patient, which was combined with clinical factors and imaging features of the HBP to construct a logistic regression model and subsequent nomogram model. The clinicoradiologic, radiomics and nomogram models performance was assessed by the area under the curve (AUC), calibration, and decision curve analysis (DCA). In the validation cohort,the nomogram performance was assessed by the area under the curve (AUC).ResultsIn the training cohort, a total of 1688 radiomics features were extracted from each patient. Next, radiomics with ICCs<0.75 were excluded, 1587 features were judged as stable using intra- and inter-class correlation coefficients (ICCs), 26 features were subsequently screened using the t-test, and 11 radiomics features were finally screened using LASSO. The nomogram combining Radscore, age, serum alpha-fetoprotein (AFP) >400ng/mL, and non-smooth tumor margin (AUC=0.888, sensitivity 77.7%, specificity 91.2%) was superior to the radiomics (AUC=0.822, sensitivity 81.6%, specificity 70.6%) and clinicoradiologic (AUC=0.746, sensitivity 76.7%, specificity 64.7%) models, with good consistency in calibration curves. DCA also showed that the nomogram had the highest net clinical benefit for predicting GPC3 expression.In the validation cohort, the ROC curve results showed predicted GPC3-positive expression nomogram model AUC, sensitivity, and specificity of 0.800, 58.5%, and 100.0%, respectively.ConclusionHBP radiomics features are closely associated with GPC3-positive expression, and combined clinicoradiologic factors and radiomics features nomogram may provide an effective way to non-invasively and individually screen patients with GPC3-positive HCC

A nomogram model to predict the portal vein thrombosis risk after surgery in patients with pancreatic cancer

BackgroundPortal vein thrombosis (PVT) is a common postoperative complication in patients with pancreatic cancer (PC), significantly affecting their quality of life and long-term prognosis. Our aim is to establish a new nomogram to predict the risk of PVT after PC surgery.MethodWe collected data from 416 patients who underwent PC surgery at our hospital between January 2011 and June 2022. This includes 87 patients with PVT and 329 patients without PVT. The patients were randomly divided into a training group and a validation group at a ratio of 7:3. We constructed a nomogram model using the outcomes from both univariate and multivariate logistic regression analyses conducted on the training group. The nomogram’s predictive capacity was assessed using calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA).ResultsIn the study, the prevalence of PVT was 20.9%. Age, albumin, vein reconstruction and preoperative D-dimer were independent related factors. The model achieved a C-index of 0.810 (95% confidence interval: 0.752–0.867), demonstrating excellent discrimination and calibration performance. The area under the ROC curve of the nomogram was 0.829 (95% CI: 0.750–0.909) in the validation group. DCA confirmed that the nomogram model was clinically useful when the incidence of PVT in patients was 5%–60%.ConclusionWe have established a high-performance nomogram for predicting the risk of PVT in patients undergoing PC surgery. This will assist clinical doctors in identifying individuals at high risk of PVT and taking appropriate preventive measures

Aerosols in the E3SM Version 1: New Developments and Their Impacts on Radiative Forcing

The new Energy Exascale Earth System Model Version 1 (E3SMv1) developed for the U.S. Department of Energy has significant new treatments of aerosols and lightâ absorbing snow impurities as well as their interactions with clouds and radiation. This study describes seven sets of new aerosolâ related treatments (involving emissions, new particle formation, aerosol transport, wet scavenging and resuspension, and snow radiative transfer) and examines how they affect global aerosols and radiative forcing in E3SMv1. Altogether, they give a reduced total aerosol radiative forcing (â 1.6 W/m2) and sensitivity in cloud liquid water to aerosols, but an increased sensitivity in cloud droplet size to aerosols. A new approach for H2SO4 production and loss largely reduces a low bias in small particles concentrations and leads to substantial increases in cloud condensation nuclei concentrations and cloud radiative cooling. Emitting secondary organic aerosol precursor gases from elevated sources increases the column burden of secondary organic aerosol, contributing substantially to global clearâ sky aerosol radiative cooling (â 0.15 out of â 0.5 W/m2). A new treatment of aerosol resuspension from evaporating precipitation, developed to remedy two shortcomings of the original treatment, produces a modest reduction in aerosols and cloud droplets; its impact depends strongly on the model physics and is much stronger in E3SM Version 0. New treatments of the mixing state and optical properties of snow impurities and snow grains introduce a positive presentâ day shortwave radiative forcing (0.26 W/m2), but changes in aerosol transport and wet removal processes also affect the concentration and radiative forcing of lightâ absorbing impurities in snow/ice.Plain Language SummaryAerosol and aerosolâ cloud interactions continue to be a major uncertainty in Earth system models, impeding their ability to reproduce the observed historical warming and to project changes in global climate and water cycle. The U.S. DOE Energy Exascale Earth System Model version 1 (E3SMv1), a stateâ ofâ theâ science Earth system model, was developed to use exascale computing to address the grand challenge of actionable predictions of variability and change in the Earth system critical to the energy sector. It has been publicly released with new treatments in many aspects, including substantial modifications to the physical treatments of aerosols in the atmosphere and lightâ absorbing impurities in snow/ice, aimed at reducing some known biases or correcting model deficiencies in representing aerosols, their life cycle, and their impacts in various components of the Earth system. Compared to its predecessors (without the new treatments) and observations, E3SMv1 shows improvements in characterizing global distributions of aerosols and their radiative effects. We conduct sensitivity experiments to understand the impact of individual changes and provide guidance for future development of E3SM and other Earth system models.Key PointsA description and assessment of new aerosol treatments in the Energy Exascale Earth System Model Version 1 (E3SMv1) is providedContributions to the total aerosolâ related radiative forcing by individual new treatments and different processes are quantifiedSome of the new treatments are found to depend on model physics and require further improvement for E3SM or other Earth system modelsPeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153241/1/jame21034-sup-0001-Figure_SI-S01.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153241/2/jame21034.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153241/3/jame21034_am.pd

Deubiquitination of MITF-M Regulates Melanocytes Proliferation and Apoptosis

Microphthalmia-associated transcription factor-M (MITF-M) is the key gene in the proliferation and differentiation of melanocytes, which undergoes an array of post-translation modifications. As shown in our previous study, deubiquitinase USP13 is directly involved in melanogenesis. However, it is still ambiguous that the effect of USP13-mediated MITF-M expression on melanocytes proliferation and apoptosis. Herein, we found that MITF-M overexpressing melanocytes showed high cell proliferation, reduced apoptosis, and increased melanin levels. Besides, melanin-related genes, TYR, DCT, GPNMB, and PMEL, were significantly up-regulated in MITF-M overexpressing melanocytes. Furthermore, Exogenous USP13 significantly upregulated the endogenous MITF-M protein level, downregulated USP13 significantly inhibited MITF-M protein levels, without altering MITF-M mRNA expression. In addition, USP13 upregulation mitigated the MITF-M degradation and significantly increased the half-life of MITF-M. Also, USP13 stabilized the exogenous MITF protein levels. In conclusion, the MITF-M level was regulated by USP13 deubiquitinase in melanocytes, affecting melanocytes proliferation and apoptosis. This study provides the theoretical basis for coat color transformation that could be useful in the development of the new breed in fur animals

Large-Scale Vertical Velocity, Diabatic Heating and Drying Profiles Associated with Seasonal and Diurnal Variations of Convective Systems Observed in the GoAmazon2014/5 Experiment

This study describes the characteristics of large-scale vertical velocity, apparent heating source (Q1) and apparent moisture sink (Q2) profiles associated with seasonal and diurnal variations of convective systems observed during the two intensive operational periods (IOPs) that were conducted from 15 February to 26 March 2014 (wet season) and from 1 September to 10 October 2014 (dry season) near Manaus, Brazil, during the Green Ocean Amazon (GoAmazon2014/5) experiment. The derived large-scale fields have large diurnal variations according to convective activity in the GoAmazon region and the morning profiles show distinct differences between the dry and wet seasons. In the wet season, propagating convective systems originating far from the GoAmazon region are often seen in the early morning, while in the dry season they are rarely observed. Afternoon convective systems due to solar heating are frequently seen in both seasons. Accordingly, in the morning, there is strong upward motion and associated heating and drying throughout the entire troposphere in the wet season, which is limited to lower levels in the dry season. In the afternoon, both seasons\ud exhibit weak heating and strong moistening in the boundary layer related to the vertical convergence of eddy fluxes. A set of case studies of three typical types of convective systems occurring in Amazonia – i.e., locally occurring systems, coastal-occurring systems and basin-occurring systems – is also conducted to investigate the variability of the large-scale environment with different types of convective systems

Toward understanding of differences in current cloud retrievals of ARM ground-based measurements

Accurate observations of cloud microphysical properties are needed for evaluating and improving the representation of cloud processes in climate models and better estimate of the Earth radiative budget. However, large differences are found in current cloud products retrieved from ground-based remote sensing measurements using various retrieval algorithms. Understanding the differences is an important step to address uncertainties in the cloud retrievals. In this study, an in-depth analysis of nine existing ground-based cloud retrievals using ARM remote sensing measurements is carried out. We place emphasis on boundary layer overcast clouds and high level ice clouds, which are the focus of many current retrieval development efforts due to their radiative importance and relatively simple structure. Large systematic discrepancies in cloud microphysical properties are found in these two types of clouds among the nine cloud retrieval products, particularly for the cloud liquid and ice particle effective radius. Note that the differences among some retrieval products are even larger than the prescribed uncertainties reported by the retrieval algorithm developers. It is shown that most of these large differences have their roots in the retrieval theoretical bases, assumptions, as well as input and constraint parameters. This study suggests the need to further validate current retrieval theories and assumptions and even the development of new retrieval algorithms with more observations under different cloud regimes