cssi/SciSciGPT-SciSciNet huggingface dataset:
Deep-learning convolution neural network for computer-aided detection of microcalcifications in digital breast tomosynthesis

A deep learning convolution neural network (DLCNN) was designed to differentiate microcalcification candidates detected during the prescreening stage as true calcifications or false positives in a computer-aided detection (CAD) system for clustered microcalcifications. The microcalcification candidates were extracted from the planar projection image generated from the digital breast tomosynthesis volume reconstructed by a multiscale bilateral filtering regularized simultaneous algebraic reconstruction technique. For training and testing of the DLCNN, true microcalcifications are manually labeled for the data sets and false positives were obtained from the candidate objects identified by the CAD system at prescreening after exclusion of the true microcalcifications. The DLCNN architecture was selected by varying the number of filters, filter kernel sizes and gradient computation parameter in the convolution layers, resulting in a parameter space of 216 combinations. The exhaustive grid search method was used to select an optimal architecture within the parameter space studied, guided by the area under the receiver operating characteristic curve (AUC) as a figure-of-merit. The effects of varying different categories of the parameter space were analyzed. The selected DLCNN was compared with our previously designed CNN architecture for the test set. The AUCs of the CNN and DLCNN was 0.89 and 0.93, respectively. The improvement was statistically significant (p < 0.05).
Mental Health Consultations to Welfare Agencies

Epidemiological studies of psychiatric disorders have repeatedly shown that in most populations low social and low economic positions are associated with higher rates of psychopathology.1 The disadvantaged status contributes to the intensity and frequency of all social indicators of impaired mental health. Welfare workers, who are called upon to assist these segments of the population,2 often have only limited professional and technical preparation to cope with the mental health needs of disturbed clients and their troubled families. This alone would make it desirable for welfare staff to have easy access to support and consultations by mental health professionals.
Acceptance of the 2016 Eminent Parasitologist Award: Chemotherapy in the Context of Emerging Parasitic Diseases

It seems inevitable that chemotherapy will continue, at least in the near-term, to be a significant factor in the control of infectious diseases. The effectiveness of new drugs has invariably been reduced by the emergence of drug resistance. Efforts to thwart resistance should continue, but there are also other areas that might profitably be re-examined. They include (1) methods of new-drug discovery; (2) selection of parasite life-cycle targets; (3) epidemiological determinants of effectiveness in large-scale control programs; and (4) the economic, managerial, psychological, and political ramifications of drug discovery and drug utilization.
Proteomic Studies of HIV-1

The application of proteomics has become routine in many fields allowing for the simultaneous measurement of proteins representing a vast array of different processes in tissues, cells, and biological fluids. The application of proteomics to the study of viruses remains a challenge due to many factors including the limited sample, sample preparation requirements, and specialized bioinformatics that have to be applied to studying viruses like HIV-1. Here we detail an extensive overview of all of the sample preparation strategies as they apply to HIV-1, a primer in the understanding of mass spectrometry (MS) as it applies to HIV-1 proteomic and basic bioinformatic approaches that need to be taken to ensure success. We also introduce new and emerging technologies that will allow for the application of HIV-1 proteomics to the clinic for potential clinical applications. Finally, we describe alternative approaches to mass spectrometry and discuss strategies that can be used for systems biology approaches to the study of HIV-1.
Toward the Safer and More Effective Use of Prescription Drugs: Pharmacogenetics

An individual’s response to a drug is influenced by factors that regulate absorption of the drug, distribution of the drug throughout the body, the interaction between the drug and the drug’s molecular targets, metabolism of the drug and excretion of the drug’s metabolites. The specialized proteins that regulate these processes all have variable levels of activity in different individuals. At present, however, drugs are often prescribed in a disease-oriented manner; any patient who presents with that disease gets the standard first-line drug and dose. After that, the doctor engages in an iterative trial-and-error process to find the safest and most effective drug/dose combination for that patient. This process wastes time and money, may allow the disease to worsen, and sometimes puts the patient at risk for an adverse drug reaction. The pharmacogenetic tests that are currently available have significant limitations. As our understanding of genetics and genomics grows, however, the tests will improve. Ultimately, the predictive algorithms will include not only the presence or absence of certain gene variants, but also nongenetic factors and personal and clinical data. In addition, the algorithms will be modified to reflect the interactions that occur between genes, and between genetic factors and nongenetic factors. At present there are several gene variants that are known to influence the pharmacokinetics of many prescribed drugs. These tests, while limited, can help guide dosing strategies for some patients, thereby reducing the frequency of adverse drug reactions. Researchers are also identifying increasing numbers of gene variants that influence the pharmacodynamics of drugs.
A generalized association test based on U statistics.

Motivation Second generation sequencing technologies are being increasingly used for genetic association studies, where the main research interest is to identify sets of genetic variants that contribute to various phenotypes. The phenotype can be univariate disease status, multivariate responses and even high-dimensional outcomes. Considering the genotype and phenotype as two complex objects, this also poses a general statistical problem of testing association between complex objects. Results We here proposed a similarity-based test, generalized similarity U (GSU), that can test the association between complex objects. We first studied the theoretical properties of the test in a general setting and then focused on the application of the test to sequencing association studies. Based on theoretical analysis, we proposed to use Laplacian Kernel-based similarity for GSU to boost power and enhance robustness. Through simulation, we found that GSU did have advantages over existing methods in terms of power and robustness. We further performed a whole genome sequencing (WGS) scan for Alzherimer's disease neuroimaging initiative data, identifying three genes, APOE , APOC1 and TOMM40 , associated with imaging phenotype. Availability and Implementation We developed a C ++ package for analysis of WGS data using GSU. The source codes can be downloaded at https://github.com/changshuaiwei/gsu . Contact weichangshuai@gmail.com ; qlu@epi.msu.edu. Supplementary information Supplementary data are available at Bioinformatics online.
Efficacy of Endotherapy in the Treatment of Pain Associated With Chronic Pancreatitis: A Systematic Review and Meta-Analysis.

Background Endotherapy is a treatment modality that can be used to manage the pain associated with chronic pancreatitis. The aim of this systematic review and meta-analysis is to evaluate the efficacy of endotherapy in the management of pain associated with chronic pancreatitis. Methods A search of Medline, Pubmed, and Embase databases between 1988 to December 2014 was conducted to evaluate the use of endotherapy for pain relief in patients with chronic pancreatitis. We included large prospective studies, randomized controlled trials and retrospective analyses. Exclusion criteria included studies not written in the English language, small studies with less than 10 patients, case series/case reports and studies that enrolled patients treated with dual therapies including surgery or celiac plexus neurolysis. In addition, a subgroup analysis was conducted to evaluate studies that included patients with pancreatic duct strictures. A meta-analysis was performed and the data on pain relief was subsequently extracted, pooled, and analyzed. I2 index estimates were calculated to test for variability and heterogeneity across the included studies. Results Our final analysis included sixteen studies, comprising 1498 patients. Eleven studies presented data on immediate pain relief after endotherapy and twelve studies presented data on both immediate and long term pain relief (mean follow up was 47.4 months). The compiled result of the sixteen studies for immediate pain relief demonstrated 88% efficacy (95% NT CI [81.0%, 94%]) of endotherapy. Similarly, analysis of pain relief on long term follow-up showed a 67% efficacy of endotherapy (95% NT CI [58%, 76%]). The compiled complication rate for endotherapy in this review was 7.85% per ERCP/endotherapeutic procedure and the most common complications were acute pancreatitis, stent occlusion and stent migration. Conclusions Endotherapy is beneficial for both immediate and long term management of pain associated with chronic pancreatitis. The efficacy of endotherapy decreases over time as assessed by evaluating pain relief on long term follow up. Given the considerable heterogeneity of reported data, additional prospective and standardized multicenter studies need to be conducted to evaluate the efficacy of this modality in controlling pain associated with chronic pancreatitis.
Convergence and Performance in H∞-Based Parameter Identification

Abstract This paper addresses the problem of identifying the parameters of linear state-space models using the _ -gain criterion. The present work contributes in two areas whereupon the counterpart of H ∞ norm minimization in nonlinear systems needs improvement. First, the parameter estimator under consideration, which meets the aforementioned criterion within a first-order approximation, produces recursive estimates that are close to the off-line estimates for a large number of data. Second, a method to update the bound on the disturbance attenuation is proposed and shown to enhance the performance of the estimator. A numerical example demonstrates the results by solving the direction-of-arrival estimation problem associated with an array of antenna elements.
A multifactorial analysis of acceptance of evolution

Despite decades of education reform efforts, the percent of the general US population accepting biological evolution as the explanation for the diversity of life has remained relatively unchanged over the past 35 years. Previous work has shown the importance of both educational and non-educational (sociodemographic and psychological) factors on acceptance of evolution, but has often looked at such factors in isolation. Our study is among the first attempts to model quantitatively how the unique influences of evolutionary content knowledge, religiosity, epistemological sophistication, and an understanding of the nature of science collectively predict an individual’s acceptance or rejection of evolution. Our study population had a high acceptance of evolution, with an average score of 77.17 (95% C.I. ± 1.483) on the Measure of Acceptance of the Theory of Evolution (MATE) instrument. Our combined general linear model showed that, of the variables in our model, an understanding of the nature of science explained the greatest amount of variation in acceptance of evolution. This was followed in amount of variance explained by a measure of religiosity, openness to experience, religious denomination, number of biology courses previously taken, and knowledge of evolutionary biology terms. Understanding of the nature of science was the single most important factor associated with acceptance of evolution in our study and explained at least four times more variation than measures of evolutionary knowledge. This suggests that educational efforts to impact evolutionary acceptance should focus on increasing an understanding of the nature of science (which may be expected to have additional benefits towards generalized science denial). Additionally, our measure of epistemological sophistication had a unique, significant impact on acceptance of evolution. Both epistemological sophistication and an understanding of the nature of science are factors that might change throughout a liberal arts education, independent of the effect of direct evolutionary instruction.
Loss of humoral immunity in a mouse model of ovarian cancer

Although a low incidence cancer, ovarian carcinoma (OvCa) has a high mortality rate due to late detection. To study the humoral immune response to OvCa we transplant ID8 cells (mouse epithelial carcinoma) into the murine peritoneal cavity (PerC). We found that as the OvCa developed PerC B cells, particularly B-1 B cells, were depleted. To assess the systemic impact of this depletion we assessed humoral immunity. We found a reduction in “natural” IgM and IgG 3 production and increased IgA and IgG 1 . Following immunization, there was loss of the TI-2 response (FITC-dextran, FITC-Ficoll); the TI-1 (FITC-LPS) response was intact until very late stage disease. Since B-1 cells also serve a housekeeping role in apoptotic corpse clearance, we used a FACS assay and a cell-based ELISA to monitor antibodies directed at apoptotic ID8 cells. Mice with OvCa had lower titers of sera that bound apoptotic ID8 cells. Collectively these data validate the systemic loss of B-1 B cells in mice with OvCa. These results could serve to inform strategies designed for early detection of OvCa.
Straight Line Motion and Universal Coupling

Every link in a mechanism performs a repeated motion. Therefore any point on these links also performs a repeated motion passing through a specified curve called a coupler curve. In this chapter we will study special cases where the path traced is a straight line or special cases when two inclined shafts are connected through a universal coupling.
The Case for Consumer-Based Use Tax Enforcement

This essay argues that state governments’ current focus on getting vendors to collect their sales and use taxes is insufficient, especially in regard to e-commerce transactions. If state governments want their use taxes to serve as effective and lawful backstops to their sales taxes—as state governments claim is their goal—then states must also focus on the consumer side of the use-tax equation. This essay explains that both economic and rule of law considerations make it imperative for state governments to better enforce their sales and use taxes with respect to consumer taxpayers.
Choosing iPads and Accessories

In this chapter, we’ll consider how to choose the right iPads for your school’s needs and how to select suitable accessories to enable you, your students, and your colleagues to make the most of the iPads.
Phase II trial of 6 months ADT/abiraterone acetate plus prednisone (AAP) and definitive radiotherapy (AbiRT) for men with intermediate to high risk localized prostate cancer.

11Background: Combined external beam radiotherapy (RT) and androgen deprivation therapy (ADT) improves survival over RT alone for high risk prostate cancer (PC). Long-term ADT use, currently recommended for high risk PC, also increases toxicity. Recent data suggests synergistic efficacy with the addition of abiraterone acetate plus prednisone (AAP) to RT/ADT. Potent androgen blockade may provide biochemical control with short-term ADT course in men with aggressive but localized PC. Methods: This was a two center prospective phase 2 single arm clinical trial within the Department of Defense PCCTC (NCT01717053). Eligibility included 2+ intermediate or 1 high NCCN risk factors and no metastatic disease. Men received 6 months of ADT concurrently with 1000mg AA/5mg P daily and 78 Gy RT to prostate/SV. Primary endpoint was PSA < 0.1 ng/ml at 1 year. Secondary objectives included BPFS, PSA nadir, testosterone recovery, toxicity, and patient-reported QOL. Results: We enrolled 37 men (82% white, 18% black) with in...
Biochemistry and Biology of 2-Acetyl-Aminofluorene in Primary Cultures of Adult Rat Hepatocytes

Most hepatocarcinogenesis models assume that chemical carcinogens (or their reactive metabolites) bind to hepatocyte DNA and, from mutations caused by this event, “initiate” malignant transformation (1). Recent studies of oncogene transfection (2), structure (3), and expression in normal regenerating rat liver (4) tend to strengthen — but not prove (5) — these concepts. For example, liver stem cells might instead be tumor progenitors and macromolecules besides DNA might instead be initiating “targets” (6). Nonetheless, if the “hepatocyte DNA target” point of view prevails, long-term primary cultures of such adult cells will be useful to analyze the molecular and cellular basis of chemical carcinogenesis in normal epithelial systems. We have been working since 1970 to develop a system of this kind. We highlight, here, some of our results along these lines (see also refs. 7–11). Detailed accounts, mainly with 2-acetyl-aminofluorene (AAF), will appear elsewhere (12–15).
Transplantation of Stem Cells From Bone Marrow, Peripheral Blood, and the Umbilical Cord

Hematopoietic stem cells have two important functions: they give rise to all blood cell lineages and they also recapitulate themselves. These processes are thought to occur through asymmetric division, in which one daughter cell is identical to the parent and the other daughter is committed to further differentiation into mature blood cells. True hematopoietic stem cells occur rarely in the bone marrow, they divide infrequently, and the forces that regulate their proliferation and differentiation are incompletely understood. Stem cells are identified in clinical practice by their expression of the CD34 antigen, which functions as an adhesion protein to the bone marrow stroma. Although hematopoietic stem cells express CD34, only a small fraction of CD34+ cells are capable of giving rise to all peripheral blood cell lineages (pluripotent). The majority of CD34+ cells have limited proliferative capacity, and they have been committed to produce a restricted spectrum of cells types.
Hardware Obfuscation Using Strong PUFs

IC piracy is a significant security threat, where malicious manufacturers can produce unauthorized extra chips and/or steal the information of a design through reverse engineering attempts. As a countermeasure, hardware obfuscation schemes usually withhold a part of the design (which thereafter constitutes the "key") by replacing it with configurable modules. Enforcing the configurable module to be filled in with the withheld key information enables a post-manufacturing activation of each authenticate chip, albeit with a a need to state the threat of a leaked common key. To ensure that each chip has a unique key, Physically Unclonable Functions (PUFs) have been proposed to be integrated with hardware obfuscation. Such a paradigm is constrained to use weak PUFs, because, to uniquely set the key (the content of the configurable module) for each chip, the designer needs to fully characterize the PUFs for all the chips. In this paper, we argue that a powerful attacker in the position of a manufacturer can fully characterize all the weak PUFs, and use any leaked key to break the obfuscation framework. This paper proposes a strong PUF-based hardware obfuscation scheme to effectively prevent IC piracy even in the case of a leaked key from some activated chip.
Beyond Academics: A Model for Simultaneously Advancing Campus-Based Supports for Learning Disabilities, STEM Students' Skills for Self-Regulation, and Mentors' Knowledge for Co-regulating and Guiding.

Learning disabilities are highly prevalent on college campuses, yet students with learning disabilities graduate at lower rates than those without disabilities. Academic and psychosocial supports are essential for overcoming challenges and for improving postsecondary educational opportunities for students with learning disabilities. A holistic, multi-level model of campus-based supports was established to facilitate culture and practice changes at the institutional level, while concurrently bolstering mentors’ abilities to provide learning disability-knowledgeable support, and simultaneously creating opportunities for students’ personal and interpersonal development. Mixed methods were used to investigate implementation of coordinated personal, interpersonal, and institutional level supports for undergraduate science, technology, engineering, and math (STEM) students with learning disabilities. A one-group pre-test post-test strategy was used to examine undergraduate outcomes. Participants included 52 STEM undergraduates with learning disabilities, 57 STEM graduate student mentors, 34 STEM faculty mentors, and 34 university administrators and personnel as members of a university-wide council. Enrolled for two years, undergraduates were engaged in group meetings involving psychoeducation and reflective discussions, development of self-advocacy projects, and individual mentorship. Undergraduates reported improved self efficacy (p = .001), campus connection (p < .001), professional development (p ≤ .002), and self advocacy (p < .001) after two academic years. Graduate student mentors increased their understanding about learning disabilities and used their understanding to support both their mentees and other students they worked with. Council members identified and created opportunities for delivering learning disability-related trainings to faculty, mentors and advisors on campus, and for enhancing coordination of student services related to learning and related disorders. Disability-focused activities became integrated in broader campus activities regarding diversity. This research explicates a role that college campuses can play in fostering the wellbeing and the academic and career development of its students with developmental learning and related disorders. It offers an empirically tested campus-based model that is multilevel, holistic, and strengths-based for supporting positive outcomes of young people with learning disabilities in STEM. Moreover, findings advance the knowledge of supports and skills that are important for self-regulating and navigating complex and multi-faceted disability-related challenges within both the post-secondary educational environment and the young adults’ sociocultural context.
Anoctamin 5/TMEM16E facilitates muscle precursor cell fusion.

Limb-girdle muscular dystrophy type 2L (LGMD2L) is a myopathy arising from mutations in ANO5; however, information about the contribution of ANO5 to muscle physiology is lacking. To explain the role of ANO5 in LGMD2L, we previously hypothesized that ANO5-mediated phospholipid scrambling facilitates cell–cell fusion of mononucleated muscle progenitor cells (MPCs), which is required for muscle repair. Here, we show that heterologous overexpression of ANO5 confers Ca2+-dependent phospholipid scrambling to HEK-293 cells and that scrambling is associated with the simultaneous development of a nonselective ionic current. MPCs isolated from adult Ano5−/− mice exhibit defective cell fusion in culture and produce muscle fibers with significantly fewer nuclei compared with controls. This defective fusion is associated with a decrease of Ca2+-dependent phosphatidylserine exposure on the surface of Ano5−/− MPCs and a decrease in the amplitude of Ca2+-dependent outwardly rectifying ionic currents. Viral introduction of ANO5 in Ano5−/− MPCs restores MPC fusion competence, ANO5-dependent phospholipid scrambling, and Ca2+-dependent outwardly rectifying ionic currents. ANO5-rescued MPCs produce myotubes having numbers of nuclei similar to wild-type controls. These data suggest that ANO5-mediated phospholipid scrambling or ionic currents play an important role in muscle repair.
State actions on reproductive health issues in 1996

PIP: States took steps in 1996 to increase their level of control over health care, welfare reform, education, and the environment. While many of the initiatives resulted from the federal government's delegation of more power and responsibilities to the states, sometimes states independently asserted their authority over policy issues in which they had a particular interest. Reproductive health policy and the provision of services attracted state legislator and official concern. There was a particularly high level of legislative activity on the issues of abortion services and postpartum hospital stays. While the majority of the hundreds of reproductive health-related legislative initiatives launched in 1996 were neither implemented nor considered by the end of the year, they have clearly spawned a heightened awareness of fertility-related matters and their impact upon women's reproductive lives. State actions on abortion, family planning, maternal and child health, and sex education are discussed.
The healthcare IoT ecosystem: advantages of fog computing near the edge

The Internet of Things (IoT) provides numerous opportunities for the connected healthcare industry, especially in the distributed environment known as fog which resides in a middle architectural layer adjacent to the network edge and user devices. This paper provides an overview of recent research and industry advances and challenges on fog technologies focusing on connected healthcare applications. We present and review for IoT and fog: concepts and architectures; development and lifecycle frameworks; security vulnerabilities, threats, and best practices; and connected medical device regulations.
Basolateral amygdala neurons are activated during threat expectation.

The basolateral amygdala (BL) is thought to contain neurons that signal threat, in turn eliciting defensive behaviors. In contrast, the present study reports that very few principal BL cells are re...
A Nonlinear Rank Regression Method for Ensemble Kalman Filter Data Assimilation

AbstractIt is possible to describe many variants of ensemble Kalman filters without loss of generality as the impact of a single observation on a single state variable. For most ensemble algorithms...
Beyond low rank + sparse: Multi-scale low rank matrix decomposition

The recent low rank + sparse matrix decomposition [1,2] enables us to decompose a matrix into sparse and globally low rank components. In this paper, we present a natural generalization and consider the decomposition of matrices into low rank components of multiple scales. The proposed multi-scale low rank decomposition is well motivated in practice, since natural data often exhibit multi-scale structure instead of globally or sparsely. Concretely, we propose a multi-scale low rank modeling to represent a data matrix as a sum of block-wise low rank matrices with increasing scales of block sizes. We then consider the inverse problem of decomposing the data matrix into its multi-scale low rank components, and approach the problem via a convex formulation. Theoretically, we show that under a deterministic incoherence condition, the convex program recovers the multi-scale low rank components exactly. Empirically, we show that the multi-scale low rank decomposition provides a more intuitive decomposition than existing low rank methods, and demonstrate its effectiveness in four applications, including illumination normalization for face images, motion separation for surveillance videos, multi-scale modeling of the dynamic contrast enhanced magnetic resonance imaging and collaborative filtering with age information.
Social isolation proxy variables and prescription opioid and benzodiazepine misuse among older adults in the U.S.: A cross-sectional analysis of data from the National Survey on Drug Use and Health, 2015-2017.

Abstract Background Prescription drug misuse in older adults is a growing public health problem. It is important to understand factors which predispose older adults to misuse prescription drugs, and social isolation may play an important role. In this study, we examined the association between social isolation proxy variables (living alone, being unmarried, and not attending religious services) and prescription opioid/benzodiazepine misuse in older adults. Methods With pooled cross-sectional data from the National Survey on Drug Use and Health (2015–2017), we used multinomial multiple logistic regression models to analyze the association between each social isolation proxy variable and past-year prescription opioid/benzodiazepine misuse. We controlled for potentially confounding variables including sociodemographic, physical/mental health, and substance use variables. Results Being unmarried was associated with approximately three times increased odds of combined opioid and benzodiazepine misuse (OR 2.98, 95% CI 1.75, 5.08), a finding that persisted after adjusting for multiple potential confounders. Further analysis showed this finding persisted for divorced/separated and never married individuals, but not widowed. Not attending religious services was also associated with prescription opioid/benzodiazepine misuse, but only in unadjusted analyses. There was no association between living alone and opioid/benzodiazepine misuse. Conclusion Increased odds of combined opioid and benzodiazepine prescription drug misuse was observed among unmarried older adults. Given the susceptibility of older adults to the harms of these medications, further exploration of the role of marital relationships and other forms of social connectedness in prescription drug misuse in this vulnerable population is indicated.
A Knowledge Packet for Teaching Badminton to Upper Elementary Students

Badminton is a popular sport played across the lifespan. This article introduces a knowledge packet for the teaching of badminton to upper elementary students. The knowledge packet consists of a co...
CATCHA: When Cats Track Your Movements Online.

Any website can record its users’ mouse interactions within that site, an emerging practice used to learn about users’ regions of interests usually for personalization purposes. However, the dark side of such recording is that it is oblivious to the users as no permissions are solicited from the users prior to recording (unlike other resources like webcam or microphone). Since mouse dynamics may be correlated with users’ behavioral patterns, any website with nefarious intentions (“cat”) could thus try to surreptitiously infer such patterns, thereby compromising users’ privacy and making them prone to targeted attacks. In this paper, we show how users’ personal information, specifically their demographic characteristics, could leak in the face of such mouse movement eavesdropping. As a concrete case study along this line, we present CATCHA, a mouse analytic attack system that gleans potentially sensitive demographic attributes—age group, gender, and educational background—based on mouse interactions with a game CAPTCHA system (a simple drag-and-drop animated object game to tell humans and machines apart).
Debottlenecking mevalonate pathway for antimalarial drug precursor amorphadiene biosynthesis in Yarrowia lipolytica.

Abstract World Health Organization reports that half of the population in developing countries are at risk of malaria infection. Artemisinin, the most potent anti-malaria drug, is a sesquiterpene endoperoxide extracted from the plant Artemisia annua. Due to scalability and economics issues, plant extraction or chemical synthesis could not provide a sustainable route for large-scale manufacturing of artemisinin. The price of artemisinin has been fluctuating from 200$/Kg to 1100$/Kg, due to geopolitical and climate factors. Microbial fermentation was considered as a promising method to stabilize the artemisinin supply chain. Yarrowia lipolytica, is an oleaginous yeast with proven capacity to produce large quantity of lipids and oleochemicals. In this report, the lipogenic acetyl-CoA pathways and the endogenous mevalonate pathway of Y. lipolytica were harnessed for amorphadiene production. Gene overexpression indicate that HMG-CoA and acetyl-CoA supply are two limiting bottlenecks for amorphadiene production. We have identified the optimal HMG-CoA reductase and determined the optimal gene copy number for the precursor pathways. Amorphadiene production was improved further by either inhibiting fatty acids synthase or activating the fatty acid degradation pathway. With co-expression of mevalonate kinase (encoded by Erg12), a push-and-pull strategy enabled the engineered strain to produce 171.5 ​mg/L of amorphadiene in shake flasks. These results demonstrate that balancing carbon flux and manipulation of precursor competing pathways are key factors to improve amorphadiene biosynthesis in oleaginous yeast; and Y. lipolytica is a promising microbial host to expand nature’s biosynthetic capacity, allowing us to quickly access antimalarial drug precursors.
Tobacco Use in High-Risk Populations.

Invited commentary: As cigarette smoking in the Unites States has declined overall, it has also become more concentrated into high-risk populations, namely among those who are less educated, have fewer resources, and have comorbid psychiatric disorders (both substance-related and non–substance-related). A stark reminder of this health disparity is the extraordinarily high rate of current cigarette smoking found in the sample of rural individuals who inject drugs included in the study by Akhtar and colleagues. While opioid misuse is a critical problem that the country has been mobilized to address, populations that experience opioid use disorder (and other severe addictive disorders) also experience multiple other comorbidities. Addiction to tobacco is one of these important comorbidities, and Akhtar and colleagues document current tobacco smoking among more than 90% of their sample of 986 rural individuals who inject drugs. Akhtar et al also documented very high rates of recent experiences of homelessness (62.5%) and low overall rates of contact with health care (ie, 42.0% of the study population had received any primary care within the previous 6 months), providing clear evidence for the extreme nature of adversity that these individuals experience and the overall lack of engagement with health care systems.
Acoustic topological pumping in space-modulated materials (Conference Presentation)

In this work, we theoretically design and numerically realize topological pumpings in 2D and 3D spatially modulated acoustic metamaterials. By adiabatically changing the pumping parameters along the synthetic dimension, we observe topologically protected states, which are shown to be pumped from one edge to the other in 2D materials, and from edge to edge and corner to corner in 3D materials. This spatially modulated metamaterials could pave the way for acoustic topological wave trapping and manipulation and serve as a platform for the study of higher-dimensional topological effects among different physical systems.
Drug delivery in catheterized arterial blood flow with atherosclerosis

Abstract We study the problem of drug delivery in a catheterized artery in the presence of atherosclerosis. The problem is modeled in the context of a two-phase flow system which consists of red blood cells and blood plasma. The coupled differential equations for fluid (plasma) and particles (red cells) are solved for the relevant quantities in the reasonable limits. The drug delivery problem is modeled with a partial differential equation that is developed in terms of the drug concentration, blood plasma velocity, hematocrit value and the diffusion coefficient of the drug/fluid. A conservative-implicit finite difference scheme is develop in order to numerically solve the drug concentration model with an atherosclerosis region. We find that the evolution of the drug concentration varies in magnitude depending on the roles played by the convection and diffusion effects. For the cases where the diffusion coefficient is not too small, then convection effect is not strong enough and drug was delivered mostly in the central part of the blood flow region and could not reach effectively the atherosclerosis zone. However, for sufficiently small values of the diffusion coefficient, the convective effect dominates over the diffusion effect and the drug was delivered effectively over the blood flow region and on the atherosclerosis zone.
Practical approaches for diagnosis and management of prurigo nodularis: United States expert panel consensus.

Background Prurigo nodularis (PN) is a chronic disease characterized by intensely pruritic, raised, nodular lesions. Because there are currently no United States Food and Drug Administration-approved therapies specifically for PN, management is highly variable, and no consensus exists on treatment regimens. Objective To provide practical guidance to help United States dermatologists diagnose and effectively treat patients with PN. Methods We participated in a roundtable discussion to develop consensus recommendations on diagnosis and treatment of PN from a United States perspective. Results The core findings in PN are the presence of firm, nodular lesions; pruritus lasting at least 6 weeks; and a history or signs, or both, of repeated scratching, picking, or rubbing. The diagnostic workup involves a complete review of systems, considering potential systemic diseases, and assessment of disease severity, including disease burden and pruritus intensity. Treatment should be selected based on a patient's clinical presentation, comorbidities, and response to prior treatments and should address both neural and immunologic components of pruritus. Limitations Data on PN are from anecdotal or small clinical trials, and all treatments are currently used off-label. Conclusion An effective treatment approach for patients with PN should be based on clinical judgment and tailored to the individual needs of the patient.
Assessment of Sucralose, Caffeine and Acetaminophen as Anthropogenic Tracers in Aquatic Systems Across Florida

Sucralose is one of the most popular artificial sweeteners worldwide. Due to its high stability, persistence and low removal efficiency in wastewater treatment plants, sucralose has been used as an indicator of wastewater intrusion into aquatic systems. However, its stability has also been a reason for discussion whether sucralose’s presence in surface water could indicate a recent anthropogenic input. Caffeine and acetaminophen have been considered as tracers in human impacted aquatic ecosystems and potentially good indicators of recent anthropogenic inputs into the environment due to their short half-lives in water. Here, a novel, high throughput and sensitive method based on online SPE-LC-HRMS for the determination of caffeine, sucralose and acetaminophen was developed and validated for both fresh and seawater samples and applied to environmental water samples to evaluate the efficiency of these compounds as tracers of aquatic pollution. Caffeine and sucralose were detected in > 70% of samples, while acetaminophen was only detected in 3% of samples above the MDL, demonstrating its limited environmental applicability.
Effects of pimobendan on left atrial transport function in cats.

Background Arterial thromboembolism is a sequela of hypertrophic cardiomyopathy (HCM) in cats related to left atrial (LA) enlargement and dysfunction. Hypothesis Pimobendan improves LA transport function in cats. Animals Twenty-two client-owned cats with HCM and 11 healthy cats. Methods Prospective, double-blind, randomized, placebo-controlled clinical cohort study. Cats were randomized to receive either pimobendan (0.25 mg/kg PO q12h) or placebo for 4 to 7 days. Nineteen echocardiographic variables of LA size and function were evaluated. Statistical comparisons included t tests, analysis of variance, and multivariable analyses. Results Peak velocity of left auricular appendage flow (LAapp peak; mean ± SD, 0.85 ± 0.20 vs 0.71 ± 0.22 m/s; P = .01), maximum LA volume (P = .03), LA total emptying volume (P = .03), peak velocity of late diastolic transmitral flow (A peak velocity; 0.77 ± 0.12 vs 0.62 ± 0.17 m/s; P = .05), and A velocity time integral (A VTI; 3.05 ± 0.69 vs 3.37 ± 0.49; P = .05) were increased after pimobendan. Mean change after pimobendan was larger in cats with HCM compared to healthy cats for LA fractional shortening (2.1% vs -2.1%; P = .05), A VTI (0.58 vs 0.01 cm; P = .01), LAapp peak (0.20 vs 0.02 m/s; P = .02), LA kinetic energy (3.51 vs -0.10 kdynes-cm; P = .05), and LA ejection force (1.93 vs -0.07 kdynes; P = .01) in the multivariable model. The stronger effect of pimobendan in cats with HCM was independent of LA size. Conclusions and clinical importance We identified positive, albeit minor, effects of pimobendan on LA function in cats with HCM. Whether or not treatment with pimobendan decreases the risk of cardiogenic embolism deserves further study.
Financial Relationship Between the Industry and Clinical Neurophysiology: Analysis of Open Payments Data from 2013 to 2018 (915)

Objective: To analyze the financial relationships between the healthcare industry and physicians in the clinical neurophysiology specialty. Background: There is substantial concern about the potential impact of the physician’s financial relationship with the industry on clinical practice. Transparent reporting of payments to physicians and teaching hospitals from drug and device manufacturers is mandated by the Centers for Medicare and Medicaid Services (CMS) Open Payments Data (OPD) program. Design/Methods: A retrospective descriptive analysis was performed to characterize the nature, trend, contribution, and distribution of payments using the publicly available CMS OPD database from 2013 to 2018. Results: In the Clinical Neurophysiology specialty, 49,482 payments totaled $7.7 million from 2013 to 2018, of which 99.4% of records and 93.4% of values were for general/non-research-related payments. The annual total amount increased from $570,000 in 2013, peaked at $1.65 million in 2015, and dropped to $1.15 million in 2018. Among 3,035 board-certified clinical neurophysiologists, 1,483 (48.9%) received at least one payment from the industry, with the median amount of $142.85 (IQR: $41.83 to $607.50). With respect to the value of payments, the top 10 sponsors contributed to 71.2% of the total amount (ranging from $302,000 to $767,000), and the top 10 anti-epilepsy medications contributed to 36.0% (ranging from $30,000 to $739,000). The top 10 physicians received 56.8% of the total amount of payments (ranging from $129,000 to $1,268,000), of which 85.9% of the values were not related to anti-epilepsy medications. Conclusions: Payments from industry to the clinical neurophysiology, largely driven by non-research related payments, has increased from 2013 to 2015 and declined since then. There was a disparity of payments with respect to the contribution by sponsors as well as distribution to physicians, and the majority of payments were unrelated to anti-epilepsy products. Disclosure: Dr. Marszalek has nothing to disclose. Dr. Chi has received research support from CSL Behring, Portola Pharmaceuticals, Bayer, and Janssen Scientific Affairs. Dr. Shojaei has nothing to disclose. Dr. Yadala has nothing to disclose. Dr. Veerapaneni has nothing to disclose. Dr. Nalleballe has nothing to disclose.
Association of intraoperative hypothermia with oncologic outcomes following radical cystectomy.

Abstract Introduction Intraoperative hypothermia (IOH) has been suggested to adversely impact outcomes following surgery. The objective of this study was to evaluate the association between IOH and survival following radical cystectomy (RC). Methods Patients who underwent RC for bladder cancer from 2003 to 2018 were identified in our cystectomy registry. Intraoperative temperatures were extracted from the anesthesia record. IOH was defined as a median intraoperative temperature Results A total of 852 patients were identified, among whom 274 (32%) had IOH. Median follow up among survivors was 4.9 years (IQR 2.4–8.7), during which time 483 patients died, including 343 from bladder cancer. Two-year survival was not significantly different between patients with and without IOH (CSS: 74% vs. 71%, P= 0.31; OS: 68% vs. 67%, P= 0.13). Following multivariable adjustment, neither IOH nor time under 36°C was significantly associated with survival. A total of 37 patients (4.3%) had severe IOH. These patients were observed to have significantly lower 2-year OS (56% vs. 68%, P= 0.005); however, this association did not remain statistically significant after multivariable adjustment (P= 0.92). Conclusion IOH was not independently associated with survival following RC. These data do not support IOH as a prognostic factor for cancer outcomes among patients undergoing RC.
Revolutionizing Simulation Education With Smart Glass Technology

Abstract Background “Smart” technology offers hands-free communication, assessment, and documentation that includes dictation, pictures, and video. Smart wearables offer nursing students and faculty real-world applicability to prepare them for future demands in clinical practice and nursing education. Method A quantitative study of junior baccalaureate nursing students participated in a pre- and post-survey using QualtricsXM to investigate the perceptions of smart glasses technology as an effective learning tool in simulation. Surveys also measured students’ perceived usage of smart glasses to access patient and family assessment data. Results Nursing students found the utilization of smart glass wearable technology benefited their learning in the simulation laboratory. Students found by reviewing their own first-person videos helpful to self-reflect on their competency and needs for improvement in clinical practice. Conclusions Incorporating smart glasses in simulation may enrich learning and performance of nursing students.
Depression and Means Restriction

Depression affects between 3% and 4% of children and adolescents worldwide. However, it is often unrecognized or undiagnosed and frequently untreated. One of the most adverse outcomes of depression is suicide. Within the United States (US), suicide is the second leading cause of death in adolescents and young adults between the ages of 10 and 34 years. Firearms are involved in about a third of these cases, related to the intertwined issues of depression and the impulsivity of adolescence as well as access to firearms in one-third of US households. At the state level, for each 10% rise in household gun ownership, the risk of youth suicide rises by 27%. Unfortunately, this relationship between gun ownership and youth suicide is underappreciated. Adolescents with depression, suicide attempts, or a history of mental health issues have almost the same access to firearms as those without these mental health concerns. Primary care clinicians are often the first point of contact for depressed children and their families. It is therefore important that depression screening, risk assessment, and advice related to means restriction (including removing access to firearms) become standard practice in these clinical settings. This necessitates that the clinician not only assesses for the safety risk but also intervenes to ensure appropriate safety planning takes place and referrals for mental health treatment occur.