Principles for data analysis workflows

Traditional data science education often omits training on research workflows: the process that moves a scientific investigation from raw data to coherent research question to insightful contribution. In this paper, we elaborate basic principles of a reproducible data analysis workflow by defining three phases: the Exploratory, Refinement, and Polishing Phases. Each workflow phase is roughly centered around the audience to whom research decisions, methodologies, and results are being immediately communicated. Importantly, each phase can also give rise to a number of research products beyond traditional academic publications. Where relevant, we draw analogies between principles for data-intensive research workflows and established practice in software development. The guidance provided here is not intended to be a strict rulebook; rather, the suggestions for practices and tools to advance reproducible, sound data-intensive analysis may furnish support for both students and current professionals

Listen to the Voices: A Reflection on How 2020 and COVID-19 Have Affected Lives

Throughout the last few months of 2019, stories of a new and deadly virus were on every news channel around the world. Many Americans saw it as foreign news, others worried about the virus’ spread, and some felt that it would be contained quickly never making it past the Atlantic or Pacific. By March of 2020, COVID-19 made its way to the United States, forcing a new normal of quarantining, remote-learning/teaching, and teleworking. Graduate students and educators of Professional Opportunities Supporting Scholarly Engagement (POSSE), a College of Education program focused on research and contributing to the educational field of discourse, came together with a notion and a desire to provide support during this challenging time. Using a Google form questionnaire, POSSE reached out to as many people throughout the United States and the world to share their experiences with the changes, good and bad, over the past year

A rapid bioluminescence assay for measuring ​myeloperoxidase activity in human plasma

Myeloperoxidase (MPO) is a circulating cardiovascular disease (CVD) biomarker used to estimate clinical risk and patient prognosis. Current enzyme-linked immunosorbent assays (ELISA) for MPO concentration are costly and time-intensive. Here we report a novel bioluminescence assay, designated MPO activity on a polymer surface (MAPS), for measuring MPO activity in human plasma samples using the bioluminescent substrate L-012. The method delivers a result in under an hour and is resistant to confounding effects from endogenous MPO inhibitors. In a pilot clinical study, we compared MAPS and two clinical ELISAs using 72 plasma samples from cardiac catheterization patients. Results from parallel MAPS and ELISAs were concordant within 2±11 μg l(−1) MPO with similar uncertainty and reproducibility. Results between parallel MAPS and ELISA were in better agreement than those between independent ELISAs. MAPS may provide an inexpensive and rapid assay for determining MPO activity in plasma samples from patients with CVD or potentially other immune and inflammatory disorders

Slope of the anterior mitral valve leaflet: A new measurement of left ventricular unloading for left ventricular assist devices and systolic dysfunction

Left ventricular assist device (LVAD)-supported patients are evaluated routinely with use of transthoracic echocardiography. Values of left ventricular unloading in this unique patient population are needed to evaluate LVAD function and assist in patient follow-up. We introduce a new M-mode measurement, the slope of the anterior mitral valve leaflet (SLAM), and compare its efficacy with that of other standard echocardiographically evaluated values for left ventricular loading, including E/e′ and pulmonary artery systolic pressures. Average SLAM values were determined retrospectively for cohorts of random, non-LVAD patients with moderately to severely impaired left ventricular ejection fraction (LVEF) (<0.35, n=60). In addition, pre- and post-LVAD implantation echocardiographic images of 81 patients were reviewed. The average SLAM in patients with an LVEF <0.35 was 11.6 cm/s (95% confidence interval, 10.4–12.8); SLAM had a moderately strong correlation with E/e′ in these patients. Implantation of LVADs significantly increased the SLAM from 7.3 ± 2.44 to 14.7 ± 5.01 cm/s (n=42, P <0.0001). The LVAD-supported patients readmitted for exacerbation of congestive heart failure exhibited decreased SLAM from 12 ± 3.93 to 7.3 ± 3.5 cm/s (n=6, P=0.041). In addition, a cutpoint of 10 cm/s distinguished random patients with LVEF <0.35 from those in end-stage congestive heart failure (pre-LVAD) with an 88% sensitivity and a 55% specificity. Evaluating ventricular unloading in LVAD patients remains challenging. Our novel M-mode value correlates with echocardiographic values of left ventricular filling in patients with moderate-to-severe systolic function and dynamically improves with the ventricular unloading of an LVAD

Switching from a protease inhibitor-based regimen to a dolutegravir-based regimen : a randomized clinical trial to determine the effect on peripheral blood and ileum biopsies from antiretroviral therapy-suppressed human immunodeficiency virus-infected individuals

Background: Optimization of combination antiretroviral therapy (cART) can impact the human immunodeficiency virus (HIV) reservoir. We evaluated the effect on the HIV reservoir in peripheral blood and ileum biopsies in patients switching from boosted protease inhibitor (PI/r)-based therapy to dolutegravir (DTG)-based therapy. Methods: Impact of Integrase-inhibitor DOlutegravir On the viral Reservoir (INDOOR) is a phase 4 open-label clinical trial that randomly included 42 HIV type 1-infected individuals on effective cART: 20 who switched from PI/r-based to DTG-based cART (switch group), and 22 who remained in PI/r-based regimens (control group). We analyzed blood and ileum biopsies to quantify episomal, total, and integrated HIV DNA, cell-associated HIV RNA, residual plasma viremia, T-cell subsets, cell activation, and inflammation markers. Results: There were no related adverse events or treatment discontinuations due to drug intolerance. The HIV reservoir was consistently larger in ileal than in peripheral CD4(+) T cells in both groups (P <.01). Residual viremia in plasma decreased in the switch group (P =.03). However, we did not observe significant longitudinal changes in low-level viral replication, total and integrated HIV reservoir, HIV transcription, T-cell maturation subsets, immunoactivation markers, inflammatory soluble proteins, or cellular markers of latently infected cells. Conclusions: The INDOOR study is the first evaluation of changes in HIV reservoir size in ileum biopsies and in peripheral blood in individuals switched from PI/r- to DTG-based cART. Although this switch was safe and well tolerated, it had no impact on a large array of immunological and inflammatory markers or on HIV reservoir markers in peripheral or in ileal CD4(+) T cells

Estimating the Relative Stiffness between a Hepatic Lesion and the Liver Parenchyma through Biomechanical Simulations of the Breathing Process

[EN] In this paper, a method to in vivo estimate the relative stifness between a hepatic lesion and the liver parenchyma is presented. Tis method is based on the fnite element simulation of the deformation that the liver undergoes during the breathing process. Boundary conditions are obtained through a registration algorithm known as Coherent Point Drif (CPD), which compares the liver form in two phases of the breathing process. Finally, the relative stifness of the tumour with respect to the liver parenchyma is calculated by means of a Genetic Algorithm, which does a blind search of this parameter. Te relative stifness together with the clinical information of the patient can be used to establish the type of hepatic lesion. Te developed methodology was frst applied to a test case, i.e., to a control case where the parameters were known, in order to verify its validity. Afer that, the method was applied to two real cases and low errors were obtained.This work has been funded by the Spanish Ministry of Economy and Competitiveness (MINECO) through research projects DPI2013-40859-R and TIN2014-52033-R, both also supported by European FEDER funds.Martinez-Sanchis, S.; Rupérez Moreno, MJ.; Nadal, E.; Pareja, E.; Brugger, S.; Borzacchiello, D.; López, R.... (2018). Estimating the Relative Stiffness between a Hepatic Lesion and the Liver Parenchyma through Biomechanical Simulations of the Breathing Process. Mathematical Problems in Engineering. 1-10. https://doi.org/10.1155/2018/5317324S110Kmieć, Z. (2001). Introduction — Morphology of the Liver Lobule. Advances in Anatomy Embryology and Cell Biology, 1-6. doi:10.1007/978-3-642-56553-3_1Cequera, A., & García de León Méndez, M. C. (2014). Biomarkers for liver fibrosis: Advances, advantages and disadvantages. Revista de Gastroenterología de México (English Edition), 79(3), 187-199. doi:10.1016/j.rgmxen.2014.07.001Vilar-Gomez, E., & Chalasani, N. (2018). Non-invasive assessment of non-alcoholic fatty liver disease: Clinical prediction rules and blood-based biomarkers. Journal of Hepatology, 68(2), 305-315. doi:10.1016/j.jhep.2017.11.013Giannini, E. G. (2005). Liver enzyme alteration: a guide for clinicians. Canadian Medical Association Journal, 172(3), 367-379. doi:10.1503/cmaj.1040752Oliva, M. R. (2004). Liver cancer imaging: role of CT, MRI, US and PET. Cancer Imaging, 4(Special Issue A), S42-S46. doi:10.1102/1470-7330.2004.0011Mouw, J. K., Yui, Y., Damiano, L., Bainer, R. O., Lakins, J. N., Acerbi, I., … Weaver, V. M. (2014). Tissue mechanics modulate microRNA-dependent PTEN expression to regulate malignant progression. Nature Medicine, 20(4), 360-367. doi:10.1038/nm.3497Paszek, M. J., Zahir, N., Johnson, K. R., Lakins, J. N., Rozenberg, G. I., Gefen, A., … Weaver, V. M. (2005). Tensional homeostasis and the malignant phenotype. Cancer Cell, 8(3), 241-254. doi:10.1016/j.ccr.2005.08.010Kuo, Y.-H., Lu, S.-N., Hung, C.-H., Kee, K.-M., Chen, C.-H., Hu, T.-H., … Wang, J.-H. (2010). Liver stiffness measurement in the risk assessment of hepatocellular carcinoma for patients with chronic hepatitis. Hepatology International, 4(4), 700-706. doi:10.1007/s12072-010-9223-1Heide, R., Strobel, D., Bernatik, T., & Goertz, R. (2010). Characterization of Focal Liver Lesions (FLL) with Acoustic Radiation Force Impulse (ARFI) Elastometry. Ultraschall in der Medizin - European Journal of Ultrasound, 31(04), 405-409. doi:10.1055/s-0029-1245565Frulio, N., Laumonier, H., Carteret, T., Laurent, C., Maire, F., Balabaud, C., … Trillaud, H. (2013). Evaluation of Liver Tumors Using Acoustic Radiation Force Impulse Elastography and Correlation With Histologic Data. Journal of Ultrasound in Medicine, 32(1), 121-130. doi:10.7863/jum.2013.32.1.121Ma, X., Zhan, W., Zhang, B., Wei, B., Wu, X., Zhou, M., … Li, P. (2014). Elastography for the differentiation of benign and malignant liver lesions: a meta-analysis. Tumor Biology, 35(5), 4489-4497. doi:10.1007/s13277-013-1591-4Guo, L.-H., Wang, S.-J., Xu, H.-X., Sun, L.-P., Zhang, Y.-F., Xu, J.-M., … Xu, X.-H. (2015). Differentiation of benign and malignant focal liver lesions: value of virtual touch tissue quantification of acoustic radiation force impulse elastography. Medical Oncology, 32(3). doi:10.1007/s12032-015-0543-9Dietrich, C., Bamber, J., Berzigotti, A., Bota, S., Cantisani, V., Castera, L., … Thiele, M. (2017). EFSUMB Guidelines and Recommendations on the Clinical Use of Liver Ultrasound Elastography, Update 2017 (Long Version). Ultraschall in der Medizin - European Journal of Ultrasound, 38(04), e16-e47. doi:10.1055/s-0043-103952Ferraioli, G., Filice, C., Castera, L., Choi, B. I., Sporea, I., Wilson, S. R., … Kudo, M. (2015). WFUMB Guidelines and Recommendations for Clinical Use of Ultrasound Elastography: Part 3: Liver. Ultrasound in Medicine & Biology, 41(5), 1161-1179. doi:10.1016/j.ultrasmedbio.2015.03.007Sigrist, R. M. S., Liau, J., Kaffas, A. E., Chammas, M. C., & Willmann, J. K. (2017). Ultrasound Elastography: Review of Techniques and Clinical Applications. Theranostics, 7(5), 1303-1329. doi:10.7150/thno.18650Cosgrove, D., Piscaglia, F., Bamber, J., Bojunga, J., Correas, J.-M., Gilja, O., … Dietrich, C. (2013). EFSUMB Guidelines and Recommendations on the Clinical Use of Ultrasound Elastography.Part 2: Clinical Applications. Ultraschall in der Medizin - European Journal of Ultrasound, 34(03), 238-253. doi:10.1055/s-0033-1335375Palmeri, M. L., & Nightingale, K. R. (2011). What challenges must be overcome before ultrasound elasticity imaging is ready for the clinic? Imaging in Medicine, 3(4), 433-444. doi:10.2217/iim.11.41Samir, A. E., Dhyani, M., Vij, A., Bhan, A. K., Halpern, E. F., Méndez-Navarro, J., … Chung, R. T. (2015). Shear-Wave Elastography for the Estimation of Liver Fibrosis in Chronic Liver Disease: Determining Accuracy and Ideal Site for Measurement. Radiology, 274(3), 888-896. doi:10.1148/radiol.14140839Toshima, T., Shirabe, K., Takeishi, K., Motomura, T., Mano, Y., Uchiyama, H., … Maehara, Y. (2011). New method for assessing liver fibrosis based on acoustic radiation force impulse: a special reference to the difference between right and left liver. Journal of Gastroenterology, 46(5), 705-711. doi:10.1007/s00535-010-0365-7Barr, R. G., Ferraioli, G., Palmeri, M. L., Goodman, Z. D., Garcia-Tsao, G., Rubin, J., … Levine, D. (2015). Elastography Assessment of Liver Fibrosis: Society of Radiologists in Ultrasound Consensus Conference Statement. Radiology, 276(3), 845-861. doi:10.1148/radiol.2015150619Venkatesh, S. K., Yin, M., & Ehman, R. L. (2013). Magnetic resonance elastography of liver: Technique, analysis, and clinical applications. Journal of Magnetic Resonance Imaging, 37(3), 544-555. doi:10.1002/jmri.23731Low, G. (2016). General review of magnetic resonance elastography. World Journal of Radiology, 8(1), 59. doi:10.4329/wjr.v8.i1.59Thompson, S. M., Wang, J., Chandan, V. S., Glaser, K. J., Roberts, L. R., Ehman, R. L., & Venkatesh, S. K. (2017). MR elastography of hepatocellular carcinoma: Correlation of tumor stiffness with histopathology features—Preliminary findings. Magnetic Resonance Imaging, 37, 41-45. doi:10.1016/j.mri.2016.11.005Myronenko, A., & Xubo Song. (2010). Point Set Registration: Coherent Point Drift. IEEE Transactions on Pattern Analysis and Machine Intelligence, 32(12), 2262-2275. doi:10.1109/tpami.2010.46Martínez-Martínez, F., Lago, M. A., Rupérez, M. J., & Monserrat, C. (2013). Analysis of several biomechanical models for the simulation of lamb liver behaviour using similarity coefficients from medical image. Computer Methods in Biomechanics and Biomedical Engineering, 16(7), 747-757. doi:10.1080/10255842.2011.637492Untaroiu, C. D., & Lu, Y.-C. (2013). Material characterization of liver parenchyma using specimen-specific finite element models. Journal of the Mechanical Behavior of Biomedical Materials, 26, 11-22. doi:10.1016/j.jmbbm.2013.05.013Large deformation isotropic elasticity – on the correlation of theory and experiment for incompressible rubberlike solids. (1972). Proceedings of the Royal Society of London. A. Mathematical and Physical Sciences, 326(1567), 565-584. doi:10.1098/rspa.1972.0026Chui, C., Kobayashi, E., Chen, X., Hisada, T., & Sakuma, I. (2006). Transversely isotropic properties of porcine liver tissue: experiments and constitutive modelling. Medical & Biological Engineering & Computing, 45(1), 99-106. doi:10.1007/s11517-006-0137-yHostettler, A., George, D., Rémond, Y., Nicolau, S. A., Soler, L., & Marescaux, J. (2010). Bulk modulus and volume variation measurement of the liver and the kidneys in vivo using abdominal kinetics during free breathing. Computer Methods and Programs in Biomedicine, 100(2), 149-157. doi:10.1016/j.cmpb.2010.03.003Chatterjee, S., Laudato, M., & Lynch, L. A. (1996). Genetic algorithms and their statistical applications: an introduction. Computational Statistics & Data Analysis, 22(6), 633-651. doi:10.1016/0167-9473(96)00011-4Martínez-Martínez, F., Rupérez, M. J., Martín-Guerrero, J. D., Monserrat, C., Lago, M. A., Pareja, E., … López-Andújar, R. (2013). Estimation of the elastic parameters of human liver biomechanical models by means of medical images and evolutionary computation. Computer Methods and Programs in Biomedicine, 111(3), 537-549. doi:10.1016/j.cmpb.2013.05.005Lago, M. A., Rupérez, M. J., Martínez-Martínez, F., Monserrat, C., Larra, E., Güell, J. L., & Peris-Martínez, C. (2015). A new methodology for the in vivo estimation of the elastic constants that characterize the patient-specific biomechanical behavior of the human cornea. Journal of Biomechanics, 48(1), 38-43. doi:10.1016/j.jbiomech.2014.11.009Lago, M. A., Rupérez, M. J., Martínez-Martínez, F., Martínez-Sanchis, S., Bakic, P. R., & Monserrat, C. (2015). Methodology based on genetic heuristics for in-vivo characterizing the patient-specific biomechanical behavior of the breast tissues. Expert Systems with Applications, 42(21), 7942-7950. doi:10.1016/j.eswa.2015.05.058Hoyt, K., Castaneda, B., Zhang, M., Nigwekar, P., di Sant’Agnese, P. A., Joseph, J. V., … Parker, K. J. (2008). Tissue elasticity properties as biomarkers for prostate cancer. Cancer Biomarkers, 4(4-5), 213-225. doi:10.3233/cbm-2008-44-505Xu, W., Mezencev, R., Kim, B., Wang, L., McDonald, J., & Sulchek, T. (2012). Cell Stiffness Is a Biomarker of the Metastatic Potential of Ovarian Cancer Cells. PLoS ONE, 7(10), e46609. doi:10.1371/journal.pone.0046609Martinez-Sanchis, S., Rupérez, M. J., Nadal, E., Borzacchiello, D., Monserrat, C., Pareja, E., … López-Andújar, R. (2017). Estimating the Patient-Specific Relative Stiffness Between a Hepatic Lesion and the Liver Parenchyma. Lecture Notes in Computational Vision and Biomechanics, 485-494. doi:10.1007/978-3-319-68195-5_5

Matrix metalloproteinase-10 is upregulated by thrombin in endothelial cells and increased in patients with enhanced thrombin generation

OBJECTIVE: Thrombin is a multifunctional serine protease that promotes vascular proinflammatory responses whose effect on endothelial MMP-10 expression has not previously been evaluated. METHODS AND RESULTS: Thrombin induced endothelial MMP-10 mRNA and protein levels, through a protease-activated receptor-1 (PAR-1)-dependent mechanism, in a dose- and time-dependent manner. This effect was mimicked by a PAR-1 agonist peptide (TRAP-1) and antagonized by an anti-PAR-1 blocking antibody. MMP-10 induction was dependent on extracellular regulated kinase1/2 (ERK1/2) and c-jun N-terminal kinase (JNK) pathways. By serial deletion analysis, site-directed mutagenesis and electrophoretic mobility shift assay an AP-1 site in the proximal region of MMP-10 promoter was found to be critical for thrombin-induced MMP-10 transcriptional activity. Thrombin and TRAP-1 upregulated MMP-10 in murine endothelial cells in culture and in vivo in mouse aorta. This effect of thrombin was not observed in PAR-1-deficient mice. Interestingly, circulating MMP-10 levels (P<0.01) were augmented in patients with endothelial activation associated with high (disseminated intravascular coagulation) and moderate (previous acute myocardial infarction) systemic thrombin generation. CONCLUSIONS: Thrombin induces MMP-10 through a PAR-1-dependent mechanism mediated by ERK1/2, JNK, and AP-1 activation. Endothelial MMP-10 upregulation could be regarded as a new proinflammatory effect of thrombin whose pathological consequences in thrombin-related disorders and plaque stability deserve further investigation

Calcified Lesion Assessment and Intervention in Complex Percutaneous Coronary Intervention: Overview of Angioplasty, Atherectomy, and Lithotripsy

Calcific coronary artery disease intervention is associated with uniformly worse short-term procedural and long-term clinical results compared with treatment of non-calcified lesions. Multiple intravascular imaging tools currently exist to aid the identification and detailed characterization of intracoronary calcium, and guide appropriate follow-on management strategies. Several unique device therapies, to include angioplasty, atherectomy, and lithotripsy may be employed to enhance lesion preparation, stent implantation and optimization, and improve patient outcomes. Current low use of both imaging and ablative technologies in the US offers significant future opportunities for improving the comprehensive evaluation and management of these complex lesion subsets and patients