Biomarker comparison and selection for prostate cancer detection in Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI)

[EN] In this work, the capability of imaging biomarkers obtained from multivariate curve resolution-alternating least squares (MCR-ALS), in combination with those obtained from first and second-generation pharmacokinetic models, have been studied for improving prostate cancer tumor depiction using partial least squares- discriminant analysis (PLS-DA). The main goal of this work is to improve tissue classification properties selecting the best biomarkers in terms of prediction. A wrapped double cross-validation method has been applied for the variable selection process. Using the best PLS-DA model, prostate tissues can be classified obtaining 13.4% of false negatives and 7.4% of false positives. Using MCR-ALS biomarkers yields the best models in terms of parsimony and classification performance.This research has been supported by "Generalitat Valenciana (Conselleria d'Educacio, Investigacio, Cultura I Esport)" under the project AICO/2016/061.Aguado-Sarrió, E.; Prats-Montalbán, JM.; Sanz-Requena, R.; Garcia-Marti, G.; Marti-Bonmati, L.; Ferrer, A. (2017). Biomarker comparison and selection for prostate cancer detection in Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI). Chemometrics and Intelligent Laboratory Systems. 165:38-45. https://doi.org/10.1016/j.chemolab.2017.04.003S384516

A complex storm system in Saturn’s north polar atmosphere in 2018

Producción CientíficaSaturn’s convective storms usually fall in two categories. One consists of mid-sized storms ∼2,000 km wide, appearing as irregular bright cloud systems that evolve rapidly, on scales of a few days. The other includes the Great White Spots, planetary-scale giant storms ten times larger than the mid-sized ones, which disturb a full latitude band, enduring several months, and have been observed only seven times since 1876. Here we report a new intermediate type, observed in 2018 in the north polar region. Four large storms with east–west lengths ∼4,000–8,000 km (the first one lasting longer than 200 days) formed sequentially in close latitudes, experiencing mutual encounters and leading to zonal disturbances affecting a full latitude band ∼8,000 km wide, during at least eight months. Dynamical simulations indicate that each storm required energies around ten times larger than mid-sized storms but ∼100 times smaller than those necessary for a Great White Spot. This event occurred at about the same latitude and season as the Great White Spot in 1960, in close correspondence with the cycle of approximately 60 years hypothesized for equatorial Great White Spots.Ministerio de Economía, Industria y Competitividad - Fondo Europeo de Desarrollo Regional (project AYA2015-65041-P)Gobierno Vasco (project IT-366-19

Prostate Diffusion Weighted-Magnetic Resonance Image analysis using Multivariate Curve Resolution methods

[EN] Multivariate Curve Resolution (MCR) has been applied on prostate Diffusion Weighted-Magnetic Resonance Images (DW-MRI). Different physiological-based modeling approaches of the diffusion process have been submitted to validation by sequentially incorporating prior knowledge on the MCR constraints. Results validate the biexponential diffusion modeling approach and show the capability of the MCR models to find, characterize and locate the behaviors related to the presence of an early prostate tumor.The authors want to thank prof. Anna de Juan for her comments and help in using the software for this study. This research work was partially supported by the Spanish Ministry of Economy and Competitiveness under the project DPI 2011-28112-004-02.Aguado Sarrió, E.; Prats-Montalbán, JM.; Sanz Requena, R.; Marti Bonmati, L.; Alberich Bayarri, Á.; Ferrer Riquelme, AJ. (2015). Prostate Diffusion Weighted-Magnetic Resonance Image analysis using Multivariate Curve Resolution methods. Chemometrics and Intelligent Laboratory Systems. 140:43-48. https://doi.org/10.1016/j.chemolab.2014.11.002S434814

Convective storms in closed cyclones in Jupiter's South Temperate Belt: (I) observations

On May 31, 2020 a short-lived convective storm appeared in one of the small cyclones of Jupiter's South Temperate Belt (STB) at planetographic latitude 30.8S. The outbreak was captured by amateur astronomer Clyde Foster in methane-band images, became widely known as Clyde's Spot, and was imaged at very high resolution by the Junocam instrument on board the Juno mission 2.5 days later. Junocam images showed a white two-lobed cyclonic system with high clouds observed in the methane-band at 890 nm. The storm evolved over a few days to become a dark feature that showed turbulence for months, presented oscillations in its drift rate, and slowly expanded, first into a Folded Filamentary Region (FFR), and later into a turbulent segment of the STB over a timescale of one year. On August 7, 2021, a new storm strikingly similar to Clyde's Spot erupted in a cyclone of the STB. The new storm exhibited first a similar transformation into a turbulent dark feature, and later transformed into a dark cyclone fully formed by January 2022. We compare the evolution into a FFR of Clyde's Spot with the formation of a FFR observed by Voyager 2 in 1979 in the South South Temperate Belt (SSTB) after a convective outburst in a cyclone that also developed a two-lobed shape. We also discuss the contemporaneous evolution of an additional cyclone of the STB, which was similar to the one were Clyde's Spot developed. This cyclone did not exhibit visible internal convective activity, and transformed from pale white in 2019, with low contrast with the environment, to dark red in 2020, and thus, was very similar to the outcome of the second storm. This cyclone became bright again in 2021 after interacting with Oval BA. We present observations of these phenomena obtained by amateur astronomers, ground-based telescopes, Hubble Space Telescope and Junocam. This study reveals that short-lived small storms that are active for only a few days can produce complex longterm changes that extend over much larger areas than those initially covered by the storms. In a second paper [In tilde urrigarro et al., 2022] we use the EPIC numerical model to simulate these storms and study moist convection in closed cyclones.We are very thankful to the large community of amateur observers operating small telescopes that submit their Jupiter observations to databases such as PVOL and ALPO-Japan. We are also grateful to two anonymous reviewers for their comments that improved the clarity of this paper. This work has been supported by Grant PID2019-109467GB-I00 funded by MCIN/AEI/10.13039/501100011033/and by Grupos Gobierno Vasco IT1366-19. PI acknowledges a PhD scholarship from Gobierno Vasco. GSO and TM were supported by NASA with funds distributed to the Jet Propulsion Laboratory, California Institute of Technology under contract 80NM0018D0004. C. J. Hansen was sup-ported by funds from NASA, USA to the Juno mission via the Planetary Science Institute. IOE was supported by a contract funded by Europlanet 2024 RI to navigate Junocam images, now available as maps in PVOL at http://pvol2.ehu.eus. Europlanet 2024 RI has received funding from the European Unions Horizon 2020 research and innovation programme under grant agreement No 871149. G.S. Orton, S. R. Brueshaber, T. W. Momary, K. H. Baines and E. K. Dahl were visiting Astronomers at the Infrared Telescope Facility, which is operated by the University of Hawaii under contract 80HQTR19D0030 with the National Aeronautics and Space Administration. In addition, support from NASA Juno Participating Scientist award 80NSSC19K1265 was provided to M.H. Wong. This work has used data acquired from the NASA/ESA Hubble Space Telescope (HST) , which is operated by the Association of 807 Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555. These HST observations are associated with several HST observing programs: GO/DD 14661 (PI: M.H. Wong) , GO/DD 15665 (PI: I. de Pater) , GO/DD 15159 (PI: M. H. Wong) , GO/DD 15502 (PI: A. Simon) , GO/DD 14661 (PI: M. H. Wong) , GO/DD 16074 (PI: M.H. Wong) , GO/DD 16053 (PI: I. de Pater) , GO/DD 15929 (PI: A. Simon) , GO/DD 16269 (PI: A. Simon) . PlanetCam observations were collected at the Centro Astronomico Hispanico en Andalucia (CAHA) , operated jointly by the Instituto de Astrofisica de Andalucia (CSIC) and the Andalusian Universities (Junta de Andalucia) . This work was enabled by the location of the IRTF and Gemini North telescopes within the Mauakea Science Reserve, adjacent to the summit of Maunakea. We are grateful for the privilege of observing Kaawela (Jupiter) from a place that is unique in both its astronomical quality and its cultural signifi-cance. This research has made use of the USGS Integrated Software for Imagers and Spectrometers (ISIS) . Voyager 2 images were accessed through The PDS Ring-Moon Systems Nodes OPUS search service

Multi-parametric MR Imaging Biomarkers Associated to Clinical Outcomes in Gliomas: A Systematic Review

[EN] Purpose: To systematically review evidence regarding the association of multi-parametric biomarkers with clinical outcomes and their capacity to explain relevant subcompartments of gliomas. Materials and Methods: Scopus database was searched for original journal papers from January 1st, 2007 to February 20th , 2017 according to PRISMA. Four hundred forty-nine abstracts of papers were reviewed and scored independently by two out of six authors. Based on those papers we analyzed associations between biomarkers, subcompartments within the tumor lesion, and clinical outcomes. From all the articles analyzed, the twenty-seven papers with the highest scores were highlighted to represent the evidence about MR imaging biomarkers associated with clinical outcomes. Similarly, eighteen studies defining subcompartments within the tumor region were also highlighted to represent the evidence of MR imaging biomarkers. Their reports were critically appraised according to the QUADAS-2 criteria. Results: It has been demonstrated that multi-parametric biomarkers are prepared for surrogating diagnosis, grading, segmentation, overall survival, progression-free survival, recurrence, molecular profiling and response to treatment in gliomas. Quantifications and radiomics features obtained from morphological exams (T1, T2, FLAIR, T1c), PWI (including DSC and DCE), diffusion (DWI, DTI) and chemical shift imaging (CSI) are the preferred MR biomarkers associated to clinical outcomes. Subcompartments relative to the peritumoral region, invasion, infiltration, proliferation, mass effect and pseudo flush, relapse compartments, gross tumor volumes, and high-risk regions have been defined to characterize the heterogeneity. For the majority of pairwise cooccurrences, we found no evidence to assert that observed co-occurrences were significantly different from their expected co-occurrences (Binomial test with False Discovery Rate correction, alpha=0.05). The co-occurrence among terms in the studied papers was found to be driven by their individual prevalence and trends in the literature. Conclusion: Combinations of MR imaging biomarkers from morphological, PWI, DWI and CSI exams have demonstrated their capability to predict clinical outcomes in different management moments of gliomas. Whereas morphologic-derived compartments have been mostly studied during the last ten years, new multi-parametric MRI approaches have also been proposed to discover specific subcompartments of the tumors. MR biomarkers from those subcompartments show the local behavior within the heterogeneous tumor and may quantify the prognosis and response to treatment of gliomas.This work was supported by the Spanish Ministry for Investigation, Development and Innovation project with identification number DPI2016-80054-R.Oltra-Sastre, M.; Fuster García, E.; Juan -Albarracín, J.; Sáez Silvestre, C.; Perez-Girbes, A.; Sanz-Requena, R.; Revert-Ventura, A.... (2019). 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Neuro-oncol 2013,15(5),607-617Shankar J.J.S.; Woulfe J.; Silva V.D.; Nguyen T.B.; Evaluation of perfusion CT in grading and prognostication of high-grade gliomas at diagnosis: a pilot study. AJR Am J Roentgenol 2013,200(5)Zinn P.O.; Mahajan B.; Sathyan P.; Radiogenomic mapping of edema/cellular invasion MRI-phenotypes in glioblastoma multiforme. PLoS One 2011,6(10)Matsusue E.; Fink J.R.; Rockhill J.K.; Ogawa T.; Maravilla K.R.; Distinction between glioma progression and post-radiation change by combined physiologic MR imaging. Neuroradiology 2010,52(4),297-306Juan-Albarracín J.; Fuster-Garcia E.; Manjón J.V.; Automated glioblastoma segmentation based on a multiparametric structured unsupervised classification. PLoS One 2015,10(5)Itakura H.; Achrol A.S.; Mitchell L.A.; Magnetic resonance image features identify glioblastoma phenotypic subtypes with distinct molecular pathway activities. Sci Transl Med 2015,7(303)Ion-Margineanu A.; Van Cauter S.; Sima D.M.; Tumour relapse prediction using multiparametric MR data recorded during follow-up of GBM patients. BioMed Res Int 2015,2015Durst C.R.; Raghavan P.; Shaffrey M.E.; Multimodal MR imaging model to predict tumor infiltration in patients with gliomas. Neuroradiology 2014,56(2),107-115Yoon J.H.; Kim J.H.; Kang W.J.; Grading of cerebral glioma with multi-parametric MR Imaging and 18F-FDG-PET: concordance and accuracy. European Radiol 2014,24(2),380-389Demerath T.; Simon-Gabriel C.P.; Kellner E.; Mesoscopic imaging of glioblastomas: are diffusion, perfusion and spectroscopic measures influenced by the radiogenetic phenotype? Neuroradiol J 2017,30(1),36-47Qin L.; Li X.; Stroiney A.; Advanced MRI assessment to predict benefit of anti-programmed cell death 1 protein immunotherapy response in patients with recurrent glioblastoma. Neuroradiology 2017,59(2),135-145Boult J.K.R.; Borri M.; Jury A.; Investigating intracranial tumour growth patterns with multiparametric MRI incorporating Gd-DTPA and USPIO-enhanced imaging. NMR Biomed 2016,29(11),1608-1617Server A.; Kulle B.; Gadmar Ø.B.; Josefsen R.; Kumar T.; Nakstad P.H.; Measurements of diagnostic examination performance using quantitative apparent diffusion coefficient and proton MR spectroscopic imaging in the preoperative evaluation of tumor grade in cerebral gliomas. Eur J Radiol 2011,80(2),462-470Chang P.D.; Chow D.S.; Yang P.H.; Filippi C.G.; Lignelli A.; Predicting glioblastoma recurrence by early changes in the apparent diffusion coefficient value and signal intensity on FLAIR images. AJR Am J Roentgenol 2017,208(1),57-65Yi C.; Shangjie R.; Volume of high-risk intratumoralsubregions at multi-parametric MR imaging predicts overall survival and complements molecular analysis of glioblastoma. 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ELISA versus PCR for diagnosis of chronic Chagas disease: systematic review and meta-analysis

<p>Abstract</p> <p>Background</p> <p>Most current guidelines recommend two serological tests to diagnose chronic Chagas disease. When serological tests are persistently inconclusive, some guidelines recommend molecular tests. The aim of this investigation was to review chronic Chagas disease diagnosis literature and to summarize results of ELISA and PCR performance.</p> <p>Methods</p> <p>A systematic review was conducted searching remote databases (MEDLINE, LILACS, EMBASE, SCOPUS and ISIWeb) and full texts bibliography for relevant abstracts. In addition, manufacturers of commercial tests were contacted. Original investigations were eligible if they estimated sensitivity and specificity, or reliability -or if their calculation was possible - of ELISA or PCR tests, for chronic Chagas disease.</p> <p>Results</p> <p>Heterogeneity was high within each test (ELISA and PCR) and threshold effect was detected only in a particular subgroup. Reference standard blinding partially explained heterogeneity in ELISA studies, and pooled sensitivity and specificity were 97.7% [96.7%-98.5%] and 96.3% [94.6%-97.6%] respectively. Commercial ELISA with recombinant antigens studied in phase three investigations partially explained heterogeneity, and pooled sensitivity and specificity were 99.3% [97.9%-99.9%] and 97.5% [88.5%-99.5%] respectively. ELISA's reliability was seldom studied but was considered acceptable. PCR heterogeneity was not explained, but a threshold effect was detected in three groups created by using guanidine and boiling the sample before DNA extraction. PCR sensitivity is likely to be between 50% and 90%, while its specificity is close to 100%. PCR reliability was never studied.</p> <p>Conclusions</p> <p>Both conventional and recombinant based ELISA give useful information, however there are commercial tests without technical reports and therefore were not included in this review. Physicians need to have access to technical reports to understand if these serological tests are similar to those included in this review and therefore correctly order and interpret test results. Currently, PCR should not be used in clinical practice for chronic Chagas disease diagnosis and there is no PCR test commercially available for this purpose. Tests limitations and directions for future research are discussed.</p

Deep winds beneath Saturn's upper clouds from a seasonal long-lived planetary-scale storm

The original publication is available at www.nature.com/nature.International audienceConvective storms occur regularly in Saturn's atmosphere. Huge storms known as Great White Spots, which are ten times larger than the regular storms, are rarer and occur about once per Saturnian year (29.5 Earth years). Current models propose that the outbreak of a Great White Spot is due to moist convection induced by water. However, the generation of the global disturbance and its effect on Saturn's permanent winds have hitherto been unconstrained by data, because there was insufficient spatial resolution and temporal sampling to infer the dynamics of Saturn's weather layer (the layer in the troposphere where the cloud forms). Theoretically, it has been suggested that this phenomenon is seasonally controlled. Here we report observations of a storm at northern latitudes in the peak of a weak westward jet during the beginning of northern springtime, in accord with the seasonal cycle but earlier than expected. The storm head moved faster than the jet, was active during the two-month observation period, and triggered a planetary-scale disturbance that circled Saturn but did not significantly alter the ambient zonal winds. Numerical simulations of the phenomenon show that, as on Jupiter, Saturn's winds extend without decay deep down into the weather layer, at least to the water-cloud base at pressures of 10-12bar, which is much deeper than solar radiation penetrates

Antibody responses to α-Gal in African children vary with age and site and are associated with malaria protection.

Naturally-acquired antibody responses to malaria parasites are not only directed to protein antigens but also to carbohydrates on the surface of Plasmodium protozoa. Immunoglobulin M responses to α-galactose (α-Gal) (Galα1-3Galβ1-4GlcNAc-R)-containing glycoconjugates have been associated with protection from P. falciparum infection and, as a result, these molecules are under consideration as vaccine targets; however there are limited field studies in endemic populations. We assessed a wide breadth of isotype and subclass antibody response to α-Gal in children from Mozambique (South East Africa) and Ghana (West Africa) by quantitative suspension array technology. We showed that anti-α-Gal IgM, IgG and IgG1-4 levels vary mainly depending on the age of the child, and also differ in magnitude in the two sites. At an individual level, the intensity of malaria exposure to P. falciparum and maternally-transferred antibodies affected the magnitude of α-Gal responses. There was evidence for a possible protective role of anti-α-Gal IgG3 and IgG4 antibodies. However, the most consistent findings were that the magnitude of IgM responses to α-Gal was associated with protection against clinical malaria over a one-year follow up period, especially in the first months of life, while IgG levels correlated with malaria risk

Sequential multiblock partial least squares discriminant analysis for assessing prostate cancer aggressiveness with multiparametric magnetic resonance imaging

[EN] In current radiology practice, multi-parametric magnetic resonance imaging (mpMRI) has recently become a key tool in diagnostic and therapeutic decisions. Although it is based on the subjective assessment of T2-weighted images, as well as perfusion-weighted and diffusion-weighted sequences, further quantitative parameters can also be derived from them for improving lesion phenotyping. Despite these parameters are usually exploited in a univariate way, ignoring the benefits of a real multivariate approach, still it is the gold standard imaging technique to assess prostate cancer location and probability of malignancy. In this paper, pharmacokinetic (perfusion) and exponential (diffusion) clinical models, as well as latent variable-based multivariate statistical models like multivariate curve resolution-alternating least squares (MCR-ALS), have been calculated and analyzed with sequential multi block-partial least squares discriminant analysis (SMB-PLS-DA) including technique-block differentiation, in order to better assess for cancer aggressiveness based on Gleason scales. The best prediction result was achieved by the ordered combination of diffusion blocks (MCR-ALS and exponential models) and normalized T2 values. The perfusion blocks did not improve the results obtained by diffusion and T2-weighted based parameters alone, so they can be removed from the SMB-PLS-DA model.Acknowledgements This research was partially supported by the Spanish Government (Science and Innovation Ministry) under the project PID2020-119262RB-I00, and by the Generalitat Valenciana under the project AICO/2021/111.Aguado-Sarrió, E.; Prats-Montalbán, JM.; Sanz-Requena, R.; Duchesne, C.; Ferrer, A. (2022). Sequential multiblock partial least squares discriminant analysis for assessing prostate cancer aggressiveness with multiparametric magnetic resonance imaging. Chemometrics and Intelligent Laboratory Systems. 226:1-13. https://doi.org/10.1016/j.chemolab.2022.10458811322

Quantitative phase-contrast MRI study of cerebrospinal fluid flow: a method for identifying patients with normal-pressure hydrocephalus

Objectives: The aim of this study was to evaluate the use of phase-contrast MR imaging to diagnose normal pressure hydrocephalus (NPH) and differentiate it from other neurological disorders with similar clinical symptoms. Methods: The study included 108 subjects, of whom 61 were healthy controls and 47, patients; in the patient group, 19 had cerebrovascular disease (CVD) and 28 had NPH. All patients underwent a phase-contrast MRI study and several CSF flow and velocity parameters were measured at the aqueduct of Sylvius. Discriminant analyses were performed to evaluate the classification capacity of both individual parameters and the combination of different parameters. Results: Maximum diastolic velocity, mean flow, and stroke volume showed statistically significant differences that could be used to distinguish between NPH and CVD patients (P < .001). Stroke volume and mean flow showed no false positive results and successful classification rates of 86% and 79%, respectively. No other parameters or combination produced better results. Conclusions: Phase-contrast MR imaging is a useful tool for the early diagnosis of patients with NPH. CSF flow quantitative parameters, along with morphological features in a conventional MR study, enable us to differentiate between NPH and CVD patients. Resumen: Objetivos: El objetivo de este estudio es valorar si la RM en contraste de fase es una herramienta útil en el diagnóstico de la hidrocefalia a presión normal (HPN), así como su diferenciación con otras afecciones neurológicas muy similares clínicamente. Métodos: Se incluyó a un total de 108 sujetos, de los cuales 61 eran sujetos sanos control, y 47 pacientes; 19 de ellos fueron clasificados en el grupo de pacientes con enfermedad cerebrovascular isquémica (ECI) y 28 pacientes dentro del grupo de HPN. A todos los pacientes se les realizó una RM en contraste de fase con cuantificación de parámetros de flujo y velocidad de LCR en el acueducto de Silvio. Se evaluó la capacidad de clasificación de los parámetros individualmente y combinándolos mediante análisis discriminantes. Resultados: Los parámetros de velocidad máxima diastólica, flujo promedio y volumen por ciclo mostraron diferencias estadísticamente significativas para separar a los pacientes con HPN y con ECI (p < 0,001). El volumen por ciclo y el flujo promedio no presentaron falsos positivos, con tasas de acierto del 86% y 79%, respectivamente. El resto de parámetros y la combinación de todos ellos no mejoraron los resultados. Conclusiones: La RM en contraste de fase es una herramienta muy útil para el diagnóstico precoz de los pacientes con HPN. La cuantificación de parámetros de flujo de LCR junto con la valoración del estudio morfológico de la RM convencional permite diferenciar a los pacientes con HPN de los pacientes con ECI. Keywords: Aqueduct of sylvius, Quantitative evaluation, Cerebrospinal fluid shunt, Encephalopathy, Normal pressure hydrocephalus, Magnetic resonance imaging, Palabras clave: Acueducto de Silvio, Evaluación cuantitativa, Derivación de líquido cefalorraquídeo, Encefalopatía, Hidrocefalia a presión normal, Imagen por resonancia magnétic