Opening the Black Box: Explaining the Process of Basing a Health Recommender System on the I-Change Behavioral Change Model

Recommender systems are gaining traction in healthcare because they can tailor recommendations based on users' feedback concerning their appreciation of previous health-related messages. However, recommender systems are often not grounded in behavioral change theories, which may further increase the effectiveness of their recommendations. This paper's objective is to describe principles for designing and developing a health recommender system grounded in the I-Change behavioral change model that shall be implemented through a mobile app for a smoking cessation support clinical trial. We built upon an existing smoking cessation health recommender system that delivered motivational messages through a mobile app. A group of experts assessed how the system may be improved to address the behavioral change determinants of the I-Change behavioral change model. The resulting system features a hybrid recommender algorithm for computer tailoring smoking cessation messages. A total of 331 different motivational messages were designed using 10 health communication methods. The algorithm was designed to match 58 message characteristics to each user pro le by following the principles of the I-Change model and maintaining the bene ts of the recommender system algorithms. The mobile app resulted in a streamlined version that aimed to improve the user experience, and this system's design bridges the gap between health recommender systems and the use of behavioral change theories. This article presents a novel approach integrating recommender system technology, health behavior technology, and computer-tailored technology. Future researchers will be able to build upon the principles applied in this case study.European Union's Horizon 2020 Research and Innovation Programme under Grant 68112

Cezanne regulates E2F1-dependent HIF2α expression

Mechanisms regulating protein degradation ensure the correct and timely expression of transcription factors such as hypoxia inducible factor (HIF). Under normal O2 tension, HIFα subunits are targeted for proteasomal degradation, mainly through vHL-dependent ubiquitylation. Deubiquitylases are responsible for reversing this process. Although the mechanism and regulation of HIFα by ubiquitin-dependent proteasomal degradation has been the object of many studies, little is known about the role of deubiquitylases. Here, we show that expression of HIF2α (encoded by EPAS1) is regulated by the deubiquitylase Cezanne (also known as OTUD7B) in an E2F1-dependent manner. Knockdown of Cezanne downregulates HIF2α mRNA, protein and activity independently of hypoxia and proteasomal degradation. Mechanistically, expression of the HIF2α gene is controlled directly by E2F1, and Cezanne regulates the stability of E2F1. Exogenous E2F1 can rescue HIF2α transcript and protein expression when Cezanne is depleted. Taken together, these data reveal a novel mechanism for the regulation of the expression of HIF2α, demonstrating that the HIF2α promoter is regulated by E2F1 directly and that Cezanne regulates HIF2α expression through control of E2F1 levels. Our results thus suggest that HIF2α is controlled transcriptionally in a cell-cycle-dependent manner and in response to oncogenic signalling

Strongly coupled matter near phase transition

In the Hartree approximation of Cornwall-Jackiw-Tomboulis (CJT) formalism of the real scalar field theory, we show that for the strongly coupled scalar system near phase transition, the shear viscosity over entropy density is small, however, the bulk viscosity over entropy density is large. The large bulk viscosity is related to the highly nonconformal equation of state. It is found that the square of the sound velocity near phase transition is much smaller than the conformal value 1/3, and the trace anomaly at phase transition deviates far away from 0. These results agree well with the lattice results of the complex QCD system near phase transition.Comment: 6 pages, 2 figures, 1 table, contributed to the International Conference on Strangeness in Quark Matter 2008, Beijing, China, 6-10 October 200

Monoubiquitination of syntaxin 3 leads to retrieval from the basolateral plasma membrane and facilitates cargo recruitment to exosomes

Syntaxin 3 (Stx3), a SNARE protein located and functioning at the apical plasma membrane of epithelial cells, is required for epithelial polarity. A fraction of Stx3 is localized to late endosomes/lysosomes, although how it traffics there and its function in these organelles is unknown. Here we report that Stx3 undergoes monoubiquitination in a conserved polybasic domain. Stx3 present at the basolateral—but not the apical—plasma membrane is rapidly endocytosed, targeted to endosomes, internalized into intraluminal vesicles (ILVs), and excreted in exosomes. A nonubiquitinatable mutant of Stx3 (Stx3-5R) fails to enter this pathway and leads to the inability of the apical exosomal cargo protein GPRC5B to enter the ILV/exosomal pathway. This suggests that ubiquitination of Stx3 leads to removal from the basolateral membrane to achieve apical polarity, that Stx3 plays a role in the recruitment of cargo to exosomes, and that the Stx3-5R mutant acts as a dominant-negative inhibitor. Human cytomegalovirus (HCMV) acquires its membrane in an intracellular compartment and we show that Stx3-5R strongly reduces the number of excreted infectious viral particles. Altogether these results suggest that Stx3 functions in the transport of specific proteins to apical exosomes and that HCMV exploits this pathway for virion excretion

Transport coefficients and resonances for a meson gas in Chiral Perturbation Theory

We present recent results on a systematic method to calculate transport coefficients for a meson gas (in particular, we analyze a pion gas) at low temperatures in the context of Chiral Perturbation Theory (ChPT). Our method is based on the study of Feynman diagrams taking into account collisions in the plasma by means of the non-zero particle width. This implies a modification of the standard ChPT power counting scheme. We discuss the importance of unitarity, which allows for an accurate high energy description of scattering amplitudes, generating dynamically the $\rho (770)$ and $f_0(600)$ mesons. Our results are compatible with analyses of kinetic theory, both in the non-relativistic very low-$T$ regime and near the transition. We show the behavior with temperature of the electrical and thermal conductivities as well as of the shear and bulk viscosities. We obtain that bulk viscosity is negligible against shear viscosity, except near the chiral phase transition where the conformal anomaly might induce larger bulk effects. Different asymptotic limits for transport coefficients, large-$N_c$ scaling and some applications to heavy-ion collisions are studied.Comment: Invited talk given at the international workshop Hot Quarks 2008, Estes Park, Colorado, USA, August 18-23 2008. Accepted as a regular article in Eur.Phys.J.C. 18 pages EPJC style, 23 figure

The moment protein (NSm) of Tomato spotted wilt virus is the avirulence determinant in the Sw-5 gene-based resistance

This is the accepted version of the following article: Peiró Morell, A.; Cañizares, MC.; Rubio, L.; López Del Rincón, C.; Moriones, E.; Aramburu, J.; Sanchez Navarro, JA. (2014). The moment protein (NSm) of Tomato spotted wilt virus is the avirulence determinant in the Sw-5 gene-based resistance. Molecular Plant Pathology. 15:802-813. doi:10.1111/mpp.12142., which has been published in final form at http://dx.doi.org/10.1111/mpp.12142 .The avirulence determinant triggering the resistance conferred by the tomato gene Sw-5 against Tomato spotted wilt virus (TSWV) is still unresolved. Sequence comparison showed two substitutions (C118Y and T120N) in the movement protein NSm present only in TSWV resistance-breaking (RB) isolates. In this work, transient expression of NSm of three TSWV isolates [RB1 (T120N), RB2 (C118Y) and non-resistance-breaking (NRB)] in Nicotiana benthamiana expressing Sw-5 showed a hypersensitive response (HR) only with NRB. Exchange of the movement protein of Alfalfa mosaic virus (AMV) with NSm supported cell-to-cell and systemic transport of the chimeric AMV RNAs into N.tabacum with or without Sw-5, except for the constructs with NBR when Sw-5 was expressed, although RB2 showed reduced cell-to-cell transport. Mutational analysis revealed that N120 was sufficient to avoid the HR, but the substitution V130I was required for systemic transport. Finally, co-inoculation of RB and NRB AMV chimeric constructs showed different prevalence of RB or NBR depending on the presence or absence of Sw-5. These results indicate that NSm is the avirulence determinant for Sw-5 resistance, and mutations C118Y and T120N are responsible for resistance breakdown and have a fitness penalty in the context of the heterologous AMV system.A.P. was a recipient of a JAE-Pre contract from the Consejo Superior de Investigaciones Cientificas (CSIC), and M. C. C was a recipient of an I3P contract from CSIC (co-financed by Fondo Social Europeo, FSE). We thank L. Corachan for excellent technical assistance and Dr Marcel Prins for providing the Nt/Sw5-b and Nb/Sw5-b seeds. This work was supported by grant BIO2011-25018 from the Spanish granting agency DGICYT, grant PAID05-11/2888 from the Universidad Politecnica de Valencia and by grant RTA2008-00010-C03 from the Instituto Nacional de Investigaciones Agrarias (INIA). All authors have no conflicts of interest to declare.Peiró Morell, A.; Cañizares, MDC.; Rubio, L.; López Del Rincón, C.; Moriones, E.; Aramburu, J.; Sanchez Navarro, JA. (2014). The moment protein (NSm) of Tomato spotted wilt virus is the avirulence determinant in the Sw-5 gene-based resistance. Molecular Plant Pathology. 15(8):802-813. https://doi.org/10.1111/mpp.12142S802813158Agudelo-Romero, P., de la Iglesia, F., & Elena, S. F. (2008). The pleiotropic cost of host-specialization in Tobacco etch potyvirus. 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Identification of domains of the Tomato spotted wilt virus NSm protein involved in tubule formation, movement and symptomatology. Virology, 390(1), 110-121. doi:10.1016/j.virol.2009.04.027Lopez, C., Aramburu, J., Galipienso, L., Soler, S., Nuez, F., & Rubio, L. (2010). Evolutionary analysis of tomato Sw-5 resistance-breaking isolates of Tomato spotted wilt virus. Journal of General Virology, 92(1), 210-215. doi:10.1099/vir.0.026708-0Margaria, P., Ciuffo, M., Pacifico, D., & Turina, M. (2007). Evidence That the Nonstructural Protein of Tomato spotted wilt virus Is the Avirulence Determinant in the Interaction with Resistant Pepper Carrying the Tsw Gene. Molecular Plant-Microbe Interactions, 20(5), 547-558. doi:10.1094/mpmi-20-5-0547Martinez-Gil, L., Sanchez-Navarro, J. A., Cruz, A., Pallas, V., Perez-Gil, J., & Mingarro, I. (2009). Plant Virus Cell-to-Cell Movement Is Not Dependent on the Transmembrane Disposition of Its Movement Protein. 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Vacuum Instabilities with a Wrong-Sign Higgs-Gluon-Gluon Amplitude

The recently discovered 125 GeV boson appears very similar to a Standard Model Higgs, but with data favoring an enhanced h to gamma gamma rate. A number of groups have found that fits would allow (or, less so after the latest updates, prefer) that the h-t-tbar coupling have the opposite sign. This can be given meaning in the context of an electroweak chiral Lagrangian, but it might also be interpreted to mean that a new colored and charged particle runs in loops and produces the opposite-sign hGG amplitude to that generated by integrating out the top, as well as a contribution reinforcing the W-loop contribution to hFF. In order to not suppress the rate of h to WW and h to ZZ, which appear to be approximately Standard Model-like, one would need the loop to "overshoot," not only canceling the top contribution but producing an opposite-sign hGG vertex of about the same magnitude as that in the SM. We argue that most such explanations have severe problems with fine-tuning and, more importantly, vacuum stability. In particular, the case of stop loops producing an opposite-sign hGG vertex of the same size as the Standard Model one is ruled out by a combination of vacuum decay bounds and LEP constraints. We also show that scenarios with a sign flip from loops of color octet charged scalars or new fermionic states are highly constrained.Comment: 20 pages, 8 figures; v2: references adde

How immunological profle drives clinical phenotype of primary Sjögren’s syndrome at diagnosis: analysis of 10,500 patients (Sjögren Big Data Project)

To evaluate the influence of the main immunological markers on the disease phenotype at diagnosis in a large international cohort of patients with primary Sjögren´s syndrome (SjS).METHODS:The Big Data Sjögren Project Consortium is an international, multicentre registry created in 2014. As a first step, baseline clinical information from leading centres on clinical research in SjS of the 5 continents was collected. The centres shared a harmonised data architecture and conducted cooperative online efforts in order to refine collected data under the coordination of a big data statistical team. Inclusion criteria were the fulfillment of the 2002 classification criteria. Immunological tests were carried out using standard commercial assays.RESULTS:By January 2018, the participant centres had included 10,500 valid patients from 22 countries. The cohort included 9,806 (93%) women and 694 (7%) men, with a mean age at diagnosis of primary SjS of 53 years, mainly White (78%) and included from European countries (71%). The frequency of positive immunological markers at diagnosis was 79.3% for ANA, 73.2% for anti-Ro, 48.6% for RF, 45.1% for anti- La, 13.4% for low C3 levels, 14.5% for low C4 levels and 7.3% for cryoglobulins. Positive autoantibodies (ANA, Ro, La) correlated with a positive result in salivary gland biopsy, while hypocomplementaemia and especially cryoglo-bulinaemia correlated with systemic activity (mean ESSDAI score of 17.7 for cryoglobulins, 11.3 for low C3 and 9.2 for low C4, in comparison with 3.8 for negative markers). The immunological markers with a great number of statistically-significant associations (p<0.001) in the organ-by-organ ESS- DAI evaluation were cryoglobulins (9 domains), low C3 (8 domains), anti-La (7 domains) and low C4 (6 domains).CONCLUSIONS:We confirm the strong influence of immunological markers on the phenotype of primary SjS at diagnosis in the largest multi-ethnic international cohort ever analysed, with a greater influence for cryoglobulinaemic-related markers in comparison with Ro/La autoantibodies and ANA. Immunological patterns play a central role in the phenotypic expression of the disease already at the time of diagnosis, and may guide physicians to design a specific personalised management during the follow-up of patients with primary SjS.Fil: Brito Zerón, Pilar. Hospital Sanitas CIMA; España. Universidad de Barcelona; EspañaFil: Acar Denizli, Nihan. Mimar Sinan Fine Arts University; TurquíaFil: Ng, Wan Fai. University of Newcastle; Reino UnidoFil: Zeher, Margit. University of Debrecen; HungríaFil: Rasmussen, Astrid. Oklahoma Medical Research Foundation; Estados UnidosFil: Mandl, Thomas. Lund University; SueciaFil: Seror, Raphaele. Université Paris Sud; FranciaFil: Xiaolin, Li. Anhui Provincial Hospital; ChinaFil: Baldini, Chiara. Università degli Studi di Pisa; ItaliaFil: Gottenberg, Jaques. Université de Strasbourg; Francia. Centre National de la Recherche Scientifique; FranciaFil: Danda, Debashish. Christian Medical College & Hospital; IndiaFil: Quartuccio, Luca. University Hospital “Santa María della Misericordia”; ItaliaFil: Priori, Roberta. Università degli Studi di Roma "La Sapienza"; ItaliaFil: Hernandez Molina, Gabriela. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán; MéxicoFil: Armagan, Berkan. Hacettepe University. Faculty of Medicine.Department of Internal Medicine; TurquíaFil: Kruize, Aike. University Medical Center Utrecht; Países BajosFil: Kwok, Seung Ki. The Catholic University of Korea; Corea del SurFil: Kvarnström, Marika. Karolinska University Hospital.Department of Medicine.Unit of Rheumatology. Karolinska Institutet ; SueciaFil: Praprotnik, Sonja. University Medical Centre; EsloveniaFil: Sene, Damien. Université Paris Diderot - Paris 7; FranciaFil: Bartoloni, Elena. Università di Perugia; ItaliaFil: Solans, R.. Hospital Vall d’Hebron; ItaliaFil: Rischmueller, M.. University of Western Australia; AustraliaFil: Suzuki, Y.. Kanazawa University Hospital; JapónFil: Isenberg, D. A.. University College London; Estados UnidosFil: Valim, V.. Federal University of Espírito Santo; BrasilFil: Wiland, P.. Wroclaw Medical Hospital; PoloniaFil: Nordmark, G.. Uppsala Universitet; SueciaFil: Fraile, G.. Hospital Ramón y Cajal; EspañaFil: Retamozo, Maria Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; Argentina. Hospital Privado Centro Medico de Córdoba; Argentina; Argentina. Instituto Universitario de Ciencias Biomédicas de Córdoba; Argentin