Temporal Interpolation of Dynamic Digital Humans using Convolutional Neural Networks

In recent years, there has been an increased interest in point cloud representation for visualizing digital humans in cross reality. However, due to their voluminous size, point clouds require high bandwidth to be transmitted. In this paper, we propose a temporal interpolation architecture capable of increasing the temporal resolution of dynamic digital humans, represented using point clouds. With this technique, bandwidth savings can be achieved by transmitting dynamic point clouds in a lower temporal resolution, and recreating a higher temporal resolution on the receiving side. Our interpolation architecture works by first downsampling the point clouds to a lower spatial resolution, then estimating scene flow using a newly designed neural network architecture, and finally upsampling the result back to the original spatial resolution. To improve the smoothness of the results, we additionally apply a novel technique called neighbour snapping. To be able to train and test our newly designed network, we created a synthetic point cloud data set of animated human bodies. Results from the evaluation of our architecture through a small-scale user study show the benefits of our method with respect to the state of the art in scene flow estimation for point clouds. Moreover, correlation between our user study and existing objective quality metrics confirm the need for new metrics to accurately predict the visual quality of point cloud contents

Depression and treatment with anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies for migraine

Background and purpose: The aim was to evaluate the effect of anti-calcitonin gene related peptide (CGRP) (ligand or receptor) antibodies on depressive symptoms in subjects with migraine and to determine whether depressive symptoms predict treatment response. Methods: Patients with migraine treated with erenumab and fremanezumab at the Leiden Headache Centre completed daily E-headache diaries. A control group was included. Depressive symptoms were assessed using the Hospital Anxiety and Depression Scale (HADS) and the Center for Epidemiological Studies Depression Scale (CES-D) questionnaires at baseline (T0) and after 3 months (T1). First, the effect of treatment on the reduction in HADS-D and CES-D scores was assessed, with reduction in depression scores as the dependent variable and reduction in monthly migraine days (MMD) and treatment with anti-CGRP medication as independent variables. Second, depression as a predictor of treatment response was investigated, using the absolute reduction in MMD as a dependent variable and age, gender, MMD, active depression, impact, stress and locus of control scores as independent variables. Results: In total, n = 108 patients were treated with erenumab, n = 90 with fremanezumab and n = 68 were without active treatment. Treatment with anti-CGRP medication was positively associated with a reduction in the HADS-D (β = 1.65, p = 0.01) compared to control, independent of MMD reduction. However, the same effect was not found for the CES-D (β = 2.15, p = 0.21). Active depression predicted poorer response to erenumab (p = 0.02) but not to fremanezumab (p = 0.09). Conclusion: Anti-CGRP (ligand or receptor) monoclonals lead to improvement of depressive symptoms in individuals with migraine, independent of migraine reduction. Depression may predict treatment response to erenumab but not to fremanezumab.</p

Circulating gamma-glutamyltransferase fractions in cirrhosis.

Background: Four GGT fractions (b-, m-, s-, and f-GGT) have been identified in human plasma and their concentrations and ratios vary in different pathological conditions. Aim: To assess the behavior of fractional GGT in cirrhotic patients evaluated for liver transplantation. Methods: This was a single-center, cross-sectional study; GGT fractions were determined by gel-filtration chromatography. Results: 264 cirrhotic patients (215 males; median age 54.5 years) were included and compared against a group of 200 healthy individuals (100 males; median age 41.5). Median (25th-75th percentile) total and fractional GGT were higher in cirrhotics, with s-GGT showing the greatest increase [36.6 U/L (21.0-81.4) vs. 5.6 U/L (3.2-10.2), (p<0.0001)], while the median b-GGT/s-GGT ratio was lower in cirrhotics than in healthy controls [0.06 (0.04-0.10)] vs. 0.28 (0.20-0.40), p<0.0001]. The ratio showed higher diagnostic accuracy (ROC-AUC, 95% CI: 0.951, 0.927-0.969) then either s-GGT (0.924, 0.897-0.947; p<0.05) or total GGT (0.900, 0.869-0.925; p<0.001). The diagnostic accuracy of the ratio was maintained (0.940, 0.907-0.963) in cirrhotic patients (n=113) with total GGT values within the reference range. The s-GGT fraction consisted of two components, with one (s2-GGT) showing a significant positive correlation with serum AST, ALT, LDH, ALP and bilirubin, and negative with albumin. The b-GGT fraction showed a positive correlation with albumin, fibrinogen, and platelet counts, and negative with INR, bilirubin and LDH. Conclusions: The ratio performs as a sensitive biomarker of the liver parenchymal rearrangement, irrespective of etiology of cirrhosis and presence of hepatocellular carcinoma, even in patients with total GGT values within the reference range

Competências em saúde global na visão de docentes de enfermagem de instituições de ensino superior brasileiras

OBJETIVOS: identificar a concordância de docentes vinculados a instituições de ensino superior brasileiras, quanto às competências em saúde global, necessárias para a formação do aluno de enfermagem, durante o curso de graduação, e se as competências eram contempladas no currículo atual da instituição em que atuavam. MÉTODO: estudo exploratório-descritivo, realizado com 222 docentes que responderam a versão brasileira do "Questionário sobre Competências Básicas Essenciais de Saúde Global", disponibilizado em formato eletrônico no website Survey Monkey. RESULTADOS: houve predomínio de doutores (75,8%), sexo feminino (91,9%) e faixa etária entre 40 e 59 anos (69,3%). A média e o desvio-padrão de todas as competências questionadas variaram de 3,04 (0,61) a 3,88 (0,32), sendo que a pontuação atribuída para cada competência foi de 1 "discordo totalmente" a 4 "concordo totalmente". Os resultados demonstraram nível de concordância satisfatório dos respondentes em relação às competências de saúde global. CONCLUSÕES: o estudo demonstrou alta média de concordância dos enfermeiros docentes de instituições de ensino superior brasileiras, quanto às competências em saúde global do questionário, e, também, que os currículos das instituições de ensino superior em que atuavam comtemplavam parcialmente algumas delas, sendo que as competências do domínio "Globalização da saúde e da assistência à saúde" são as menos contempladas.OBJECTIVES: to identify the agreement of faculty affiliated with Brazilian higher education institutions about the global health competencies needed for undergraduate nursing students' education and whether these competencies were covered in the curriculum offered at the institution where they were teaching. METHOD: exploratory-descriptive study, involving 222 faculty members who answered the Brazilian version of the "Questionnaire on Core Competencies in Global Health", made available electronically on the website Survey Monkey. RESULTS: participants predominantly held a Ph.D. (75.8%), were women (91.9%) and were between 40 and 59 years of age (69.3%). The mean and standard deviation of all competencies questioned ranged between 3.04 (0.61) and 3.88 (0.32), with scores for each competency ranging from 1 "strongly disagree" to 4 "strongly agree". The results demonstrated the respondents' satisfactory level of agreement with the global health competencies. CONCLUSIONS: the study demonstrated a high mean agreement level of the nursing faculty from Brazilian HEI with the global health competencies in the questionnaire. The curricula of the HEI where they teach partially address some of these. The competencies in the domain "Globalization of health and health care" are the least addressed.OBJETIVOS: identificar la concordancia de docentes vinculados a Instituciones de Educación Superior brasileñas respecto a las competencias en salud global necesarias para la formación del alumno de enfermería durante el curso de pregrado y si las competencias eran contempladas en el currículo actual de la institución en que actuaban. MÉTODO: estudio exploratorio-descriptivo, llevado a cabo con 222 docentes que respondieron a la versión brasileña del "Cuestionario sobre Competencias Básicas Esenciales de Salud Global" disponible en formato electrónico en la página Survey Monkey. RESULTADOS: predominaron doctores (75,8%), sexo femenino (91,9%) y rango de edad entre 40 y 59 años (69,3%). El promedio y desvío estándar de todas las competencias cuestionadas variaron de 3,04 (0,61) a 3,88 (0,32), siendo que la puntuación atribuida para cada competencia varió de 1 "completamente en desacuerdo" a 4 "completamente de acuerdo". Los resultados demostraron nivel de concordancia satisfactorio de los respondientes respecto a las competencias de salud global. CONCLUSIONES: el estudio demostró alta concordancia media de los enfermeros docentes de IES brasileñas respecto a las competencias en salud global del cuestionario y que los currículos de las IES en que actúan contemplan parcialmente algunas de ellas, siendo que las competencias del dominio "Globalización de la salud y de la atención a la salud" son las menos contempladas

NirA is an alternative nitrite reductase from Pseudomonas aeruginosa with potential as an antivirulence target

The opportunistic pathogen Pseudomonas aeruginosa produces an arsenal of virulence factors causing a wide range of diseases in multiple hosts and is difficult to eradicate due to its intrinsic resistance to antibiotics. With the antibacterial pipeline drying up, antivirulence therapy has become an attractive alternative strategy to the traditional use of antibiotics to treat P. aeruginosa infections. To identify P. aeruginosa genes required for virulence in multiple hosts, a random library of Tn5 mutants in strain PAO1-L was previously screened in vitro for those showing pleiotropic effects in the production of virulence phenotypes. Using this strategy, we identified a Tn5 mutant with an insertion in PA4130 showing reduced levels of a number of virulence traits in vitro. Construction of an isogenic mutant in this gene presented results similar to those for the Tn5 mutant. Furthermore, the PA4130 isogenic mutant showed substantial attenuation in disease models of Drosophila melanogaster and Caenorhabditis elegans as well as reduced toxicity in human cell lines. Mice infected with this mutant demonstrated an 80% increased survival rate in acute and agar bead lung infection models. PA4130 codes for a protein with homology to nitrite and sulfite reductases. Overexpression of PA4130 in the presence of the siroheme synthase CysG enabled its purification as a soluble protein. Methyl viologen oxidation assays with purified PA4130 showed that this enzyme is a nitrite reductase operating in a ferredoxin-dependent manner. The preference for nitrite and production of ammonium revealed that PA4130 is an ammonia:ferredoxin nitrite reductase and hence was named NirA. IMPORTANCE The emergence of widespread antimicrobial resistance has led to the need for development of novel therapeutic interventions. Antivirulence strategies are an attractive alternative to classic antimicrobial therapy; however, they require identification of new specific targets which can be exploited in drug discovery programs. The host-specific nature of P. aeruginosa virulence adds complexity to the discovery of these types of targets. Using a sequence of in vitro assays and phylogenetically diverse in vivo disease models, we have identified a PA4130 mutant with reduced production in a number of virulence traits and severe attenuation across all infection models tested. Characterization of PA4130 revealed that it is a ferredoxin-nitrite reductase and hence was named NirA. These results, together with attenuation of nirA mutants in different clinical isolates, high level conservation of its gene product in P. aeruginosa genomes, and the lack of orthologues in human genomes, make NirA an attractive antivirulence target

A-quasiconvexity : relaxation and homogenization

Integral representation of relaxed energies and of Γ-limits of functionals (u, v)↦→�Ω f(x, u(x), v(x))dx are obtained when sequences of fields v may develop oscillations and are constrained to satisfy a system of first order linear partial differential equations. This framework includes the treatement of divergence-free fields, Maxwell’s equations in micromagnetics, and curl-free fields. In the latter case classical relaxation theorems in W 1,p are recovered

Neuroticism and Conscientiousness Moderate the Effect of Oral Medication Beliefs on Adherence of People with Mental Illness during the Pandemic

Background. After the declaration of the pandemic status in several countries, the continuity of face-to-face visits in psychiatric facilities has been delayed or even interrupted to reduce viral spread. Little is known about the personality factors associated with medication beliefs and adherence amongst individuals with mental illness during the COVID-19 pandemic. This brief report describes a preliminary naturalistic longitudinal study that explored whether the Big Five personality traits prospectively moderate the effects of medication beliefs on changes in adherence during the pandemic for a group of outpatients with psychosis or bipolar disorder. Methods. Thirteen outpatients undergoing routine face-to-face follow-up assessments during the pandemic were included (41 observations overall) and completed the Revised Italian Version of the Ten-Item Personality Inventory, the Beliefs about Medicines Questionnaire, the Morisky Medication Adherence Scale-8-item and the Beck Depression Inventory-II. Results. Participants had stronger concerns about their psychiatric medications rather than beliefs about their necessity, and adherence to medications was generally low. Participants who had more necessity beliefs than concerns had better adherence to medications. People scoring higher in Conscientiousness and Neuroticism traits and more concerned about the medication side effects had poorer adherence. Conclusions. These preliminary data suggest the importance of a careful assessment of the adherence to medications amongst people with psychosis/bipolar disorder during the pandemic. Interventions aimed to improve adherence might focus on patients' medication beliefs and their Conscientiousness and Neuroticism personality traits

Cost-effectiveness analysis of personalised versus standard dosimetry for selective internal radiation therapy with TheraSphere in patients with hepatocellular carcinoma

Aims: To perform a cost-effectiveness analysis (CEA) comparing personalised dosimetry with standard dosimetry in the context of selective internal radiation therapy (SIRT) with TheraSphere for the management of adult patients with locally advanced hepatocellular carcinoma (HCC) from the Italian Healthcare Service perspective. Materials and methods: A partition survival model was developed to project costs and the quality-adjusted life years (QALYs) over a lifetime horizon. Clinical inputs were retrieved from a published randomised controlled trial. Health resource utilisation inputs were extracted from the questionnaires administered to clinicians in three oncology centres in Italy, respectively. Cost parameters were based on Italian official tariffs. Results: Over a lifetime horizon, the model estimated the average QALYs of 1.292 and 0.578, respectively, for patients undergoing personalised and standard dosimetry approaches. The estimated mean costs per patient were €23,487 and €19,877, respectively. The incremental cost-utility ratio (ICUR) of personalised versus standard dosimetry approaches was €5,056/QALY. Conclusions: Personalised dosimetry may be considered a cost-effective option compared to standard dosimetry for patients undergoing SIRT for HCC in Italy. These findings provide evidence for clinicians and payers on the value of personalised dosimetry as a treatment option for patients with HCC

Effective targeting of breast cancer stem cells by combined inhibition of Sam68 and Rad51

: Breast cancer (BC) is the second cause of cancer-related deceases in the worldwide female population. Despite the successful treatment advances, 25% of BC develops resistance to current therapeutic regimens, thereby remaining a major hurdle for patient management. Current therapies, targeting the molecular events underpinning the adaptive resistance, still require effort to improve BC treatment. Using BC sphere cells (BCSphCs) as a model, here we showed that BC stem-like cells express high levels of Myc, which requires the presence of the multifunctional DNA/RNA binding protein Sam68 for the DNA-damage repair. Analysis of a cohort of BC patients displayed that Sam68 is an independent negative factor correlated with the progression of the disease. Genetic inhibition of Sam68 caused a defect in PARP-induced PAR chain synthesis upon DNA-damaging insults, resulting in cell death of TNBC cells. In contrast, BC stem-like cells were able to survive due to an upregulation of Rad51. Importantly, the inhibition of Rad51 showed synthetic lethal effect with the silencing of Sam68, hampering the cell viability of patient-derived BCSphCs and stabilizing the growth of tumor xenografts, including those TNBC carrying BRCA mutation. Moreover, the analysis of Myc, Sam68 and Rad51 expression demarcated a signature of a poor outcome in a large cohort of BC patients. Thus, our findings suggest the importance of targeting Sam68-PARP1 axis and Rad51 as potential therapeutic candidates to counteract the expansion of BC cells with an aggressive phenotype

CHK1 inhibitor sensitizes resistant colorectal cancer stem cells to nortopsentin

Limited therapeutic options are available for advanced colorectal cancer (CRC). Herein, we report that exposure to a neo-synthetic bis(indolyl)thiazole alkaloid analog, nortopsentin 234 (NORA234), leads to an initial reduction of proliferative and clonogenic potential of CRC sphere cells (CR-CSphCs), followed by an adaptive response selecting the CR-CSphC-resistant compartment. Cells spared by the treatment with NORA234 express high levels of CD44v6, associated with a constitutive activation of Wnt pathway. In CR-CSphC-based organoids, NORA234 causes a genotoxic stress paralleled by G2-M cell cycle arrest and activation of CHK1, driving the DNA damage repair of CR-CSphCs, regardless of the mutational background, microsatellite stability, and consensus molecular subtype. Synergistic combination of NORA234 and CHK1 (rabusertib) targeting is synthetic lethal inducing death of both CD44v6-negative and CD44v6-positive CRC stem cell fractions, aside from Wnt pathway activity. These data could provide a rational basis to develop an effective strategy for the treatment of patients with CRC