Perspectives for cancer immunotherapy mediated by p19Arf plus interferon-beta gene transfer

While cancer immunotherapy has gained much deserved attention in recent years, many areas regarding the optimization of such modalities remain unexplored, including the development of novel approaches and the strategic combination of therapies that target multiple aspects of the cancer-immunity cycle. Our own work involves the use of gene transfer technology to promote cell death and immune stimulation. Such immunogenic cell death, mediated by the combined transfer of the alternate reading frame (p14ARF in humans and p19Arf in mice) and the interferon-b cDNA in our case, was shown to promote an antitumor immune response in mouse models of melanoma and lung carcinoma. With these encouraging results, we are now setting out on the road toward translational and preclinical development of our novel immunotherapeutic approach. Here, we outline the perspectives and challenges that we face, including the use of human tumor and immune cells to verify the response seen in mouse models and the incorporation of clinically relevant models, such as patient-derived xenografts and spontaneous tumors in animals. In addition, we seek to combine our immunotherapeutic approach with other treatments, such as chemotherapy or checkpoint blockade, with the goal of reducing dosage and increasing efficacy. The success of any translational research requires the cooperation of a multidisciplinary team of professionals involved in laboratory and clinical research, a relationship that is fostered at the Cancer Institute of Sao Paulo

Immunogenicity and Reactogenicity of 2009 Influenza A (H1N1) Inactivated Monovalent Non-Adjuvanted Vaccine in Elderly and Immunocompromised Patients

Background\ud \ud Immunosuppressed individuals present serious morbidity and mortality from influenza, therefore it is important to understand the safety and immunogenicity of influenza vaccination among them.\ud Methods\ud \ud This multicenter cohort study evaluated the immunogenicity and reactogenicity of an inactivated, monovalent, non-adjuvanted pandemic (H1N1) 2009 vaccine among the elderly, HIV-infected, rheumatoid arthritis (RA), cancer, kidney transplant, and juvenile idiopathic arthritis (JIA) patients. Participants were included during routine clinical visits, and vaccinated according to conventional influenza vaccination schedules. Antibody response was measured by the hemagglutination-inhibition assay, before and 21 days after vaccination.\ud Results\ud \ud 319 patients with cancer, 260 with RA, 256 HIV-infected, 149 elderly individuals, 85 kidney transplant recipients, and 83 with JIA were included.\ud \ud The proportions of seroprotection, seroconversion, and the geometric mean titer ratios postvaccination were, respectively: 37.6%, 31.8%, and 3.2 among kidney transplant recipients, 61.5%, 53.1%, and 7.5 among RA patients, 63.1%, 55.7%, and 5.7 among the elderly, 59.0%, 54.7%, and 5.9 among HIV-infected patients, 52.4%, 49.2%, and 5.3 among cancer patients, 85.5%, 78.3%, and 16.5 among JIA patients. The vaccine was well tolerated, with no reported severe adverse events.\ud Conclusions\ud \ud The vaccine was safe among all groups, with an acceptable immunogenicity among the elderly and JIA patients, however new vaccination strategies should be explored to improve the immune response of immunocompromised adult patients. (ClinicalTrials.gov, NCT01218685)Fundação Butantan funded the study, and employed several of the authors. The funder had a role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

A list of land plants of Parque Nacional do Caparaó, Brazil, highlights the presence of sampling gaps within this protected area

Brazilian protected areas are essential for plant conservation in the Atlantic Forest domain, one of the 36 global biodiversity hotspots. A major challenge for improving conservation actions is to know the plant richness, protected by these areas. Online databases offer an accessible way to build plant species lists and to provide relevant information about biodiversity. A list of land plants of “Parque Nacional do Caparaó” (PNC) was previously built using online databases and published on the website "Catálogo de Plantas das Unidades de Conservação do Brasil." Here, we provide and discuss additional information about plant species richness, endemism and conservation in the PNC that could not be included in the List. We documented 1,791 species of land plants as occurring in PNC, of which 63 are cited as threatened (CR, EN or VU) by the Brazilian National Red List, seven as data deficient (DD) and five as priorities for conservation. Fifity-one species were possible new ocurrences for ES and MG states

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

Low-dimensional phase-locked states in the zakharov equations

In this paper we identify phase-locked states among the solutions of the Zakharov equations. Locked states appear as resonant island chains in the appropriate Poincaré plots, with the relevant surface of section obtained by projecting out the full dynamical set on a subspace defined in terms of a pair of center-manifold variables. This pair allows an accurate canonical description of the system immediately after an inverse pitchfork bifurcation destabilizes an initial homogeneous steady state. If one is very close to the bifurcation point, nonlinear saturation of the initial instability is provided by quasistatic integrable ion-acoustic fluctuations, but as one proceeds away from that point, resonant nonintegrable ion-acoustic fluctuations become gradually more important; we show that the phase-locked states result from those resonant fluctuations. If one is not too far from the pitchfork bifurcation, locking is the stable asymptotic state of the interaction. As one moves farther away, locking exists only over long but finite amounts of time. In addition, the resonance separatrix appears to bring the first chaotic activity into the system

Multivariate control charts for monitoring non-linear batch processes

Processos industriais em bateladas são empregados com frequência na produção de certos itens. Tais processos disponibilizam uma estrutura de dados peculiar; diante disso, existe um crescente interesse no desenvolvimento de gráficos de controle multivariados mais apropriados para seu monitoramento. Investiga-se aqui uma abordagem recente que utiliza gráficos de controle baseados no método Statis. O Statis constitui-se em uma técnica exploratória que permite avaliar similaridade entre matrizes de dados. Entretanto, essa técnica considera a similaridade em um contexto linear, investigando estruturas de correlação lineares nos dados. Propõe-se neste artigo a utilização de gráficos de controle baseados no Statis em conjunto com kernels para monitoramento de processos com presença de não linearidades fortes. Através dos kernels, definem-se funções não lineares dos dados para melhor representação da estrutura a ser caracterizada pelo método Statis. Essa nova abordagem, denominada Kernel-Statis, é desenvolvida e avaliada utilizando dados de um processo simulado.Industrial batch processes are widely used in the production of certain items. Such processes provide a peculiar data structure; therefore there is a growing interest in the development of customized multivariate control charts for their monitoring. We investigate a recent approach that uses control charts based on the Statis method. Statis is an exploratory technique for measuring similarities between data matrices. However, the technique only assesses similarities in a linear context, i.e. investigating structures of linear correlation in the data. In this paper we propose control charts based on the Statis method in conjunction with a kernel for monitoring processes in the presence of strong nonlinearities. Through kernels we define nonlinear functions of data for better representing the structure to be characterized by the Statis method. The new approach, named Kernel-Statis, is developed and illustrated using simulated data

Multivariate control charts for monitoring non-linear batch processes

Processos industriais em bateladas são empregados com frequência na produção de certos itens. Tais processos disponibilizam uma estrutura de dados peculiar; diante disso, existe um crescente interesse no desenvolvimento de gráficos de controle multivariados mais apropriados para seu monitoramento. Investiga-se aqui uma abordagem recente que utiliza gráficos de controle baseados no método Statis. O Statis constitui-se em uma técnica exploratória que permite avaliar similaridade entre matrizes de dados. Entretanto, essa técnica considera a similaridade em um contexto linear, investigando estruturas de correlação lineares nos dados. Propõe-se neste artigo a utilização de gráficos de controle baseados no Statis em conjunto com kernels para monitoramento de processos com presença de não linearidades fortes. Através dos kernels, definem-se funções não lineares dos dados para melhor representação da estrutura a ser caracterizada pelo método Statis. Essa nova abordagem, denominada Kernel-Statis, é desenvolvida e avaliada utilizando dados de um processo simulado.Industrial batch processes are widely used in the production of certain items. Such processes provide a peculiar data structure; therefore there is a growing interest in the development of customized multivariate control charts for their monitoring. We investigate a recent approach that uses control charts based on the Statis method. Statis is an exploratory technique for measuring similarities between data matrices. However, the technique only assesses similarities in a linear context, i.e. investigating structures of linear correlation in the data. In this paper we propose control charts based on the Statis method in conjunction with a kernel for monitoring processes in the presence of strong nonlinearities. Through kernels we define nonlinear functions of data for better representing the structure to be characterized by the Statis method. The new approach, named Kernel-Statis, is developed and illustrated using simulated data