Tameness and Artinianness of Graded Generalized Local Cohomology Modules

Let $R=\bigoplus_{n\geq 0}R_n$, \fa\supseteq \bigoplus_{n> 0}R_n and $M$ and $N$ be a standard graded ring, an ideal of $R$ and two finitely generated graded $R$-modules, respectively. This paper studies the homogeneous components of graded generalized local cohomology modules. First of all, we show that for all $i\geq 0$, H^i_{\fa}(M, N)_n, the $n$-th graded component of the $i$-th generalized local cohomology module of $M$ and $N$ with respect to \fa, vanishes for all $n\gg 0$. Furthermore, some sufficient conditions are proposed to satisfy the equality \sup\{\en(H^i_{\fa}(M, N))| i\geq 0\}= \sup\{\en(H^i_{R_+}(M, N))| i\geq 0\}. Some sufficient conditions are also proposed for tameness of H^i_{\fa}(M, N) such that i= f_{\fa}^{R_+}(M, N) or i= \cd_{\fa}(M, N), where f_{\fa}^{R_+}(M, N) and \cd_{\fa}(M, N) denote the $R_+$-finiteness dimension and the cohomological dimension of $M$ and $N$ with respect to \fa, respectively. We finally consider the Artinian property of some submodules and quotient modules of H^j_{\fa}(M, N), where $j$ is the first or last non-minimax level of H^i_{\fa}(M, N).Comment: 18pages, with some revisions and correction

Content Analysis of Articles Published in Iranian Scientific Nursing Journals From 2009 Through 2011

Background: Little is known about the features of Iranian nursing journals, specifically the subject areas used in articles, study designs, sampling methods, international collaboration of Iranian nursing scholars, specialty and academic rank of authors, and the most frequently contributing academic institutions in articles. Objectives: The aim of this study was to analyze the content of the articles published in Iranian scientific nursing journals. Materials and Methods: Quantitative content analysis was implemented to study Iranian nursing journals, which were approved by the commission for accreditation and improvement of Iranian medical journals in 2011. Thus, 763 articles from six journals, published from 2009 through 2011, were investigated. Data were extracted from the abstracts and when necessary, from the full-text of articles by visiting the websites of these journals. Descriptive statistics were used to analyze the data. Results: The main subjects of published articles in Iranian scientific nursing journals were consecutively renal dialysis (n = 21), intensive care unit (n = 16), nursing education (n = 15), patient satisfaction (n = 13), quality of life (n = 12), health education (n = 11), patient education (n = 11), pain (n = 10), and education (n = 9). The majority of authors had nursing and midwifery specialty (52.59%) followed by epidemiology/biostatistics specialty (7.72%). Isfahan, Tehran, Shahid Beheshti, Iran, Baqiyatallah, and Urmia universities of medical sciences had consecutively the largest number of publications in the studied journals. Only three papers (0.39%) were published by the international collaboration. Conclusions: Iranian nursing journals should publish special issues in the neglected subject areas. These journals should encourage authors to publish research evidence with higher quality

First-in-human phase I/IIa trial to evaluate the safety and initial clinical activity of DuoBody®-PD-L1×4–1BB (GEN1046) in patients with advanced solid tumors

Agonistic 4-1BB monoclonal antibodies were preclinically validated as promising cancer immunotherapies, both as monotherapy and as potentiators of the activity of PD-(L) 1–blocking agents. However, toxicity and a narrow therapeutic window have hampered their clinical development. DuoBodyPD-L1×4-1BB, a first-in-class, bispecific, next-generation checkpoint immunotherapy, was designed to overcome these limitations by activating T cells through conditional 4-1BB costimulation, while simultaneously blocking the PD-L1 axis. We present preliminary data from the ongoing, first-in-human, open-label, phase I/IIa trial of DuoBody-PD-L1×4-1BB in advanced solid tumors (NCT03917381)

Evaluation of different total leishmania amazonensis antigens for the development of a first-generation vaccine formulated with a toll-like receptor-3 agonist to prevent cutaneous leishmaniasis

Unfortunately, no any vaccine against leishmaniasis has been developed for human use. Therefore, a vaccine based on total Leishmania antigens could be a good and economic approach; and there are different methodologies to obtain these antigens. However, it is unknown whether the method to obtain the antigens affects the integrity and immune response caused by them. OBJECTIVES: to compare the protein profile and immune response generated by total L. amazonensis antigens (TLA) produced by different methods, as well as to analyse the immune response and protection by a first-generation vaccine formulated with sonicated TLA (sTLA) and polyinosinic:polycytidylic acid [Poly (I:C)]. METHODS: TLA were obtained by four different methodologies and their integrity and immune response were evaluated. Finally, sTLA was formulated with Poly (I:C) and their protective immune response was measured. FINDINGS: sTLA presented a conserved protein profile and induced a strong immune response. In addition, Poly (I:C) improved the immune response generated by sTLA. Finally, sTLA + Poly (I:C) formulation provided partial protection against L. amazonensis infection. MAIN CONCLUSIONS: The protein profile and immune response depend on the methodology used to obtain the antigens. Also, the formulation sTLA + Poly (I:C) provides partial protection against cutaneous leishmaniasis in mice.Fil: Germano, Maria Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Lozano, Esteban Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Sanchez, María Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Bruna, Flavia Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Garcia Bustos, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Salta. Instituto de Patología Experimental. Universidad Nacional de Salta. Facultad de Ciencias de la Salud. Instituto de Patología Experimental; ArgentinaFil: Sosa Lochedino, Arianna Lourdes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Salomón, María Cristina. Universidad Nacional de Cuyo; ArgentinaFil: Fernandes, Ana Paula. Universidade Federal de Minas Gerais; BrasilFil: Mackern Oberti, Juan Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Cargnelutti, Diego Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin

Constant curvature f(R) gravity minimally coupled with Yang-Mills field

We consider the particular class of f(R) gravities minimally coupled with Yang - Mills (YM) field in which the Ricci scalar =R_{0}= constant in all dimensions d\geq4. Even in this restricted class the spacetime has unlimited scopes determined by an equation of state of the form P_{eff}={\omega}{\rho}. Depending on the distance from the origin (or horizon of a black hole) the state function {\omega}(r) takes different values. It is observed that {\omega}\rightarrow(1/3) (the ultra relativistic case in 4 - dimensions) and {\omega}\rightarrow-1 (the cosmological constant) are the limiting values of our state function {\omega}(r) in a spacetime centered by a black hole. This suggests that having a constant {\omega} throughout spacetime around a charged black hole in f(R) gravity with constant scalar curvature is a myth.Comment: 12 pages 2 figures, Some references and 2 figures are added with minor changes. Final version for publication in European Physical Journal

Melatonin protects rats from radiotherapy-induced small intestine toxicity

Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.This study was partially supported by grant no. SAF2009-14037 from the Spanish Ministry of Economy and Competitivity (MINECO), GREIB.PT_2010_04 from the CEIBiotic Program of the University of Granada, Spain, and CTS-101 from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain

Daratumumab plus lenalidomide and dexamethasone for untreated myeloma

This is an accepted manuscript of an article published by Massachusetts Medical Society in New England Journal of Medicine on 30/05/2019, available online: https://doi.org/10.1056/NEJMoa1817249 The accepted version of the publication may differ from the final published version.Copyright © 2019 Massachusetts Medical Society. Lenalidomide plus dexamethasone is a standard treatment for patients with newly diagnosed multiple myeloma who are ineligible for autologous stem-cell transplantation. We sought to determine whether the addition of daratumumab would significantly reduce the risk of disease progression or death in this population. METHODS We randomly assigned 737 patients with newly diagnosed multiple myeloma who were ineligible for autologous stem-cell transplantation to receive daratumumab plus lenalidomide and dexamethasone (daratumumab group) or lenalidomide and dexamethasone alone (control group). Treatment was to continue until the occurrence of disease progression or unacceptable side effects. The primary end point was progression-free survival. RESULTS At a median follow-up of 28.0 months, disease progression or death had occurred in 240 patients (97 of 368 patients [26.4%] in the daratumumab group and 143 of 369 patients [38.8%] in the control group). The estimated percentage of patients who were alive without disease progression at 30 months was 70.6% (95% confidence interval [CI], 65.0 to 75.4) in the daratumumab group and 55.6% (95% CI, 49.5 to 61.3) in the control group (hazard ratio for disease progression or death, 0.56; 95% CI, 0.43 to 0.73; P<0.001). The percentage of patients with a complete response or better was 47.6% in the daratumumab group and 24.9% in the control group (P<0.001). A total of 24.2% of the patients in the daratumumab group, as compared with 7.3% of the patients in the control group, had results below the threshold for minimal residual disease (1 tumor cell per 105 white cells) (P<0.001). The most common adverse events of grade 3 or 4 were neutropenia (50.0% in the daratumumab group vs. 35.3% in the control group), anemia (11.8% vs. 19.7%), lymphopenia (15.1% vs. 10.7%), and pneumonia (13.7% vs. 7.9%).Published versio

Identification of research communities in cited and uncited publications using a co-authorship network

Patterns of co-authorship provide an effective means of probing the structures of research communities. In this paper, we use the CiteSpace social network tool and co-authorship data from the Web of Science to analyse two such types of community. The first type is based on the cited publications of a group of highly productive authors in a particular discipline, and the second on the uncited publications of those highly productive authors. These pairs of communities were generated for three different countries—the People’s Republic of China (PRC), the United Kingdom (UK) and the United States of America (USA)—and for four different disciplines (as denoted by Web of Science subject categories)—Chemistry Organic, Engineering Environmental, Economics, and Management. In the case of the UK and USA, the structures of the cited and uncited communities in each of the four disciplines were markedly different from each other; in the case of the PRC, conversely, the cited and uncited PRC communities had broadly similar structures that were characterised by large groups of connected authors. We suggest that this may arise from a greater degree of guest or honorary authorship in the PRC than in the UK or the USA