Injectable hybrid hydrogels physically crosslinked based on carrageenan and green graphene for tissue repair

Injectable and biocompatible novel hybrid hydrogels based on physically crosslinked natural biopolymers and green graphene for potential use in tissue engineering are reported. Kappa and iota carrageenan, locust bean gum and gelatin are used as biopolymeric matrix. The effect of green graphene content on the swelling behavior, mechanical properties and biocompatibility of the hybrid hydrogels is investigated. The hybrid hydrogels present a porous network with three-dimensionally interconnected microstructures, with lower pore size than that of the hydrogel without graphene. The addition of graphene into the biopolymeric network improves the stability and the mechanical properties of the hydrogels in phosphate buffer saline solution at 37 °C without noticeable change in the injectability. The mechanical properties of the hybrid hydrogels were enhanced by varying the dosage of graphene between 0.025 and 0.075 w/v%. In this range, the hybrid hydrogels preserve their integrity during mechanical test and recover the initial shape after removing the applied stress. Meanwhile, hybrid hydrogels with graphene content of up to 0.05 w/v% exhibit good biocompatibility for 3T3-L1 fibroblasts; the cells proliferate inside the gel structure and show higher spreading after 48 h. These injectable hybrid hydrogels with graphene have promising future as materials for tissue repair.The research leading to these results received funding from the Xunta de Galicia Government: program of consolidation and structuring competitive research units [grant number: ED431C 2019/17]. Y.F. is a ‘Sara Borrell’ researcher funded by Instituto de Salud Carlos III (ISCIII) and co-funded by Fondo Europeo de Desarrollo Regional (FEDER) [CD21/00042]. Thanks to Corfo 22CVID-206836, CIPA, ANID Regional, GORE BIO BIO, R17A10003, ACE210016, ACE210012. Funding for open access charge was provided by Universidade da Coruna/CISU

Dendritic cells delivered inside human carcinomas are sequestered by interleukin-8

In the course of a clinical trial consisting of intratumoral injections of dendritic cells (DCs) transfected to produce interleukin-12, the use of (111)In-labeled tracing doses of DCs showed that most DCs remained inside tumor tissue, instead of migrating out. In search for factors that could explain this retention, it was found that tumors from patients suffering hepatocellular carcinoma, colorectal or pancreatic cancer were producing IL-8 and that this chemokine attracted monocyte-derived dendritic cells that uniformly express both IL-8 receptors CXCR1 and CXCR2. Accordingly, neutralizing antihuman IL-8 monoclonal antibodies blocked the chemotactic attraction of DCs by recombinant IL-8, as well as by the serum of the patients or culture supernatants of human colorectal carcinomas. In addition, tissue culture supernatants of colon carcinoma cells inhibited DC migration induced by MIP-3beta in an IL-8-dependent fashion. IL-8 production in malignant tissue and the responsiveness of DCs to IL-8 are a likely explanation of the clinical images, which suggest retention of DCs inside human malignant lesions. Impairment of DC migration toward lymphoid tissue could be involved in cancer immune evasion

Modeling Sustainability Reporting with Ternary Attractor Neural Networks

International Conference on Mining Intelligence and Knowledge Exploration. Cluj-Napoca, Romania, December 20–22, 2018This work models the Corporate Sustainability General Reporting Initiative (GRI) using a ternary attractor network. A dataset of years evolution of the GRI reports for a world-wide set of companies was compiled from a recent work and adapted to match the pattern coding for a ternary attractor network. We compare the performance of the network with a classical binary attractor network. Two types of criteria were used for encoding the ternary network, i.e., a simple and weighted threshold, and the performance retrieval was better for the latter, highlighting the importance of the real patterns’ transformation to the three-state coding. The network exceeds the retrieval performance of the binary network for the chosen correlated patterns (GRI). Finally, the ternary network was proved to be robust to retrieve the GRI patterns with initial noise.This work has been supported by Spanish grants MINECO (http://www.mineco.gob.es/) TIN2014-54580-R, TIN2017-84452-R, and by UAMSantander CEAL-AL/2017-08, and UDLA-SIS.MG.17.02

Intratumoral injection of dendritic cells engineered to secrete interleukin-12 by recombinant adenovirus in patients with metastatic gastrointestinal carcinomas.

PURPOSE: To evaluate the feasibility and safety of intratumoral injection of autologous dendritic cells (DCs) transfected with an adenovirus encoding interleukin-12 genes (AFIL-12) for patients with metastatic gastrointestinal carcinomas. Secondarily, we have evaluated biologic effects and antitumoral activity. PATIENTS AND METHODS: Seventeen patients with metastatic pancreatic (n = 3), colorectal (n = 5), or primary liver (n = 9) malignancies entered the study. DCs were generated from CD14+ monocytes from leukapheresis, cultured and transfected with AFIL-12 before administration. Doses from 10 x 10(6) to 50 x 10(6) cells were escalated in three cohorts of patients. Patients received up to three doses at 21-day intervals. RESULTS: Fifteen (88%) and 11 of 17 (65%) patients were assessable for toxicity and response, respectively. Intratumoral DC injections were mainly guided by ultrasound. Treatment was well tolerated. The most common side effects were lymphopenia, fever, and malaise. Interferon gamma and interleukin-6 serum concentrations were increased in 15 patients after each treatment, as well as peripheral blood natural killer activity in five patients. DC transfected with AFIL-12 stimulated a potent antibody response against adenoviral capsides. DC treatment induced a marked increase of infiltrating CD8+ T lymphocytes in three of 11 tumor biopsies analyzed. A partial response was observed in one patient with pancreatic carcinoma. Stable disease was observed in two patients and progression in eight patients, with two of the cases fast-progressing during treatment. CONCLUSION: Intratumoral injection of DC transfected with an adenovirus encoding interleukin-12 to patients with metastatic gastrointestinal malignancies is feasible and well tolerated. Further studies are necessary to define and increase clinical efficacy

Properties of the CsI(Tl) detector elements of the CALIFA detector

In the R3B experiment at FAIR, charged particles with energies up to 600 MeV and forward boosted γ-rays with energies up to 20 MeV need to be detected in scattering experiments. Calorimeters for nuclear physics experiments of this kind, using relativistic radioactive ion beams, require high energy resolution and high efficiency for simultaneous detection of strongly Doppler shifted γ-rays and high-energy charged particles. A calorimeter design that can meet these requirements, using CsI(Tl) scintillators, results in detector elements that may exhibit light output variations with crystal depth, which can limit the attainable resolution. In this paper we present results from a systematic study of 478 detector modules of CALIFA, the R3B calorimeter, in order to determine and minimize such variations. To facilitate further systematic studies we also present results for the total absorption length of the scintillation light, using spectrophotometry, light crosstalk between adjacent detector modules, and surface topography of the CsI(Tl) crystals from atomic force microscopy.Swedish research council | Ref. 2017-03986Swedish research council | Ref. 2014-06644Swedish research council | Ref. 2013-04178Swedish research council | Ref. 2012-04550BMBF, Alemania | Ref. 05P15WOFNABMBF, Alemania | Ref. 05P19WOFN1BMBF, Alemania | Ref. 05P15RDFN1BMBF, Alemania | Ref. 05P19RDFN

Commissioning of the CALIFA Barrel Calorimeter of the R3^{3}B Experiment at FAIR

CALIFA is the high efficiency and energy resolution calorimeter for the R$^{3}$B experiment at FAIR, intended for detecting high energy charged particles and $\gamma$-rays in inverse kinematics direct reactions. It surrounds the reaction target in a segmented configuration of Barrel and Forward End-Cap pieces. The CALIFA Barrel consists of 1952 detection units made of CsI(Tl) long-shaped scintillator crystals, and it is being commissioned during the Phase0 experiments at FAIR. The first setup for the CALIFA Barrel commissioning is presented here. Results of detector performance with $\gamma$-rays are obtained, and show that the system fulfills the design requirements

Impact of uterine manipulator on oncological outcome in endometrial cancer surgery

Background: There are limited data available to indicate whether oncological outcomes might be influenced by the uterine manipulator, which is used at the time of hysterectomy for minimally invasive surgery in patients with endometrial cancer. The current evidence derives from retrospective studies with limited sample sizes. Without substantial evidence to support its use, surgeons are required to make decisions about its use based only on their personal choice and surgical experience. Objective: To evaluate the use of the uterine manipulator on oncological outcomes after minimally invasive surgery, for apparent early-stage endometrial cancer. Study Design: We performed a retrospective multicentric study to assess the oncological safety of uterine manipulator use in patients with apparent early-stage endometrial cancer, treated with minimally invasive surgery. The type of manipulator, surgical staging, histology, lymphovascular space invasion, International Federation of Gynecology and Obstetrics stage, adjuvant treatment, recurrence, and pattern of recurrence were evaluated. The primary objective was to determine the relapse rate. The secondary objective was to determine recurrence-free survival, overall survival, and the pattern of recurrence. Results: A total of 2661 women from 15 centers were included; 1756 patients underwent hysterectomy with a uterine manipulator and 905 without it. Both groups were balanced with respect to histology, tumor grade, myometrial invasion, International Federation of Gynecology and Obstetrics stage, and adjuvant therapy. The rate of recurrence was 11.69% in the uterine manipulator group and 7.4% in the no-manipulator group (P<.001). The use of the uterine manipulator was associated with a higher risk of recurrence (hazard ratio, 2.31; 95% confidence interval, 1.27–4.20; P=.006). The use of uterine manipulator in uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics [FIGO] I–II) was associated with lower disease-free survival (hazard ratio, 1.74; 95% confidence interval, 0.57–0.97; P=.027) and higher risk of death (hazard ratio, 1.74; 95% confidence interval, 1.07–2.83; P=.026). No differences were found regarding the pattern of recurrence between both groups (chi-square statistic, 1.74; P=.63). Conclusion: In this study, the use of a uterine manipulator was associated with a worse oncological outcome in patients with uterus-confined endometrial cancer (International Federation of Gynecology and Obstetrics I–II) who underwent minimally invasive surgery. Prospective trials are essential to confirm these results

Corporate Social Responsibility Strategies of Spanish Listed Firms and Controlling Shareholders’ Representatives

This article aims at analyzing how controlling shareholders’ representatives on boards affect corporate social responsibility (CSR) strategies (disclosing CSR matters) in Spain, a context characterized by high ownership concentration, one-tier boards, little board independence, weak legal protection for investors, and the presence of large shareholders, especially institutional shareholders. Furthermore, among controlling shareholders’ representatives, we can distinguish between those appointed by insurance companies and banks and those appointed by mutual funds, investment funds, and pension funds. The effect of these categories of directors on CSR strategies is, therefore, also analyzed. Our findings suggest that controlling shareholders’ representatives have a positive effect on CSR strategies, as do directors appointed by investment funds, pension funds, and mutual funds, while directors appointed by banks and insurance companies have no impact on CSR strategies. This analysis offers new insights into the role played by certain types of directors on CSR strategies