Differentiation, Quantification and Identification of Abrin and Abrus precatorius Agglutinin

Abrin, the toxic lectin from the rosary pea plant Abrus precatorius, has gained considerable interest in the recent past due to its potential malevolent use. However, reliable and easy-to-use assays for the detection and discrimination of abrin from related plant proteins such as Abrus precatorius agglutinin or the homologous toxin ricin from Ricinus communis are sparse. To address this gap, a panel of highly specific monoclonal antibodies was generated against abrin and the related Abrus precatorius agglutinin. These antibodies were used to establish two sandwich ELISAs to preferentially detect abrin or A. precatorius agglutinin (limit of detection 22 pg/mL for abrin; 35 pg/mL for A. precatorius agglutinin). Furthermore, an abrin-specific lateral flow assay was developed for rapid on-site detection (limit of detection ~1 ng/mL abrin). Assays were validated for complex food, environmental and clinical matrices illustrating broad applicability in different threat scenarios. Additionally, the antibodies turned out to be suitable for immuno-enrichment strategies in combination with mass spectrometry-based approaches for unambiguous identification. Finally, we were able to demonstrate for the first time how the developed assays can be applied to detect, identify and quantify abrin from a clinical sample derived from an attempted suicide case involving A. precatorius.Peer Reviewe

Prospective study of the 532 nm laser (KTP) versus diode laser 980 nm in the resection of hyperplastic lesions of the oral cavity

The aim of this study is to evaluate the resection of hyperplastic lesions on the buccal mucosa comparing the 532nm laser (KTP), versus diode 980nm laser, considering pain, scarring, inflammation and drug consumption that occurred postoperatively with each lasers. A prospective study of consecutive series of 20 patients in two groups that presents hyperplastic lesions on the buccal mucosa. The choice of the KTP laser or diode 980nm laser for the surgery was made randomly. The power used was 1.5W in both groups in a continuous wave mode with a 320 ?m optical fiber. Parameters of pain, scarring, inflammation and consumption of drugs were recorded by a Numerical Rating Scale and evaluated postoperatively. These recordings were made the day of the surgery, 24 hours after, 14 and 28 days after. Pain and inflammation was light - moderate. The consumption of paracetamol was somewhat higher in the diode 980nm laser versus the KTP laser after 24 hours, although data was not statistically significant; significant differences were found after 28 days in regards to pain (p = 0.023) and inflammation (p = 0.023), but always in the absence parameter so we find no pain in both lasers. Scarring in the two types of laser showed no differences along the visits, with not detected scar retractable. Although there is a slight histological difference regarding the KTP laser in the oral soft tissues for clinical use, both wavelengths are very suitable for excision of oral fibroma

Complete surgical resection improves outcome in INRG high-risk patients with localized neuroblastoma older than 18 months

Background: Although several studies have been conducted on the role of surgery in localized neuroblastoma, the impact of surgical timing and extent of primary tumor resection on outcome in high-risk patients remains controversial. Methods: Patients from the German neuroblastoma trial NB97 with localized neuroblastoma INSS stage 1-3 age > 18 months were included for retrospective analysis. Imaging reports were reviewed by two independent physicians for Image Defined Risk Factors (IDRF). Operation notes and corresponding imaging reports were analyzed for surgical radicality. The extent of tumor resection was classified as complete resection (95-100%), gross total resection (90-95%), incomplete resection (50-90%), and biopsy (<50%) and correlated with local control rate and outcome. Patients were stratified according to the International Neuroblastoma Risk Group (INRG) staging system. Survival curves were estimated according to the method of Kaplan and Meier and compared by the log-rank test. Results: A total of 179 patients were included in this study. 77 patients underwent more than one primary tumor operation. After best surgery, 68.7% of patients achieved complete resection of the primary tumor, 16. 8% gross total resection, 14.0% incomplete surgery, and 0.5% biopsy only. The cumulative complication rate was 20.3% and the surgery associated mortality rate was 1.1%. Image defined risk factors (IDRF) predicted the extent of resection. Patients with complete resection had a better local-progression-free survival (LPFS), event-free survival (EFS) and OS (overall survival) than the other groups. Subgroup analyses showed better EFS, LPFS and OS for patients with complete resection in INRG high-risk patients. Multivariable analyses revealed resection (complete vs. other), and MYCN (non-amplified vs. amplified) as independent prognostic factors for EFS, LPFS and OS. Conclusions: In patients with localized neuroblastoma age 18 months or older, especially in INRG high-risk patients harboring MYCN amplification, extended surgery of the primary tumor site improved local control rate and survival with an acceptable risk of complications

On Assessing Trustworthy AI in Healthcare. Machine Learning as a Supportive Tool to Recognize Cardiac Arrest in Emergency Calls

Artificial Intelligence (AI) has the potential to greatly improve the delivery of healthcare and other services that advance population health and wellbeing. However, the use of AI in healthcare also brings potential risks that may cause unintended harm. To guide future developments in AI, the High-Level Expert Group on AI set up by the European Commission (EC), recently published ethics guidelines for what it terms “trustworthy” AI. These guidelines are aimed at a variety of stakeholders, especially guiding practitioners toward more ethical and more robust applications of AI. In line with efforts of the EC, AI ethics scholarship focuses increasingly on converting abstract principles into actionable recommendations. However, the interpretation, relevance, and implementation of trustworthy AI depend on the domain and the context in which the AI system is used. The main contribution of this paper is to demonstrate how to use the general AI HLEG trustworthy AI guidelines in practice in the healthcare domain. To this end, we present a best practice of assessing the use of machine learning as a supportive tool to recognize cardiac arrest in emergency calls. The AI system under assessment is currently in use in the city of Copenhagen in Denmark. The assessment is accomplished by an independent team composed of philosophers, policy makers, social scientists, technical, legal, and medical experts. By leveraging an interdisciplinary team, we aim to expose the complex trade-offs and the necessity for such thorough human review when tackling socio-technical applications of AI in healthcare. For the assessment, we use a process to assess trustworthy AI, called 1Z-Inspection® to identify specific challenges and potential ethical trade-offs when we consider AI in practice.</jats:p

Classification of current anticancer immunotherapies

© 2014. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into "passive" and "active" based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches.info:eu-repo/semantics/publishedVersio

Climate seasonality limits leaf carbon assimilation and wood productivity in tropical forests

The seasonal climate drivers of the carbon cycle in tropical forests remain poorly known, although these forests account for more carbon assimilation and storage than any other terrestrial ecosystem. Based on a unique combination of seasonal pan-tropical data sets from 89 experimental sites (68 include aboveground wood productivity measurements and 35 litter productivity measurements), their associated canopy photosynthetic capacity (enhanced vegetation index, EVI) and climate, we ask how carbon assimilation and aboveground allocation are related to climate seasonality in tropical forests and how they interact in the seasonal carbon cycle. We found that canopy photosynthetic capacity seasonality responds positively to precipitation when rainfall is  < 2000 mm yr⁻¹ (water-limited forests) and to radiation otherwise (light-limited forests). On the other hand, independent of climate limitations, wood productivity and litterfall are driven by seasonal variation in precipitation and evapotranspiration, respectively. Consequently, light-limited forests present an asynchronism between canopy photosynthetic capacity and wood productivity. First-order control by precipitation likely indicates a decrease in tropical forest productivity in a drier climate in water-limited forest, and in current light-limited forest with future rainfall  < 2000 mm yr⁻¹

Rectore Magnificentissimo, Serenissimo Ivventvtis Principe, Ac Domino, Dn. Friderico Avgvsto, Principe Regio, Atqve Elect. Sax. Herede ... Posteriorem De Sacris Mvlhvsinis Dissertationem Praeses M. Christianvs Gvilhelmvs Vollandvs, Et Respondens, Ioannes Martinvs Akivs, Mvlhvsini, ... Anno A.O.R. M D CCIIII. Horis Pomeridianis.

RECTORE MAGNIFICENTISSIMO, SERENISSIMO IVVENTVTIS PRINCIPE, AC DOMINO, DN. FRIDERICO AVGVSTO, PRINCIPE REGIO, ATQVE ELECT. SAX. HEREDE ... POSTERIOREM DE SACRIS MVLHVSINIS DISSERTATIONEM PRAESES M. CHRISTIANVS GVILHELMVS VOLLANDVS, ET RESPONDENS, IOANNES MARTINVS AKIVS, MVLHVSINI, ... ANNO A.O.R. M D CCIIII. HORIS POMERIDIANIS. Rectore Magnificentissimo, Serenissimo Ivventvtis Principe, Ac Domino, Dn. Friderico Avgvsto, Principe Regio, Atqve Elect. Sax. Herede ... Posteriorem De Sacris Mvlhvsinis Dissertationem Praeses M. Christianvs Gvilhelmvs Vollandvs, Et Respondens, Ioannes Martinvs Akivs, Mvlhvsini, ... Anno A.O.R. M D CCIIII. Horis Pomeridianis. (1) Titelblatt (1) Dissert. II. De Sacris Mulhusinis (3

Stereochemical course of the reaction between thiocarbonyl compounds and oxiranes: reaction with cis- and trans-2,3-dimethyloxirane

The reactions of thiocarbonyl compounds with cis-2,3-dimethyloxirane (1a) in CH2Cl2 in the presence of BF3.Et2O or SnCl4 led to trans-4,5-dimethyl-1,3-oxathiolanes, whereas with trans-2,3-dimethyloxirane (1b) cis-4,5-dimethyl-1,3-oxathiolanes were formed. With the stronger Lewis acid SnCl4 , the formation of side-products was also observed. In the case of 1,3-thiazole-5(4H)-thione 2, these side-products are the corresponding 1,3- thiazol-5(4H)-one 5 and the 1:2 adduct 8 (Schemes 2-4). Their formation can be rationalized by the decomposition of the initially formed spirocyclic 1,3-oxathiolane and by a second addition onto the C=N bond of the 1 : 1 adduct, respectively. The secondary epimerization by inversion of the configuration of the spiro-C-atom (Schemes 5 - 7) can be explained by a Lewis-acid-catalyzed ring opening of the 1,3-oxathiolane ring and subsequent ring closure to the thermodynamically more stable isomer (Scheme 12). In the case of 2,2,4,4-tetramethyl-3-thioxocyclobutanone (20), apart from the expected spirocyclic 1,3-oxathiolanes 21 and 23, dispirocyclic 1 : 2 adducts were formed by a secondary addition onto the C=O group of the four-membered ring (Schemes 9 and 10)