Effect of moderate hydrostatic pressures on the enzymatic activity and bioactive composition of pineapple by-products

Special Issue Original ArticleThe application of abiotic stresses by moderate hydrostatic pressures (MHP) is still underdeveloped. Abiotic stresses allow activating the enzymatic complexes inducing the synthesis of de novo bioactive compounds. Pineapple by-products are rich in bromelain and bioactive compounds that can be enhanced through abiotic stresses. The aim of this study was to evaluate the effect of MHP on the enzymatic activity of pineapple by-products. Pineapple by-products were submitted to MHP (50–400 MPa between 1 and 15 min) according to a central composite factorial design matrix. Samples were stored at 5 ± 1 C for 24 hr, to allow enzymatic activity to occur. Enzymatic and antioxidant activities and total phenolic compounds (TPC) were quantified. MHP promoted a 262% increase in the phenylalanine ammonia-lyase activity and 36% increase in TPC, in shell samples. In core the activity of bromelain increased 350%. These results pinpoint the potential to increase the value of pineapple by-products by enhancing the amounts of bioactive compounds through MHP applicationinfo:eu-repo/semantics/publishedVersio

Regression-based Deep-Learning predicts molecular biomarkers from pathology slides

Deep Learning (DL) can predict biomarkers from cancer histopathology. Several clinically approved applications use this technology. Most approaches, however, predict categorical labels, whereas biomarkers are often continuous measurements. We hypothesized that regression-based DL outperforms classification-based DL. Therefore, we developed and evaluated a new self-supervised attention-based weakly supervised regression method that predicts continuous biomarkers directly from images in 11,671 patients across nine cancer types. We tested our method for multiple clinically and biologically relevant biomarkers: homologous repair deficiency (HRD) score, a clinically used pan-cancer biomarker, as well as markers of key biological processes in the tumor microenvironment. Using regression significantly enhances the accuracy of biomarker prediction, while also improving the interpretability of the results over classification. In a large cohort of colorectal cancer patients, regression-based prediction scores provide a higher prognostic value than classification-based scores. Our open-source regression approach offers a promising alternative for continuous biomarker analysis in computational pathology

Evaluation of the pharmacotherapeutic profile of HIV/AIDS bearers

In this work was evaluated the pharmacotherapeutic profile of HIV/AIDS bearers registered in the Service of Specialized Attendance located in Campina Grande–PB, Brazil. The research was of the type traverse, documental, descriptive and analytical and was realized in the period of August to October 2010. Were appraised the patient records of 188 people being 66 % males and 34% females. The most part (36 %) just studied the education fundamental level and presented age group between 40-49 years old. Antiretrovirals more prescribed were nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse-transcriptase inhibitors (NNRTIs). Schemes no recommended by the Ministry of Health also were evidenced. The Negative Results associated to the use of medicine was registered in the three supra-categories. It is necessary a larger integration of the multidisciplinary team of prescribers (physicians and dentists) and pharmacists in the evaluation of the pharmacotherapy to guarantee the reduction of the morbidity and the presence of opportunists infections, guaranteeing so a better surviving for the seropositive patients.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Recommendations for the use of next-generation sequencing (NGS) for patients with metastatic cancers: a report from the ESMO Precision Medicine Working Group

Next-generation sequencing (NGS) allows sequencing of a high number of nucleotides in a short time frame at an affordable cost. While this technology has been widely implemented, there are no recommendations from scientific societies about its use in oncology practice. The European Society for Medical Oncology (ESMO) is proposing three levels of recommendations for the use of NGS. Based on the current evidence, ESMO recommends routine use of NGS on tumour samples in advanced non-squamous non-small-cell lung cancer (NSCLC), prostate cancers, ovarian cancers and cholangiocarcinoma. In these tumours, large multigene panels could be used if they add acceptable extra cost compared with small panels. In colon cancers, NGS could be an alternative to PCR. In addition, based on the KN158 trial and considering that patients with endometrial and small-cell lung cancers should have broad access to anti-programmed cell death 1 (anti-PD1) antibodies, it is recommended to test tumour mutational burden (TMB) in cervical cancers, well- and moderately-differentiated neuroendocrine tumours, salivary cancers, thyroid cancers and vulvar cancers, as TMB-high predicted response to pembrolizumab in these cancers. Outside the indications of multigene panels, and considering that the use of large panels of genes could lead to few clinically meaningful responders, ESMO acknowledges that a patient and a doctor could decide together to order a large panel of genes, pending no extra cost for the public health care system and if the patient is informed about the low likelihood of benefit. ESMO recommends that the use of off-label drugs matched to genomics is done only if an access programme and a procedure of decision has been developed at the national or regional level. Finally, ESMO recommends that clinical research centres develop multigene sequencing as a tool to screen patients eligible for clinical trials and to accelerate drug development, and prospectively capture the data that could further inform how to optimise the use of this technology

Integrated Functional, Gene Expression and Genomic Analysis for the Identification of Cancer Targets

The majority of new drug approvals for cancer are based on existing therapeutic targets. One approach to the identification of novel targets is to perform high-throughput RNA interference (RNAi) cellular viability screens. We describe a novel approach combining RNAi screening in multiple cell lines with gene expression and genomic profiling to identify novel cancer targets. We performed parallel RNAi screens in multiple cancer cell lines to identify genes that are essential for viability in some cell lines but not others, suggesting that these genes constitute key drivers of cellular survival in specific cancer cells. This approach was verified by the identification of PIK3CA, silencing of which was selectively lethal to the MCF7 cell line, which harbours an activating oncogenic PIK3CA mutation. We combined our functional RNAi approach with gene expression and genomic analysis, allowing the identification of several novel kinases, including WEE1, that are essential for viability only in cell lines that have an elevated level of expression of this kinase. Furthermore, we identified a subset of breast tumours that highly express WEE1 suggesting that WEE1 could be a novel therapeutic target in breast cancer. In conclusion, this strategy represents a novel and effective strategy for the identification of functionally important therapeutic targets in cancer

Single hadron response measurement and calorimeter jet energy scale uncertainty with the ATLAS detector at the LHC

The uncertainty on the calorimeter energy response to jets of particles is derived for the ATLAS experiment at the Large Hadron Collider (LHC). First, the calorimeter response to single isolated charged hadrons is measured and compared to the Monte Carlo simulation using proton-proton collisions at centre-of-mass energies of sqrt(s) = 900 GeV and 7 TeV collected during 2009 and 2010. Then, using the decay of K_s and Lambda particles, the calorimeter response to specific types of particles (positively and negatively charged pions, protons, and anti-protons) is measured and compared to the Monte Carlo predictions. Finally, the jet energy scale uncertainty is determined by propagating the response uncertainty for single charged and neutral particles to jets. The response uncertainty is 2-5% for central isolated hadrons and 1-3% for the final calorimeter jet energy scale.Comment: 24 pages plus author list (36 pages total), 23 figures, 1 table, submitted to European Physical Journal