A phase II randomized clinical trial to assess toxicity and quality of life of breast cancer patients with hypofractionated versus conventional fractionation radiotherapy with regional nodal irradiation in the context of COVID-19 crisis.

Purpose: This study, conducted during the COVID-19 crisis, primarily aimed to compare the acute toxicity between conventional fractionated radiation therapy (CF-RT) with hypofractionated radiation therapy (HF-RT) among patients who underwent breast-conserving surgery or mastectomy in whom breast or chest wall and regional nodal irradiation (RNI) were indicated. The secondary endpoints were both acute and subacute toxicity, cosmesis, quality of life, and lymphedema features. Methods: In this open and non-inferiority randomized trial, patients (n = 86) were randomly allocated 2:1 in the CF-RT arm (n = 33; 50 Gy/25 fractions ± sequential boost [10 Gy/5 fractions]) versus the HF-RT arm (n = 53; 40 Gy/15 fractions ± concomitant boost [8 Gy/15 fractions]). Toxic effects and cosmesis evaluation used the Common Terminology Criteria for Adverse Events, version 4.03 (CTCAE) and the Harvard/National Surgical Adjuvant Breast and Bowel Project (NSABP)/Radiation Therapy Oncology Group (RTOG) scale. For the patient-reported quality of life (QoL), the European Organisation for Research and Treatment of Cancer quality of life questionnaire (EORTC QLQ-C30) and the breast cancer-specific supplementary questionnaire (QLQ-BR23) were used. Lymphedema was assessed by comparing volume differences between the affected and contralateral arms using the Casley-Smith formula. Results: Grade 2 and grade 3 dermatitis were lower with HF-RT than with CF-RT (28% vs. 52%, and 0% vs. 6%, respectively; p = 0.022). HF-RT had a lower rate of grade 2 hyperpigmentation (23% vs. 55%; p = 0.005), compared to CF-RT. No other differences in overall rates of physician-assessed grade 2 or higher and grade 3 or higher acute toxicity between HF-RT and CF-RT were registered. There was no statistical difference between groups regarding cosmesis, lymphedema rate (13% vs. 12% HF-RT vs. CF-RT; p = 1.000), and functional and symptom scales, during both the irradiation period and after 6 months of the end of treatment. The results revealed that the subset of patients up to 65 years or older did not show a statistical difference between both arm fractionation schedules (p > 0.05) regarding skin rash, fibrosis, and lymphedema. Conclusion: HF-RT was non-inferior to CF-RT, and moderate hypofractionation showed lower rates of acute toxicity, with no changes in quality-of-life outcomes. Clinical trial registration: ClinicalTrials.gov, identifier NCT40155531.

A new circular economy approach for integrated production of tomatoes and mushrooms.

Spent mushroom Substrate is the by-product generated at the end of the mushroom growing cycle. It can be used in agriculture for different purposes, including seedling production, soil conditioning or application as an organic fertilizer. Tomato is one of the world́s most important crops, requiring considerable care, in terms of both nutrition and disease control. The objective of this study was to investigate the viability of spent mushroom substrate as a nutrient source for tomato seedlings and develop an integrated tomato and mushroom co-production system. For seedling production, different compositions were evaluated with spent mushroom substrate from Pleurotus ostreatus or substrate colonized with Agaricus bisporus. The parameters evaluated comprised germination rate, seedling quality and physicochemical analysis. A tomato and mushroom integrated production system was developed using a 40-liter pot divided into upper (spent mushroom substrate and soil), middle (spent mushroom substrate from P. ostreatus) and lower (gravel) layers. For seedlings production, plants treated with the substrate colonized with A. bisporus presented a superior root length (10.1 cm) and aerial part length (6.6 cm). Co-production of tomato and mushrooms was also shown to be viable. In this co-cultivation system between tomato and mushroom, the treatment with the substrate colonized with A. bisporus differed from others, with this treatment presenting high yields of tomato (2.35 kg/plant pot) and mushrooms (1.33 kg/plant pot) within the same bucket. With this co-production system, the tomato production time was reduced by 60 days and prolonged continuous mushroom production by 120 days. These findings show a sustainable approach to manage different agroindustrial residues, encouraging the use of these residues for olericulture and fungiculture production.

Outdoor versus indoor cultivation: Effects on the metabolite profile of Agaricus subrufescens strains analyzed by untargeted metabolomics.

Agaricus subrufescens has emerged as an important culinary-medicinal mushroom over the last decades. Efforts have been dedicated to upgrade the A. subrufescens productive process via strain selection and cultivation scaling-up. However, little is known on the influence of those variables on the metabolite profiles and nutraceutical properties of this mushroom. In this work, the effects of outdoor versus indoor cultivation on the metabolite profiles of five commercial strains of A. subrufescens were investigated by untargeted metabolomics. UHPLC-MS coupled to multivariate data analysis revealed that the concentration of several metabolites with reported health-related properties as well as related to taste and browning varied significantly between strains and were affected by the cultivation system in a strain-dependent manner. Data suggest that increasing the production scale by means of indoor cultivation may decrease the nutraceutical quality of some A. subrufescens strains while also affecting taste and browning susceptibility to different extents.

Cerebrospinal Fluid Chitinases as Biomarkers for Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease that affects motor neurons controlling voluntary muscles. Survival is usually 2-5 years after onset, and death occurs due to respiratory failure. The identification of biomarkers would be very useful to help in disease diagnosis and for patient stratification based on, e.g., progression rate, with implications in therapeutic trials. Neurofilaments constitute already-promising markers for ALS and, recently, chitinases have emerged as novel marker targets for the disease. Here, we investigated cerebrospinal fluid (CSF) chitinases as potential markers for ALS. Chitotriosidase (CHIT1), chitinase-3-like protein 1 (CHI3L1), chitinase-3-like protein 2 (CHI3L2) and the benchmark marker phosphoneurofilament heavy chain (pNFH) were quantified by an enzyme-linked immunosorbent assay (ELISA) from the CSF of 34 ALS patients and 24 control patients with other neurological diseases. CSF was also analyzed by UHPLC-mass spectrometry. All three chitinases, as well as pNFH, were found to correlate with disease progression rate. Furthermore, CHIT1 was elevated in ALS patients with high diagnostic performance, as was pNFH. On the other hand, CHIT1 correlated with forced vital capacity (FVC). The three chitinases correlated with pNFH, indicating a relation between degeneration and neuroinflammation. In conclusion, our results supported the value of CHIT1 as a diagnostic and progression rate biomarker, and its potential as respiratory function marker. The results opened novel perspectives to explore chitinases as biomarkers and their functional relevance in ALS.

Data sharing in PredRet for accurate prediction of retention time: Application to plant food bioactive compounds.

Prediction of retention times (RTs) is increasingly considered in untargeted metabolomics to complement MS/MS matching for annotation of unidentified peaks. We tested the performance of PredRet (http://predret.org/) to predict RTs for plant food bioactive metabolites in a data sharing initiative containing entry sets of 29-103 compounds (totalling 467 compounds, >30 families) across 24 chromatographic systems (CSs). Between 27 and 667 predictions were obtained with a median prediction error of 0.03-0.76 min and interval width of 0.33-8.78 min. An external validation test of eight CSs showed high prediction accuracy. RT prediction was dependent on shape and type of LC gradient, and number of commonly measured compounds. Our study highlights PredRet's accuracy and ability to transpose RT data acquired from one CS to another CS. We recommend extensive RT data sharing in PredRet by the community interested in plant food bioactive metabolites to achieve a powerful community-driven open-access tool for metabolomics annotation.

Esthetic harmonization of front upper teeth using composite resin: a clinical case report / Harmonização estética de dentes ântero-superiores com resina composta: relato de caso clínico

ABSTRACT Every day, professionals who work with esthetics are faced with the challenge of meeting patients expectations who longs for a perfect smile, where every detail must show harmony and naturality. In this context, composite resin reanatomization is widely indicated for small corrections of color and shape in one or more dental elements, for diastema closure and sometimes for correction of small dental misalignment. The case report presented here discuss the planning and treatment for the esthetic and functional improvement of the dental units 1.1, 1.2, 2.1 and 2.2, by making direct restorations in composite resin. The patient sought the Faculty of Dentistry of UFBA in search of esthetic treatment, reporting dissatisfaction with the smile. During an evaluation, the thickness and size of the upper back teeth were dissonant, besides of the interincisal diastema and a discrete gyroversion of the lateral incisors, which together compromised the esthetic area of the smile. Therefore, the proposed treatment for solving this clinical situation was direct esthetic rehabilitation with composite resin in units 1.2 to 2.2. After obtaining the study models, it was accomplished diagnostic waxing and silicone guide as auxiliary resources on the planning and restorative stage. Nanoparticulate composite resins were used, making a stratification technique to obtain a harmonic result. The treatment was able to reproduce the esthetic and natural appearance of the teeth, through a conservative alternative, fast and with an excellent cost-benefit relation when compared to the indirect techniques.

RESUMO Profissionais que trabalham com estética se deparam diariamente com o desafio de atender as expectativas dos pacientes que anseiam por um sorriso perfeito, onde cada detalhe deve evidenciar harmonia e naturalidade. Neste contexto, a reanatomização em resina composta é amplamente indicada, para pequenas correções de cor e forma, em um ou mais elementos dentais, para fechamento de diastemas e, por vezes, para correção de pequenos desalinhamentos dentais. O relato de caso aqui apresentado discute o planejamento e tratamento realizado para a melhora estética e funcional das unidades dentais 1.1, 1.2, 2.1 e 2.2, por meio da confecção de restaurações diretas em resina composta. A paciente procurou a Faculdade de Odontologia da UFBA em busca de tratamento estético, relatando insatisfação com o sorriso. Durante a avaliação, foi observada desarmonia de espessura e tamanho em dentes ântero-superiores, além de diastema interincisal e discreta giroversão dos incisivos laterais, que em conjunto comprometia a zona estética do sorriso. O tratamento proposto para solucionar esta situação clínica foi a reabilitação estética direta com resina composta nas unidades 1.2 ao 2.2. Após a obtenção dos modelos de estudo, foi realizado o enceramento diagnóstico e guia de silicona como recursos auxiliares no planejamento e etapa restauradora. Foram utilizadas resinas compostas nanoparticuladas, realizando a técnica de estratificação para a obtenção de um resultado harmônico. O tratamento realizado conseguiu reproduzir a aparência estética e natural dos dentes, através de uma alternativa conservadora, rápida e com ótima relação custo-benefício quando comparada às técnicas indiretas.

Exploring the analytical power of the QTOF MS platform to assess monoclonal antibodies quality attributes.

The biopharmaceutical industry is growing at a fast pace, making nowadays 20% of the pharma market. Within this market, therapeutic monoclonal antibodies (mAbs) are the dominant product class. With the patent expirations, biosimilars and, perhaps more relevant, biobetters, are in fast development. Thus, a comprehensive characterization at the molecular level of antibodies heterogeneity such as glycoforms, post-translational modifications (PTMs) and sequence variations is of utmost importance. Mass spectrometry (MS)-based approaches are undoubtedly the most powerful analytical strategies to monitor and define an array of critical quality attributes on mAbs. In this work, we demonstrate the analytical power of the Q-TOF MS platform for comprehensive and detailed analysis at molecular levels of an in-house produced mAb. This methodology involves minimal sample preparation procedures and provides an extensive collection of valuable data in a short period of time.

Interlaboratory Coverage Test on Plant Food Bioactive Compounds and their Metabolites by Mass Spectrometry-Based Untargeted Metabolomics.

Bioactive compounds present in plant-based foods, and their metabolites derived from gut microbiota and endogenous metabolism, represent thousands of chemical structures of potential interest for human nutrition and health. State-of-the-art analytical methodologies, including untargeted metabolomics based on high-resolution mass spectrometry, are required for the profiling of these compounds in complex matrices, including plant food materials and biofluids. The aim of this project was to compare the analytical coverage of untargeted metabolomics methods independently developed and employed in various European platforms. In total, 56 chemical standards representing the most common classes of bioactive compounds spread over a wide chemical space were selected and analyzed by the participating platforms (n = 13) using their preferred untargeted method. The results were used to define analytical criteria for a successful analysis of plant food bioactives. Furthermore, they will serve as a basis for an optimized consensus method.

First report of Dirofilaria immitis in the Republic of Cape Verde.

In Maio Island, Republic of Cape Verde, a seven-year old mongrel female dog exhibiting severe generalized adenomegaly and a poor body condition was examined during an animal welfare campaign. A blood smear was drawn from peripheral blood collection and several organisms consistent with Dirofilaria immitis microfilariae were identified. Both the antigen test conducted from plasma and the RT-PCR test performed from the blood smear sample were positive for D. immitis. This is, to the best of our knowledge, the first report of D. immitis in Cape Verde. The fact that the dog was autochthonous and had never left the island strongly suggests there might be other animals infected with the parasite. Our finding confirms the existence of the parasite in the canine population and necessarily implies the presence of a competent vector. As a serious cardiopulmonary disease and with the risk of the pathogen spreading rapidly, broader epidemiological studies need to be conducted to determine D. immitis prevalence in the canine population of Maio Island.