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INDUCTION: chemotherapy (IC) followed by chemoradiation (CRT) is an attractive approach in high-risk locally advanced rectal cancer. Additionally, ASA has shown potential to improve outcomes alongside CRT in rectal cancer. The ICAR trial aimed to evaluate the safety and efficacy of IC followed by CRT with or without ASA on MRI tumor response.Single-center, double-blind, randomized phase II trial to evaluate induction treatment with CAPOX, followed by capecitabine-based chemoradiotherapy with ASA (arm 1) or placebo (arm 2) in high-risk stage II-III rectal adenocarcinoma staged by MRI. The primary endpoint was MRI tumor regression grade (mrTRG). Secondary endpoints were pathological response, surgical outcomes, postoperative complications, treatment tolerance, DFS, and OS.Between January 2018 and August 2019, 27 patients were eligible, 25 (92.5%) completed IC, and 23 patients were randomly assigned (12 to ASA group; 11 to placebo group). In the ASA arm, 3 pts (25%) presented distant disease progression at restaging. Seven patients (30.4%) had cCR after neoadjuvant treatment. All 13 patients submitted to surgery after neoadjuvant treatment underwent R0 resections except for 1 patient with positive CRM, and 12 patients (92.3%) had sphincter preservation. After a median follow-up of 34.9 months, the 2-year DFS was 83.1% and 3-year OS was 81.5%.There was good compliance in both treatment arms and encouraging cCR rate. ASA during CRT was safe but failed to improve on MRI tumor response. The study was closed due to the absence of benefits.

Made available in DSpace on 2022-04-28T19:48:52Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) We used a high-precision weighing system and flow-through respirometry to quantify cutaneous evaporative water loss rates in woolly sheep (wool thickness, ca. 6.5 cm) and haired goats (coat thickness, ca. 2.5 cm), while simultaneously recording parallel data obtained from (1) a flow-through ventilated capsule, (2) a closed hand-held electronic evaporimeter chamber, and (3) a closed colorimetric paper disc chamber. In comparison to the weighing system and respirometry, used here as a “gold standard” measure of cutaneous evaporative water loss rate, we found relatively good agreement with data obtained from the flow-through ventilated capsules. However, we found poor agreement with data obtained from the closed electronic evaporimeter chambers (underestimated by 60%, on average) and the closed colorimetric paper disc chambers (overestimated by 52%, on average). This deviation was likely associated with a requirement for shaved skin in the closed chamber methods. Our results therefore cast doubt on the validity of the closed chamber methods for measurement of cutaneous evaporative water loss rates in furred and fleeced mammals, and instead show that more accurate values can be obtained using flow-through ventilated capsules. Innovation Group of Biometeorology and Animal Welfare Animal Science Department Universidade Federal da Paraíba Brain Function Research Group School of Physiology University of the Witwatersrand Innovation Group of Biometeorology and Animal Welfare Animal Science Department Universidade Estadual Paulista Department of Anatomy and Physiology Faculty of Veterinary Science University of Pretoria Centre for Veterinary Wildlife Research Faculty of Veterinary Science University of Pretoria Innovation Group of Biometeorology and Animal Welfare Animal Science Department Universidade Estadual Paulista FAPESP: 2016/12278-1 FAPESP: 2018/12218-4

Background: Patients with recurrent cervical cancer have a poor prognosis. Cemiplimab, the fully human programmed cell death 1 (PD-1)-blocking antibody approved to treat lung and skin cancers, has been shown to have preliminary clinical activity in this population. Methods: In this phase 3 trial, we enrolled patients who had disease progression after first-line platinum-containing chemotherapy, regardless of their programmed cell death ligand 1 (PD-L1) status. Women were randomly assigned (1:1) to receive cemiplimab (350 mg every 3 weeks) or the investigator's choice of single-agent chemotherapy. The primary end point was overall survival. Progression-free survival and safety were also assessed. Results: A total of 608 women were enrolled (304 in each group). In the overall trial population, median overall survival was longer in the cemiplimab group than in the chemotherapy group (12.0 months vs. 8.5 months; hazard ratio for death, 0.69; 95% confidence interval [CI], 0.56 to 0.84; two-sided P

In the agriculture sector, livestock are considered extremely resilient to climate change and are tipped to play a significant role in ensuring food security to meet the increased demands of growing human population by 2050. Compared to other domestic species, goats are considered the ideal animal model for climate change due to its high thermal and drought resilience, ability to survive on limited pastures, and high disease resistance. This review is therefore a revisit to the advantages of rearing goats over other livestock species under current and future trends of changes in climate, particularly to cope with recurrent multiple stressors such as heat load, and lack of water and feed. In summary, goats, also called as poor man's cow, are preferred by the small-scale landless farmers due to their low input and assured higher output system, as they require low initial investment, with minimum specialized facilities and labors. Furthermore, they perceive goats as better resilient animal to cope with multiple stressors such as heat load, and water and feed scarcity, and possess better skills to cope with bush, when compared with sheep and cattle. The unique capacity for employing behavioral plasticity and morphological features of goats gives them clear advantage over sheep and cattle, when coping with seasonal biotopes, and experiences of water and feed shortage. When facing with low-quality feed, they also are superior to cattle and sheep to digest dry matter and to recycle nitrogen. Additionally, goats have superior ability to desiccate feces and concentrate urine, when compared with sheep and cattle. These advantages make goat the go-to species for efficiently countering the adversities associated with climate change and to optimize appropriate economic return through sustained production. Therefore, goats are tipped to be the future animals with extreme potential to counter the projected alarming climate change impacts and expected to play a significant role in ensuring food security to meet the demands of the growing human population by the end of this century.

Context Cactus is an important feed resource, widely cultivated in the semi-arid Brazilian north-east owing to its resistance to drought, high production potential and high nutritional value. It is also an excellent source of energy. Therefore, its use in the diet of sheep should be optimised. Aims This study was designed to evaluate effects of different ratios of a spineless cactus (Nopalea cochenillifera) to sugarcane (Saccharum officinarum) (Cac:Sug ratio) as source of dietary roughage on the physicochemical properties and fatty acid (FA) profile of meat from lambs. Methods Experimental treatments were diets with four Cac:Sug ratios (0:3, 1:2, 2:1 and 3:0) (477 g/kg as fed) in a complete randomised block design, using 36 uncastrated male lambs (Santa Ines breed) of average initial bodyweight 22.0 ± 2.3 kg housed in individual pens. Lambs were slaughtered after 100 days and meat samples (longissimus lumborum (LL) muscle) taken. Key results Cac:Sug ratio in the roughage of the diet did not influence (P > 0.05) moisture, protein, total lipid or ash contents, pH24h, expressed juice, cooking weight losses, shear force, or colour parameters of LL muscle. However, there was a linear increase in cholesterol (P = 0.013) concentration of the meat. Increasing Cac:Sug ratio in the diet did not affect (P > 0.05) the saturated FAs (SFAs) C10:0, C12:0, C14:0, C15:0, C16:0, C17:0 and C20:0; monounsaturated FAs (MUFAs) C14:1 n–5cis, C17:1 n–7cis and C20:1 n–9cis; polyunsaturated FAs (PUFAs) C18:2 n–6cis, C18:3 n–6, C18:3 n–3, C20:2 n–6cis, C20:5 n–3cis (eicosapentaenoic acid) and C22:5 n–3 (docosapentaenoic acid); ∑n–6:∑n–3 ratio; or nutraceutical compounds. There was a linear decrease in Δ9-desaturases C16 (P = 0.042) and C18 (P < 0.001) with the increasing Cac:Sug ratio, and a quadratic decrease in C18:2 n–6trans concentration (P = 0.045). The ∑SFAs and ∑MUFAs of LL muscle tended to increase linearly with increasing Cac:Sug ratio. Conclusion Most of the physicochemical parameters of the meat of lambs were not changed by the Cac:Sug ratio in the diets. A diet containing up to 48% of DM as spineless cactus plus sugarcane in a 1:2 ratio was found to be satisfactory for finishing lambs. Implications Cac:Sug ratio up to 1:2 (spineless cactus 159 g and sugarcane 318 g/kg DM total diet) may be a useful feed strategy for lamb meat producers because improved lipid composition enriched with C18:0 and higher ∑PUFA:∑SFA ratio is considered healthy for human consumption without affecting most physical and chemical properties.

At the end of 2019, the first cases of COVID-19 were registered. As the disease spread across continents culminating in a pandemic, countries suffered from a shortage of personal protective equipment. In Brazil, the first case was recorded on February 2020. This study aims to describe the experience of creating an interinstitutional network to meet the pandemic’s demands and the experience of transforming an academic design laboratory into space for the production of personal protective equipment using 3D printing and laser cutting techniques. The actions described in this study, made it possible to meet the high emergency demand for PPE in the city of Rio de Janeiro, as well as the construction of knowledge both within the scope of building networks to solve complex social problems and about the possibilities of production in an academic environment. The work addresses and reflexes this action on society's perception of Design professionals.

Made available in DSpace on 2021-06-25T11:08:38Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-04-01 Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Termites are well recognized by their complex development trajectories, involving dynamic differentiation process between non-reproductive castes, workers and soldiers. These insects are associated with endosymbiotic microorganisms, which help in lignocellulose digestion and nitrogen metabolism. Aiming to identify genes harbouring biotechnological potential, we analyzed workers and soldiers RNA-Seq data of three neotropical termites: Heterotermes tenuis (Isoptera: Rhinotermitidae), Velocitermes heteropterus (Isoptera: Termitidae) and Cornitermes cumulans (Isoptera: Termitidae). We observed differences in the microbiota associated with each termite family, and found protists' genes in both Termitidae species. We found an opposite pattern of caste-biased gene expression between H. tenuis and the termitids studied. Moreover, the two termitids are considerably different concerning the number of differentially expressed genes (DEGs). Functional annotation indicated considerable differences in caste-biased gene content between V. heteropterus and C. cumulans, even though they share similar diet and biological niche. Among the most DEGs, we highlighted those involved in caste differentiation and cellulose digestion, which are attractive targets for studying more efficient technologies for termite control, biomass digestion and other biotechnological applications. Departamento de Genética e Evolução Centro de Ciências Biológicas e da Saúde Universidade Federal de São Carlos Departamento de Genética Evolução Microbiologia e Imunologia Instituto de Biologia Universidade Estadual de Campinas Laboratório de Cupins Instituto de Biociências Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP) campus de Rio Claro Laboratório de Cupins Instituto de Biociências Universidade Estadual Paulista “Júlio de Mesquita Filho” (UNESP) campus de Rio Claro CNPq: CNPq: 139192/2015-8 CAPES: DS-CAPES 88882.426720/2019-01 CAPES: DS-CAPES 88882.426727/2019-01 CAPES: Finance Code 001 CNPq: PIBIC: 2743

Aims This study evaluated whether by-products from industrial processing of acerola (Malpighia glabra L.; AB) and guava (Psidium guajava L.; GB) fruit may stimulate the growth and metabolism of probiotic Lactobacillus and Bifidobacterium and induce changes in human colonic microbiota. Methods and results The ability of non-digested and digested AB or GB to stimulate the growth ad metabolism of Lactobacillus acidophilus LA-05, Lactobacillus casei L-26 and Bifidobacterium animalis subsp. lactis BB-12 was evaluated. Changes in populations of distinct bacterial groups of human colonic microbiota induced by digested AB and GB were evaluated using an in vitro colonic fermentation system. Non-digested and digested AB and GB favoured probiotic growth. No difference among counts of probiotics in media with glucose, fructooligosaccharides and non-digested and digested AB and GB was found during a 48-h cultivation. Cultivation of probiotics in media with non-digested and digested AB and GB resulted in decreased pH, increased organic acid production and sugar consumption over time. Digested AB and GB caused overall beneficial changes in abundance of Bifidobacterium spp., Lactobacillus-Enterococcus, Eubacterium rectall-Clostridium coccoides and Bacteroides-Provotella populations, besides to decrease the pH and increase the short-chain fatty acid production during a 24-h in vitro colonic fermentation. Conclusion AB and GB could be novel prebiotic ingredients because they can stimulate the growth and metabolism of probiotics and induce overall beneficial changes in human colonic microbiota. Significance and impact of the study AB and GB stimulated the growth and metabolism of probiotics, in addition to induce beneficial alterations in human colonic microbiota composition and increase short-chain fatty acid production. These results characterize AB and GB as potential prebiotic ingredients and fruit processing by-products as sources of added-value compounds.

The transport and optical properties of semiconducting transition metal dichalcogenides around room temperature are dictated by electron-phonon scattering mechanisms within a complex, spin-textured and multi-valley electronic landscape. The relative positions of the valleys are critical, yet they are sensitive to external parameters and very difficult to determine directly. We propose a first-principle model as a function valley positions to calculate carrier mobility and Kerr rotation angles. The model brings valuable insights, as well as quantitative predictions of macroscopic properties for a wide range of carrier density. The doping-dependant mobility displays a characteristic peak, the height depending on the position of the valleys. The Kerr rotation signal is enhanced when same spin-valleys are aligned, and quenched when opposite spin-valleys are populated. We provide guidelines to optimize these quantities with respect to experimental parameters, as well as the theoretical support for \emph{in situ} characterization of the valley positions., Comment: 24 pages, 11 figures

Machine learning-based drug discovery success depends on molecular representation. Yet traditional molecular fingerprints omit both the protein and pointers back to structural information that would enable better model interpretability. Therefore, we propose LUNA, a Python 3 toolkit that calculates and encodes protein-ligand interactions into new hashed fingerprints inspired by Extended Connectivity Finger-Print (ECFP): EIFP (Extended Interaction FingerPrint), FIFP (Functional Interaction FingerPrint), and Hybrid Interaction FingerPrint (HIFP). LUNA also provides visual strategies to make the fingerprints interpretable. We performed three major experiments exploring the fingerprints’ use. First, we trained machine learning models to reproduce DOCK3.7 scores using 1 million docked Dopamine D4 complexes. We found that EIFP-4,096 performed (R2 = 0.61) superior to related molecular and interaction fingerprints. Secondly, we used LUNA to support interpretable machine learning models. Finally, we demonstrate that interaction fingerprints can accurately identify similarities across molecular complexes that other fingerprints over-look. Hence, we envision LUNA and its interface fingerprints as promising methods for machine learning-based virtual screening campaigns. LUNA is freely available at https://github.com/keiserlab/LUNA.

Mechanochemistry approach is addressed herein for the green formation of a novel 1:1 drug–drug cocrystal (DDC) involving the antifungal prodrug Flucytosine (5FC) and the non-steroidal anti-inflammatory acetylsalicylic acid (AAS). This DDC was designed considering the huge market demand for new antifungal agents and the antifungal activity reported for some non–steroidal anti–inflammatory drugs, including AAS. The structure-properties characterization of the 5FC-AAS cocrystal was determined by X–ray diffraction (single crystal and powder), differential scanning calorimetry, thermogravimetric analysis, spectroscopic techniques (Raman and Fourier transform infrared), and hot–stage microscopy. The strong O–H…O and N–H…O hydrogen bonds formed between the hydroxyl group of AAS and the carbonyl and amine groups of two symmetry–related 5FC molecules maintain the crystalline packing, together with the same classical R 2 2 ( 8 ) homodimers observed in other 5FC cocrystals. The direct exposure under accelerated conditions (75 % relative humidity/40°C for 7 days) and at 12–months at room condition were also evaluated. Although the hygroscopicity addressed to 5FC was observed in the cocrystal during the stability studies, nevertheless this property discrepancy can easily be handled with the use of appropriate excipients and packing. DDC production was interestingly achieved by solvent evaporation, neat, and solvent-drop grinding (manually and in a ball-milling), resulting in a very fast production with suitable yield. In this sense, it is believed that this new model DDC will serve as a potential binary base cocrystal system for further developments of related higher dimensional cocrystals in this field, alongside other important drug molecules or in relation to the feasibility of using it therapeutically.

The present work investigates the production of sodium bicarbonate in combination with the co-utilization of saline brine and carbon capture, utilization, and sequestration (CCUS). The use of ammonia in the traditional Solvay process could be eliminated by using a modified Solvay process. This study compared the modification with the addition of three buffering additives: Ca(OH)2, KOH, and NH4HCO3. The effectiveness of these processes, using two qualities of saline brine (desalination and aquifer), is compared based on the purity of the produced NaHCO3. It was found that the use of Ca(OH)2 did not produce high-purity NaHCO3, while NH4HCO3 and KOH performed better. Desalination brine utilization with NH4HCO3 resulted in the production of high-purity NaHCO3, while the second most suitable method involved the use of KOH, and the main co-product formed was Na2CO3. Geochemical modeling is performed in order to have insights into the carbonation (in the reactor) and precipitation (in the oven) behavior of the reactions. It predicted the precipitation of mineral phases well, though kinetics might hinder some saturated solids to dissolve first. The present study shows that accurate characterization is critical to accurately assess the success of modified Solvay processes. The use of QXRD and SEM analyses, complemented with geochemical modeling, helped to better understand the processes and the formation of NaHCO3. Further investigations on diverse brines could provide for their better utilization by the geological carbon sequestration and water desalination industries that produce them.

Bergenin is a glycosidic derivative of trihydroxybenzoic acid that was discovered in 1880 by Garreau and Machelart from the rhizomes of the medicinal plant Bergenia crassifolia (currently: Saxifraga crassifolia—Saxifragaceae), though was later isolated from several other plant sources. Since its first report, it has aroused interest because it has several pharmacological activities, mainly antioxidant and anti-inflammatory. In addition to this, bergenin has shown potential antimalarial, antileishmanial, trypanocidal, antiviral, antibacterial, antifungal, antinociceptive, antiarthritic, antiulcerogenic, antidiabetic/antiobesity, antiarrhythmic, anticancer, hepatoprotective, neuroprotective and cardioprotective activities. Thus, this review aimed to describe the sources of isolation of bergenin and its in vitro and in vivo biological and pharmacological activities. Bergenin is distributed in many plant species (at least 112 species belonging to 34 families). Both its derivatives (natural and semisynthetic) and extracts with phytochemical proof of its highest concentration are well studied, and none of the studies showed cytotoxicity for healthy cells.

Failure rates in spinal anesthesia are generally low in experienced hands. However, studies report a failure rate variation of 1% to 17% in this procedure. The aim of this study is to bring the main characteristics of in vivo procedure to the virtual reality simulated environment. The first step is to model the behavior of tissue layers being punctured by a needle to then make its inclusion in medical training possible. The simulation proposed here is implemented using a Phantom Omni haptic device. Every crucial sensation of the method mentioned here was assessed by a dozen volunteers who participated in two experiments designed to validate the modeled response. Each user answered six questions (three for each experiment). Good results were achieved in certain essential aspects of the process, such as identifying the number of layers, the most rigid layer to puncture, and the most resistant layers to pass through. These results indicated that it is possible to represent many typical behaviors through virtual needle insertion in spinal anesthesia with the correct use of haptic properties.Clinical relevance- The idea is to create a spinal anesthesia simulator that could work as a complementary step in training new anesthetists. The use of a simulator avoids introducing the first puncture haptic sensation directly in patients.

The electroweak properties of light and charmed D and Ds pseudoscalar mesons are investigated within a unified covariant constituent quark model. The quark-antiquark-meson vertices are assumed to have a symmetric form by the exchange of quark momenta, which is successful in describing the light pseudoscalar meson properties. The flavor decomposition of the elastic electromagnetic form factors, electromagnetic charge radii, and weak decay constants are calculated. Based on the results a discussion on the SU(3) and SU(4) symmetry breaking is made and a comparison with the pion and kaon properties to highlight the Higgs contribution to the structure of these mesons., 21 pages, 22 eps figures, latex PRD style, Sub. PRD (2021). To appear Phys. Rev. D (2021). All comments are welcome

Resumo Fundamento: A proteína C-reativa (PCR) é um biomarcador de inflamação preditor de eventos adversos em procedimentos cardiovasculares. Na avaliação do implante da válvula aórtica transcateter (transcatheter aortic valve implantation, TAVI) em relação ao prognóstico de longo prazo ainda é incipiente. Objetivo: Avaliar a PCR como marcador prognóstico no primeiro ano pós-TAVI na estenose aórtica (EAo). Métodos: A PCR foi avaliada na primeira semana do peroperatório numa coorte de casos retrospectiva com EAo. Correlacionou-se a PCR pré- e pós-TAVI com a mortalidade e foram pesquisados fatores preditores de mortalidade em 1 ano. Realizada regressão de Cox multivariada para identificar os preditores independentes de óbito em 1 ano. Resultados: Estudados 130 pacientes submetidos a TAVI, com mediana de idade de 83 anos, sendo 49% deles do sexo feminino. A PCR pré-TAVI elevada (> 0,5 mg/dL) ocorreu em 34,5% dos casos. O pico de PCR foi 7,0 (5,3-12,1) mg/dL no quarto dia. A mortalidade em 1 ano foi 14,5% (n = 19), sendo maior nos grupos com PCR pré-TAVI elevada (68,8% vs 29,1%; p = 0,004) e pico de PCR ≥ 10,0 mg/dL (64,7% vs 30,8%; p = 0,009). Os fatores preditores independentes de mortalidade foram insuficiência renal aguda (IRA) [razão de risco (RR) = 7,43; intervalo de confiança de 95% (IC95%), 2,1-24,7; p = 0,001], PCR pré-TAVI elevada [RR = 4,15; IC95%, 1,3-12,9; p=0,01] e hemotransfusão volumosa [HR = 4,68; 1,3-16,7; p = 0,02]. Conclusões: A PCR pré-TAVI elevada mostrou-se fator preditor independente de mortalidade no primeiro ano, assim como a ocorrência de IRA e hemotransfusões volumosas.

Lipases (E.C. 3.1.1.3) have buried active sites and used access tunnels in the transport of substrates and products for biotransformation processes. Computational methods are used to predict the trajectory and energy profile of ligands through these tunnels, and they complement the experimental methodologies because they filter data, optimizing laboratory time and experimental costs. Access tunnels of Burkholderia cepacia lipase (BCL), Candida rugosa lipase (CRL), and porcine pancreas lipase (PPL) and the transport of fatty acids, alcohols and esters through the tunnels were evaluated using the online server CaverWeb V1.0, and server calculation results were compared with experimental data (productivity). BCL showed higher productivity with palmitic acid-C16:0 (4029.95 µmol/h mg); CRL obtained productivity for oleic acid-C18:1 (380.80 µmol/h mg), and PPL achieved productivity for lauric acid-C12:0 (71.27 µmol/h mg). The highest probability of transport for BCL is through the tunnels 1 and 2, for CRL through the tunnel 1, and for PPL through the tunnels 1, 2, 3 and 4. Thus, the best in silico result was the transport of the substrates palmitic acid and ethanol and product ethyl palmitate in tunnel 1 of BCL. This result corroborates with the best result for the productivity data (higher productivity for BCL with palmitic acid-4029.95 µmol/h mg). The combination of in silico evaluation and experimental data gave similar results, demonstrating that in silico approaches are a promising alternative for reducing screening tests and minimizing laboratory time in the bio-catalysis area by identifying the lipases with the greatest reaction potential, as in the case of this proposal.

The use of biodiesel blends with petroleum diesel in vehicular engines demands the evaluation of the possible impacts and effects of the gases emitted from their combustion on the environment. Among studies on these questions, biomonitoring using lichens is a viable alternative, given their interactions with the elements dispersed in the atmosphere, as well as its sensitivity and capacity to retain contaminants. In this study, we analyzed the effects of gas emissions from the combustion of biodiesel mixture with petroleum diesel on Cladonia verticillaris thalli. Samples of the lichen (10 g) were exposed to the gases emitted by the exhaust of the generator engine during the combustion process of biodiesel mixtures to petroleum diesel (7% (B7), 10% (B10), 40% (B40), 50% (B50), and 70% (B70)). At 90 days after exposure, samples were analyzed for n-alkane profiles, thallus morphology, photosynthetic pigment contents, and secondary lichen metabolites (protocetraric and fumarprotocetraric acids). Sets B7 and B10 showed better resistance of the lichen to pollutants. Set B40 showed a high stress evidenced by the chain elongation of n-alkanes structure and high chlorophyll production, presenting high morphological damages when compared to the control sets, B7 and B10. The results showed significant reductions of n-alkanes profiles for mixtures with high concentrations of biodiesel (B50 and B70), as well as decreases in the chlorophyll content. These groups showed an increase in the synthesis of secondary metabolites, corroborating the hypothesis that high concentrations of biodiesel in the mixture with petroleum diesel have greater impacts on the lichen. Schematic model for demonstration of using the lichen Cladonia verticillaris as biomonitor of effects from gas emissions from the combustion of biodiesel blends with petroleum diesel by a stationary engine.

In this work, a procedure is proposed for the direct analysis of powdered refreshments by fast sequential flame atomic absorption spectrometry (FS-F AAS), after a simple treatment of the sample. A full 23 factorial design was applied, and the variables chosen were as follows: acid concentration, acid type, and sonication time. Optimization provided the best conditions considering a mass of powdered refreshment of about 0.18 g diluted to a final volume of 15 mL with 0.5 mol L−1 HCl. The matrix effect was investigated, and external calibration was feasible for the determination of Cd, Co, Cu, Fe, Mg, Mn, Ni, Pb, and Zn. The limit of quantification (LoQ) obtained was between 0.6 (Cd) and 25 mg kg−1 (Pb). The analyte addition and recovery test were applied to evaluate the accuracy, and recovery percentage values ranging from 83.9 to 109.7% were obtained, which is considered adequate for quantitative analysis. Precision was expressed as relative standard deviation (% RSD); it was less than or equal to 5.0% (n = 7) for all analytes. The procedure was applied to 21 samples of powdered refreshment commercialized in Salvador (Brazil) and Buenos Aires (Argentina). The concentration range and average of the analytes in the samples (in mg kg−1) commercialized in Brazil (BZ) and Argentina (AG) were as follows: Co (BZ

Lately, numerous works have characterized the effectiveness of games in the process of learning. Benefits such as pleasure, stimulation, creativity, and enthusiasm have captivated people’s interest in science through interactive games. Hence, many games for teaching subjects in biochemistry have been developed. However, understanding molecular interactions in proteins can still be a difficult task for students in biochemistry classes. One of the main issues reported by them is the fact they cannot visually see an interaction that happens between proteins. More specifically, the atomic structure, the particulate nature of matter, the molecule, and the chemical interactions are considered abstract concepts by teachers and students. In this paper, we present the conception, development, and evaluation of Proteingo: a game created to build a crowdsourced database of protein-protein interactions. An experiment was conducted during the X-meeting 2016 Congress in Brazil, where 27 users played the Proteingo game. The development of the players along the plays, together with the answers of a post-test questionnaire, give substantial evidence of user’s incidental learning of chemical interactions through the Proteingo game. Also, 96.3% of the players consider the use of the game in classrooms as a didactic-pedagogical resource. Proteingo is available at http://bioinfo.dcc.ufmg.br/proteingo/ .

Sulfamethoxazole (SMZ) is a synthetic broad-spectrum antibiotic of biopharmaceutical classification system (BCS) class IV, with both low solubility and permeability, requiring probably higher drug doses in orally-administered formulations to promote an expected systemic absorption. To overcome such limitations and especially to increase its solubility, this study has a main purpose of the development of novel optimized crystalline forms of SMZ. Herein, two crystalline salts of SMZ (SMZBr and SMZNO3) have been synthesized from solution crystallization and characterized using X-ray (single and powder), spectroscopic (infrared, FT-IR) and thermal (DSC and TGA) techniques. Furthermore, a solubility study was performed in pure water and compared with the SMZCl salt and SMZ form I. It was observed that the SMZBr salt exhibits phase stability in water media and shows enhanced solubility compared to the SMZCl salt and SMZ form I. Additionally, a qualitative litmus paper test was employed to verify the volatiles released during the thermal drug degradation.

Selecting a trait linked to metabolic pathways that enhance resistance and tolerance to biotic and abiotic stresses may be an excellent alternative. A practical approach to increase the productivity of annual crops is to maximize the photosynthetic efficiency in plant breeding. The purpose of this study was to discriminate common bean genotypes during physiological senescence with regard to the stay-green trait and analyze its effects on other traits of agronomic interest. Ten common bean genotypes were analyzed in a randomized complete block design with three replications. The stay-green trait was assessed by visual scores at harvest. The chlorophyll a content, chlorophyll b and green pod color were also evaluated during senescence (75, 80, 85, 90, and 95 days after sowing). Pod maturation of all evaluated genotypes was standard when they reached 95 days after sowing. The stay - green feature was detected only in the genotypes BRS Expedito, FT - Tarumã and BAF071. Genetic variability in the mechanisms related to late senescence is indicated by: i) a high initial chlorophyll a content; and ii) reduced chlorophyll degradation throughout senescence. Plants with stay-green properties were significantly correlated with a lower incidence and severity of plant pathology, greater stem diameter, and higher grain yield. Selecionar uma característica relacionada às vias metabólicas responsáveis pelo aumento da resistência e/ou tolerância a estresses bióticos e abióticos pode ser uma excelente alternativa no melhoramento de plantas. Uma abordagem prática para aumentar a produtividade das culturas anuais é maximizar a eficiência fotossintética. O objetivo do trabalho foi discriminar genótipos de feijão durante a senescência fisiológica quanto ao caráter stay-green e correlacionar os efeitos sobre outros caracteres de interesse agronômico. Foram avaliados dez genótipos de feijão submetidos ao delineamento de blocos casualizados com três repetições. O caráter stay-green foi mensurado por escores de notas visuais na colheita. Também foram avaliados o teor de clorofila a, teor de clorofila b e coloração verde do legume no decorrer da senescência (75, 80, 85, 90, 95 dias após semeadura). A maturação dos legumes foi padrão para todos os genótipos avaliados. Os genótipos BRS Expedito, FT - Tarumã e BAF071 apresentaram stay-green, diferentemente dos demais. A variabilidade genética nos mecanismos relacionados a senescência tardia, são detectadas pela: i) elevado teor de clorofila a inicial; e ii) reduzida degradação de clorofila ao longo da senescência. As plantas com stay-green apresentaram correlações significativas com menor incidência e severidade de fitopatologias, maior diâmetro do caule e rendimento de grãos.

In the agriculture sector, livestock are considered extremely resilient to climate change and are tipped to play a significant role in ensuring food security to meet the increased demands of growing human population by 2050. Compared to other domestic species, goats are considered the ideal animal model for climate change due to its high thermal and drought resilience, ability to survive on limited pastures, and high disease resistance. This review is therefore a revisit to the advantages of rearing goats over other livestock species under current and future trends of changes in climate, particularly to cope with recurrent multiple stressors such as heat load, and lack of water and feed. In summary, goats, also called as poor man's cow, are preferred by the small-scale landless farmers due to their low input and assured higher output system, as they require low initial investment, with minimum specialized facilities and labors. Furthermore, they perceive goats as better resilient animal to cope with multiple stressors such as heat load, and water and feed scarcity, and possess better skills to cope with bush, when compared with sheep and cattle. The unique capacity for employing behavioral plasticity and morphological features of goats gives them clear advantage over sheep and cattle, when coping with seasonal biotopes, and experiences of water and feed shortage. When facing with low-quality feed, they also are superior to cattle and sheep to digest dry matter and to recycle nitrogen. Additionally, goats have superior ability to desiccate feces and concentrate urine, when compared with sheep and cattle. These advantages make goat the go-to species for efficiently countering the adversities associated with climate change and to optimize appropriate economic return through sustained production. Therefore, goats are tipped to be the future animals with extreme potential to counter the projected alarming climate change impacts and expected to play a significant role in ensuring food security to meet the demands of the growing human population by the end of this century.

Yellow fever virus (YFV) is the agent of the most severe mosquito-borne disease in the tropics. Recently, Brazil suffered major YFV outbreaks with a high fatality rate affecting areas where the virus has not been reported for decades, consisting of urban areas where a large number of unvaccinated people live. We developed a machine learning framework combining three different algorithms (XGBoost, random forest and regularized logistic regression) to analyze YFV genomic sequences. This method was applied to 56 YFV sequences from human infections and 27 from non-human primate (NHPs) infections to investigate the presence of genetic signatures possibly related to disease severity (in human related sequences) and differences in PCR cycle threshold (Ct) values (in NHP related sequences). Our analyses reveal four non-synonymous single nucleotide variations (SNVs) on sequences from human infections, in proteins NS3 (E614D), NS4a (I69V), NS5 (R727G, V643A) and six non-synonymous SNVs on NHP sequences, in proteins E (L385F), NS1 (A171V), NS3 (I184V) and NS5 (N11S, I374V, E641D). We performed comparative protein structural analysis on these SNVs, describing possible impacts on protein function. Despite the fact that the dataset is limited in size and that this study does not consider virus-host interactions, our work highlights the use of machine learning as a versatile and fast initial approach to genomic data exploration.

The use of biodiesel blends with petroleum diesel in vehicular engines demands the evaluation of the possible impacts and effects of the gases emitted from their combustion on the environment. Among studies on these questions, biomonitoring using lichens is a viable alternative, given their interactions with the elements dispersed in the atmosphere, as well as its sensitivity and capacity to retain contaminants. In this study, we analyzed the effects of gas emissions from the combustion of biodiesel mixture with petroleum diesel on Cladonia verticillaris thalli. Samples of the lichen (10 g) were exposed to the gases emitted by the exhaust of the generator engine during the combustion process of biodiesel mixtures to petroleum diesel (7% (B7), 10% (B10), 40% (B40), 50% (B50), and 70% (B70)). At 90 days after exposure, samples were analyzed for n-alkane profiles, thallus morphology, photosynthetic pigment contents, and secondary lichen metabolites (protocetraric and fumarprotocetraric acids). Sets B7 and B10 showed better resistance of the lichen to pollutants. Set B40 showed a high stress evidenced by the chain elongation of n-alkanes structure and high chlorophyll production, presenting high morphological damages when compared to the control sets, B7 and B10. The results showed significant reductions of n-alkanes profiles for mixtures with high concentrations of biodiesel (B50 and B70), as well as decreases in the chlorophyll content. These groups showed an increase in the synthesis of secondary metabolites, corroborating the hypothesis that high concentrations of biodiesel in the mixture with petroleum diesel have greater impacts on the lichen. Schematic model for demonstration of using the lichen Cladonia verticillaris as biomonitor of effects from gas emissions from the combustion of biodiesel blends with petroleum diesel by a stationary engine.

TPS5617 Background: Despite therapeutic advances in ovarian cancer, platinum-resistant recurrent ovarian cancer (PROC) remains an area of high unmet clinical need and there is an urgent need for new treatments to further improve clinical outcomes. Addition of bevacizumab to non-platinum-based chemotherapy significantly improved PFS in patients with PROC but did not show a clear OS benefit. Thus far, the combination of paclitaxel and bevacizumab has shown the most promise in treatment of PROC, although the proportion of patients eligible for bevacizumab is limited by treatment-associated toxicities. Combination of the anti-PD-1 antibody pembrolizumab with weekly paclitaxel showed antitumor activity and manageable toxicity in patients with PROC in a single-arm, phase 2 study (Wenham Int J Gynecol Cancer 2018). The current study ENGOT-ov65/KEYNOTE-B96 (NCT05116189) compares the efficacy and safety of the addition of pembrolizumab to standard of care chemotherapy (weekly paclitaxel) with/without bevacizumab vs placebo plus weekly paclitaxel with/without bevacizumab in patients with PROC. Methods: In this randomized, placebo-controlled, double-blind, phase 3 study, eligible patients are aged ≥18 y with histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal carcinoma with 1-2 prior lines of systemic therapy, including at least 1 prior platinum-based therapy with ≥4 cycles in first line. Patients must have platinum-resistant disease (radiographic evidence of PD ≤6 mo after last platinum-based therapy dose), be eligible for paclitaxel (with/without bevacizumab per investigator discretion), have ECOG PS ≤1, radiographically evaluable disease per RECIST v1.1, and have a tumor sample for central evaluation of PD-L1 status. Approximately 616 patients will be randomized 1:1 to receive pembrolizumab 400 mg IV or placebo Q6W for up to 18 cycles (̃2 y) plus paclitaxel 80 mg/m2 on days 1, 8, and 15 of each Q3W cycle (with/without bevacizumab 10 mg/kg Q2W per investigator discretion) until PD or unacceptable toxicity. Randomization is stratified by planned bevacizumab use (yes vs no), region (US vs Europe vs rest of world), and PD-L1 status (combined positive score [CPS] < 1 vs CPS 1- < 10 vs CPS ≥10). Tumor PD-L1 status is determined using the PD-L1 IHC 22C3 pharmDx (Investigational Use Only) diagnostic kit. Tumor imaging is performed Q9W from randomization to week 54 and Q12W thereafter. The primary endpoint is PFS per RECIST version 1.1 by investigator review in patients with tumor PD-L1 CPS ≥1 and in all patients. Secondary endpoints are OS in patients with tumor PD-L1 CPS ≥1 and in all patients, PFS per RECIST version 1.1 by blinded independent central review in patients with tumor PD-L1 CPS ≥1 and in all patients, safety, and patient-reported outcomes. Enrollment is ongoing. Clinical trial information: NCT05116189.

Evolutionarily related proteins can present similar structures but very dissimilar sequences. Hence, understanding the role of the inter-residues contacts for the protein structure has been the target of many studies. Contacts comprise non-covalent interactions, which are essential to stabilize macromolecular structures such as proteins. Here we show VTR, a new method for the detection of analogous contacts in protein pairs. VTR performs structural alignment between proteins and detects interactions that occur in similar regions. To evaluate our tool, we proposed three case studies: (i) we compared a vertebrate myoglobin and a truncated invertebrate hemoglobin; (ii) analyzed interactions between the spike protein RBD of SARS-CoV-2 and the cell receptor ACE2; and (iii) compared a glucose-tolerant and a non-tolerant β-glucosidase enzyme used for biofuel production. The case studies demonstrate the potential of VTR for the understanding of functional similarities between distantly sequence-related proteins, as well as the exploration of important drug targets and rational design of enzymes for industrial applications. We envision VTR as a promising tool for understanding differences and similarities between homologous proteins with similar 3D structures but different sequences. VTR is available at http://bioinfo.dcc.ufmg.br/vtr.

Motivation The discovery of protein–ligand-binding sites is a major step for elucidating protein function and for investigating new functional roles. Detecting protein–ligand-binding sites experimentally is time-consuming and expensive. Thus, a variety of in silico methods to detect and predict binding sites was proposed as they can be scalable, fast and present low cost. Results We proposed Graph-based Residue neighborhood Strategy to Predict binding sites (GRaSP), a novel residue centric and scalable method to predict ligand-binding site residues. It is based on a supervised learning strategy that models the residue environment as a graph at the atomic level. Results show that GRaSP made compatible or superior predictions when compared with methods described in the literature. GRaSP outperformed six other residue-centric methods, including the one considered as state-of-the-art. Also, our method achieved better results than the method from CAMEO independent assessment. GRaSP ranked second when compared with five state-of-the-art pocket-centric methods, which we consider a significant result, as it was not devised to predict pockets. Finally, our method proved scalable as it took 10–20 s on average to predict the binding site for a protein complex whereas the state-of-the-art residue-centric method takes 2–5 h on average. Availability and implementation The source code and datasets are available at https://github.com/charles-abreu/GRaSP. Supplementary information Supplementary data are available at Bioinformatics online.

Macro- and microelement determination in chocolate bars by microwave-induced plasma optical emission spectrometry (MIP OES) was evaluated after microwave-assisted sample digestion. Optimization of the sample digestion was carried out, and the recommended conditions were obtained at a temperature of 190 °C, with a digestion time of 40 min and in a mixture constituted by 2.3 mL of nitric acid, 1.0 mL of hydrogen peroxide and 4.7 mL of water. The method was applied in the analysis of chocolate bars, and the concentration ranges of the elements determined were (in mg kg−1): Ca (653–3096); Cr (

The use of the electrical activity from the muscles may provide a natural way to control exoskeletons or other robotic devices seamlessly. The major challenges to achieve this goal are human motor redundancy and surface electromyography (sEMG) variability. The goal of this work is to find a feature extraction and classification procedures to estimate accurately elbow angular trajectory by means of a NARX Neural Network. The processing time-step should be small enough to make it feasible its further use for online control of an exoskeleton. In order to do so we analysed the Biceps and Triceps Brachii data from an elbow flexo-extension Coincident Timing task performed in the horizontal plane. The sEMG data was pre-processed and its energy was divided in five frequency intervals that were fed to a Nonlinear Auto Regressive with Exogenous inputs (NARX) Neural Network. The estimated angular trajectory was compared with the measured one showing a high correlation between them and a RMSE error maximum of 7 degrees. The procedure presented here shows a reasonably good estimation that, after training, allows real-time implementation. In addition, the results are encouraging to include more complex tasks including the shoulder joint.