Advancing Efficiency Sustainability in Poultry Farms through Data Envelopment Analysis in a Brazilian Production System.

The production efficiency factor is widely used to measure the zootechnical performance of a batch of broilers. The unit cost of production brings new elements to improve efficiency evaluation and financial sustainability for this activity in agriculture. This research aims to evaluate the production efficiency level of the crop to maximize the return on investment. This study uses Data Envelopment Analysis (DEA) with the computational processing of the SIAD software (Integrated Decision Support System). The variables selected were poultry housing, age at slaughter, feed consumed, mortality, and unit cost. The chosen output variable was the total available weight. The analysis spans 31 decision-making units (DMUs) composed of integrated producers, unveiling a frontier of efficiency delineated by the most exemplary DMUs. Notably, only two DMUs, specifically DMU 4 and DMU 23, approached the threshold of maximum relative efficiency. This research illuminates the critical role of unit cost in enhancing the assessment of production efficiency and financial sustainability within the agriculture environment. By setting benchmarks for efficient management and operational protocols, our findings serve as a cornerstone for improving practices among less efficient DMUs, contributing significantly to the literature on agricultural efficiency and offering actionable insights for the poultry farming sector.

Molecular Insights into O-Linked Sialoglycans Recognition by the Siglec-Like SLBR-N (SLBRUB10712) of Streptococcus gordonii.

Streptococcus gordonii is a Gram-positive bacterial species that typically colonizes the human oral cavity, but can also cause local or systemic diseases. Serine-rich repeat (SRR) glycoproteins exposed on the S. gordonii bacterial surface bind to sialylated glycans on human salivary, plasma, and platelet glycoproteins, which may contribute to oral colonization as well as endocardial infections. Despite a conserved overall domain organization of SRR adhesins, the Siglec-like binding regions (SLBRs) are highly variable, affecting the recognition of a wide range of sialoglycans. SLBR-N from the SRR glycoprotein of S. gordonii UB10712 possesses the remarkable ability to recognize complex core 2 O-glycans. We here employed a multidisciplinary approach, including flow cytometry, native mass spectrometry, isothermal titration calorimetry, NMR spectroscopy from both protein and ligand perspectives, and computational methods, to investigate the ligand specificity and binding preferences of SLBR-N when interacting with mono- and disialylated core 2 O-glycans. We determined the means by which SLBR-N preferentially binds branched α2,3-disialylated core 2 O-glycans: a selected conformation of the 3'SLn branch is accommodated into the main binding site, driving the sTa branch to further interact with the protein. At the same time, SLBR-N assumes an open conformation of the CD loop of the glycan-binding pocket, allowing one to accommodate the entire complex core 2 O-glycan. These findings establish the basis for the generation of novel tools for the detection of specific complex O-glycan structures and pave the way for the design and development of potential therapeutics against streptococcal infections.

BRCA1, BRCA2, and TP53 germline and somatic variants and clinicopathological characteristics of Brazilian patients with epithelial ovarian cancer.

BACKGROUND: Approximately 3/4 of ovarian cancers are diagnosed in advanced stages, with the high-grade epithelial ovarian carcinoma (EOC) accounting for 90% of the cases. EOC present high genomic instability and somatic loss-of-function variants in genes associated with homologous recombination mutational repair pathway (HR), such as BRCA1 and BRCA2, and in TP53. The identification of germline variants in HR genes in EOC is relevant for treatment of platinum resistant tumors and relapsed tumors with therapies based in synthetic lethality such as PARP inhibitors. Patients with somatic variants in HR genes may also benefit from these therapies. In this work was analyzed the frequency of somatic variants in BRCA1, BRCA2, and TP53 in an EOC cohort of Brazilian patients, estimating the proportion of variants in tumoral tissue and their association with progression-free survival and overall survival. METHODS: The study was conducted with paired blood/tumor samples from 56 patients. Germline and tumoral sequences of BRCA1, BRCA2, and TP53 were obtained by massive parallel sequencing. The HaplotypeCaller method was used for calling germline variants, and somatic variants were called with Mutect2. RESULTS: A total of 26 germline variants were found, and seven patients presented germline pathogenic or likely pathogenic variants in BRCA1 or BRCA2. The analysis of tumoral tissue identified 52 somatic variants in 41 patients, being 43 somatic variants affecting or likely affecting protein functionality. Survival analyses showed that tumor staging was associated with overall survival (OS), while the presence of somatic mutation in TP53 was not associated with OS or progression-free survival. CONCLUSION: Frequency of pathogenic or likely pathogenic germline variants in BRCA1 and BRCA2 (12.5%) was lower in comparison with other studies. TP53 was the most altered gene in tumors, with 62.5% presenting likely non-functional or non-functional somatic variants, while eight 14.2% presented likely non-functional or non-functional somatic variants in BRCA1 or BRCA2.

JAGGER localization and function are dependent on GPI anchor addition.

KEY MESSAGE: GPI anchor addition is important for JAGGER localization and in vivo function. Loss of correct GPI anchor addition in JAGGER, negatively affects its localization and function. In flowering plants, successful double fertilization requires the correct delivery of two sperm cells to the female gametophyte inside the ovule. The delivery of a single pair of sperm cells is achieved by the entrance of a single pollen tube into one female gametophyte. To prevent polyspermy, Arabidopsis ovules avoid the attraction of multiple pollen tubes to one ovule-polytubey block. In Arabidopsis jagger mutants, a significant number of ovules attract more than one pollen tube to an ovule due to an impairment in synergid degeneration. JAGGER encodes a putative arabinogalactan protein which is predicted to be anchored to the plasma membrane by a glycosylphosphatidylinositol (GPI) anchor. Here, we show that JAGGER fused to citrine yellow fluorescent protein (JAGGER-cYFP) is functional and localizes mostly to the periphery of ovule integuments and transmitting tract cells. We further investigated the importance of GPI-anchor addition domains for JAGGER localization and function. Different JAGGER proteins with deletions in predicted ω-site regions and GPI attachment signal domain, expected to compromise the addition of the GPI anchor, led to disruption of JAGGER localization in the cell periphery. All JAGGER proteins with disrupted localization were also not able to rescue the polytubey phenotype, pointing to the importance of GPI-anchor addition to in vivo function of the JAGGER protein.

Human Papillomavirus 16 Lineage D is Associated with High Risk of Cervical Cancer in the Brazilian Northeast Region.

OBJECTIVE: Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil. METHODS: A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage (p < 0.05). RESULTS: According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer (p = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p = 0.023. CONCLUSION: HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer.

OBJETIVO: Tanto os tipos quanto as linhagens do Papilomavírus Humano (HPV) parecem ter diferentes capacidades carcinogênicas e estão associados a riscos variados para o desenvolvimento de neoplasia intraepitelial cervical (NIC) e câncer de colo do útero. O presente estudo tem como objetivo analisar a diversidade genética do genótipo HPV 16 nos casos de NIC2/NIC3 e câncer de colo de útero em mulheres da região Nordeste do Brasil. MéTODOS: Estudo transversal de base hospitalar realizado na região Nordeste do Brasil no período de 2014 a 2016. A amostra foi composta por 196 casos da variante HPV-16 (59 casos de NIC2/NIC3 e 137 de câncer do colo do útero). O teste de diferença de proporção foi usado para comparar os grupos NIC2/NIC3 e câncer de colo do útero por linhagem viral em relação à prevalência da linhagem HPV-16. Foi considerada significância estatística o valor de p < 0,05. RESULTADOS: As frequências de linhagem por diagnóstico histopatológico mostraram diferença limítrofe da linhagem A no grupo NIC2/NIC3 em relação ao grupo câncer de colo de útero (p = 0,053). Por outro lado, em relação à linhagem D, houve uma proporção maior nos casos de câncer (32,8%) quando comparado ao grupo NIC2/NIC3 (16,9%) e esta diferença se mostrou estatisticamente significante (p = 0,023). CONCLUSãO: A linhagem A do HPV-16 foi a mais frequente tanto nas amostras CIN2/CIN3 quanto nas amostras de câncer de colo de útero, enquanto a linhagem D predominou no câncer de colo do útero, sugerindo uma possível associação da linhagem D de HPV-16 com câncer de colo de útero.

Unveiling CD59-Antibody Interactions to Design Paratope-Mimicking Peptides for Complement Modulation.

CD59 is an abundant immuno-regulatory human protein that protects cells from damage by inhibiting the complement system. CD59 inhibits the assembly of the Membrane Attack Complex (MAC), the bactericidal pore-forming toxin of the innate immune system. In addition, several pathogenic viruses, including HIV-1, escape complement-mediated virolysis by incorporating this complement inhibitor in their own viral envelope. This makes human pathogenic viruses, such as HIV-1, not neutralised by the complement in human fluids. CD59 is also overexpressed in several cancer cells to resist the complement attack. Consistent with its importance as a therapeutical target, CD59-targeting antibodies have been proven to be successful in hindering HIV-1 growth and counteracting the effect of complement inhibition by specific cancer cells. In this work, we make use of bioinformatics and computational tools to identify CD59 interactions with blocking antibodies and to describe molecular details of the paratope-epitope interface. Based on this information, we design and produce paratope-mimicking bicyclic peptides able to target CD59. Our results set the basis for the development of antibody-mimicking small molecules targeting CD59 with potential therapeutic interest as complement activators.

Setting qualitative performance parameters of elite surfing aerial manoeuvres with 360° rotation / Establecimiento de parámetros cualitativos de rendimiento de maniobras aéreas de surf de élite con rotación de 360 grados / Definição de parâmetros qualitativos de desempenho de manobras aéreas de surf de elite com rotação de 360 graus

El objetivo fue analizar parámetros de maniobras aéreas de surf de alto nivel, apoyando el entrenamiento específico y la prevención de lesiones. Utilizando análisis de video de maniobras aéreas completadas porsurfistas masculinos de top-5en 19 eventos durante las temporadas 2018y 2019del World Championship Tour, se seleccionaron (n=97): Frontside Air, Frontside Air Reverse 360, Backside Air y Backside Air Reverse 360.Se trata de una investigación de métodomixto. Tiene un análisis de tarea cualitativo, realizado a través del análisisen fases, considerando características clave de las acciones corporales y principios de movimiento. A través de la metodologíaobservacional (nomotético, puntual y multidimensional) se midió laaltura del aéreo, el ancho del BoS y los ángulos de flexión de la rodilla y del tobillo delanteros.Las referencias en el análisis cualitativo fueron: rotación de cabeza y tronco, triple flexión de miembros inferiores (preparación) y máspronunciada en larecuperación; flexión de cabeza, tronco y brazos desde el despegue (preparación) hasta el pico del vuelo (principal) provocando el desplazamiento anterosuperior del CoM; ampliación de la BoS para aéreos frontales (principal). El análisiscuantitivo permitió identificarlamedia dela altura del aéreo (169,60±52,85cm), del ancho de la base de sustentación (BoS) (79,17±13,72cm), y de los ángulos de flexión de la rodilla (113,78±19,90º) y del tobillo(32,74±14,51º)delanteros durante el aterrizaje. El análisis descriptivo puede contribuir al desarrollo de programas de formación específicos para la enseñanza y el aprendizaje, con el objetivo de mejorar el rendimiento de las maniobras aéreas. (AU)

Purpose was to analyse parameters of high-level surfing aerial manoeuvres, supporting specific training and injury prevention. Using video analysis ofaerials completed by top-5male surfersin 19 events during 2018and 2019 seasonsof the World Championship Tour, were selected (n=97): Frontside Air, Frontside Air Reverse 360, Backside Air and Backside Air Reverse 360. This is a mixed method research. Has a qualitative task analysis, carried out through phaseanalysis, considering key features from body actions and principles of movement. Through observational methodology (nomothetic, single point and multidimensional)was measured the aerial height, theBoS width, and flexion angles of front knee and front ankle.Qualitative analysis references were: rotation of the head and trunk, triple-flexion of the lower limbs (retraction) and more pronounced in the follow-through; head, trunk, and arms flexion fromthe take-off (retraction) to the peak of the flight (action) causing the anterosuperior CoM displacement; widening of the BoS for frontside aerials (action). Quantitative analysis allowed to identify the mean of aerial height (169.60±52.85cm), of base of support (BoS) width (79.17±13.72cm), and flexion anglesof front knee (113.78±19.90º) and front ankle (32.74±14.51º) during landing.Descriptive analysis may contribute to the development of specific training programs for teaching and learning, aiming to improve performance of aerial manoeuvres. (AU)

O objetivo foi analisar parâmetros de manobras aéreas de surf de alto nível, dando suporte ao treino específico e à prevenção de lesões. Através da análisede vídeode manobras aéreas concluídaspor surfistas masculinos do top-5,em 19 eventos durante as temporadas 2018 e 2019do World Championship Tour, foram selecionados (n=97): Frontside Air, Frontside Air Reverse 360, Backside Air e Backside Air Reverse 360.Esteé um estudo com um método misto. Temos uma análise da tarefa qualitativa, realizada através da análise por fases, considerando as principais características das ações corporais e dos princípios do movimento.Através da metodologia observacional (nomotético, pontual e multidimensional) foi medida a altura do aéreo, a largura do BoS e os ângulos de flexão do joelho e do tornozelodianteiros. As referências da análise qualitativa foram: arotação de cabeça e tronco, tripla flexão dos membros inferiores (preparação) e mais acentuada na finalização; flexão da cabeça, tronco e braços desde a descolagem (preparação) até o pico do voo (ação principal) causando o deslocamento antero-superior do CoM; alargamento da BoS paraaéreos frontais (ação principal). A análise quantitativa permitiu identificar a média da altura do aéreo (169,60±52,85cm), da largura da base de sustentação (BoS) (79,17±13,72cm) e dos ângulos de flexão do joelho(113,78±19,90º) e tornozelo (32,74±14,51º)dianteiros durante a aterragem. A análise descritiva pode contribuir para o desenvolvimento de programas de treino específicos para ensino e aprendizagem, visando melhorar o desempenho das manobras aéreas. (AU)

Human Papillomavirus 16 Lineage D is Associated with High Risk of Cervical Cancer in the Brazilian Northeast Region / Papillomavirus humano 16 da linhagem D associado a alto risco de câncer de colo do útero em região do nordeste brasileiro

Abstract Objective Similar to Human Papillomavirus (HPV) genotypes, different lineages of a genotype also have different carcinogenic capabilities. Studies have shown that specific genotype lineages of oncogenic HPV are associated with variable risks for the development of cervical intraepithelial neoplasia (CIN2/CIN3) and cervical cancer. The present study aimed to analyze the genetic diversity of the HPV16 genotype in women with CIN2/CIN3 and cervical cancer, from the northeast region of Brazil. Methods A cross-sectional multicenter study was conducted in the northeast region of Brazil, from 2014 to 2016. This study included 196 cases of HPV16 variants (59 and 137 cases of CIN2/CIN3 and cervical cancer, respectively). The difference of proportion test was used to compare patients with CIN2/CIN3 and cervical cancer, based on the prevalent HPV16 lineage (p < 0.05). Results According to the histopathological diagnosis, the percentage of lineage frequencies revealed a marginal difference in the prevalence of lineage A in CIN2/CIN3, compared with that in cervical cancer (p = 0.053). For lineage D, the proportion was higher in cancer cases (32.8%), than in CIN2/CIN3 cases (16.9%), with p = 0.023. Conclusion HPV16 lineage A was the most frequent lineage in both CIN2/CIN3 and cervical cancer samples, while lineage D was predominant in cervical cancer, suggesting a possible association between HPV16 lineage D and cervical cancer.

Resumo Objetivo Tanto os tipos quanto as linhagens do Papilomavírus Humano (HPV) parecem ter diferentes capacidades carcinogênicas e estão associados a riscos variados para o desenvolvimento de neoplasia intraepitelial cervical (NIC) e câncer de colo do útero. O presente estudo tem como objetivo analisar a diversidade genética do genótipo HPV 16 nos casos de NIC2/NIC3 e câncer de colo de útero em mulheres da região Nordeste do Brasil. Métodos Estudo transversal de base hospitalar realizado na região Nordeste do Brasil no período de 2014 a 2016. A amostra foi composta por 196 casos da variante HPV-16 (59 casos de NIC2/NIC3 e 137 de câncer do colo do útero). O teste de diferença de proporção foi usado para comparar os grupos NIC2/NIC3 e câncer de colo do útero por linhagem viral em relação à prevalência da linhagem HPV-16. Foi considerada significância estatística o valor de p < 0,05. Resultados As frequências de linhagem por diagnóstico histopatológico mostraram diferença limítrofe da linhagem A no grupo NIC2/NIC3 em relação ao grupo câncer de colo de útero (p = 0,053). Por outro lado, em relação à linhagem D, houve uma proporção maior nos casos de câncer (32,8%) quando comparado ao grupo NIC2/NIC3 (16,9%) e esta diferença se mostrou estatisticamente significante (p = 0,023). Conclusão A linhagem A do HPV-16 foi a mais frequente tanto nas amostras CIN2/CIN3 quanto nas amostras de câncer de colo de útero, enquanto a linhagem D predominou no câncer de colo do útero, sugerindo uma possível associação da linhagem D de HPV-16 com câncer de colo de útero.

High APOBEC3B mRNA Expression Is Associated with Human Papillomavirus Type 18 Infection in Cervical Cancer.

The APOBEC3 (A3) proteins are cytidine deaminases that exhibit the ability to insert mutations in DNA and/or RNA sequences. APOBEC3B (A3B) has been evidenced as a DNA mutagen with consistent high expression in several cancer types. Data concerning the A3B influence on HPV infection and cervical cancer are limited and controversial. We investigated the role of A3B expression levels in cervical cancer in affected women positive for infection by different HPV types. Tumor biopsies from cancerous uterine cervix were collected from 216 women registered at Hospital do Câncer II of Instituto Nacional de Câncer, and infecting HPV was typed. A3B expression levels were quantified from RNA samples extracted from cervical biopsies using real-time quantitative PCR. Median A3B expression levels were higher among HPV18+ samples when compared to HPV16+ counterparts and were also increased compared to samples positive for other HPV types. In squamous cell carcinoma, HPV18+ samples also showed increased median A3B expression when compared to HPV Alpha-9 species or only to HPV16+ samples. Our findings suggest that A3B expression is differentially upregulated in cervical cancer samples infected with HPV18. A3B could be potentially used as a biomarker for HPV infection and as a prognostic tool for clinical outcomes in the context of cervical cancer.

Multi-criteria analysis applied to humanitarian assistance: an approach based on ELECTRE-MOr.

The recent increase in the number of cases of COVID-19 in Brazil and worldwide, caused by the Omicron Variant, has brought to light concern to the population and the government, especially in the states most affected by the pandemic. To find a way to help combat the pandemic, a case study was conducted to acquire new speedboats by the Brazilian Navy (BN), through the application of the ELECTRE-MOr multicriteria method. The boats would be employed as mobile hospitals, aiming to perform first aid and evacuation of patients from riverside regions to qualified hospitals. Another important use would be the transport of vaccines, medicines and basic supplies for riverside populations, such as water, food and hygiene materials. For the proposed analysis, we consulted three specialists from the BN, who evaluated eight boat models in seven tactical, operational and medical criteria. After the application of the method, the Guardian 25 and RAC boats were chosen to be employed in humanitarian assistance. This study brings a valuable contribution to academia and society since it represents the application of a multi-criteria decision-aid method in the state of the art to contribute to the solution of a real problem that affects millions of people in Brazil and worldwide.

Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service.

Several studies have demonstrated the cost-effectiveness of genetic testing for surveillance and treatment of carriers of germline pathogenic variants associated with hereditary breast/ovarian cancer syndrome (HBOC). In Brazil, seventy percent of the population is assisted by the public Unified Health System (SUS), where genetic testing is still unavailable. And few studies were performed regarding the prevalence of HBOC pathogenic variants in this context. Here, we estimated the prevalence of germline pathogenic variants in BRCA1, BRCA2 and TP53 genes in Brazilian patients suspected of HBOC and referred to public healthcare service. Predictive power of risk prediction models for detecting mutation carriers was also evaluated. We found that 41 out of 257 tested patients (15.9%) were carriers of pathogenic variants in the analyzed genes. Most frequent pathogenic variant was the founder Brazilian mutation TP53 c.1010G > A (p.Arg337His), adding to the accumulated evidence that supports inclusion of TP53 in routine testing of Brazilian HBOC patients. Surprisingly, BRCA1 c.5266dupC (p.Gln1756fs), a frequently reported pathogenic variant in Brazilian HBOC patients, was not observed. Regarding the use of predictive models, we found that familial history of cancer might be used to improve selection or prioritization of patients for genetic testing, especially in a context of limited resources.

Feasibility of a Hospital Information System for a Military Public Organization in the Light of the Multi-Criteria Analysis.

The healthcare environment presents a large volume of personal and sensitive patient data that needs to be available and secure. Information and communication technology brings a new reality to healthcare, promoting improvements, agility and integration. Regarding high-level and complex decision-making scenarios, the Brazilian Navy (BN), concerning its healthcare field, is seeking to provide better management of its respective processes in its hospital facilities, allowing accurate control of preventive and curative medicine to members who work or have served there in past years. The study addresses the understanding, structure and clarifying variables related to the feasibility of technological updating and installing of a Hospital Information System (HIS) for BN. In this scenario, through interviews and analysis of military organization business processes, criteria and alternatives were established based on multi-criteria methodology as a decision aid. As methodological support for research and data processing, THOR 2 and PROMETHEE-SAPEVO-M1 methods were approached, both based on the scenarios of outranking alternatives based on the preferences established by the stakeholders in the problem. As a result of the methodological implementation, we compare the two implemented methods in this context, exposing the Commercial Software Purchase and Adoption of Free Software, integrated into Customization by the Marine Studies Foundation, as favorable actions to be adopted concerning HIS feasibility. This finding generates a comprehensive discussion regarding the BN perspective and changes in internal development in the military environment, prospecting alignment to the culture of private organizations in Information Technology for healthcare management. In the end, we present some conclusions concerning the study, exploring the main points of the decision-making analysis and for future research.

Virasoro conjecture for the stable pairs descendent theory of simply connected 3-folds (with applications to the Hilbert scheme of points of a surface).

This paper concerns the recent Virasoro conjecture for the theory of stable pairs on a 3-fold proposed by Oblomkov, Okounkov, Pandharipande, and the author. Here we extend the conjecture to 3-folds with non- ( p , p ) -cohomology and we prove it in two specializations. For the first specialization, we let S be a surface with H 1 ( S ) = 0 and consider the moduli space P n ( S × P 1 , n [ P 1 ] ) , which happens to be isomorphic to the Hilbert scheme S [ n ] of n points on S . The Virasoro constraints for stable pairs, in this case, can be formulated entirely in terms of descendents in the Hilbert scheme of points. The two main ingredients of the proof are the toric case and the existence of universal formulas for integrals of descendents on S [ n ] . The second specialization consists in taking the 3-fold X to be a cubic and the curve class ß to be the line class. In this case we compute the full theory of stable pairs using the geometry of the Fano variety of lines.

Bilirubin oxidase as a single enzymatic oxygen scavenger for the development of reductase-based biosensors in the open air and its application on a nitrite biosensor.

The commercialization of amperometric or voltammetric biosensors that operate at potentials lower than -0.2 V vs SHE has been hindered by the need for anoxic working conditions due to the interference of molecular oxygen, whose electrochemical reduction can potentially mask other redox processes and generate reactive oxygen species (ROS). A deoxygenation step must be thus integrated into the analytical process. To this end, several (bio)chemical oxygen scavenging systems have been proposed, such as the bi-enzyme system, glucose oxidase/catalase. Still, a few issues persist owing to enzyme impurities and the formation of oxygen reactive species. Here in, we propose a new mono-enzymatic oxygen scavenging system composed of a multicopper oxidase as a single biocatalytic oxygen reducer. As a model, we used bilirubin oxidase (BOD), which catalyzes the direct reduction of oxygen to water in the presence of an electron donor substrate, without releasing hydrogen peroxide. Both the direct electron transfer and mediated electrochemical approach using different co-substrates were screened for the ability to promote the enzymatic reduction of oxygen. An optimal combination of BOD with sodium ascorbate proved to be quick (5 min) and effective. It was subsequently employed, as a proof-of-concept, in a voltammetric biosensor based on a multiheme cytochrome c nitrite reductase, which performs the reduction of nitrite to ammonia at potentials below -0.3 V vs SHE. The nitrite biosensor performed well under ambient air, with no need for a second enzyme to account for the build-up of oxygen reactive intermediaries.

Strategic support for the distribution of vaccines against Covid-19 to Brazilian remote areas: A multicriteria approach in the light of the ELECTRE-MOr method.

The pandemic caused by the new coronavirus has brought to light a series of concerns for the Brazilian population and government departments due to the different costly consequences that it has generated. It has also mobilized different strategic fronts that plan and implement several mitigating measures against the virus. Besides, the search for solutions for adequate care for individuals in need of support has been constant. This work uses ELECTRE-MOr, a Multi-Criteria Decision Aid (MCDA) method, to support the logistic plan for the vaccine distribution throughout Brazil, essentially to remote areas. The method allows an objective and structured classification of ideal types of thermal boxes for the storage of immunobiological inside the Cold Chain, presenting the best alternative that maintains the quality of materials until the final destination and has the best cost-benefit. Currently, the ELECTRE-MOr model is under development in a computational tool in Python, allowing the use of the method intuitively and clearly, enabling professionals of any area of expertise to apply it.

Sensitivity Analysis by the PROMETHEE-GAIA method: Algorithms evaluation for COVID-19 prediction.

With the expansion of coronavirus in the World, the search for technology solutions based on the analysis and prospecting of diseases has become constant. The paper addresses a machine learning algorithms analysis used to predict and identify infected patients. For analysis, we use a multicriteria approach using the PROMETHEE-GAIA method, providing the structuring of alternatives respective to a set of criteria, thus enabling the obtaining of their importance degree under the perspective of multiple criteria. The study approaches a sensitivity analysis, evaluating the alternatives using the PROMETHEE I and II methods, along with the GAIA plan, both implemented by the Visual PROMETHEE computational tool, exploring numerical and graphical resources. The analysis model proves to be effective, guaranteeing the ranking of alternatives by inter criterion evaluation and local results with intra criterion evaluation, providing a transparent analysis concerning the selection of prediction algorithms to combat the COVID-19 pandemic.

Naso-oropharyngeal microbiome from breast cancer patients diagnosed with COVID-19.

Due to immunosuppressive cancer therapies, cancer patients diagnosed with COVID-19 have a higher chance of developing severe symptoms and present a higher mortality rate in comparison to the general population. Here we show a comparative analysis of the microbiome from naso-oropharyngeal samples of breast cancer patients with respect to SARS-CoV-2 status and identified bacteria associated with symptom severity. Total DNA of naso-oropharyngeal swabs from 74 women with or without breast cancer, positive or negative for SARS-CoV-2 were PCR-amplified for 16S-rDNA V3 and V4 regions and submitted to massive parallel sequencing. Sequencing data were analyzed with QIIME2 and taxonomic identification was performed using the q2-feature-classifier QIIME2 plugin, the Greengenes Database, and amplicon sequence variants (ASV) analysis. A total of 486 different bacteria were identified. No difference was found in taxa diversity between sample groups. Cluster analysis did not group the samples concerning SARS-CoV-2 status, breast cancer diagnosis, or symptom severity. Three taxa (Pseudomonas, Moraxella, and Klebsiella,) showed to be overrepresented in women with breast cancer and positive for SARS-CoV-2 when compared to the other women groups, and five bacterial groups were associated with COVID-19 severity among breast cancer patients: Staphylococcus, Staphylococcus epidermidis, Scardovia, Parasegitibacter luogiensis, and Thermomonas. The presence of Staphylococcus in COVID-19 breast cancer patients may possibly be a consequence of nosocomial infection.

Molecular alterations in retinoblastoma beyond RB1.

Retinoblastoma is the most common malignant ocular tumor in children. Although RB1 alterations are most frequently involved in the etiology of retinoblastoma, candidate driver events and somatic alterations leading to cell transformation, tumor onset and progression remain poorly understood. In this study, we identified novel genomic alterations in tumors with a panel of 160 genes. Sanger sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) were initially performed for identifying patients without apparent RB1 alterations in blood DNA. Subsequently, NGS analyses of 24 paired (blood/tumor) samples of these patients were carried out for identifying somatic mutations and copy number variation in RB1 and other 159 genes. One novel pathogenic RB1 mutation and seven novel VUS were identified as well as 90 novel pathogenic mutations in 61 other genes. Twenty-three genes appeared exclusively mutated in tumors without altered RB1 alleles and three frequently affected biological pathways while five other tumors did not show pathogenic RB1 alterations or SNV/indels in 159 other genes. Curiously, deletion of GATA2, AKT1, ARID1A, DNMT3A, MAP2K2, MEN1, MTOR, PTCH1 and SUFU (in homo- or heterozygosity) were exclusively found in these tumors when compared to those with any pathogenic alterations, probably indicating genes that might be essential for the development of retinoblastoma regardless of a functional RB1. Identification of genes associated with retinoblastoma will contribute to understanding presently unknown aspects of this malignancy, which might be essential for its initiation and progression, as well as providing valuable molecular markers.

Expression of Retroelements in Cervical Cancer and Their Interplay with HPV Infection and Host Gene Expression.

Retroelements are expressed in diverse types of cancer and are related to tumorigenesis and to cancer progression. We characterized the expression of retroelements in cervical cancer and explored their interplay with HPV infection and their association with expression of neighboring genes. Forty biopsies of invasive cervical carcinoma (squamous cell carcinomas and adenocarcinomas) with genotyped HPV were selected and analyzed for human endogenous retrovirus (HERV) and long interspersed nuclear element 1 (L1) expression through RNA-seq data. We found 8060 retroelements expressed in the samples and a negative correlation of DNA methyltransferase 1 expression with the two most expressed L1 elements. A total of 103 retroelements were found differentially expressed between tumor histological types and between HPV types, including several HERV families (HERV-K, HERV-H, HERV-E, HERV-I and HERV-L). The comparison between HPV mono- and co-infections showed the highest proportion of differentially expressed L1 elements. The location of retroelements affected neighboring gene expression, such as shown for the interleukin-20 gene family. Three HERVs and seven L1 were located close to this gene family and two L1 showed a positive association with IL20RB expression. This study describes the expression of retroelements in cervical cancer and shows their association with HPV status and host gene expression.

Interfacing the enzyme multiheme cytochrome c nitrite reductase with pencil lead electrodes: Towards a disposable biosensor for cyanide surveillance in the environment.

The present study reports a novel voltammetric biosensor for cyanide based on its inhibitory effect on cytochrome c nitrite reductase (ccNiR). Interestingly, the earlier development of a point-of-care test for nitrite based on the direct electrochemistry of ccNiR has shown that the cyanide inhibition depends on the type of carbon material employed as transducer (Monteiro et al., 2019). In this work, commercial graphite pencil leads were employed in the construction of both working and pseudo-reference electrodes, with ccNiR being simply drop casted onto the former. In this way, we produced a functional and fully integrated voltammetric biosensor for nitrite quantification that also allows to observe a decrease in the catalytic current due to cyanide addition. Under turnover conditions, the biosensor showed a linear response with the logarithm of cyanide concentration in the 5-76 µM (cyclic voltammetry) and 1-40 µM (square-wave voltammetry) ranges, with a sensitivity of 20-25% ln [cyanide µM]-1 and a detection limit of 0.86-4.4 µM. The application of the pencil lead as a putative pseudo-reference was very promising, since the potentials profile matched those observed with a true reference electrode (Ag/AgCl). Overall, the direct electron transfer between ccNiR and a pencil lead electrode was demonstrated for the first time, with cyanide-induced inhibition being easily monitored, paving the way for the employment of these low-cost bioelectrodes as cyanide probes for on-site surveillance of aquatic environments.