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Single-chain variable fragments (scFvs) are small-sized artificial constructs composed of the immunoglobulin heavy and light chain variable regions connected by a peptide linker. We have previously described an anti-fibroblast growth factor 2 (FGF2) immunoglobulin G (IgG) monoclonal antibody (mAb), named 3F12E7, with notable antitumor potential revealed by preclinical assays. FGF2 is a known angiogenesis-associated molecule implicated in tumor progression. In this report, we describe a recombinant scFv format for the 3F12E7 mAb. The results demonstrate that the generated 3F12E7 scFv, although prone to aggregation, comprises an active anti-FGF2 product that contains monomers and small oligomers. Functionally, the 3F12E7 scFv preparations specifically recognize FGF2 and inhibit tumor growth similar to the corresponding full-length IgG counterpart in an experimental model. In silico molecular analysis provided insights into the aggregation propensity and the antigen-recognition by scFv units. Antigen-binding determinants were predicted outside the most aggregation-prone hotspots. Overall, our experimental and prediction dataset describes an scFv scaffold for the 3F12E7 mAb and also provides insights to further engineer non-aggregated anti-FGF2 scFv-based tools for therapeutic and research purposes.

Transgender women (TGW) are one of the most vulnerable groups, including higher prevalence of HIV and mental health disorders, such as anxiety and depression than in the general population. Major Depression Disorder (MDD) is one of the most important mental health conditions due to an increasing trend in prevalence in the general population. This study aims at describing the prevalence of symptoms of MDD (SMDD) and associated factors among TGW in capitals of three States in Northeast Brazil. TGW n = (864) were selected from the cities of Salvador (n = 166), Recife (n = 350), and Fortaleza (n = 348) using Respondent Driven Sampling methodology. Symptoms of MDD were defined according to the Patient Health Questionnaire-9 scale. Multinomial logistic regression was used to compare those with mild/moderate or moderately severe/severe symptoms of depression with those with no depression, respectively, using complex sample design. Weighted Odds Ratio with 95% confidence interval were estimated. 51.1% of the sample was classified as mild/moderate and 18.9% as moderately severe/severe SMDD. Mild/moderate SMDD was associated with a history of sexual violence (OR = 2.06, 95%CI: 1.15-3.68), history of physical violence (OR = 2.09, 95%CI: 1.20-3.67),) and poor self-rated quality of life (OR = 2.14, 95%CI: 1.31-3.49).). Moderately severe/severe SMDD was associated with history of sexual violence (OR = 3.02, 95%CI: 1.17-7.77), history of physical violence (OR = 4.34, 95% CI:1.88-6.96), poor self-rated quality of life (OR = 3.32, 95%CI:1.804-6.12), lack of current social support (OR = 2.53, 95%IC: 1.31-4.88) and lack of family support in childhood (OR = 2.17, 95%IC 1.16-4.05)). Our findings strengthens the evidence of a higher prevalence of SMDD among TGW as compared to the general population. Public health policies and actions that target social determinants of risk and protection for MDD among TGW must be urgently implemented.

Anti-idiotype antibodies have been considered for vaccination approaches against different diseases, including cancers. Based on that, we previously described an anti-bevacizumab idiotype monoclonal antibody, 10.D7, that revealed detectable antitumor effects on a vascular endothelial growth factor (VEGF)-dependent tumor model. Herein, we evaluated the possible applicability of a single-chain variable fragment (scFv) for the 10.D7 antibody in a gene immunization strategy. After checking that mammalian cells transfected to express the 10.D7 scFv are recognized by bevacizumab, it was explored the ability of our scFv construction, in a gene-based scheme, to elicit an immune response containing VEGF-binding antibodies. The results provide evidence that the designed 10.D7 scFv construct maintains the anti-bevacizumab idiotype features and has potential to activate an immune response recognizing VEGF.

PurposeThis paper aimed to evaluate the differences in the use and knowledge of export promotion programs (EPPs) between Brazilian SMEs that internationalized early and SMEs that internationalized in a gradual, traditional fashion. Additionally, it tested hypotheses that distinguish these two types of SME internationalization processes in an emerging market context.Design/methodology/approachThe authors tested four hypotheses in a sample of 540 SME Brazilian exporters. The sample was divided into two groups according to the born global (BG) criteria: 379 SMEs with gradual or traditional internationalization (TI) and 161 SMEs with early internationalization (EI).FindingsThe results indicate that Brazilian EI SMEs operate in more countries and continents than TI SMEs. In emerging countries such as Brazil, the domestic market continues to play an important role both for SMEs that internationalize early and those whose process is slower. Even though logistic regression could not classify the sample of TI and EI SMEs according to their knowledge about EPPs, the results led to the idea that EI SMEs currently use more specific EPPs than do TI SMEs.Practical implicationsManagers of successful SMEs from emerging markets need to incorporate EPPs into their internationalization strategy. In emerging markets with large domestic markets, SME managers can meet their growth needs by exploiting opportunities in both domestic and international markets.Originality/valueResearch on the early internationalization of SMEs has long focused on SMEs from developed markets and on internal factors. Moreover, the effects of EPPs on the firm' performance of large and SME firms has also been the subject of study. The value of this paper relies on the intersection of EPPs and the early internationalization of SMEs, even for firms in developed markets.

PurposeThe main objective of this study is to investigate the 7 new quality control or the 7 new management tools and their use in manufacturing organisations. This research investigates the understanding, knowledge of the tools and the level of application of the tools within the manufacturing sector. In addition, this paper aims to identify the benefits, challenges and critical success factors (CSFs) for the application of the 7 new quality control (QC) tools.Design/methodology/approachAn online survey instrument was developed, and data collection was performed utilising a stratified random sampling strategy. The primary strata/clusters were formed by quality professionals working in all aspects of manufacturing organisations and functions. A total of 86 participants from different countries responded to the survey.FindingsThe main finding of this study is that 10% of participants within the manufacturing sector perceived that the 7 new QC tools could solve above 80% of organisational problems. Another relevant finding presented in this paper is that tree diagrams were the most utilised of the 7 new QC tools within the manufacturing sector. The least utilised tools are arrow diagrams. The common benefits of using 7 new QC tools in the manufacturing sector are helping people define, measure and analyse the problem areas or even prioritises them and providing some form of structure to the problem-solving efforts. This paper also revealed that the 7 new QC tools were most used in the manufacturing area but least utilised in the new products and research and development (R&D) functions. This work also presents a list of CSFs and challenges required to properly apply the 7 new QC tools in the manufacturing sector.Research limitations/implicationsThis study was just carried out in manufacturing organisations. It would be interesting to try and expand to services sectors and compare use within the services sector.Originality/valueAuthors understand that this is the very first empirical study analysing the use and understanding of the 7 new QC or management tools within the manufacturing sector. The results of this study represent an important first step towards a complete understanding of the applicability of these tools in continuous improvement programs on a global scale and the context in which they can be utilized.

Purpose Process improvement initiatives, such as Lean, Six Sigma and Lean Six Sigma, typically have common characteristics that are carried through projects. Whilst a project’s performance is an important determinant of the successful implementation of continuous improvement (CI) initiatives, its failure can undermine the impact of any CI initiative on business performance. As a result, an understanding of the reasons of process improvement project failures is crucial. The purpose of this paper is to present the results of a pilot survey highlighting the most common reasons for process improvement project failures. Design/methodology/approach This paper presents a pilot survey of 42 Brazilian manufacturing specialists who have been involved in process improvement projects. The participants of this survey were Six Sigma Master Black Belts, Black Belts, Green Belts and Six Sigma champions from manufacturing companies in Brazil. The survey questionnaire was piloted with five experts in the field in order to ensure that the questions were valid and technically sound. Findings The execution of Six Sigma projects in organizations results in a moderate rate of project failures. These failures can cost organizations several millions of dollars especially within the context of larger organizations. The main reasons for project failure, as cited by the specialists include: resistance to change, lack of commitment and support from top management and incompetent teams. Research limitations/implications The authors report the findings from a pilot survey having a limited sample size. Moreover, the data have been collected from one country and primarily from large manufacturing companies. Originality/value To the best of the authors’ knowledge, this is the first empirical study looking into the reasons for process improvement project failures. The authors argue that if the top reasons for such failures are understood, a framework can be developed in the future that can mitigate the chance of project failures during project execution. This could potentially lead to significant savings to the bottom-line of many organizations.

Obesity is a chronic clinical condition that is considered one of the most serious health problems in the world because it can cause other chronic metabolic disorders. A meta-analysis was conducted to evaluate the safety and efficacy of 4 central-acting drugs, all approved in Brazil's market for weight loss. PubMed, EMBASE, and Cochrane library databases were searched from inception until January 2018 to retrieve randomized controlled trials comparing sibutramine, diethylpropion, mazindol, and fenproporex versus placebo in overweight or obese patients. Language was not a restriction for the database searches. We extracted and combined data from studies that reported adverse drug events and weight change. A random effects meta-analytic model was applied in all calculations. The Cochrane Collaboration tool was used to assess the quality and bias of all included studies. Quality of evidence was assessed by using the Grading of Recommendations, Assessment, Development, and Evaluation criteria. Fifty-three studies were included, with a total of 16,903 patients with a median follow-up of 12 weeks (2–260 weeks). The appetite suppressants showed a significant weight loss compared with placebo (mean difference [MD], −4.70 kg; 95% CI, −5.25 to −4.15; I2 = 100%; 43 studies). There was an increased total number of adverse events, dry mouth, constipation, insomnia, dizziness, and tachycardia reported in the intervention group (risk ratio [RR], 1.06; 95% CI, 1.01 to 1.10; I2 = 20% [22 studies]; RR, 2.08; 95% CI, 1.76 to 2.47; I2 = 34% [25 studies]; RR, 2.31; 95% CI, 1.88 to 2.84; I2 = 0% [25 studies]; RR, 1.84; 95% CI, 1.40 to 2.39; I2 = 0% [17 studies]; RR, 1.78; 95% CI, 1.24 to 2.58; I2 = 0% [13 studies]; and RR, 2.01; 95% CI, 1.42 to 2.86; I2 = 0% [10 studies], respectively). Sibutramine showed a significant increase in heart rate and mean diastolic pressure compared with placebo (MD, 4.17 beats/min [95% CI, 3.60 to 4.74; I2 = 99%; 23 studies]; MD, 1.68 mm Hg [95% CI, 1.29 to 2.07; I2 = 98%; 22 studies]). These drugs are effective for weight loss in overweight and obese patients; however, they increase the risk of adverse events. In fact, the evidence is of low quality, the data availability of studied agents (especially for cardiovascular outcomes) are limited, and the studies are of short duration. PROSPERO identifier: CRD42018091083.

Thoracic aortic diseases (or aortopathies) result from complex interactions between genetic and hemodynamic factors. Often clinically silent, these diseases can lead to lethal complications such as aortic dissection or rupture. This study focused on a Brazilian cohort of 79 individuals with thoracic aortic diseases and explored genetic factors through targeted next-generation sequencing (tNGS) of 15 priority genes and FBN1 direct sequencing. The majority of individuals had nonsyndromic aortopathy, with eight diagnosed with Marfan syndrome (MFS). Pathogenic or likely pathogenic variants (PV/LPV) were found in five genes, namely, FBN1 , ACTA2 , TGFBR2 , MYLK , and SMAD3 . Notably, novel variants in FBN1 were identified that contributed to Marfan-like phenotypes. The diagnostic yield for isolated aortopathies was 7.1%, which increased to 55.5% for syndromic cases. Variants of uncertain significance (VUS) were identified, emphasizing the need for further research and familial investigations to refine variant classifications. This study provides valuable insights into the genetic landscape of aortopathies in Brazil, aiding early diagnosis and personalized management.

Beef cows herd accounts for 70% of the total energy used in the beef production system. However, there are still limited studies regarding improvement of production efficiency in this category, mainly in developing countries and in tropical areas. One of the limiting factors is the difficulty to obtain reliable estimates of weight variation in mature cows. This occurs due to the interaction of weight of maternal tissues with specific physiological stages such as pregnancy. Moreover, variation in gastrointestinal contents due to feeding status in ruminant animals is a major source of error in body weight measurements. Develop approaches to estimate the individual proportion of weight from maternal tissues and from gestation in pregnant cows, adjusting for feeding status and stage of gestation. Dataset of 49 multiparous non-lactating Nellore cows (32 pregnant and 17 non-pregnant) were used. To establish the relationships between the body weight, depending on the feeding status of pregnant and non-pregnant cows as a function of days of pregnancy, a set of general equations was tested, based on theoretical suppositions. We proposed the concept of pregnant compound (PREG), which represents the weight that is genuinely related to pregnancy. The PREG includes the gravid uterus minus the non-pregnant uterus plus the accretion in udder related to pregnancy. There was no accretion in udder weight up to 238 days of pregnancy. By subtracting the PREG from live weight of a pregnant cow, we obtained estimates of the weight of only maternal tissues in pregnant cows. Non-linear functions were adjusted to estimate the relationship between fasted, non-fasted and empty body weight, for pregnant and non-pregnant cows. Our results allow for estimating the actual live weight of pregnant cows and their body constituents, and subsequent comparison as a function of days of gestation and feeding status.

ObjectiveTo assess the current evidence for the efficacy of care bundles in reducing unplanned extubations (UEs) in critically ill children.DesignSystematic review according to the Cochrane guidelines and meta-analysis using random-effects modelling.MethodsWe searched MEDLINE, EMBASE, CINAHL, Web of Science, Scopus, Cochrane and SciELO databases from inception until April 2021. We conducted a quality appraisal for each study using the Newcastle–Ottawa Scale and Standards for Quality Improvement Reporting Excellence (SQUIRE) V.2.0 checklist.Main outcomeThe primary outcome measure was UE rates per 100 intubation days.ResultsWe screened 10 091 records and finally included 11 studies. Six studies were pre/post-intervention studies, and five were interrupted time-series studies. The methodological quality was ‘good’ in 70%, and the remaining as ‘fair’ (30%). The most frequently used implementation strategies were staff education (100%), root cause analysis (100%), and audit and feedback (82%). Key bundle care components comprised identification of high-risk patients, endotracheal tube care and sedation protocol. Not all studies fully completed the SQUIRE V.2.0 checklist. Meta-analysis revealed a reduction in UE rate following the introduction of care bundles (rate ratio: 0.40 (95% CI: 0.19 to 0.84); p=0.02), which equates to a 60% reduction in UE rates.ConclusionsWe found that identifying high-risk patients, endotracheal tube care and protocol-directed sedation are core elements in care bundles for preventing UEs. However, there are several methodological gaps in the literature, including poor evaluation of adherence to bundle components. Future studies should address these gaps to strengthen their validity.