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BACKGROUND: Obesity causes significant difficulties in successful extracorporeal membrane oxygenation (ECMO) support and may interfere with patient outcomes. During the COVID-19 pandemic, we experienced an increased number of obese patients supported with ECMO in our intensive care unit due to severe illness in this population. METHODS: We designed a single-center retrospective study to identify prognostic factors for 180-day survival in obese critical COVID-19 patients receiving venovenous ECMO (VV-ECMO). We included adult critical COVID-19 patients on VV-ECMO, who were obese and overweight (according to the World Health Organization) and admitted to a tertiary hospital's intensive care unit from April 1, 2020, to May 31, 2022. Univariate logistic regression analysis was performed to assess differences in 180-day mortality. RESULTS: Forty-one patients were included. The median age was 55 (IQR 45-60) years, and 70.7% of the patients were male. The median body mass index (BMI) was 36 (IQR 31-42.5) kg/m2; 39% of patients had a BMI ≥ 40 kg/m2. The participants had 3 (IQR 1.5-4) days of mechanical ventilation prior to ECMO, and 63.4% were weaned from VV-ECMO support after a median of 19 (IQR 10-34) days. The median ICU length of stay was 31.9 (IQR 17.5-44.5) days. The duration of mechanical ventilation was 30 (IQR 19-49.5) days. The 180-day mortality rate was 41.5%. Univariate logistic regression analysis revealed that a higher BMI was associated with greater 180-day survival (OR 1.157 [1.038-1.291], p = 0.009). Younger age, female sex, less invasive ventilation time before ECMO, and fewer complications at the time of ECMO cannulation were associated with greater 180-day survival [OR 0.858 (0.774-0.953), p 0.004; OR 0.074 (0.008-0.650), p 0.019; OR 0.612 (0.401-0.933), p 0.022; OR 0.13 (0.03-0.740), p 0.022), respectively]. CONCLUSION: In this retrospective cohort of critical COVID-19 obese adult patients supported by VV-ECMO, a higher BMI, younger age, and female sex were associated with greater 180-day survival. A shorter invasive ventilation time before ECMO and fewer complications at ECMO cannulation were also associated with increased survival.
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Parkinson's disease is the second most common neurodegenerative disease, but therapeutic options such as neuromodulation continue to show variable effects, making clinical management of the disease difficult. This systematic review with meta-analysis and meta-regression aimed to analyze the isolated effect of cortical modulation with transcranial direct current stimulation (tDCS) compared to sham stimulation on cognitive changes in people with Parkinson's disease. The databases used were: Web of Science, Scopus, PsycINFO, PubMed, and Cochrane. The results showed that tDCS can influence the improvement of cognition in PD (Inverse Variance:0.24 [95% Confidence Interval: 0.09 to -0.40], p < 0.00). The meta-analysis showed that active tDCS can influence cognitive function by improving aspects related to memory (Inverse Variance:0.34 [95% Confidence Interval: 0.07 to 0.61], p < 0.01) and reducing reaction time in cognitive tasks (Inverse Variance:0.42 [95% Confidence Interval: 0.07 to 0.76], p < 0.02). Innovative meta-regression analyses showed that variables such as age (Q = 2.54, df = 1, p < 0.11), education level (Q = 2.62, df = 1, p < 0.10), disease duration (Q = 0.01, df = 1, p < 0.92), and Unified PD Rating Scale stage (Q = 0.01, df = 1, p < 0.92) did not influence the results. Thus, tDCS may be a therapeutic option for cognitive changes in people with PD, and we suggest further studies to identify protocols that can be replicated.
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Several multiplex approaches for the simultaneous detection of pathogens in food have been developed in recent years, but the use of a single enrichment medium remains a problem. In this study, six enrichment broths (five non-selective media, tryptic soy broth (TSB), brain heart infusion broth (BHI), buffered peptone water (BPW), universal pre-enrichment broth (UPB), no. 17 broth, and a selective, Salmonella Escherichia Listeria broth (SEL)), were studied for the simultaneous detection of E. coli O157:H7, Salmonella spp., and L. monocytogenes, to validate the suitable enrichment broth to be used for the detection methods. Different ratios of E. coli O157:H7, Salmonella spp., and L. monocytogenes were used. Almost all non-selective broths evaluated in this study showed similar growth parameters and profiles among each other. The only selective enrichment broth under analysis (SEL) showed distinct growth features compared to the non-selective media, allowing for a slower but balanced growth of the three pathogens, which could be beneficial in preventing the overgrowth of fast-growing bacteria. In addition, when tested in ground beef samples, SEL broth seems to be the most distinctive medium with a balanced growth pattern observed for the three pathogens. Overall, this study is intended to provide the basis for the selection of suitable enrichment broths according to the technology detection to be used, the desired time of enrichment, and the expected balanced concentration of pathogens.
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The impacts of grazing on rangelands have historically been studied within the framework of the equilibrium model, which predicts significant impacts of grazing on ecosystems. However, in recent decades, studies have observed a non-equilibrium pattern, suggesting that abiotic factors play a primary role compared to grazing. These studies are primarily focused on rangelands, despite animal husbandry occurring in other biomes, such as seasonally dry tropical forests. Our study examines the influence of goat grazing on biodiversity and forest succession in the Brazilian dry forest (Caatinga). Considering its high interannual precipitation variability, we hypothesize a response that aligns with the non-equilibrium paradigm. We established a gradient of grazing intensity and history in areas at different stages of vegetation succession. A survey of tree - shrub and herbaceous species was conducted at each site and the biomass of both strata was quantified. Linear mixed models and Permanova were employed to assess differences in richness, composition, structure, and biomass among the areas. Our results suggest that grazing (history and intensity) and forest fallow age did not affect species richness, but only species composition. Low and high grazing intensity drive ecosystems toward similar compositions, which align with the non-equilibrium model predictions. Biomass in the herbaceous layer remained unaffected by grazing history, intensity, or forest fallow age, whereas woody biomass was influenced by grazing intensity in older forest fallows. Although trees in low-intensity grazing sites were significantly taller compared to those in other levels, overall, grazing did not disrupt the natural succession process. Older forest fallows exhibited greater diversity and higher basal area compared to new forest fallows, irrespective of grazing intensity. Our findings suggest that: a) grazing has minimal effects on biodiversity and biomass due to non-equilibrium dynamics, and b) with appropriate management, grazing can coexist with the conservation of the Caatinga.
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Biodiversidad , Bosques , Herbivoria , Brasil , Animales , Biomasa , Cabras , Monitoreo del Ambiente , ÁrbolesRESUMEN
This study aimed to analyze the distribution of short interspersed elements (SINEs) in the chromosomes of five species of rodents of the genus Proechimys and in a variant karyotype of P. guyannensis. Molecular cytogenetic techniques were used to characterize the sequences of the B1, B4, MAR and THER SINEs, which were used as probes for hybridization in metaphase chromosomes. A wide distribution of SINEs was observed in the chromosomes of the Proechimys species examined, thus indicating differentiation of these retroelements. The signal of the B4 SINE was more evident than that of the B1 SINE, especially in P. echinothrix, P. longicaudatus, and P. cuvieri. Although the signal of the MAR SINE was more explosive than that of the THER SINE, in the species P. echinothrix, P. guyannensis (2n = 46) and P. longicaudatus, its distribution in the karyotypes was similar. The signals of these retroelements occurred at specific heterochromatic sites and were centromeric/pericentromeric and at the terminal regions in most chromosomes. This appears to be a typical distribution pattern of the SINEs and may indicate involvement with rearrangements during karyotypic diversification in Proechimys. The variation of the SINEs in the genome of Proechimys species demonstrates that these elements are distributed in a specific way in this genus and the preference for some sites, considered hotspots for chromosomal breakage, allows us to propose that these elements are related to the karyotypic evolution of Proechimys.
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A growing body of scientific literature stresses the need to advance current environmental risk assessment (ERA) methodologies and associated regulatory frameworks to better address the landscape-scale and long-term impact of pesticide use on biodiversity and the ecosystem. Moreover, more collaborative and integrative approaches are needed to meet sustainability goals. The One Health approach is increasingly applied by the European Food Safety Authority (EFSA) to support the transition towards safer, healthier and more sustainable food. To this end, EFSA commissioned the development of a roadmap for action to establish a European Partnership for next-generation, systems-based Environmental Risk Assessment (PERA). Here, we summarise the main conclusions and recommendations reported in the 2022 PERA Roadmap. This roadmap highlights that fragmentation of data, knowledge and expertise across regulatory sectors results in suboptimal processes and hinders the implementation of integrative ERA approaches needed to better protect the environment. To advance ERA, we revisited the underlying assumptions of the current ERA paradigm; that chemical risks are generally assessed and managed in isolation with a substance-by-substance, realistic worst-case and tiered approach. We suggest optimising the use of the vast amount of information and expertise available with pesticides as a pilot area. It is recommended to as soon as possible adopt a systems-based approach, i.e. within the current regulatory framework, to spark a step-wise transition towards an ERA framed at a system level of ecological and societal relevance. Tangible systems-based and integrative steps are available. For instance, the rich sources of existing data for prospective and retrospective ERA of pesticides could be used to reality-benchmark existing and new ERA methods. To achieve these goals, collaboration among stakeholders across scientific disciplines and regulatory sectors must be strengthened.
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Plaguicidas , Medición de Riesgo , Europa (Continente) , Análisis de Sistemas , Proyectos Piloto , Monitoreo del Ambiente/métodos , Contaminantes Ambientales/análisis , Política AmbientalRESUMEN
The Morada Nova sheep breed is essential for the economy of the semi-arid region of Northeast Brazil, standing out for its adaptability, resistance to parasites and reproductive ability. However, the white variant is endangered, highlighting the importance of studies on its productivity to support conservation efforts. This study focuses on the growth curve of the Morada Nova sheep breed, using nonlinear models and analyzing flock profiles. Total of 764 observations of 165 animals from four farms in Ceará and Rio Grande do Norte, Brazil, were analyzed. Canonical discriminant analysis (CDA) was used for the exploratory analysis and four nonlinear models were used to study the growth curve. Weight from birth to 270 days of age, absolute growth rate (AGR), and the impact of sex on growth curves were assessed. Sex and farm are significant discriminating variables (P < 0.05) for the studied effects (weight and age). Weight was the primary phenotypic biomarker that discriminated between the two indicators, while age was a discriminating indicator only for the core effect. The Gompertz model was the most efficient, presenting the lowest residuals and greatest convergence. The study reveals new information about the growth of Morada Nova sheep, the white variety, including weight differences between the sexes at all analyzed ages and an inflection point before 90 days of age. These discoveries contribute to the understanding of the breed's growth and help in the formulation of conservation strategies.
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Oveja Doméstica , Animales , Brasil , Masculino , Femenino , Oveja Doméstica/crecimiento & desarrollo , Oveja Doméstica/genética , Oveja Doméstica/fisiología , Peso Corporal , Ovinos/crecimiento & desarrollo , CruzamientoRESUMEN
Members of the genus Lysinibacillus attract attention for their mosquitocidal, bioremediation, and plant growth-promoting abilities. Despite this interest, comprehensive studies focusing on genomic traits governing plant growth and stress resilience in this genus using whole-genome sequencing are still scarce. Therefore, we sequenced and compared the genomes of three endophytic Lysinibacillus irui strains isolated from Canary Island date palms with the ex-type strain IRB4-01. Overall, the genomes of these strains consist of a circular chromosome with an average size of 4.6 Mb and a GC content of 37.2%. Comparative analysis identified conserved gene clusters within the core genome involved in iron acquisition, phosphate solubilization, indole-3-acetic acid biosynthesis, and volatile compounds. In addition, genome analysis revealed the presence of genes encoding carbohydrate-active enzymes, and proteins that confer resistance to oxidative, osmotic, and salinity stresses. Furthermore, pathways of putative novel bacteriocins were identified in all genomes. This illustrates possible common plant growth-promoting traits shared among all strains of L. irui. Our findings highlight a rich repertoire of genes associated with plant lifestyles, suggesting significant potential for developing inoculants to enhance plant growth and resilience. This study is the first to provide insights into the overall genomic signatures and mechanisms of plant growth promotion and biocontrol in the genus Lysinibacillus. KEY POINTS: ⢠Pioneer study in elucidating plant growth promoting in L. irui through comparative genomics. ⢠Genome mining identified biosynthetic pathways of putative novel bacteriocins. ⢠Future research directions to develop L. irui-based biofertilizers for sustainable agriculture.
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Bacillaceae , Genoma Bacteriano , Genómica , Bacillaceae/genética , Bacillaceae/metabolismo , Composición de Base , Familia de Multigenes , Arecaceae/microbiología , Desarrollo de la Planta , Secuenciación Completa del Genoma , Bacteriocinas/genética , Bacteriocinas/metabolismo , Bacteriocinas/biosíntesis , Filogenia , Reguladores del Crecimiento de las Plantas/metabolismo , Ácidos Indolacéticos/metabolismo , Estrés FisiológicoRESUMEN
Implementation of marker-assisted selection (MAS) in modern beekeeping would improve sustainability, especially in breeding programs aiming for resilience against the parasitic mite Varroa destructor. Selecting honey bee colonies for natural resistance traits, such as brood-intrinsic suppression of varroa mite reproduction, reduces the use of chemical acaricides while respecting local adaptation. In 2019, eight genomic variants associated with varroa non-reproduction in drone brood were discovered in a single colony from the Amsterdam Water Dune population in the Netherlands. Recently, a new study tested the applicability of these eight genetic variants for the same phenotype on a population-wide scale in Flanders, Belgium. As the properties of some variants varied between the two studies, one hypothesized that the difference in genetic ancestry of the sampled colonies may underly these contribution shifts. In order to frame this, we determined the allele frequencies of the eight genetic variants in more than 360 Apis mellifera colonies across the European continent and found that variant type allele frequencies of these variants are primarily related to the A. mellifera subspecies or phylogenetic honey bee lineage. Our results confirm that population-specific genetic markers should always be evaluated in a new population prior to using them in MAS programs.
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Obesity is a worldwide epidemic, and bariatric surgery is considered the primary treatment for long-term weight loss and managing obesity-related health issues. Sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) are the most performed procedures. Nutritional deficiencies are a significant concern following bariatric surgery and can have serious consequences. This study aims to compare the incidence of nutritional deficiencies in patients undergoing RYGB and SG. A retrospective analysis was conducted on the nutritional status of 505 consecutive patients who underwent either RYGB or SG between January and December 2019. Data were collected regarding vitamin B12, folic acid, vitamin D, calcium, PTH, magnesium, hemoglobin, iron, ferritin, and transferrin at preoperative, 6-month, and 12-month intervals post-surgery. The RYGB group showed significantly higher excess weight loss. Vitamin B12, hemoglobin, and ferritin levels were consistently higher in the SG group throughout the study. Vitamin D deficiency was prevalent, with no significant difference between the groups. Vitamin B12 deficiency was significantly more common in the RYGB group (6 months: 17.46% vs. 4.69%, p < 0.001; 12 months: 16.74% vs. 0.93%, p < 0.001). Despite differences in their mechanisms, bariatric surgeries were associated with nutritional deficiencies. It is crucial to efficiently assess, prevent, and manage these deficiencies tailored to each surgical procedure.
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The objective of this study is to investigate the effects of a moderate intensity physical training protocol, on alveolar bone morphology of rats submitted to ligature-induced periodontitis. Twenty-eight male Wistar rats were divided into four groups, considering the presence/absence of periodontitis and presence/absence of training. The training protocol was performed on a treadmill, 30 min/day, 5 days a week, for 4 weeks. In the experimental periodontal breakdown, with/without training, ligatures were placed on the lower first molars on the 14th day of the experiment, and were followed until the end of the protocol. At the end of the experiment, animals were euthanized and samples of plasma and mandibles were collected for immunoenzymatic evaluation of interleukins (IL)-1ß, IL-6, TNF-α and IL-10, evaluation of serum concentrations of C-reactive protein, analysis of lipid peroxidation (LPO) and reduced glutathione, histological and microtomographic analyses were performed. Physical training resulted in a reduced levels of IL-1ß, IL-6, TNF-α C-reactive protein and LPO and an increase in the levels of IL-10 in rats with periodontitis (p<0.05); a reduction in the inflammatory infiltrate and decreased fiber degradation was identified in histological analysis. Additionally, it was shown a decrease in vertical bone loss and an increase in the bone volume/trabecular volume ratio was identified in periodontitis+physical training group (p<0.05). Based on the results, the practice of frequent physical exercise, at moderate intensity, can contribute to the reduction of damage related to the disproportionate inflammatory response in periodontitis.
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Peroxidación de Lípido , Estrés Oxidativo , Periodontitis , Condicionamiento Físico Animal , Ratas Wistar , Animales , Periodontitis/metabolismo , Periodontitis/patología , Masculino , Ratas , Proteína C-Reactiva/metabolismo , Pérdida de Hueso Alveolar/patología , Pérdida de Hueso Alveolar/metabolismo , Glutatión/metabolismo , Modelos Animales de Enfermedad , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Citocinas/metabolismo , Citocinas/sangreRESUMEN
This systematic review aimed to verify whether there is evidence of an association between apical periodontitis and the presence of systemic biomarkers. This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA. For this, the acronym PECO was used; population (P) of adult humans exposed (E) to the presence of apical periodontitis, compared (C) to adult humans without apical periodontitis, and the outcome (O) of the presence of biomarkers was observed. The articles were searched in PubMed, Scopus, Web of Science, LILACS, Cochrane Library, OpenGray, and Google Scholar grey databases. Subsequently, studies were excluded based on title, abstract, and full article reading, following the eligibility criteria. The methodological quality of the selected studies was evaluated using the Newcastle-Ottawa qualifier. After exclusion, 656 studies were identified, resulting in 17 final articles that were divided into case-control, cross-sectional, and cohort studies. Eight studies were considered to have a low risk of bias, one had a medium risk of bias, and eight had a high risk of bias. In addition, 12 articles evaluated biomarkers in blood plasma, four evaluated them in saliva, and only one evaluated them in gingival crevicular fluid. The results of these studies indicated an association between apical periodontitis and the systemic presence of biomarkers. These markers are mainly related to inflammation, such as interleukins IL-1, IL-2, and IL-6, oxidative markers, such as nitric oxide and superoxide anions, and immunoglobulins IgG and IgM. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier (CRD42023493959).
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Biomarcadores , Periodontitis Periapical , Humanos , Biomarcadores/sangre , Periodontitis Periapical/sangre , Periodontitis Periapical/metabolismoRESUMEN
BACKGROUND: Antibodies against leucine-rich glioma inactivated protein 1 (LGI1) constitute a common form of autoimmune encephalitis. On MR imaging, it may show T2 FLAIR hyperintensities of the medial temporal lobe (T2 FLAIR-MTL), involve the basal ganglia, or be unremarkable. PURPOSE: We performed a systematic review and meta-analysis to obtain prevalence estimates of abnormal findings on MR imaging in anti-LGI1 encephalitis. A human brain map of the LGI1 microarray gene expression was derived from the Allen Human Brain Atlas. DATA SOURCES: PubMed and Web of Science were searched with the terms "LGI1" and "encephalitis" from inception to April 7, 2022. STUDY SELECTION: Thirty-one research publications, encompassing case series and retrospective cohort and case-control studies, with >10 patients with anti-LGI1 encephalitis and MR imaging data were included. DATA ANALYSIS: Pooled prevalence estimates were calculated using Freeman-Tukey double-arcsine transformation. Meta-analysis used DerSimonian and Laird random effects models. DATA SYNTHESIS: Of 1318 patients in 30 studies, T2 FLAIR-MTL hyperintensities were present in 54% (95% CI, 0.48-0.60; I2 = 76%). Of 394 patients in 13 studies, 27% showed bilateral (95% CI, 0.19-0.36; I2 = 71%) and 24% unilateral T2 FLAIR-MTL abnormalities (95% CI, 0.17-0.32; I2 = 61%). Of 612 patients in 15 studies, basal ganglia abnormalities were present in 10% (95% CI, 0.06-0.15; I2 = 67%). LGI1 expression was highest in the amygdala, hippocampus, and caudate nucleus. LIMITATIONS: Only part of the spectrum of MR imaging abnormalities in anti-LGI1 encephalitis could be included in a meta-analysis. MR imaging findings were not the main outcomes in most studies, limiting available information. I2 values ranged from 62% to 76%, representing moderate-to-large heterogeneity. CONCLUSIONS: T2 FLAIR-MTL hyperintensities were present in around one-half of patients with anti-LGI1. The prevalence of unilateral and bilateral presentations was similar, suggesting unilaterality should raise the suspicion of this disease in the appropriate clinical context. Around 10% of patients showed basal ganglia abnormalities, indicating that special attention should be given to this region. LGI1 regional expression coincided with the most frequently reported abnormal findings on MR imaging. Regional specificity might be partially determined by expression levels of the target protein.
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Autoanticuerpos , Encefalitis , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Encefalitis/diagnóstico por imagen , Encefalitis/inmunología , Encefalitis/patología , Autoanticuerpos/inmunología , Péptidos y Proteínas de Señalización Intracelular/inmunología , Péptidos y Proteínas de Señalización Intracelular/metabolismoRESUMEN
The açai juice contains high concentrations of phenolic compounds, including cyanidin-3-glucoside and others flavonoids. The aim of this study was to evaluate the impact of açai supplementation on healthy mandibular alveolar bone in male albino rats of the Wistar strain. 24 rats were divided into 3 groups, in which one group received a daily dose of saline solution and the other two groups were treated with daily doses of clarified açai juice for 14 or 28 days. After the experiment, hemimandibles were collected and analyzed using Scanning Electron Microscopy (SEM), histological assessments, and micro-CT. Results showed changes in the integrity of the alveolar bone as seen in SEM, increased osteocyte density and higher collagen matrix area in the açai group compared to the control group as seen in histological analysis, and increased bone volume, trabecular thickness and number, and cortical bone as seen in micro-CT analysis. The space between bone trabeculae showed no difference among the groups. These results suggest that açai supplementation may have a structural change effect on alveolar bone, but further research is needed to confirm these findings in humans and to determine the exact mechanisms behind these effects.
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Background: Detailed and invasive clinical investigations are required to identify the causes of haematuria. Highly unbalanced patient population (predominantly male) and a wide range of potential causes make the ability to correctly classify patients and identify patient-specific biomarkers a major challenge. Studies have shown that it is possible to improve the diagnosis using multi-marker analysis, even in unbalanced datasets, by applying advanced analytical methods. Here, we applied several machine learning algorithms to classify patients from the haematuria patient cohort (HaBio) by analysing multiple biomarkers and to identify the most relevant ones. Materials and methods: We applied several classification and feature selection methods (k-means clustering, decision trees, random forest with LIME explainer and CACTUS algorithm) to stratify patients into two groups: healthy (with no clear cause of haematuria) or sick (with an identified cause of haematuria e.g., bladder cancer, or infection). The classification performance of the models was compared. Biomarkers identified as important by the algorithms were also analysed in relation to their involvement in the pathological processes. Results: Results showed that a high unbalance in the datasets significantly affected the classification by random forest and decision trees, leading to the overestimation of the sick class and low model performance. CACTUS algorithm was more robust to the unbalance in the dataset. CACTUS obtained a balanced accuracy of 0.747 for both genders, 0.718 for females and 0.803 for males. The analysis showed that in the classification process for the whole dataset: microalbumin, male gender, and tPSA emerged as the most informative biomarkers. For males: age, microalbumin, tPSA, cystatin C, BTA, HAD and S100A4 were the most significant biomarkers while for females microalbumin, IL-8, pERK, and CXCL16. Conclusions: CACTUS algorithm demonstrated improved performance compared with other methods such as decision trees and random forest. Additionally, we identified the most relevant biomarkers for the specific patient group, which could be considered in the future as novel biomarkers for diagnosis. Our results have the potential to inform future research and provide new personalised diagnostic approaches tailored directly to the needs of the individuals.
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BACKGROUND & AIMS: Obeticholic acid (OCA) is the only licensed second-line therapy for primary biliary cholangitis (PBC). With novel therapeutics in advanced development, clinical tools are needed to tailor the treatment algorithm. We aimed to derive and externally validate the OCA response score (ORS) for predicting the response probability of individuals with PBC to OCA. METHODS: We used data from the Italian RECAPITULATE (N = 441) and the IBER-PBC (N = 244) OCA real-world prospective cohorts to derive/validate a score including widely available variables obtained either pre-treatment (ORS) or also after 6 months of treatment (ORS+). Multivariable Cox regressions with backward selection were applied to obtain parsimonious predictive models. The predicted outcomes were biochemical response according to POISE (alkaline phosphatase [ALP]/upper limit of normal [ULN]<1.67 with a reduction of at least 15%, and normal bilirubin), or ALP/ULN<1.67, or normal range criteria (NR: normal ALP, alanine aminotransferase [ALT], and bilirubin) up to 24 months. RESULTS: Depending on the response criteria, ORS included age, pruritus, cirrhosis, ALP/ULN, ALT/ULN, GGT/ULN, and bilirubin. ORS+ also included ALP/ULN and bilirubin after 6 months of OCA therapy. Internally validated c-statistics for ORS were 0.75, 0.78, and 0.72 for POISE, ALP/ULN<1.67, and NR response, which raised to 0.83, 0.88, and 0.81 with ORS+, respectively. The respective performances in validation were 0.70, 0.72, and 0.71 for ORS and 0.80, 0.84, and 0.78 for ORS+. Results were consistent across groups with mild/severe disease. CONCLUSIONS: We developed and externally validated a scoring system capable to predict OCA response according to different criteria. This tool will enhance a stratified second-line therapy model to streamline standard care and trial delivery in PBC.
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Locally advanced breast cancer poses significant challenges to the multidisciplinary team, in particular with hormone receptor (HR) positive, HER2-negative tumors that classically yield lower pathological complete responses with chemotherapy. The increasingly significant use of CDK 4/6 inhibitors (CDK4/6i) plus endocrine therapy (ET) in different breast cancer settings has led to clinical trials focusing on this strategy as a primary treatment, with promising results. The impact of the microbiota on cancer, and vice-versa, is an emerging topic in oncology. The authors report a clinical case of a postmenopausal female patient with an invasive breast carcinoma of the right breast, Luminal B-like, staged as cT4cN3M0 (IIIB). Since the lesion was considered primarily inoperable, the patient started letrozole and ribociclib. Following 6 months of systemic therapy, the clinical response was significant, and surgery with curative intent was performed. The final staging was ypT3ypN2aM0, R1, and the patient started adjuvant letrozole and radiotherapy. This case provides important insights on primary CDK4/6i plus ET in locally advanced unresectable HR+/HER2- breast cancer and its potential implications in disease management further ahead. The patient's gut microbiota was analyzed throughout the disease course and therapeutic approach, evidencing a shift in gut microbial dominance from Firmicutes to Bacteroidetes and a loss of microbial diversity following 6 months of systemic therapy. The analysis of the intratumoral microbiota from the surgical specimen revealed high microbial dissimilarity between the residual tumor and respective margins.
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BACKGROUND RARP is an established procedure in treatment of localized prostate cancer. Hemorrhagic complications in the postoperative period are rare, but sometimes life-threatening. Adequate monitoring and prompt intervention in these unusual scenarios rely on clinical judgement and blood and imaging studies. Prostatic fossa pseudoaneurysm formation after RARP is very rare and its etiology is not well known; it may be related to small vessel trauma. It becomes apparent with the development of hematuria 1-6 weeks after surgery. CASE REPORT A 58-year-old man underwent RARP with extended lymph node dissection for intermediate-risk prostate cancer, with bilateral preservation of neurovascular bundles and puboprostatic ligaments. He was discharged on day 2 without complications. In the following 4 weeks he came to the Emergency Department 3 times with hematuria and acute urinary retention. Four weeks after surgery, a pelvic CT angiogram showed a 20-mm pseudoaneurysm in the prostatic fossa, which was embolized by percutaneous angiography, with resolution of symptoms. He was discharged soon thereafter. CONCLUSIONS This case study describes a patient with prostatic fossa pseudoaneurysm after RARP. It was diagnosed 1 month after surgery and effectively managed by percutaneous embolization. Despite being a very rare condition, it must be kept in mind, especially when postoperative hematuria develops 1-6 weeks after surgery. Use of a management algorithm including serial blood tests, CT angiogram, and percutaneous angiography can lead to early detection and avoid life-threatening hemorrhage and overall postoperative morbidity.
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Aneurisma Falso , Neoplasias de la Próstata , Robótica , Masculino , Humanos , Persona de Mediana Edad , Hematuria/etiología , Hematuria/cirugía , Aneurisma Falso/diagnóstico por imagen , Aneurisma Falso/etiología , Aneurisma Falso/terapia , Prostatectomía/efectos adversos , Prostatectomía/métodos , Neoplasias de la Próstata/cirugía , Neoplasias de la Próstata/patología , Resultado del TratamientoRESUMEN
The metathesis reaction has been an important tool in both organic and inorganic synthetic chemistry. More specifically in polymer chemistry, ring opening metathesis polymerization (ROMP), via the formation of an active metal-carbene species (MîCHR), has been widely used. The elucidation of the mechanism for ROMP opened the way for the development of well-defined catalysts, suited to local conditions. In the present study, we employed density functional theory (DFT) to investigate three reaction pathways for the formation of a species capable of activating ROMP. The active species is formed from the [RuCl2(PPh3)2(pip)] complex in the presence of norbornadiene (NBD) and the carbene source ethyl diazoacetate (EDA). Formation of a hexacoordinated intermediate [RuCl2(PPh3)2(pip)(NBD)] is favored in the first step, with NBD doubly coordinated to the [RuCl2(PPh3)2(pip)] moiety. Analysis of donation (X â Ru) and back-donation (Ru â X) processes in the [RuCl2(PPh3)2(pip)(NBD)] complex shows that piperidine behaves as a σ donor, while NBD behaves as a π donor and the PPh3 groups act as π acceptors. The intensity of the orbital component is predominant in relation to the steric component in the complex. Thus, we propose that the reaction occurs through the formation of a hexacoordinated complex, followed by the dissociation of a PPh3 group, thus forming a complex where NBD is doubly coordinated to the metal center. Coordination of EDA leads finally to the catalyst capable of forming the metallocyclobutane intermediate required for the ROMP reaction.
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Coat color is a factor affecting heat tolerance in tropical ruminant and a particular coat color can determine which is more resilient to environmental changes. The aim of this study was to measure the level of adaptation of Morada Nova sheep with different coat color by using an Adaptability Index (AI). Adult ewes were used, including two different coat colors of Morada Nova sheep (red and white) with mean of body weight of 28.02 ± 5.70 kg and 31.47 ± 3.41 kg, respectively. Physiology parameters, hematology, electrolytes, acid-base status, mineral, renal functions, metabolites, enzymes, and proteins were measured. AI was designed using a multivariate approach (principal component analysis) to "weigh" the influence of each variable in the animal responses. The variables more important for adaptive aspects of Red Morada Nova were: haematology, electrolytes and acid-base status. The hemoglobin (HG), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), sodium (Na+), oxygen pressure (PO2), glucose (GLU) and albumin (ALB) were significantly higher in Red Morada Nova sheep and hydrogen carbonate (HCO3), base excess (BE), total carbon dioxide concentration (TCO2) and URE were significantly higher in the white phenotype. The variables more important for adaptive aspects of White Morada Nova sheep were: (K+), total protein (TP), PO2, HG, cholesterol (CHO), rectal temperature (RT) and glucose (GLU). Both phenotypes showed a high adaptation level, however, a higher value was generated for the Red Morada Nova sheep (81.97). This study concludes that both phenotypes of the Morada Nova sheep breed are well adapted to the climatic condition of the Brazilian tropical region using different adaptive mechanisms.