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BackgroundRecent data suggest that breast-conserving surgery (BCS) may positively impact overall survival (OS) in early breast cancer. However, the role of BCS in locally advanced breast cancer (LABC) following neoadjuvant therapy (NAT) remains uncertain.MethodsWe conducted a retrospective cohort study involving 530 LABC patients who underwent surgery after NAT between 2010 and 2015. Outcomes examined included OS, distant recurrence rates (DRR), and loco-regional recurrence rates (LRRs).ResultsAmong the 927 breast cancer patients who received NAT, 530 were eligible for our study. Of these, 24.6% underwent BCS, while 75.4% underwent mastectomy (MS). The median follow-up duration was 79 months. BCS patients exhibited a higher pathological complete response (PCR) rate compared to those who underwent MS (22.3% vs. 10%, p < 0.001). The 6-year OS rates for BCS and MS were 81.5% and 62%, respectively (p < 0.000). In multivariate OS analysis, MS was associated with worse outcomes (OR 1.678; 95% CI 1.069–2.635; p = 0.024), as was body mass index (BMI) (OR 1.031; 95% CI 1.006–1.058; p = 0.017), and stage IIIB or IIIC (OR 2.450; 95% CI 1.561–3.846; p < 0.000). Conversely, PCR (OR 0.42; 95% CI 0.220–0.801; p = 0.008) was associated with improved survival. DRR was significantly lower in BCS (15.4%) compared to MS (36.8%) (OR 0.298; 95% CI 0.177–0.504). LRRs were comparable between BCS (9.2%) and MS (9.5%) (OR 0.693; 95% CI 0.347–1.383).ConclusionOur findings suggest that BCS is oncologically safe, even for patients with large lesions, and is associated with superior OS rates compared to MS. Additionally, lower BMI, lower pretreatment stage, and achieving PCR were associated with improved survival outcomes.

Abstract Objective To present a systematic review of the literature and a meta-analysis evaluating the oncological safety of autologous fat grafting (AFG). Summary background data: AFG for breast reconstruction presents difficulties during follow-up radiological exams, and the oncological potential of grafted fat is uncertain. Previous studies confirmed that the fatty tissue could be transferred under a good condition suitable would not interfere with mammographic follow-up, although the issue of oncological safety remains. Methods We reviewed the literature published until 01/18/2021. The outcomes were overall survival (OS), disease-free survival (DFS), and local recurrence (LR). We included studies that evaluated women with breast cancer who undergone surgery followed by reconstruction with AFG. We synthesized data using the inverse variance method on the log-HR (log of the hazard ratio) scale for time-to-event outcomes using RevMan. We assessed heterogeneity using the Chi2 and I2 statistics. Results Fifteen studies evaluating 8541 participants were included. The hazard ratios (HR) could be extracted from four studies, and there was no difference in OS between the AFG group and control (HR 0.9, 95% CI 0.53 to 1.54, p = 0.71, I2 = 58%, moderate certainty evidence), and publication bias was not detected. The HR for DFS could be extracted from six studies, and there was no difference between the AFG group and control (HR 1.01, 95% CI 0.73 to 1.38, p = 0.96, I2 = 0%, moderate certainty evidence). The HR for LR could be extracted from ten studies, and there was no difference between the AFG group and control (HR 0.86, 95% CI 0.66 to 1.12, p = 0.43, I2 = 1%, moderate certainty evidence). Conclusion According to the current evidence, AFG is a safe technique of breast reconstruction for patients that have undergone BC surgery and did not affect OS, DFS, or LR.

Summary: RNA sequencing (RNA-seq) detects estrogen receptor alpha gene (ESR1) fusion transcripts in estrogen receptor-positive (ER+) breast cancer, but their role in disease pathogenesis remains unclear. We examined multiple ESR1 fusions and found that two, both identified in advanced endocrine treatment-resistant disease, encoded stable and functional fusion proteins. In both examples, ESR1-e6>YAP1 and ESR1-e6>PCDH11X, ESR1 exons 1–6 were fused in frame to C-terminal sequences from the partner gene. Functional properties include estrogen-independent growth, constitutive expression of ER target genes, and anti-estrogen resistance. Both fusions activate a metastasis-associated transcriptional program, induce cellular motility, and promote the development of lung metastasis. ESR1-e6>YAP1- and ESR1-e6>PCDH11X-induced growth remained sensitive to a CDK4/6 inhibitor, and a patient-derived xenograft (PDX) naturally expressing the ESR1-e6>YAP1 fusion was also responsive. Transcriptionally active ESR1 fusions therefore trigger both endocrine therapy resistance and metastatic progression, explaining the association with fatal disease progression, although CDK4/6 inhibitor treatment is predicted to be effective. : Lei et al. show that transcriptionally active estrogen receptor gene (ESR1) fusions identified from late-stage, treatment-refractory estrogen receptor-positive (ER+) breast cancer drive pan-endocrine therapy resistance and metastatic progression. Growth of breast tumors driven by ESR1 fusions at primary and metastatic sties can be suppressed with a CDK4/6 inhibitor. Keywords: ESR1 fusions, breast cancer, endocrine therapy resistance, metastasis, EMT, PDX

To characterize patient-derived xenografts (PDXs) for functional studies, we made whole-genome comparisons with originating breast cancers representative of the major intrinsic subtypes. Structural and copy number aberrations were found to be retained with high fidelity. However, at the single-nucleotide level, variable numbers of PDX-specific somatic events were documented, although they were only rarely functionally significant. Variant allele frequencies were often preserved in the PDXs, demonstrating that clonal representation can be transplantable. Estrogen-receptor-positive PDXs were associated with ESR1 ligand-binding-domain mutations, gene amplification, or an ESR1/YAP1 translocation. These events produced different endocrine-therapy-response phenotypes in human, cell line, and PDX endocrine-response studies. Hence, deeply sequenced PDX models are an important resource for the search for genome-forward treatment options and capture endocrine-drug-resistance etiologies that are not observed in standard cell lines. The originating tumor genome provides a benchmark for assessing genetic drift and clonal representation after transplantation.

Neste artigo, objetiva-se analisar a adesão ao Programa Aprendizagem na Idade Certa (Mais Paic) por parte dos professores do Ensino Fundamental I de três municípios do Cariri cearense, por meio dos documentos e/ou materiais norteadores. Visa-se trazer uma discussão sobre a influência de ideais neoliberais e gerenciais no programa. Estudos atuais apontam que tais influências na educação intencionam dividir as responsabilidades das políticas educacionais, isto é, propor um modelo de gestão que valoriza aspectos como eficiência, eficácia, produtividade e resultados, em detrimento de uma formação humanística e cultural. Na pesquisa, do tipo descritiva, com abordagem quantitativa, foi realizada uma fundamentação teórica bibliográfica inspirada em estudiosos marxianos. A pesquisa trouxe, como resultados: que a adesão ocorre; o documento mais utilizado é o DCRC (87,7%), e a maioria dos professores que adere ao programa são contratados. Como também tencionam lacunas para eventuais pesquisas, cujo enfoque será esclarecer o que a pesquisa quantitativa mostra.

ABSTRACT Objectives: Evaluate the prevalence of hospital mortality in older adult patients with femoral fracture undergoing surgical treatment during the COVID-19 pandemic period, and to evaluate whether COVID-19 infection, clinical, and orthopedic factors interfered with mortality. Material and Methods: A retrospective study was conducted by reviewing medical records. Patients over 60 years of age with proximal femoral fracture undergoing surgical treatment were included. Overall mortality was calculated, as well as mortality whose primary or secondary cause was COVID-19 infection, to determine if infection influenced patient mortality. Clinical and orthopedic factors that interfered with mortality were evaluated. Categorical variables were compared using the Chi-square test or Fisher’s exact test. Both unpaired t-test (parametric variables) and Mann-Whitney test (non-parametric variables) were used. The Kaplan-Meier mortality curve was constructed. Conclusion: The mortality of older adult patients with femoral fracture undergoing surgical treatment during the COVID-19 pandemic was 4.2%. Male sex, older age, and those who underwent blood transfusion had higher mortality rates. COVID-infected patients had ten times more chance of death and died twice as fast as the non-infected population. Level of Evidence II, Retrospective Study.

IntroductionSleep disorders are common in the general population, necessitating the search for new strategies to address this public health challenge. The study aims to describe the electrocorticographic and behavioral changes in sleep deprived Wistar rats exposed to varying doses of camphor, to assess its effects on sleep and its potential as a sleep-inducing drug.Materials and MethodsFor the electrocorticographic evaluation, seventy-two rats were randomly assigned to distinct groups: a control group, a sleep-deprived group, three sleep-deprived groups receiving 10, 20, and 30 mg/kg i.p. of camphor respectively, and three groups that received these doses without sleep deprivation. For the behavioral analysis, twenty-seven rats were divided into three groups, each receiving the same doses as the previous test.Results and DiscussionOur results showed that there was a decrease in the frequency of brain oscillatory patterns when camphor was administered at 10 mg/kg i.p. whereas there was a dose-dependent increase in the spectral power and distribution following the administration of 20 and 30 mg/kg i.p., with the emergence of Delta, Theta, Alpha, and Beta waves. As for the behavioral analysis, it was demonstrated that testicular relaxation, decreased motility, and light sleep induction also occurred in a dose-dependent manner. Thus, we conclude that camphor administration intensifies occipital electrocorticographic patterns in sleep-deprived rats, and its electrocorticographic and behavioral analysis could indicate a potential as a supporting agent in the insomnia treatment.

The essential oil of rosemary (Rosmarinus officinalis) (EORO) is widely used in folk medicine and has proven therapeutic effects. Our research evaluated high doses of rosemary essential oil in 54 Wistar rats between 180 and 200 g. The study consisted of three experiments: 1) behavioral monitoring of the animals after administration of 500 mg/kg i.p.; 2) electrocorticographic records after drug administration; 3) anticonvulsant drug reaction, where phenytoin, phenobarbital, and diazepam 10 mg/kg i.p were applied. The results showed that the application of EORO presented two phases. Phase 1 was characterized by the appearance of myorelaxation and a reduction in the power of the electrocorticogram in low-frequency cerebral oscillations. Phase 2 was characterized by increased excitability, with the appearance of convulsions and the increased power of electrocorticographic recordings in cerebral oscillations up to 40 Hz. In this phase, three tracing patterns were observed. Beta oscillations were the most prevalent and were better controlled by diazepam, which demonstrates that the excitatory activity of EORO is related to the reduction of GABAergic activity.

Assessing the phenotype of cattle through human visual inspection is a very common and important practice in precision cattle breeding. This paper presents the results of a correlation analysis between scores produced by humans for Nelore cattle and a variety of measurements that can be derived from images or other instruments. It also presents a study using the k-means algorithm to generate new ways of clustering a batch of cattle using the measurements that most correlate with the animal's body weight and visual scores.

Abstract Background Surgical site infections (SSI) are the most frequent early complications of hand surgeries. However, the indications still remain uncertain for antibiotic prophylaxis in elective clean soft tissue surgeries of the hand and upper limb. Therefore, a systematic review of the literature and a meta-analysis was conducted to investigate the impact of antibiotic prophylaxis on the prevention of SSI in these types of surgeries. Methods An electronic search was performed in the following databases: MEDLINE/Pubmed, PMC/Pubmed, Web of Science/Clarivate Analytics, Embase/Elsevier, Scopus/Elsevier, BVS/Lilacs, and the Cochrane Library, with no restrictions regarding publication language or date. The primary outcome of interest was the occurrence of SSI following elective clean soft tissue surgeries of the hand and upper limb according to the administration of preoperative antibiotic prophylaxis and no antibiotic prophylaxis. Surgeries involving simultaneous bone procedures or orthopedic implants were excluded. Study selection and data extraction were conducted independently by two reviewers. RoB 2.0 and ROBINS-I are Cochrane risk-of-bias tool for randomized trials and non-randomized studies of interventions. The magnitude of the intervention effect was estimated using the relative risk (RR). The meta-analysis was performed with the Review Manager and R software tools, using the Mantel–Haenszel random-effects model and a 95% confidence interval (CI). Results with p ≤ 0.05 were considered statistically significant. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. Results The initial search yielded 1175 titles, from which 12 articles met the inclusion criteria for the systematic review, and 10 were included in the subsequent meta-analysis. The majority of these studies were nonrandomized intervention trials, exhibiting a moderate risk of bias. According to our review, preoperative antibiotic prophylaxis did not have a statistically significant impact on the incidence of SSI (RR = 1.13, 95% CI 0.91–1.40, p = 0.28). The overall quality of evidence for this outcome was rated as low. Moderate statistical heterogeneity was observed (I 2 = 44%), and the prespecified sensitivity analysis highlighted the consistency of the results. Conclusions While these results were consistent with the findings from individual studies included in this review, it is important to note that, given the threshold of p ≤ 0.05 for statistical significance, no definitive conclusions can be drawn from the quantitative analysis of the data obtained. Level of evidence: Level 2. Trial registration: CRD42023417786.

Abstract Fast Radio Bursts (FRBs) are millisecond transient radio events with a high energy. By identifying the origin of the burst, it is possible to measure the redshift of the host galaxy, which can be used to constrain cosmological and astrophysical parameters and test aspects of fundamental physics when combined with the dispersion measure (DM). However, some factors limit the cosmological application of FRBs: (i) the poor modelling of the fluctuations in the DM due to spatial variation in the cosmic electrons density; (ii) the fact that the fraction of baryon mass in the intergalactic medium ( $$f_{IGM}$$ f IGM ) is degenerated with some cosmological parameters; (iii) the limited knowledge about host galaxy contribution ( $$DM_{host}$$ D M host ). In this work, we investigate the impact of different redshift distribution models of FRBs to constrain the baryon fraction in the IGM and host galaxy contribution. We use a cosmological model-independent method developed in previous work Lemos (EPJC 83:138, 2023) to perform the analysis and combine simulated FRB data from Monte Carlo simulation and supernovae data. We assume four distribution models for the FRBs: gamma-ray bursts (GRB), star formation rate (SFR), uniform and equidistant (ED). Also, we consider samples with $$N = 15, 30, 100$$ N = 15 , 30 , 100 and 500 points and different values of the fluctuations of electron density in the DM, $$\delta = 0, 100, 200, 400, 230\sqrt{z}$$ δ = 0 , 100 , 200 , 400 , 230 z pc/cm $$^{3}$$ 3 . Our analysis shows that all the distribution models present consistent results within $$2\sigma $$ 2 σ for the free parameters $$f_{IGM}$$ f IGM and $$DM_{host,0}$$ D M h o s t , 0 and highlights the crucial role of DM fluctuations in obtaining more precise measurements.

The risk of infection transmission from mother to fetus depends on the pathogen. TORCH agents cause some neuroinfections, including Toxoplasmosis, rubella, Cytomegalovirus, herpes simplex 1 and 2, and others (Varicella Zoster, Parvovirus B-19, Epstein–Barr virus, and Zika virus). The consequences can be stillbirth, prematurity, uterine growth restriction, and congenital malformations. The detection of DNA/RNA from CSF by molecular methods is a marker of the involvement of congenital infection in the central nervous system. This study aimed to identify the frequency of these pathogens in CSF samples from newborns (1 to 28 days old) at a tertiary hospital, using PCR, and determine the clinical consequences. Methods: This was a prospective descriptive study involving the molecular analysis of 151 CSF samples from neonates, collected for cytological and biochemical diagnosis from 2017 to 2021. After the results and consent from the participants’ caregivers were obtained, the leftover material was sent to the University’s Virology Laboratory and submitted for DNA/RNA extraction and Nested-PCR/RT-PCR. A review of the patients’ medical records and descriptive statistics was performed. This work was approved by the Ethics Committee (CAAE: 86760218.3.0000.5404). Results: A total of 151 CSF samples were obtained, 16 of which were positive (10.6% [95% CI%: 6.18–16.63%]). Two of these were PCR-positive for HSV-1 (1.3%), four for VZV (2.6%), one for CMV (0.67%), two for Toxoplasmosis (1.3%), four for Parvovirus B-19 (2.6%), and four for Zika (2.6%). The proportion of positive PCR results was higher in the group that presented with malformations (25.0% vs. 8.4%, p = 0.040). Conclusions: The pathogens identified by PCR were mostly Zika virus, VZV, and B-19, and these were mainly found in newborns with malformations.