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Since 1972, the World Health Organization (WHO) has declared noise as a pollutant. Over the last decades, the quality of the urban environment has attracted the interest of researchers due to the growing urban sprawl, especially in developing countries. The objective of this study was to evaluate the effects of noise exposure in six urban soundscapes: Areas with high and low levels of noise in scenarios of leisure, work, and home. Cross-sectional study. The study was conducted in two steps: Evaluation of noise levels, with the development of noise maps, and health related inquiries. 180 individuals were interviewed, being 60 in each scenario, divided into 30 exposed to high level of noise and 30 to low level. Chi-Square test and Ordered Logistic Regression Model (P < 0,005). 70% of the interviewees reported noticing some source of noise in the selected scenarios and it was observed an association between exposure and perception of some source of noise (P < 0.001). 41.7% of the interviewees reported some degree of annoyance, being that this was associated with exposure (P < 0.001). There was also an association between exposure in different scenarios and reports of poor quality of sleep (P < 0.001). In the scenarios of work and home, the chance of reporting annoyance increased when compared with the scenario of leisure. We conclude that the use of this sort of assessment may clarify the relationship between urban noise exposure and health.

Androgen receptor pathway inhibitors (ARPIs) and docetaxel are established standards of care for chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC). We aimed to assess the efficacy and safety of adding nivolumab to docetaxel versus docetaxel alone in ARPI-pretreated, chemotherapy-naive mCRPC. CheckMate 7DX was a double-blind, randomised, phase 3 trial that enrolled adult patients (aged ≥18 years) with histologically confirmed, ARPI-pretreated, and chemotherapy-naive mCRPC at 291 hospitals and cancer centres across 27 countries. Patients had documented progression within 6 months of screening and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were randomly assigned (1:1) to nivolumab (360 mg), or equivalent placebo, and docetaxel (75 mg/m2) intravenously every 3 weeks for up to ten doses, followed by nivolumab (480 mg) or equivalent placebo every 4 weeks. Randomisation, stratified by previous ARPI therapy and visceral disease, was done using interactive response technology in permuted blocks with a block size of six. Patients, investigators, and the trial sponsor were masked to individual patient treatment assignment. The primary endpoints were radiographic progression-free survival by blinded independent central review and overall survival, assessed in all randomly assigned patients. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT04100018, and is completed. Between March 11, 2020, and Aug 2, 2022, 1414 patients were screened for eligibility, 1030 of whom were randomly assigned to nivolumab plus docetaxel (n=514) or placebo plus docetaxel (n=516). All participants were male, median age was 70 years (range 34–91), 662 (64%) were White, 240 (23%) were Asian, and 35 (3%) were Black or African American. With a median follow-up of 17·2 months (IQR 13·2–22·0), median radiographic progression-free survival was 9·4 months (95% CI 8·5–10·3) in the nivolumab plus docetaxel group versus 8·7 months (95% CI 8·4–10·0) in the placebo plus docetaxel group (hazard ratio [HR] 0·96 [99% CI 0·77–1·19]; p=0·59) and median overall survival was 18·7 months (95% CI 17·0–21·0) versus 18·9 months (95% CI 17·3–22·0, HR 1·09 [99·41% CI 0·84–1·43]; p=0·36). Grade 3–4 treatment-related adverse events occurred in 223 (44%) of 510 patients in the nivolumab plus docetaxel group and 187 (37%) of 510 in the placebo plus docetaxel group. The most common grade 3–4 events in both treatment groups were neutropenia (37 [7%] in the nivolumab plus docetaxel group and 50 [10%] in the placebo plus docetaxel group) and decreased neutrophil count (41 [8%] and 39 [8%]). Any-grade treatment-related serious adverse events occurred in 107 (21%) patients in the nivolumab plus docetaxel group and 77 (15%) in the placebo plus docetaxel group. 12 deaths were attributed to nivolumab plus docetaxel (three due to sepsis; one each due to Guillain–Barré syndrome, diverticulitis, myocarditis, liver injury, peritonitis, pneumonitis, pneumonia, and diarrhoea; and one due to unknown causes) and one was attributed to placebo plus docetaxel (due to pneumocystis). Nivolumab plus docetaxel did not improve progression-free survival or overall survival versus placebo plus docetaxel in patients with ARPI-pretreated, chemotherapy-naive mCRPC. These findings do not support the use of combinations of anti-PD-1 immune checkpoint inhibitors and docetaxel in the treatment of unselected populations of patients with ARPI-pretreated, chemotherapy-naive mCRPC. Bristol Myers Squibb.

Extracts from the stem bark of Stryphnodendron adstringens (barbatimão) exhibit relevant medicinal properties, such as anti-inflammatory, antioxidant, antimicrobial, and wound-healing activities, which reinforce their potential for developing herbal medicines. The $550 billion plant bioactive market (by 2030) demands safer, green-chemistry-aligned extraction methods for responsible industrial scaling. In this study, dry extracts obtained from the stem bark of S. adstringens were obtained by ultrasound-assisted maceration in one- and two-step extraction systems. Parameters such as yield, solvent evaporation time, cost, acute toxicity, epigallocatechin gallate (EGCG) concentration, cell viability, antioxidant potential, and anti-inflammatory activity were evaluated. High-EGCG two-step organic extracts were industrially difficult, needing more raw material and toxic solvents. In contrast, the single-step extracts showed a better balance between yield, cost, safety, and biological efficacy. All extracts showed cell viability above 70% at safe concentrations and significantly reduced the production of inflammatory cytokines. Thus, the results confirm that optimizing single-step extraction, with lower environmental impact solvents, enables producing safe and effective polyphenol-rich extracts, consolidating water as the main candidate for industrial-scale phytotherapeutic formulations of barbatimão, in line with its traditional use in infusions.

Bioenergy from sugarcane production is considered a key mitigation strategy for global warming. Improving its representation in land surface models is important to further understand the interactions between climate and bioenergy production, supporting accurate climate projections and decision‐making. This study aimed to calibrate and evaluate the Joint UK Land Environment Simulator (JULES) for climate impact assessments in sugarcane. A dataset composed of soil moisture, water and carbon fluxes and biomass measurements from field experiments across Brazil was used to calibrate and evaluate JULES‐crop and JULES‐BE parametrizations. The ability to predict the spatiotemporal variability of sugarcane yields and the impact of climate change was also tested at five Brazilian microregions. Parameters related to sugarcane allometry, crop growth and development were derived and tested for JULES‐crop and JULES‐BE, together with the response to atmospheric carbon dioxide, temperature and low‐water availability (CTW‐response). Both parametrizations showed comparable performance to other sugarcane dynamic models, with a root mean squared error of 6.75 and 6.05 t ha−1 for stalk dry matter for JULES‐crop and JULES‐BE, respectively. The parametrizations were also able to replicate the average yield patterns observed in the five microregions over 30 years when the yield gap factors were taken into account, with the correlation (r) between simulated and observed interannual variability of yields ranging from 0.33 to 0.56. An overall small positive trend was found in future yield projections of sugarcane using the new calibrations, with exception of the Jataí mesoregion which showed a clear negative trend for the SSP5 scenario from the years 2070 to 2100. Our simulations showed that an abrupt negative impact on sugarcane yields is expected if daytime temperatures above 35°C become more frequent. The newly calibrated version of JULES can be applied regionally and globally to help understand the interactions between climate and bioenergy production. In this study, we aimed to calibrate and evaluate the Joint UK Land Environment Simulator (JULES) for climate impact assessments in sugarcane. Parameters related to sugarcane allometry, crop growth and development were derived and tested for the model, together with the crop response to atmospheric carbon dioxide, temperature and drought (CTW‐response). The model showed good agreement against highly monitored experiments and represented spatiotemporal pattern of sugarcane production across five Brazilian regions. We found an overall small positive trend in future yield projections for sugarcane, but an abrupt negative impact is expected if daytime temperatures above 35°C become more frequent.

Background Cryoablation is an emerging minimally invasive ablative technique for selected patients with early-stage breast cancer. The FIRST (FreezIng bReaST cancer in Brazil) trial was designed to evaluate the pathological efficacy and safety of cryoablation followed by surgery, to assess the accuracy of imaging modalities in predicting complete pathological response, and to explore technical predictors of successful tumor ablation. Methods This prospective, multicenter, non-randomized, single-arm phase II study enrolled adults with unifocal invasive breast cancer ≤ 2.5 cm, clearly visible on ultrasound and eligible for upfront surgery. All patients underwent ultrasound-guided cryoablation using a 2.4-mm cryoprobe, followed by standard surgical resection 14–28 days later. Complete ablation was defined as the absence of residual invasive or in situ carcinoma on final pathology. Secondary outcomes included imaging–pathology correlation and the association between tumor size, ice-ball dimensions, and ablation success. Results Among 48 evaluable patients, the invasive complete ablation rate was 97.9%, with 100% success in tumors ≤ 2.0 cm on MRI. The complete ablation rate was 89.6%, increasing to 96.9% for tumors ≤ 2.0 cm and 100% for tumors ≤ 1.0 cm. Only one patient (2.1%) had residual invasive disease (3 mm). Residual ductal carcinoma in situ was observed in 12.5% of patients, with a mean size of 2.2 mm. Cryoablation was well tolerated, with one minor skin burn (2.1%) and no serious adverse events. MRI demonstrated high predictive accuracy for complete response (negative predictive value, 93.0%), whereas ultrasound and mammography were less accurate (negative predictive values, 9.3% and 34.9%, respectively). Ice-ball margins ≥ 1 cm beyond the tumor were associated with complete ablation in most cases. Conclusions Cryoablation achieved high rates of complete tumor ablation with an excellent safety profile, particularly in tumors ≤ 2.0 cm, in carefully selected patients with early-stage invasive breast cancer. These findings provide robust pathological and imaging validation of cryoablation as an effective ablative approach; however, they do not support its use as a standalone definitive therapy or, even when combined with adjuvant treatments such as radiotherapy and endocrine therapy, as a standard of care at this stage. As a phase II study, these results are not practice-changing and warrant confirmation in randomized phase III trials to evaluate long-term oncologic outcomes and to define the potential role of cryoablation within surgical de-escalation strategies. Trial registration ClinicalTrials.gov Identifier NCT05398497 (Registration date May 26, 2022). Highlights Cryoablation achieved a 97.9% invasive complete ablation rate in early-stage breast cancer, with 100% invasive complete ablation confirmed by pathology in tumors measuring ≤ 2.0 cm on MRI. MRI demonstrated high predictive accuracy for complete response after cryoablation (NPV 93.0%), outperforming ultrasound and mammography. Ice-ball margins ≥ 1 cm beyond the tumor correlated with high ablation success, reinforcing their role in procedural planning. Cryoablation was safe and well tolerated, with only one minor complication (2.1%) and no major adverse events. These findings support cryoablation as a promising minimally invasive approach warranting further evaluation within locoregional treatment de-escalation strategies in selected patients.

Medulloblastoma (MB) is the most common malignant brain tumor in children. Recent advances in molecular technologies allowed to classify MB in 4 major molecular subgroups: WNT, SHH, Group 3 and Group 4. In cancer research, cancer cell lines are important for examining and manipulating molecular and cellular process. However, it is important to know the characteristics of each cancer cell line prior to use, because there are some differences among them, even if they originate from the same cancer type. This study aimed to evaluate the similarities and differences among four human medulloblastoma cell lines, UW402, UW473, DAOY and ONS-76. The medulloblastoma cell lines were analyzed for (1) cell morphology, (2) immunophenotyping by flow cytometry for some specifics surface proteins, (3) expression level of adhesion molecules by RT-qPCR, (4) proliferative potential, (5) cell migration, and (6) in vivo tumorigenic potential. It was observed a relationship between cell growth and CDH1 (E-chaderin) adhesion molecule expression and all MB cell lines showed higher levels of CDH2 (N-chaderin) when compared to other adhesion molecule. ONS-76 showed higher gene expression of CDH5 (VE-chaderin) and higher percentage of CD144/VE-chaderin positive cells when compared to other MB cell lines. All MB cell lines showed low percentage of CD34, CD45, CD31, CD133 positive cells and high percentage of CD44, CD105, CD106 and CD29 positive cells. The DAOY cell line showed the highest migration potential, the ONS-76 cell line showed the highest proliferative potential and only DAOY and ONS-76 cell lines showed tumorigenic potential in vivo. MB cell lines showed functional and molecular differences among them, which it should be considered by the researchers in choosing the most suitable cellular model according to the study proposal.

Background The presence of untreated sexually transmitted infections (STIs) significantly increases the chance of acquiring HIV. In Brazil, testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) among Pre-Exposure Prophylaxis (PrEP) users is insufficient, and syndromic treatment is a priority in clinical practice. Multi-site testing for CT/NG improves thescreening of asymptomatic cases and ensures timely treatment. Therefore, it is essential for HIV prevention. This study aims to test the importance of two-site testing for better screening of these pathogens and to determine whether the presence of symptoms is an indicator of CT/NG infection. Methods This is a cross-sectional study carried out in four public infectious diseases clinics in São Paulo State, Brazil between January of 2022 and March of 2023. All participants had an anal swab and a first-pass or mid-stream urine collected for CT/NG analysis by Polymerase chain reaction (PCR). Data about sociodemographic, sexual behavioural and clinical aspects were collected. Pathway analysis was used to examine the direct and indirect relationships between variables according to the theoretical model. Results We screened 171 PrEP users which had two samples collected, resulting in 342 samples. Comparing the anatomic sites, the urine samples showed lower sensitivity for CT and NG than anal samples. Gonorrhoea was directly linked to lower age (β= -0.161, p  = 0.001). Time of PrEP use was directly associated with CT infection (β = 0.202; p  = 0.042) and inversely associated with dysuria (β= -0.121, p  = 0.009). Lower occurrence of yellow-green secretion was linked to detection of CT (β= -0.089, p  = 0.005) and NG (β= -0.048, p  = 0.002) infections. Foul-smelling discharge was directly associated with CT (β = 0.275, p  = 0.004) and NG (β = 0.295, p  = 0.037) infection. Conclusion The symptoms are a bad indicator of CT and NG infection, and the screening must be done in more than one site since most of the positive results would be missed if only urines were tested. In the case of testing only one anatomical site, specifically the urethra, the CT/NG incidence and prevalence would be underestimated. The two-sites testing improves detection rates of CT/NG, and PrEP follow-up benefits people offering STI testing.

BACKGROUND:Inflammatory Bowel Disease (IBD) is characterized by chronic inflammation of the gastrointestinal tract, due to inadequate interaction between immune and environmental factors in a genetic susceptible host. When the age of onset is below the age of 6 years, it is called very early onset IBD (VEO-IBD). VEO-IBD is a heterogeneous disorder clinically characterized by severe and often refractory intestinal inflammation. The goal of this study was to characterize the profile of patients with very early onset inflammatory bowel disease in a single-center in Brazil.METHODS:We performed a retrospective study using data from an IBD outpatient clinic between January 2016 and April 2018. The patients' demographic, clinical and laboratory features were assessed by retrieval of data from medical records. The diagnosis of IBD and its phenotypes were defined according to the Paris classification.RESULTS:Of the 140 patients with IBD, 36 (25.7%) were diagnosed with VEO-IBD, 50% were male. Ulcerative colitis (UC) was diagnosed in 52.9%, Crohn's disease (CD) in 41.2% and indeterminate colitis in 5.9%. The mean age at onset of symptoms was 1 year and 8 months and diagnosis at 2 years and 9 months, with an average interval for diagnosis of 11 months. The average follow-up was 7.3 years (11 months to 15 years and 6 months). Family history of autoimmunity was present in 14.7%. At diagnosis, bloody diarrhea was the main symptom (67.6%), followed by abdominal pain, fever, and weight loss. Fistulizing disease was present in 8.8% of patients and anemia in 55.8%. At follow-up, sclerosing cholangitis was the main extraintestinal manifestation presented (20.6%), followed by rheumatologic manifestations (14.7%) and severe anemia requiring blood transfusion (14.7%). Immunobiological use and/or combination therapy was indicated in 41.2% of patients and 67.6% achieved mucosal healing. 27.5% patient had low weight gain despite nutritional support and 11.8% needed intestinal resection. Twelve patients had the genetic diagnosis of VEO-IBD (XIAP (2), LRBA, DGC (3), PKI3 (2), IL10R, STAT1, ATGI6L1, RIPK1) and underwent specific treatment.CONCLUSION:Children presenting with VEO-IBD, especially those with unusual manifestation require immune and genetic evaluation to rule syndromes that may need an alternative treatment affecting long-term prognosis. Increasing awareness of monogenic disorders affecting the intestinal immune homeostasis can help diagnose VEO-IBD, guide target therapies and prevent disease complication.

Maize (Zea mays L.) is a prominent Brazilian commodity, being the second largest crop produced and fifth exported product by the country. Due to its importance for the agricultural sector, there is a concern about the effect of climate change on the crop. Process‐based models are valuable tools to evaluate the effects of climate on crop yields. The Joint UK Land Environment Simulator (JULES) is a land‐surface model that can be run with an integrated crop model parameterization. The resulting model (JULES‐crop) thus integrates crop physiology principles with the complexity of atmosphere–biosphere coupling. It has been shown to be a valuable tool for large‐scale simulations of crop yields as a function of environmental and management variables. In this study, we calibrated JULES‐crop using a robust experimental dataset collected for summer and off‐season maize fields across Brazil. A targeted local sensitivity analysis was performed to detect parameters of major importance during the calibration process. After calibration, the model was able to satisfactorily simulate both season and off‐season cultivars. Modeling efficiency (EF) was high for leaf area index (EF = .73 and .71, respectively, for summer season and off‐season datasets), crop height (EF = .89), and grain dry mass (EF = .61 and .89, respectively, for summer season and off‐season datasets). The model showed a lower accuracy for simulating leaf dry mass in summer season cultivars (EF = .39) and soil moisture (EF = .44), demonstrating the necessity of further improvements including additional parametrizations of the rainfed conditions. Core Ideas JULES‐crop was calibrated for maize in different regions of Brazil, cultivars, and water management conditions. The model well simulated the crop phenology, crop height, leaf area index, and grain dry mass. Simulations for leaf dry mass and soil moisture in rainfed conditions still need improvement.

Rabies is a viral encephalitis that affects mammals, including humans. Rapid and effective laboratory diagnosis of the rabies virus is critical for public health. This study evaluated the operational, technical, and financial viability of the RT-qPCR in replacement of inoculation in mice for diagnosing rabies in the laboratory routine. A total of 316 samples of mammalian brains were analyzed, 121 positives and 195 negatives, previously diagnosed by direct immunofluorescence (DIF) and mouse inoculation test (MIT). The samples were submitted to the duplex TaqMan RT-qPCR technique. The accuracy, sensitivity, and specificity of RT-qPCR were analyzed. We analyzed the costs for performing the RT-qPCR technique and compared it with the cost of MIT. The results showed 99.37% accuracy, 99.17% sensitivity, and 99.49% specificity by RT-qPCR when related to DIF and MIT results, which proved to be a robust and repeatable technique. The minimum time for a positive diagnosis was reduced in RT-qPCR (1 day) if compared to MIT (9.64 days), with a 17.7% reduction in the cost of the molecular technique. The present study demonstrated that the molecular biology technique is an efficient tool to diagnose rabies in the laboratory routine, being able to replace MIT. RESUMO: A raiva é uma encefalite viral que acomete os mamíferos, incluindo humanos. O diagnóstico laboratorial rápido e eficaz do vírus da raiva é importante para a saúde pública. Este estudo teve como objetivo avaliar a viabilidade operacional, técnica e financeira da RT-qPCR em substituição à inoculação em camundongos para o diagnóstico da raiva na rotina laboratorial. Foram analisadas 316 amostras de cérebros de mamíferos, 121 positivas e 195 negativas, previamente diagnosticadas por imunofluorescência direta (IFD) e isolamento viral em camundongos, por inoculação intracerebral em camundongos. As amostras foram submetidas à técnica duplex TaqMan RT-qPCR. A precisão, sensibilidade e especificidade da RT-qPCR foram analisadas. Os custos para realizar a técnica de RT-qPCR foram analisados e comparados com o custo do isolamento viral em camundongos. Os resultados demostraram 99,37% de acurácia, 99,17% de sensibilidade e 99,49% de especificidade pela RT-qPCR quando relacionada aos resultados de IFD e isolamento viral em camundongos, que se mostrou uma técnica robusta e com repetibilidade. O tempo mínimo para diagnóstico positivo foi reduzido na RT-qPCR (1 dia) quando comparado ao isolamento viral em camundongos (9,64 dias), e com redução de 17,7% no custo pela técnica molecular. O presente estudo demonstrou que a técnica de biologia molecular é uma ferramenta eficiente para o diagnóstico da raiva na rotina laboratorial, podendo substituir o isolamento viral em camundongos.