Fezolinetant for the treatment of vasomotor symptoms associated with menopause: a meta-analysis.

This systematic review and meta-analysis investigated the efficacy and safety of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) associated with menopause. PubMed, Cochrane Library, Embase and Web of Science were searched for randomized controlled trials (RCTs) published from inception to June 2023, comparing fezolinetant to placebo in postmenopausal women suffering from moderate-to-severe VMS. The mean difference and risk ratio were calculated for continuous and binary outcomes, respectively. R software was used for the statistical analysis, and RoB-2 (Cochrane) to assess the risk of bias. We performed subgroup analysis based on different dosing regimens. Five RCTs comprising 3302 patients were included. Compared with placebo, at 12-week follow-up, fezolinetant significantly reduced the daily frequency of moderate-to-severe VMS (weighted mean difference [WMD] - 2.36; 95% confidence interval [CI] - 2.92, -1.81) and daily severity of moderate-to-severe VMS (WMD -0.22; 95% CI -0.31, -0.13). Also, fezolinetant significantly improved the quality of life (WMD -0.42; 95% CI -0.58, -0.26) and sleep disturbance (WMD -1.10; 95% CI -1.96, -0.24). There were no significant differences between groups in adverse events. These findings support the efficacy and safety of fezolinetant for the treatment of VMS related to menopause.

Near-infrared spectroscopy analysis of blood plasma for predicting nonesterified fatty acid concentrations in dairy cows.

During the transition period, dairy cows are often exposed to negative energy balance (NEB), leading to lipid mobilization from adipose tissue into nonesterified fatty acids (NEFA), a common indicator of heightened illness risk. This study aimed to use blood near-infrared (NIR) spectra data to classify NEB into high or low categories, based on early-lactation cow NEFA thresholds. We collected a total of 186 plasma samples from 100 Holstein cows. The samples were categorized into critical thresholds, based on previous literature, of ≥0.60 and ≥0.70 mEq/L for identifying high NEB. Spectral data were preprocessed before the development of the predictive modes, which included the implementation of multiplicative scatter correction, standard normal variate (SNV), and first and second derivatives. The classification was performed using partial least square discriminant analyses (PLS-DA), and predictive performance was assessed using leave-one-out cross-validation. Predictive quality for each class was evaluated through specificity, precision, sensitivity, and F1 score. The study showed promising results, with the SNV technique achieving higher F1 scores. The model found 72.7% specificity, 78.9% precision, 80.8% sensitivity, and 79.8% F1 score to classify animals with NEFA levels of ≥0.60 mEq/L, and 82.1% specificity, 78.7% precision, 80.8% sensitivity, and 79.7% F1 score to classify animals with NEFA levels ≥0.70 mEq/L. These results indicate that NIR spectroscopy could serve as a tool for detecting cows under severe NEB, also showing potential for broader application across the entire transition period, as the spectral signal carried relevant information regarding cow metabolism. Furthermore, the combination of predictors derived from plasma spectra and other cow-level information can lead to more accurate disease alerts, given their relationship with the NEB.

Efficacy of the hybrid closedloop insulin delivery system in children and adolescents with type 1 diabetes: a meta-analysis with trial sequential analysis.

The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucoselevel was > 180 mg/dL (WMD-10.46%, 95% CI-13.99 to-6.93%) and the mean levels of glucose (WMD-16.67 mg/dL, 95% CI-22.25 to-11.09 mg/dL) and HbA1c (WMD-0.50%, 95% CI-0.68 to-0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or <54 mg/dL or number of episodes of ketoacidosis, hyperglycemia, and hypoglycemia. In this meta-analysis, HCL compared with control therapies was associated with improved time in range and HbA1c control in children and adolescents with T1D and a similar profile of side effects. These findings support the efficacy of HCL in the treatment of T1D in this population.

CYTOTOXICITY AND BIOLOGICAL ACTIVITIES OF GEOPOPOLIS EXTRACT FROM THE STINGLESS BEE (Melipona scutellaris) IN CLINICAL ISOLATES OF Staphylococcus aureus.

This work aims to evaluate the biological activities of the EEGP, in order to contribute with a natural therapeutic alternative, to face infections. The EEGP MIC tests showed antibacterial activity against two strains of S. aureus (LPM 63 and LPM 86), both at concentrations of 550 µg/mL. The MBC performed with the inhibition values showed that the EEGP has bacteriostatic activity in both strains. Biofilm inhibition rates exhibited an average value greater than 65% at the highest concentration. The EEGP antioxidant potential test showed good antioxidant activity (IC50) of 11.05 ± 1.55 µg/mL. In the cytotoxicity test against HaCat cells, after 24 hours, EEGP induced cell viability at the three tested concentrations (550 µg/mL: 81.68 ± 3.79%; 1100 µg/mL: 67.10 ± 3.76 % ;2200 µg/mL: 67.40 ± 1.86%). In view of the above, the safe use of EEGP from the brazilian northeast could be proven by the cytotoxicity test, and its use as an antioxidant and antibacterial agent has proven to be effective, as an alternative in combating oxidative stress and microorganisms such as S. aureus, which, through the spread and ongoing evolution of drug resistance, generates an active search for effective solutions.

Breathing mode assessment with thermography: a pilot study. / Avaliação do modo respiratório por meio da termografia: um estudo piloto.

PURPOSE: To present a method for analyzing breathing modes with infrared thermography. METHODS: This exploratory cross-sectional study used 38 thermal images of inspiration and expiration with nasal breathing and simulated mouth breathing in four nasal breathers without respiratory complaints. Three different data selection forms (line, rectangle, and ellipse) were used to extract the minimum, mean, and maximum temperatures of the regions of interest (nose and mouth) using the FLIR Tools® software. RESULTS: Among the three selection forms, there was greater temperature variability obtained with the line, revealing limitations in this measurement. There were no differences between the rectangle and ellipse values, showing that both selection forms present similar temperature extraction results. The comparison results between nose and mouth temperatures during inspiration and expiration indicated a statistically significant difference between all measurements, except for mean inspiration temperatures with the rectangle and ellipse. The breathing mode can be distinguished in both inspiration and expiration when using mean mouth temperatures with the rectangle and ellipse. CONCLUSION: Breathing modes should be assessed based on mean mouth temperatures during inspiration, using the ellipse.

OBJETIVO: Apresentar um método de análise do modo respiratório por meio da termografia infravermelha. MÉTODO: Estudo transversal exploratório de 38 imagens térmicas que representavam o momento da inspiração e da expiração durante a respiração nasal e durante a simulação da respiração oral de quatro voluntárias respiradoras nasais sem queixas respiratórias. Para a extração da temperatura das regiões de interesse (nariz e boca) foram utilizadas três formas de seleção distintas de dados (linha, retângulo e elipse) e três medidas de temperatura (mínima, média e máxima) por meio do software FLIR Tools®. RESULTADOS: Dentre as três formas de seleção houve maior variabilidade nas medidas obtidas pela linha, revelando limitações nessa medida. Não houve diferenças entre as medidas do retângulo e elipse, mostrando que ambas as formas de seleção apresentam resultados semelhantes para a extração das temperaturas. Na comparação entre as temperaturas do nariz e da boca na inspiração e expiração, os resultados indicaram que houve diferença com relevância estatística em todas as medidas realizadas, exceto para as medidas de temperatura média da inspiração, usando o retângulo e a elipse. Percebe-se diferenciação do modo respiratório tanto na inspiração quanto na expiração quando utilizada a temperatura média da boca com o retângulo e a elipse. CONCLUSÃO: Sugere-se para avaliação do modo respiratório a avaliação da boca, por meio da elipse, com análise da temperatura média durante a inspiração.

Association between the relative abundance of phyla actinobacteria, vitamin C consumption, and DNA methylation of genes linked to immune response pathways.

Introduction: There is an emerging body of evidence that vitamin C consumption can modulate microbiota abundance and can also impact DNA methylation in the host, and this could be a link between diet, microbiota, and immune response. The objective of this study was to evaluate common CpG sites associated with both vitamin C and microbiota phyla abundance. Methods: Six healthy women participated in this cohort study. They were divided into two groups, according to the amount of vitamin C they ingested. Ingestion was evaluated using the 24-h recall method. The Illumina 450 k BeadChip was used to evaluate DNA methylation. Singular value decomposition analyses were used to evaluate the principal components of this dataset. Associations were evaluated using the differentially methylated position function from the Champ package for R Studio. Results and discussion: The group with higher vitamin C (HVC) ingestion also had a higher relative abundance of Actinobacteria. There was a positive correlation between those variables (r = 0.84, p = 0.01). The HVC group also had higher granulocytes, and regarding DNA methylation, there were 207 CpG sites commonly related to vitamin C ingestion and the relative abundance of Actinobacteria. From these sites, there were 13 sites hypomethylated and 103 hypermethylated. The hypomethylated targets involved the respective processes: immune function, glucose homeostasis, and general cellular metabolism. The hypermethylated sites were also enriched in immune function-related processes, and interestingly, more immune responses against pathogens were detected. These findings contribute to understanding the interaction between nutrients, microbiota, DNA methylation, and the immune response.

Cardiovascular benefits of statin plus ezetimibe combination therapy versus statin monotherapy in acute coronary syndrome: a meta-analysis of randomized controlled trials

BACKGROUND: The efficacy of adding ezetimibe to statin therapy for event reduction in patients with acute coronary syndromes (ACS) remains a topic of ongoing debate. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing ezetimibe plus statin versus statin monotherapy in patients with ACS. We searched PubMed, Embase, and Cochrane for eligible trials. Random-effects model was used to calculate the risk ratios (RRs), with 95% confidence intervals (CIs). Statistical analyses were performed using RStudio version 4.2.3. RESULTS: Six RCTs comprising 20,574 patients with ACS were included, of whom 10,259 (49.9%) were prescribed ezetimibe plus statin. The patient population had an average age of 63.8 years and 75.1% were male. Compared with statin monotherapy, ezetimibe plus statin significantly reduced major adverse cardiovascular events (MACE) (RR 0.93; 95% CI 0.90-0.97; p<0.01) and non-fatal myocardial infarction (RR 0.88; 95% CI 0.81-0.95; p<0.01). There was no significant difference between groups for revascularization (RR 0.94; 95% CI 0.88-1.01; p=0.07), all-cause death (RR 0.87; 95% CI 0.63-1.21; p=0.42), or unstable angina (RR 1.05; 95% CI 0.86-1.27; p=0.64). CONCLUSION: In this meta-analysis of patients with ACS, the combination of ezetimibe plus statin was associated with a reduction in MACE and non-fatal myocardial infarction, compared with statin monotherapy.

Long-term impact of home-based monitoring after an admission for acute decompensated heart failure: a systematic review and meta-analysis of randomised controlled trials.

Background: Patients with heart failure have high rehospitalisation rates and poor cardiovascular outcomes. Home-based monitoring (HBM) has emerged with promising results in different settings. However, its long-term effects on patients recently admitted for acute decompensated heart failure (ADHF) remain uncertain. Methods: We systematically searched PubMed, Embase, and Cochrane Library for randomised controlled trials (RCTs) comparing HBM with usual care (UC) that were published between database inception and June 24, 2023. We included studies with patients admitted for ADHF in the previous 6 months and with a minimum follow-up of 6 months. We excluded studies with patients hospitalised for reasons other than ADHF and studies with disproportional education interventions between arms. Statistical analyses were performed using R software version 4.3.2. We pooled risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI) for categorical and continuous outcomes, respectively. Cochrane Collaboration's tool for assessing risk of bias in RCTs (RoB 2) was used to assess study quality. Publication bias was assessed via funnel plots and Egger's test, and heterogeneity was assessed through I2 statistics and sensitivity analysis. The protocol for this systematic review and meta-analysis was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42023465359). Findings: We included 16 RCTs comprising 4629 patients, of whom 2393 (51.7%) were randomised to HBM and 3150 (68%) were men. Follow-up ranged from six to fifteen months. As compared with UC, HBM significantly reduced all-cause mortality (RR 0.75; 95% CI 0.61, 0.91; p = 0.005), all-cause hospitalisations (RR 0.82; 95% CI 0.70, 0.97; p = 0.018), cardiovascular (CV) mortality (RR 0.53; 95% CI 0.36, 0.79; p = 0.002), hospitalisations for heart failure (RR 0.75; 95% CI 0.62, 0.91; p = 0.004), and CV hospitalisations (RR 0.72; 95% CI 0.55, 0.95; p = 0.018). There were no significant differences in length of hospital stay (MD 0.97 days; 95% CI -0.90, 2.84; p = 0.308). Interpretation: In patients recently admitted with ADHF, HBM significantly reduces long-term all-cause mortality and hospitalisations, CV mortality and hospitalisations, and hospitalisations for heart failure, as compared with UC. This supports the implementation of HBM as a standard practice to optimise patient outcomes following admissions for ADHF. However, future studies are warranted to evaluate the efficacy and safety of implementing HBM in the real-world setting. Funding: None.

Metabolizable Energy and Amino Acid Digestibility of Soybean Meal from Different Sources for Broiler Chickens Supplemented with Protease.

This study investigated the effect of the serine protease on metabolizable energy and amino acids' digestibility of different soybean meal for broilers. A total of 684 broilers chickens form 14 to 23 d age were distributed with nineteen treatments, six replicates, and six birds per replicate. Nine samples of soybean meal from different regions in Brazil were used, with some samples supplemented with the protease enzyme and others without addition. Apparent and corrected-for-nitrogen-balance metabolizable energy were evaluated, as well as the coefficients of amino acid digestibility. All collected data were submitted to ANOVA at a significance level of 5% and Tukey's test was applied. The results showed that the addition of the protease enzyme significantly increased the values of AME and AMEn in all soybean meal samples. The soybean meal of different origins has significant variations in AME and AMEn. The addition of the protease improved the digestibility of essential amino acids compared to soybean meal without enzyme addition. These results indicate that supplementation with serine protease can improve the metabolizable energy and amino acid digestibility of soybean meal from different regions in the diet of broilers, potentially being an effective strategy to enhance nutrient utilization and animal performance.

Efficacy and safety of Zolbetuximab plus chemotherapy for advanced CLDN18.2-positive gastric or gastro-oesophageal adenocarcinoma: a meta-analysis of randomized clinical trials.

BACKGROUND: The benefit of adding Zolbetuximab to the treatment in patients with Claudin-18 isoform 2 (CLDN18.2)-positive, human epidermal growth factor receptor 2-negative, locally advanced unresectable or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GC/GEJ) is not yet fully elucidated. METHODS: We searched PubMed, Embase and Cochrane databases for randomized controlled trials (RCTs) that investigated Zolbetuximab plus chemotherapy versus chemotherapy alone for GC or GEJ adenocarcinoma. We computed hazard-ratios (HRs) or odds-ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). RESULTS: Three studies and 1,233 patients were included. Comparing with Zolbetuximab plus chemotherapy versus chemotherapy alone, progression-free survival (PFS) rate (HR 0.64; 95% CI 0.49-0.84; p < 0.01) and overall survival (OS) rate (HR 0.72; 95% CI 0.62-0.83; p < 0.01) were significant in favor of the Zolbetuximab group. Regarding effectiveness, the Objective Response Rate (ORR) was (OR 1.15; 95% CI 0.87-1.53; p = 0.34). CONCLUSIONS: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of Zolbetuximab alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with advanced CLDN18.2-positive GC/GEJ cancer.

Simple and selective screening method for the synthetic cathinone MDPT in forensic samples using carbon nanofiber screen-printed electrodes.

3',4'-Methylenedioxy-N-tert-butylcathinone (MDPT), also known as tBuONE or D-Tertylone, is a synthetic cathinone (SC) frequently abused for recreational purposes due to its potent stimulant effects and similarity to illegal substances like methamphetamine and ecstasy. The structural diversity and rapid introduction of new SC analogs to the market poses significant challenges for law enforcement and analytical methods for preliminary screening of illicit drugs. In this work, we present, for the first time, the electrochemical detection of MDPT using screen-printed electrodes modified with carbon nanofibers (SPE-CNF). MDPT exhibited three electrochemical processes (two oxidations and one reduction) on SPE-CNF. The proposed method for MDPT detection was optimized in 0.2 mol L-1 Britton-Robinson buffer solution at pH 10.0 using differential pulse voltammetry (DPV). The SPE-CNF showed a high stability for electrochemical responses of all redox processes of MDPT using the same or different electrodes, with relative standard deviations less than 4.7% and 1.5% (N = 3) for peak currents and peak potentials, respectively. Moreover, the proposed method provided a wide linear range for MDPT determination (0.90-112 µmol L-1) with low LOD (0.26 µmol L-1). Interference studies for two common adulterants, caffeine and paracetamol, and ten other illicit drugs, including amphetamine-like compounds and different SCs, showed that the proposed sensor is highly selective for the preliminarily identification of MDPT in seized forensic samples. Therefore, SPE-CNF with DPV can be successfully applied as a fast and simple screening method for MDPT identification in forensic analysis, addressing the significant challenges posed by the structural diversity of SCs.

Continuous Glucose Monitoring Systems in Noninsulin-Treated People with Type 2 Diabetes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Introduction: Continuous glucose monitoring (CGM) has shown favorable outcomes in patients with type 2 diabetes (T2D) who are on insulin therapy. However, the efficacy of CGM in managing glucose levels in noninsulin-treated people with T2D remains controversial. Methods: PubMed, Cochrane, and Embase were searched for randomized controlled trials (RCTs) comparing CGM to self-monitoring of blood glucose (SMBG) in people with T2D not using insulin. We computed weighted mean differences (WMDs) and standard mean differences (SMD) for continuous outcomes, with 95% confidence intervals (CIs). Heterogeneity was assessed using I2 statistics. Statistical analyses were performed using R version 4.2.3. Results: We included six RCTs comprising 407 noninsulin-treated people with T2D of whom 228 were randomized to CGM. Diabetes duration ranged from 5.4 to 13.9 years. The mean age was 57.9 years and the mean body mass index was 30.8 kg/m2. Four trials used real-time CGM (rt-CGM) and two intermittent scanning CGM (is-CGM). Compared with SMBG, CGM significantly reduced the glycated hemoglobin level (WMD -0.31%; 95% CI -0.42 to -0.21; I2 = 0%), glucose level (WMD -11.16 mg/dL; 95% CI -19.94 to -2.39; I2 = 0%), time in hypoglycemia level 2 (WMD -0.28%; 95% CI -0.52 to -0.03; I2 = 91%), glucose time >180 mg/dL (WMD -7.75%; 95% CI -12.04 to -3.45; I2 = 0%), and the standard deviation of glucose variation (WMD -4.00 mg/dL; 95% CI -6.86 to -1.14; I2 = 0%). CGM also increased time in range (WMD 8.63%; 95% CI 4.54-12.71; I2 = 0%) and treatment satisfaction (SMD 0.79; 95% CI 0.54-1.05; I2 = 0%). Conclusion: In this meta-analysis, rt-CGM and is-CGM were associated with improvement in glycemic control in people with T2D not using insulin when compared to SMBG.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation on chronic hemodialysis: a meta-analysis of randomized controlled trials.

PURPOSE: Patients with atrial fibrillation (AF) and end-stage renal disease on chronic hemodialysis are at risk for thromboembolic and bleeding events. We aimed to perform a meta-analysis to evaluate the safety and efficacy of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs) in this population. METHODS: We systematically searched PubMed, Excerpta Medica Database (EMBASE) and Cochrane Library for randomized controlled trials (RCTs) comparing DOACs with VKAs in patients with AF on chronic hemodialysis from inception to February 2023 in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Outcomes were reported using risk ratios (RRs) with 95% confidence intervals (CIs). Statistical analyses were performed using R version 4.2.2. RESULTS: We selected three RCTs including 341 patients, of whom 176 (51.6%) were randomized to DOACs. Follow-up ranged from 174 days to 3.38 years. There was no significant difference between groups in terms of cardiovascular mortality (RR 1.34; 95% CI 0.69-2.60; p = 0.39), all-cause mortality (RR 0.96; 95% CI 0.72-1.27; p = 0.77), ischemic/uncertain type of stroke or transient ischemic attack (RR 0.50; 95% CI 0.19-1.35; p = 0.17), or major or life-threatening bleeding (RR 0.70; 95% CI 0.39-1.25; p = 0.22). CONCLUSION: In this meta-analysis of three RCTs, no significant difference was observed between DOACs and VKAs in cardiovascular mortality, all-cause mortality, ischemic/uncertain type of stroke or transient ischemic attack, or major or life-threatening bleeding in patients with AF on chronic hemodialysis.

Endoscopic Third Ventriculostomy versus Ventriculoperitoneal Shunt in Patients with Obstructive Hydrocephalus: An Updated Systematic Review and Meta-Analysis.

Endoscopic third ventriculostomy (ETV) and ventriculoperitoneal shunt (VPS) are surgical methods for treating obstructive hydrocephalus. However, there is still disagreement regarding the most effective technique, in terms of both operative success and postoperative complications. Therefore, we performed a systematic review and meta-analysis to compare the efficacy and safety of these two methods in patients with obstructive hydrocephalus. We performed a systematic search of the PubMed, Scopus, and Cochrane Library databases. Randomized clinical trials (RCTs) comparing ETV and VPS in pediatric or adult patients with obstructive hydrocephalus were included. The outcomes included were operative success, postoperative cerebrospinal fluid leak, postoperative infection, postoperative or intraoperative bleeding, blockage rate, and mortality. The risk ratio (RR) was calculated with a 95% confidence interval (CI). Heterogeneity was evaluated with I 2 statistics. We used a fixed-effects model for outcomes with I 2 < 25% and DerSimonian and Laird random-effects model for other conditions. The Cochrane collaboration tool for assessing the risk of bias in randomized trials was used for risk-of-bias assessment. R, version 4.2.1, was used for statistical analyses. Of the 2,353 identified studies, 5 RCTs were included, involving 310 patients with obstructive hydrocephalus, of which 163 underwent ETV. There was a significant difference in favor of ETV for postoperative infection (risk ratio [RR]: 0.11; 95% confidence interval [CI]: 0.04-0.33; p < 0.0001; I 2 = 0%) and blockage rate (RR: 0.15; 95% CI: 0.03-0.75; p = 0.02; I 2 = 53%). Meanwhile, there was no significant difference between groups for the postoperative or intraoperative bleeding (RR: 0.44; 95% CI: 0.17-1.15; p = 0.09; I 2 = 0%), postoperative cerebrospinal fluid leak (RR: 0.65; 95% CI: 0.22-1.92; p = 0.44; I 2 = 18%), operative success (RR: 1.18; 95% CI: 0.77-1.82; p = 0.44; I 2 = 84%), and mortality (RR: 0.19; 95% CI: 0.03-1.09; p = 0.06; I 2 = 0%). Three RCTs had some concerns about the risk of bias and one RCT had a high risk of bias due to the process of randomization and selection of reported results. Thus, this meta-analysis of RCTs evaluating ETV compared with VPS demonstrated that although there is no superiority of ETV in terms of operative success, the incidence of complications was significantly higher in patients who underwent VPS. Our results suggest that the use of ETV provides greater benefits for the treatment of obstructive hydrocephalus. However, more RCTs are needed to corroborate the superiority of ETV.

PD-1/PD-L1 Inhibitors plus Chemotherapy Versus Chemotherapy Alone for Resectable Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Background: The benefit of adding programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors to the treatment of early-stage non-small cell lung cancer (NSCLC), both neoadjuvant therapy (NAT) and adjuvant therapy (AT), is not yet fully elucidated. Methods: We searched PubMed, Embase, and Cochrane databases for randomized controlled trials (RCT) that investigated PD-1/PD-L1 inhibitors plus chemotherapy for resectable stage NSCLC. We computed hazard ratios (HRs) or odds ratios (ORs) for binary endpoints, with 95% confidence intervals (CIs). Results: A total of seven RCTs comprising 3915 patients with resectable stage NSCLC were randomized to chemotherapy with or without PD-1/PD-L1 inhibitors as NAT or AT. As NAT, the PD-1/PD-L1 inhibitors plus chemotherapy group demonstrated significantly improved overall survival (HR 0.66; 95% CI 0.51-0.86) and event-free survival (HR 0.53; 95% CI 0.43-0.67) compared with the chemotherapy alone group. There was a significant increase in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group for major pathological response (OR 6.40; 95% CI 3.86-10.61) and pathological complete response (OR 8.82; 95% CI 4.51-17.26). Meanwhile, as AT, disease-free survival was significant in favor of the PD-1/PD-L1 inhibitors plus chemotherapy group (HR 0.78; 95% CI 0.69-0.90). Conclusions: In this comprehensive systematic review and meta-analysis of RCTs, the incorporation of PD-1/PD-L1 inhibitors alongside chemotherapy offers a promising prospect for reshaping the established treatment paradigms for patients diagnosed with resectable stages of NSCLC. Moreover, our analyses support that neoadjuvant administration with these agents should be encouraged, in light of the fact that it was associated with an increased survival and pathological response, at the expense of a manageable safety profile.

The Essential Oil from Conyza bonariensis (L.) Cronquist (Asteraceae) Exerts an In Vitro Antimelanoma Effect by Inducing Apoptosis and Modulating the MAPKs, NF-κB, and PKB/AKT Signaling Pathways.

The characterization and cytotoxicity of the essential oil from Conyza bonariensis (L.) aerial parts (CBEO) were previously conducted. The major compound was (Z)-2-lachnophyllum ester (EZ), and CBEO exhibited significant ROS-dependent cytotoxicity in the melanoma cell line SK-MEL-28. Herein, we employed the Molegro Virtual Docker v.6.0.1 software to investigate the interactions between the EZ and Mitogen-Activated Protein Kinases (MAPKs), the Nuclear Factor kappa B (NF-κB), and the Protein Kinase B (PKB/AKT). Additionally, in vitro assays were performed in SK-MEL-28 cells to assess the effect of CBEO on the cell cycle, apoptosis, and these signaling pathways by flow cytometry and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay using MAPKs inhibitors. CBEO induced a significant increase in the sub-G1 peak, as well as biochemical and morphological changes characteristic of apoptosis. The in-silico results indicated that EZ interacts with Extracellular Signal-Regulated Kinase 1 (ERK1), c-Jun N-terminal Kinase 1 (JNK1), p38α MAPK, NF-κB, and PKB/AKT. Moreover, CBEO modulated the ERK1/2, JNK, p38 MAPK, NF-κB, and PKB/AKT activities in SK-MEL-28 cells. Furthermore, CBEO's cytotoxicity against SK-MEL-28 cells was significantly altered in the presence of MAPKs inhibitors. These findings support the in vitro antimelanoma effect of CBEO through apoptosis induction, and the modulation of ERK, JNK, p38 MAPK, NF-κB, and PKB/AKT activities.

Image analysis to automatically classify anemia based on Famacha score in sheep using ocular conjunctiva images.

Haemonchus contortus is the most pathogenic blood-feeding parasitic in sheep, causing anemia and consequently changes in the color of the ocular conjunctiva, from the deep red of healthy sheep to shades of pink to practically white of non-healthy sheep. In this context, the Famacha method has been created for detecting sheep unable to cope with the infection by H. contortus, through visual assessment of ocular conjunctiva coloration. Thus, the objectives of this study were (1) to extract ocular conjunctiva image features to automatically classify Famacha score and compare two classification models (multinomial logistic regression-MLR and random forest-RF) and (2) to evaluate the applicability of the best classification model on three sheep farms. The dataset consisted of 1,156 ocular conjunctiva images from 422 animals. RF model was used to segment the images, i.e., to select the pixels that belong to the ocular conjunctiva. After segmentation, the quantiles (1%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, and 99%) of color intensity in each image channel (red, blue, and green) were determined and used as explanatory variables in the classification models, and the Famacha scores 1 (non-anemic) to 5 (severely anemic) were the target classes to be predicted (scores 1 to 5, with 162, 255, 443, 266, and 30 images, respectively). For objective 1, the performance metrics (precision and sensitivity) were obtained using MLR and RF models considering data from all farms randomly split. For objective 2, a leave-one-farm-out cross-validation technique was used to assess prediction quality across three farms (farms A, B, and C, with 726, 205, and 225 images, respectively). The RF provided the best performances in predicting anemic animals, as indicated by the high values of sensitivity for Famacha score 3 (80.9%), 4 (46.2%), and 5 (60%) compared to the MLR model. The precision of the RF was 72.7% for Famacha score 1 and 62.5% for Famacha score 2. These results indicate that is possible to successfully predict Famacha score, especially for scores 2 to 4, in sheep via image analysis and RF model using ocular conjunctiva images collected in farm conditions. As expected, model validation excluding entire farms in cross-validation presented a lower prediction quality. Nonetheless, this setup is closer to reality because the developed models are supposed to be used across farms, including new ones, and with different environments and management conditions.

Nutritional, Productive, and Qualitative Characteristics of European Quails Fed with Diets Containing Lipid Sources of Plant and Animal Origin.

The objective of this study was to investigate the impact of alternative lipid sources on nutrient metabolism, performance, carcass characteristics, and meat quality in European quails. Trial 1 determined the energy values and nutrient metabolizability of non-conventional lipid sources. Six treatments (control, soybean oil, conventional corn oil, distilled corn oil, poultry fat, and beef tallow) were randomly assigned with 10 replicates per treatment. Trial 2 evaluated animal performance, carcass characteristics, and meat quality using a randomized design with five treatments and 10 replicates each. Statistical analysis showed no significant difference in apparent metabolizable energy corrected by nitrogen (AMEn) and coefficients of metabolizability (CM%) among the lipid sources. The AMEn values found were 8554 for soybean oil, 7701 for corn, 7937 for distilled corn oil, 7906 for poultry fat, and 7776 for beef tallow (kcal/kg). The CM values were 88.01% for soybean oil, 79.01% for corn oil, 84.10% for distilled corn oil, 81.43% for poultry fat, and 79.28% for beef tallow. The inclusion of lipid sources of plant and animal origin in the diet of 7-35-day old meat quails did not influence performance or carcass and cut characteristics. The inclusion of distilled corn oil increased carcass yield and influenced skin and meat color parameters. AMEn values varied for each lipid source. The inclusion of distilled corn oil positively influenced skin and meat color as well as carcass yield in quails.

Chemical Composition, In Vitro Antitumor Effect, and Toxicity in Zebrafish of the Essential Oil from Conyza bonariensis (L.) Cronquist (Asteraceae).

The essential oil from Conyza bonariensis (Asteraceae) aerial parts (CBEO) was extracted by hydrodistillation in a Clevenger-type apparatus and was characterized by gas chromatography-mass spectrometry. The antitumor potential was evaluated against human tumor cell lines (melanoma, cervical, colorectal, and leukemias), as well as non-tumor keratinocyte lines using the MTT assay. The effect of CBEO on the production of Reactive Oxygen Species (ROS) was evaluated by DCFH-DA assay, and a protection assay using the antioxidant N-acetyl-L-cysteine (NAC) was also performed. Moreover, the CBEO toxicity in the zebrafish model was assessed. The majority of the CBEO compound was (Z)-2-lachnophyllum ester (57.24%). The CBEO exhibited selectivity towards SK-MEL-28 melanoma cells (half maximal inhibitory concentration, IC50 = 18.65 ± 1.16 µg/mL), and induced a significant increase in ROS production. In addition, the CBEO's cytotoxicity against SK-MEL-28 cells was reduced after pretreatment with NAC. Furthermore, after 96 h of exposure, 1.5 µg/mL CBEO induced death of all zebrafish embryos. Non-lethal effects were observed after exposure to 0.50-1.25 µg/mL CBEO. Additionally, significant alterations in the activity of enzymes associated with oxidative stress in zebrafish larvae were observed. These results provide evidence that CBEO has a significant in vitro antimelanoma effect by increasing ROS production and moderate embryotoxicity in zebrafish.