Programmed death-ligand expression and lymph node involvement in penile squamous cell carcinoma.

PURPOSE: Our objective was to investigate the association between programmed death-ligand (PD-L1) immunoexpression measured as a combined positive score and clinical outcomes in penile SqCC. MATERIALS AND METHODS: We retrospectively reviewed all penile SqCC cases diagnosed in our institution between 2018 and 2023. PD-L1 immunohistochemistry was performed as a qualitative assay. Immunoexpression in both tumor and immune cells equal or superior to 1 was considered positive. RESULTS: A total of 34 patients with conventional penile SqCC were included. Eleven cases were HPV-associated (32.4%). Twelve cases were PD-L1 CPS < 1 and twenty-two were PD-L1 CPS ≥ 1. Nine cases (32.4%) were PD-L1 CPS ≥ 1 and p16 positive, but this did not translate in worse clinicopathological features. Larger tumors (3.0 cm in PD-L1 CPS ≥ 1 vs 2.5 cm in PD-L1 CPS < 1; p = 0.662), vascular invasion (36.4% in PD-L1 CPS ≥ 1 vs. 25.0% in PD-L1 CPS < 1; p = 0.705) and perineural invasion (40.9% in PD-L1 CPS≥1 vs. 16.7% in PD-L1 CPS < 1; p = 0.252) were associated with PD-L1 expression. Among the high-risk features, only lymph node involvement had statistical significance, with 14 out of 22 PD-L1 CPS ≥ 1 patients (63.6%) having lymph node metastases when lymphadenectomy was performed (p = 0.031). With a median follow-up of 16 months (IQR 27.5), PD-L1 CPS ≥ 1 patients had worse overall survival (53.4 months vs 75.9 months), but no statistical significance could be inferred (p = 0.188). CONCLUSIONS: It is noteworthy the clinical significance of lymph node involvement in PD-L1 CPS ≥ 1 cases and a trend towards worse overall survival in this group of patients.

The Effects of High-Fat Diet and Flaxseed Oil-Enriched Diet on the Lung Parenchyma of Obese Mice.

Omega-3 (ω3) fatty acids are widely investigated for their anti-inflammatory potential, however, there is little evidence regarding their action in the lung parenchyma in the context of obesity. The objective is to investigate the effects of flaxseed oil (FS), rich in α-linolenic (C18:3 - ω3), on the lungs of obese mice. Mice were fed a high-fat diet (HF) for 8 weeks to induce obesity. Subsequently, a part of these animals received HF containing FS oil for another 8 weeks. The HF consumption induced weight gain and hyperglycemia. The lung parenchyma shows a complete fatty acids profile, compared to the control group (CT). In the lung parenchyma, FS increases the ω3 content and, notwithstanding a reduction in the interleukins (IL) IL1ß and IL18 contents compared to HF. However, FS promoted increased alveolar spaces, followed by MCP1 (Monocytes Chemoattractant Protein-1) positive cell infiltration and a dramatic reduction in the anti-inflammatory cytokine, IL10. Despite reducing the pulmonary inflammatory response, the consumption of a food source of ω3 was associated with alterations in the lipid profile and histoarchitecture of the lung parenchyma, which can lead to the development of pulmonary complications. This study brings an alert against the indiscriminate use of ω3 supplements, warranting caution.

Single-cell resolution characterization of myeloid-derived cell states with implication in cancer outcome.

Tumor-associated myeloid-derived cells (MDCs) significantly impact cancer prognosis and treatment responses due to their remarkable plasticity and tumorigenic behaviors. Here, we integrate single-cell RNA-sequencing data from different cancer types, identifying 29 MDC subpopulations within the tumor microenvironment. Our analysis reveals abnormally expanded MDC subpopulations across various tumors and distinguishes cell states that have often been grouped together, such as TREM2+ and FOLR2+ subpopulations. Using deconvolution approaches, we identify five subpopulations as independent prognostic markers, including states co-expressing TREM2 and PD-1, and FOLR2 and PDL-2. Additionally, TREM2 alone does not reliably predict cancer prognosis, as other TREM2+ macrophages show varied associations with prognosis depending on local cues. Validation in independent cohorts confirms that FOLR2-expressing macrophages correlate with poor clinical outcomes in ovarian and triple-negative breast cancers. This comprehensive MDC atlas offers valuable insights and a foundation for futher analyses, advancing strategies for treating solid cancers.

Association Between Body Mass Index, Obesity, and Clinical Outcomes Following Coronary Artery Bypass Grafting in Brazil: An Analysis of One Year of Follow-up of BYPASS Registry Patients.

OBJECTIVE: To investigate the association between body mass index (BMI), obesity, clinical outcomes, and mortality following coronary artery bypass grafting (CABG) in Brazil using a large sample with one year of follow-up from the Brazilian Registry of Cardiovascular Surgeries in Adults (or BYPASS) Registry database. METHODS: A multicenter cohort-study enrolled 2,589 patients submitted to isolated CABG and divided them into normal weight (BMI 20.0-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obesity (BMI > 30.0 kg/m2) groups. Inpatient postoperative outcomes included the most frequently described complications and events. Collected post-discharge outcomes included rehospitalization and mortality rates within 30 days, six months, and one year of follow-up. RESULTS: Sternal wound infections (SWI) rate was higher in obese compared to normal-weight patients (relative risk [RR]=5.89, 95% confidence interval [CI]=2.37-17.82; P=0.001). Rehospitalization rates in six months after discharge were higher in obesity and overweight groups than in normal weight group (χ=6.03, P=0.049); obese patients presented a 2.2-fold increase in the risk for rehospitalization within six months compared to normal-weight patients (RR=2.16, 95% CI=1.17-4.09; P=0.045). Postoperative complications and mortality rates did not differ among groups during time periods. CONCLUSION: Obesity increased the risk for SWI, leading to higher rehospitalization rates and need for surgical interventions within six months following CABG. Age, female sex, and diabetes were associated with a higher risk of mortality. The obesity paradox remains controversial since BMI may not be sufficient to assess postoperative risk in light of more complex and dynamic evaluations of body composition and physical fitness.

Human protein-protein interaction networks: A topological comparison review.

Protein-Protein Interaction Networks aim to model the interactome, providing a powerful tool for understanding the complex relationships governing cellular processes. These networks have numerous applications, including functional enrichment, discovering cancer driver genes, identifying drug targets, and more. Various databases make protein-protein networks available for many species, including Homo sapiens. This work topologically compares four Homo sapiens networks using a coarse-to-fine approach, comparing global characteristics, sub-network topology, specific nodes centrality, and interaction significance. Results show that the four human protein networks share many common protein-encoding genes and some global measures, but significantly differ in the interactions and neighbourhood. Small sub-networks from cancer pathways performed better than the whole networks, indicating an improved topological consistency in functional pathways. The centrality analysis shows that the same genes play different roles in different networks. We discuss how studies and analyses that rely on protein-protein networks for humans should consider their similarities and distinctions.

Spatio-temporal Distribution of Bactrocera carambolae with and without Irrigation using CLIMEX Modeling.

The carambola fruit fly Bactrocera carambolae Drew and Hancock (Diptera: Tephritidae) is an invasive fruit fly reported in North Brazil that threatens Brazilian fruit culture. Assessing the potential risk of establishing this pest is necessary to reduce the threat of B. carambolae dispersion to other countries and Brazilian regions and to avoid damage to the fruit trade. In this study, the CLIMEX model was used to understand the response of B. carambolae to climate change and to determine its potential global distribution with and without irrigation practices. Based on ecophysiological parameters, the model simulates factors limiting species distribution concerning the climate. To assess the seasonal variation in the density of B. carambolae, monitoring data in Uiramutã municipality, Roraima, from 2013 to 2019 was used. According to the CLIMEX forecast, large parts of America, Africa, and Asia, mainly in areas closest to the equator, are highly suitable for the survival of B. carambolae. Brazil is a good part of its territory with high suitability for B. carambolae, especially the North, South, and Southeast regions and the entire coastal area. The periods of the highest climatic suitability in the five Brazilian regions were January-May and October-December. The potential distribution area expands under irrigation and is highly suitable for most areas without cold stress. The CLIMEX model for B. carambolae generated in the present study provides important information for the Brazilian eradication program and other surveillance activities established in pest-free areas.

On the feasibility of Vis-NIR spectroscopy and machine learning for real time SARS-CoV-2 detection.

The pandemic caused by Covid-19 is still present around the world. Despite advances in combating the disease, such as vaccine development, identifying infected individuals is still essential to optimize the control of human-to-human transmission of the virus. The main technique for detecting the virus is the RT-PCR method, which, despite its high relative cost, has a high accuracy in detecting the coronavirus. Given this, a method capable of performing the identification quickly, accurately, and inexpensively is necessary. Thus, this work aimed to analyze the feasibility of a new technique for identifying SARS-CoV-2 through the use of optical spectroscopy in the visible and near-infrared range (Vis-NIR) combined with machine learning algorithms. Spectral signals were obtained from nasopharyngeal swab samples previously analyzed using the RT-PCR method. The specimens were provided by the Molecular Diagnosis Laboratory of Covid-19 at Univasf. A total of 314 samples were analyzed, comprising 42 testing positive and 272 testing negative for Covid-19. Digital signal processing techniques, such as Savitzky-Golay filters and statistical methods were used to eliminate spurious elements from the original data and extract relevant features. Supervised machine learning algorithms such as SVM, Random Forest, and Naive Bayes classifiers were used to perform automatic sample identification. To evaluate the performance of the models, a 5-fold cross-validation technique was applied. With the proposed methodology, it was possible to achieve an accuracy of 75%, a sensitivity of 80%, and a specificity of 70%, in addition to an area under the ROC curve of 0.81, in the identification of nasopharyngeal swab samples from previously diagnosed individuals. From these results, it was possible to conclude that Vis-NIR spectroscopy is a promising, fast and relatively low cost technique to identify the SARS-CoV-2.

Association Between Body Mass Index, Obesity, and Clinical Outcomes Following Coronary Artery Bypass Grafting in Brazil: An Analysis of One Year of Follow-up of BYPASS Registry Patients

ABSTRACT Objective: To investigate the association between body mass index (BMI), obesity, clinical outcomes, and mortality following coronary artery bypass grafting (CABG) in Brazil using a large sample with one year of follow-up from the Brazilian Registry of Cardiovascular Surgeries in Adults (or BYPASS) Registry database. Methods: A multicenter cohort-study enrolled 2,589 patients submitted to isolated CABG and divided them into normal weight (BMI 20.0-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2), and obesity (BMI > 30.0 kg/m2) groups. Inpatient postoperative outcomes included the most frequently described complications and events. Collected post-discharge outcomes included rehospitalization and mortality rates within 30 days, six months, and one year of follow-up. Results: Sternal wound infections (SWI) rate was higher in obese compared to normal-weight patients (relative risk [RR]=5.89, 95% confidence interval [CI]=2.37-17.82; P=0.001). Rehospitalization rates in six months after discharge were higher in obesity and overweight groups than in normal weight group (χ2=6.03, P=0.049); obese patients presented a 2.2-fold increase in the risk for rehospitalization within six months compared to normal-weight patients (RR=2.16, 95% CI=1.17-4.09; P=0.045). Postoperative complications and mortality rates did not differ among groups during time periods. Conclusion: Obesity increased the risk for SWI, leading to higher rehospitalization rates and need for surgical interventions within six months following CABG. Age, female sex, and diabetes were associated with a higher risk of mortality. The obesity paradox remains controversial since BMI may not be sufficient to assess postoperative risk in light of more complex and dynamic evaluations of body composition and physical fitness.

Reproduction of Meloidogyne morocciensis (Tylenchida: Meloidogynidae) in weeds found in Brazil.

Weeds can be hosts of root-knot nematodes of the genus Meloidogyne. The importance of the species Meloidogyne morocciensis parasitizing many crops is recognized, but their reproductive capacity in weeds is not known. The present study hypothesizes the ability of M. morocciensis to parasitize and reproduce in different weed species found in Brazil. The objective was to evaluate the reproduction of M. morocciensis in 36 weed species. The plants were individually inoculated with 5,000 eggs and second stage juveniles and kept in greenhouse for 60 days. The experimental design was completely randomized with twelve replications. The root system of each plant was evaluated for gall index (GI), final nematode population (PF), number of nematode/g of root (NNGR) and reproduction factor (RF). It was verified that M. morocciensis has the capacity to parasite 36 weed species belonging to 16 different botanical families, confirming the hypothesis proposed. From the 36 species evaluated, 77.8% (28) were susceptible (FR ≥ 1.0) to M. morocciensis. The present study is the first to identify different weeds as hosts of M. morocciensis, evidencing its polyphagous habit, indicating species of plants with high capacity to multiply this nematode and that need more attention during the integrated management of these pathogen.

Prediction of dyskinesia in Parkinson's disease patients using machine learning algorithms.

Dyskinesias are non preventable abnormal involuntary movements that represent the main challenge of the long term treatment of Parkinson's disease (PD) with the gold standard dopamine precursor levodopa. Applying machine learning techniques on the data extracted from the Parkinson's Progression Marker Initiative (PPMI, Michael J. Fox Foundation), this study was aimed to identify PD patients who are at high risk of developing dyskinesias. Data regarding clinical, behavioral and neurological features from 697 PD patients were included in our study. Our results show that the Random Forest was the classifier with the best and most consistent performance, reaching an area under the receiver operating characteristic (ROC) curve of up to 91.8% with only seven features. Information regarding the severity of the symptoms, the semantic verbal fluency, and the levodopa treatment were the most important for the prediction, and were further used to create a Decision Tree, whose rules may guide the pharmacological management of PD symptoms. Our results contribute to the identification of PD patients who are prone to develop dyskinesia, and may be considered in future clinical trials aiming at developing new therapeutic approaches for PD.

Efficacy and safety outcomes of darolutamide in patients with non-metastatic castration-resistant prostate cancer with comorbidities and concomitant medications from the randomised phase 3 ARAMIS trial.

PURPOSE: In patients with non-metastatic castration-resistant prostate cancer (nmCRPC) in the Androgen Receptor Antagonizing Agent for Metastasis-free Survival (ARAMIS) trial, darolutamide significantly improved median metastasis-free survival by nearly 2 years and reduced the risk of death by 31% versus placebo, with a favourable safety/tolerability profile. This post hoc analysis of ARAMIS evaluated efficacy and safety in patients by number of comorbidities and concomitant medications. METHODS: Patients with nmCRPC were randomised 2:1 to darolutamide (n = 955) or placebo (n = 554) while continuing androgen-deprivation therapy. Overall survival (OS) and treatment-emergent adverse events (TEAEs) were evaluated in subgroups by median numbers of ongoing comorbidities and concomitant medications. HRs were determined from univariate analysis using Cox regression. FINDINGS: Median numbers of comorbidities and concomitant medications were 6 and 10, respectively, with 41.6% of patients having >6 comorbidities and 48.8% taking >10 concomitant medications. For patients with ≤ 6 and >6 comorbidities, darolutamide increased OS versus placebo (hazard ratio [HR] 0.65 and 0.73, respectively), and this benefit was consistent for cardiovascular, metabolic, and other comorbidities (HR range: 0.39-0.88). For patients taking ≤ 10 and >10 concomitant medications, increased OS was also observed with darolutamide versus placebo (HR 0.76 and 0.66, respectively), and the benefit was consistent across medication classes (HR range: 0.45-0.80). Incidences of TEAEs and TEAEs leading to treatment discontinuation with darolutamide were similar to placebo across subgroups by numbers of comorbidities and concomitant medications. CONCLUSIONS: The OS benefit and safety of darolutamide remained consistent with that observed in the overall ARAMIS population, even in patients with high numbers of comorbidities or concomitant medications. GOV REGISTRATION: NCT02200614. TWEETABLE ABSTRACT: Darolutamide increased overall survival versus placebo, and incidences of most adverse events were similar between treatments in patients with ≤ 6 or >6 comorbidities and those taking ≤ 10 or >10 concomitant medications.

Edaphic fauna in soil profile after three decades of different soil management and cover crops in a subtropical region.

This research evaluated the effects of long-term (30 years) winter cover crops under conventional farming system and no-tillage system on edaphic fauna in a Rhodic Hapludox soil, from Paraná State, Brazil. We used three winter cover crops (black oat, hairy vetch and fallow), and as a reference a fragment of natural forest. Soil monoliths were collected at two times, one during the flowering of maize (April 2013) and the other during the flowering of soybean (January 2014). The extraction of the monoliths was carried out in three layers in the soil profile (0-10, 10-20 and 20-30 cm). Seventeen taxonomic groups were sampled. The density of the edaphic fauna is inversely related to soil depth. The winter crops associated with the no-tillage system in long-term resulted in fauna densities similar to the natural environment, with a higher density (density increase of 2.2x) at a depth of 10-20 cm in areas with black oat. At 0-10 cm depth, black oat and vetch under no-tillage systems resulted in an increase of 62% and 69% (April 2013) and 46 and 44% (January 2014), respectively, in the density of soil fauna, when compared to the same winter crops in conventional farming system.

A systematic review of clinical trials for gene therapies for ß-hemoglobinopathy around the world.

BACKGROUND AIMS: Amidst the success of cell therapy for the treatment of onco-hematological diseases, the first recently Food and Drug Administration-approved gene therapy product for patients with transfusion-dependent ß-thalassemia (TDT) indicates the feasibility of gene therapy as curative for genetic hematologic disorders. This work analyzed the current-world scenario of clinical trials involving gene therapy for ß-hemoglobinopathies. METHODS: Eighteen trials for patients with sickle cell disease (SCD) and 24 for patients with TDT were analyzed. RESULTS: Most are phase 1 and 2 trials, funded by the industry and are currently recruiting volunteers. Treatment strategies for both diseases are fetal hemoglobin induction (52.4%); addition of wild-type or therapeutic ß-globin gene (38.1%) and correction of mutations (9,5%). Gene editing (52.4%) and gene addition (40.5%) are the two most used techniques. The United States and France are the countries with the greatest number of clinical trials centers for SCD, with 83.1% and 4.2%, respectively. The United States (41.1%), China (26%) and Italy (6.8%) lead TDT trials centers. CONCLUSIONS: Geographic trial concentration indicates the high costs of this technology, logistical issues and social challenges that need to be overcome for gene therapy to reach low- and middle-income countries where SCD and TDT are prevalent and where they most impact the patient's health.

Mapping Brazilian Expansion Risk Levels of Mango Weevil (Sternochetus mangiferae Fabricius) Based on MaxEnt.

The mango weevil, Sternochetus mangiferae (Fabricius) (Curculionidae), pest present in Brazil and is restricted to some municipalities in the Rio de Janeiro State. This curculionid attacks the mango crop exclusively and puts mango production globally at risk, especially those destined for export. Using ecological modeling tools, this study is the first to map the potential risk of S. mangiferae in Brazil. We aimed to identify the potential distribution of this pest in Brazilian states, drawing up thematic maps of regions that present suitable and unsuitable climatic conditions for the establishment of the pest using the MaxEnt ecological niche model. The average annual temperature, the annual precipitation, the average daytime temperature range, and the annual temperature range were the variables that contributed most to the selected model. The MaxEnt model predicted highly suitable areas for S. mangiferae throughout the Brazilian coast, especially on the northeast coast. The region responsible for more than 50% of mango production in Brazil, the São Francisco Valley, was classified by the model with suitability for the pest; it can impacts exportations due to the imposition of phytosanitary barriers. This information can be used in strategies to prevent the introduction and establishment of this pest in new areas and monitor programs in areas with recent occurrence. In addition, the model results can be used in future research plans on S. mangiferae in worldwide modeling studies and climate change scenarios.

Corrigendum to "Cross-sectional analysis of students and school workers reveals a high number of asymptomatic SARS-CoV-2 infections during school reopening in Brazilian cities" [Heliyon 8 (11) (November 2022) Article e11368].

[This corrects the article DOI: 10.1016/j.heliyon.2022.e11368.].

Organic fertilization and mycorrhization increase copper phytoremediation by Canavalia ensiformis in a sandy soil.

Organic fertilization and mycorrhization can increase the phytoremediation of copper-contaminated soils. The time of vermicomposting alters the properties of vermicompost, which can affect copper's availability and uptake. Therefore, this study sought to evaluate the effect of different organic fertilizers and mycorrhization on copper-contaminated soil phytoremediation. The soil was contaminated with 100 mg Cu kg-1 dry soil and received mineral fertilizer (MIN), bovine manure (CM), and vermicompost produced in 45 days (V45) or 120 days (V120), all in doses equivalent to 40 mg kg-1 dry soil of phosphorus. Half of the jack bean (Canavalia ensiformis) plants were inoculated with the arbuscular mycorrhizal fungus Rhizophagus clarus. At plant flowering, the dry mass and concentrations of Cu, Zn, Mn, Ca, Mg, P, and K in the soil, solution, and plant tissue were determined, in addition to mycorrhizal colonization, nodulation, photosynthetic pigments, and oxidative stress enzyme activity. Organic fertilization increased plant growth and copper accumulation in aerial tissues. These effects were more evident with the V120, making it suitable for use in copper phytoextraction. Mycorrhization increased root and nodule dry mass, making it recommended for phytostabilization. C. ensiformis nodulation in Cu-contaminated soils depends on vermicompost fertilization and mycorrhization. Hence, the copper phytoremediation by C. ensiformis is increased by using organic fertilization and mycorrhization.

Integrative systems immunology uncovers molecular networks of the cell cycle that stratify COVID-19 severity.

Several perturbations in the number of peripheral blood leukocytes, such as neutrophilia and lymphopenia associated with Coronavirus disease 2019 (COVID-19) severity, point to systemic molecular cell cycle alterations during severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, the landscape of cell cycle alterations in COVID-19 remains primarily unexplored. Here, we performed an integrative systems immunology analysis of publicly available proteome and transcriptome data to characterize global changes in the cell cycle signature of COVID-19 patients. We found significantly enriched cell cycle-associated gene co-expression modules and an interconnected network of cell cycle-associated differentially expressed proteins (DEPs) and genes (DEGs) by integrating the molecular data of 1469 individuals (981 SARS-CoV-2 infected patients and 488 controls [either healthy controls or individuals with other respiratory illnesses]). Among these DEPs and DEGs are several cyclins, cell division cycles, cyclin-dependent kinases, and mini-chromosome maintenance proteins. COVID-19 patients partially shared the expression pattern of some cell cycle-associated genes with other respiratory illnesses but exhibited some specific differential features. Notably, the cell cycle signature predominated in the patients' blood leukocytes (B, T, and natural killer cells) and was associated with COVID-19 severity and disease trajectories. These results provide a unique global understanding of distinct alterations in cell cycle-associated molecules in COVID-19 patients, suggesting new putative pathways for therapeutic intervention.

Comparative Efficacy of Superheated Dry Steam Application and Insecticide Spray Against Common Bed Bugs Under Simulated Field Conditions.

The common bed bug, Cimex lectularius L., is a difficult urban pest to control. A simulated field study was conducted to compare the efficacy of steam application and an insecticide mixture spray (0.05% acetamiprid and 0.06% bifenthrin mixture) against C. lectularius. Three types of furniture (desk chair, upholstered armchair, and wooden table) were treated in the laboratory. The efficacy of the treatments was evaluated by visual inspection and placement of interceptor traps under the legs of the furniture. One hundred mixed stages of an insecticide-resistant population of C. lectularius were released onto each furniture item. After a 10-day acclimation period, each furniture item received steam treatment, insecticide spray, or no treatment. The second application of treatment was conducted 14 d later. Bed bug counts from interceptors and visual inspections were recorded at 13 d and 28 d after the initial treatment. At 28 d, the mean (± SE) live bed bug count in the steam, spray, and control group was 1 ± 0, 2 ± 1, and 83 ± 10, respectively. Both treatment methods were highly effective in controlling bed bugs on furniture. The mean bed bug count from interceptors in the steam, spray, and control groups were 0.3 ± 0.2, 11 ± 7, and 47 ± 9, respectively. There was no significant difference in the efficacy between steam and spray treatments based on either visual inspection or bed bug counts from interceptors. However, based on interceptor counts, the steam treatment caused faster bed bug population reduction than insecticide sprays.