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Background: Selumetinib is the first approved treatment for pediatric patients with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas (PN) in the EU and US, as well as in multiple other countries. Evidence for the management of selumetinib-associated adverse events (AEs) is mostly limited to clinical trials and expanded-access programs. We gathered a panel of European healthcare practitioners with clinical experience prescribing selumetinib and/or managing pediatric patients with NF1-PN to provide recommendations on the prevention and management of AEs. Methods: A modified Delphi approach was used to develop the recommendations among the group of experts. Initial statements were developed from a literature review of current management recommendations and regulatory reports. The panel refined the statements and rated the extent to which they agreed with them in 2 sessions and a follow-up survey. The panel comprised 2 pediatric neuro-oncologists, 1 pediatric oncologist, 1 pediatrician, 1 neuropediatrician, 1 oncologist, 1 neurologist, 2 psychologists, and 1 dermatologist. Results: The experts agreed on the relative frequency and impact of AEs potentially associated with selumetinib. Consensus-level agreement was reached for 36 statements regarding the prevention and management of AEs potentially associated with selumetinib. Experts recommended treatments for AEs based on their experience. Conclusions: The development of a variety of consensus statements indicates expert agreement on best practices for the prevention and management of AEs potentially associated with selumetinib in pediatric patients with NF1-PN. These events are generally manageable and should be considered alongside treatment benefit. Information sharing is warranted as further experience is gained.

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Rubrolides are a family of naturally occurring 5-benzylidenebutenolides, which generally contain brominated phenol groups, and nearly half of them also present a chlorine attached to the butenolide core. Seven natural rubrolides were previously synthesized. When these compounds were tested against the model plant Raphanus sativus, six were found to exert a slight inhibition on plant growth. Aiming to exploit their scaffold as a model for the synthesis of new compounds targeting photosynthesis, nine new rubrolide analogues were prepared. The synthesis was accomplished in 2-4 steps with a 10-39% overall yield from 3,4-dichlorofuran-2(5H)-one. All compounds were evaluated for their ability to inhibit the whole Hill reaction or excluding photosystem I (PSI). Several natural rubrolides and their analogues displayed good inhibitory potential (IC50 = 2-8 µM). Molecular docking studies on the photosystem II-light harvesting complex II (PSII-LHCII supercomplex) binding site were also performed. Overall, data support the use of rubrolides as a model for the development of new active principles targeting the photosynthetic electron transport chain to be used as herbicides.

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In this study, cow manure was hydrothermally treated in a 2-litre reactor for 1 h at temperatures between 100 °C and 260 °C. Both the raw manure and the solid and liquid products of the hydrothermal treatment were characterized to understand the fate of the inorganic elements and to assess the suitability of the products for land applications and energy recovery. Satisfactory elemental balances were obtained for the organic and most inorganic elements and indicated that most inorganic elements were incorporated into the solids with lower solubility, with the exception of potassium and sodium, which were mostly solubilized in the process water; calcium and chlorine were also solubilized to a lesser extent in the process water. Elemental composition and surface functional groups showed that hydrochar produced within the hydrothermal carbonization range (180-260 °C) seemed better suited for utilization as a soil amendment than raw cow manure. The potential for energy recovery lies in the anaerobic digestion of the process water, from which higher methane yields can be obtained than from raw cow manure. Lower temperatures in hydrothermal carbonization are considered a compromise for the safe land applications of cow manure, energy recovery from the process water, and enhanced dewaterability. These findings can help to eliminate bottlenecks in the upscaling of cow manure hydrothermal treatment and promote the circular bio-economy.

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This study focuses on describing the diversity of pesticides, the knowledge and behaviors of their use, and the acute poisoning symptoms (APS) derived from their exposure from two agricultural production systems (papaya-Carica papaya L.- and chili-Capsicum annuum L.-) in Oaxaca, Mexico. Through surveys, sociodemographic information, characteristics of the production system, knowledge and behaviors in the handling of pesticides, and APS perceived by users were captured. Papaya producers are younger, have fewer years of activity, and have larger agricultural areas than chili producers. Insect attacks and diseases are an essential factor for the application of pesticides. Thirty-one active ingredients (Ais) were identified in papaya and thirty-seven in chili, predominantly insecticides and fungicides of toxicological category IV. Approximately 50% of users apply mixtures of different Ais, have little knowledge and inappropriate behavior in their handling, and report up to five acute pesticide poisoning symptoms, mainly burning and irritation of the skin, burning eyes, itchy skin, runny nose, headache, and watery eyes. The production of papaya and chili are relevant activities for generating economic income, but they risk the producer's and their family's health. Both systems are a potential scenario for the manifestation of diseases due to exposure to pesticides in the medium and long term.

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This study rigorously investigates the effectiveness of nonlinear filters in CMOS for 2-D signal processing to enhance image quality. We comprehensively compare traditional linear filters' performance, which operate on the principle of linearity, with nonlinear filters, such as the median-median (Med-Med) approach, designed to handle nonlinear data. To ensure the validity of our findings, we use widely accepted metrics like normalized squared error (NSE), peak signal-to-noise ratio (PSNR), and structural similarity index (SSIM) to quantify the differences. Our simulations and experiments, conducted under controlled conditions, demonstrate that nonlinear filters in CMOS outperform linear filters in removing impulse noise and enhancing images. We also address the challenges of implementing these algorithms at the hardware level, focusing on power consumption and chip area optimization. Additionally, we propose a new architecture for the Med-Med filter and validate its functionality through experiments using a 9-pixel image sensor array. Our findings highlight the potential of nonlinear filters in CMOS for real-time image quality enhancement and their applicability in various real-world imaging applications. This research contributes to visual technology by combining theoretical insights with practical implementations, paving the way for more efficient and adaptable imaging systems.

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Compound databases of natural products play a crucial role in drug discovery and development projects and have implications in other areas, such as food chemical research, ecology and metabolomics. Recently, we put together the first version of the Latin American Natural Product database (LANaPDB) as a collective effort of researchers from six countries to ensemble a public and representative library of natural products in a geographical region with a large biodiversity. The present work aims to conduct a comparative and extensive profiling of the natural product-likeness of an updated version of LANaPDB and the individual ten compound databases that form part of LANaPDB. The natural product-likeness profile of the Latin American compound databases is contrasted with the profile of other major natural product databases in the public domain and a set of small-molecule drugs approved for clinical use. As part of the extensive characterization, we employed several chemoinformatics metrics of natural product likeness. The results of this study will capture the attention of the global community engaged in natural product databases, not only in Latin America but across the world.

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Caesalpinioideae is the second largest subfamily of legumes (Leguminosae) with ca. 4680 species and 163 genera. It is an ecologically and economically important group formed of mostly woody perennials that range from large canopy emergent trees to functionally herbaceous geoxyles, lianas and shrubs, and which has a global distribution, occurring on every continent except Antarctica. Following the recent re-circumscription of 15 Caesalpinioideae genera as presented in Advances in Legume Systematics 14, Part 1, and using as a basis a phylogenomic analysis of 997 nuclear gene sequences for 420 species and all but five of the genera currently recognised in the subfamily, we present a new higher-level classification for the subfamily. The new classification of Caesalpinioideae comprises eleven tribes, all of which are either new, reinstated or re-circumscribed at this rank: Caesalpinieae Rchb. (27 genera / ca. 223 species), Campsiandreae LPWG (2 / 5-22), Cassieae Bronn (7 / 695), Ceratonieae Rchb. (4 / 6), Dimorphandreae Benth. (4 / 35), Erythrophleeae LPWG (2 /13), Gleditsieae Nakai (3 / 20), Mimoseae Bronn (100 / ca. 3510), Pterogyneae LPWG (1 / 1), Schizolobieae Nakai (8 / 42-43), Sclerolobieae Benth. & Hook. f. (5 / ca. 113). Although many of these lineages have been recognised and named in the past, either as tribes or informal generic groups, their circumscriptions have varied widely and changed over the past decades, such that all the tribes described here differ in generic membership from those previously recognised. Importantly, the approximately 3500 species and 100 genera of the former subfamily Mimosoideae are now placed in the reinstated, but newly circumscribed, tribe Mimoseae. Because of the large size and ecological importance of the tribe, we also provide a clade-based classification system for Mimoseae that includes 17 named lower-level clades. Fourteen of the 100 Mimoseae genera remain unplaced in these lower-level clades: eight are resolved in two grades and six are phylogenetically isolated monogeneric lineages. In addition to the new classification, we provide a key to genera, morphological descriptions and notes for all 163 genera, all tribes, and all named clades. The diversity of growth forms, foliage, flowers and fruits are illustrated for all genera, and for each genus we also provide a distribution map, based on quality-controlled herbarium specimen localities. A glossary for specialised terms used in legume morphology is provided. This new phylogenetically based classification of Caesalpinioideae provides a solid system for communication and a framework for downstream analyses of biogeography, trait evolution and diversification, as well as for taxonomic revision of still understudied genera.

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Sulfuric acid anodizing assisted by a hydrothermal sealing with inhibitors [Ce3+-Mo6+] was used to prevent pitting corrosion on spray-deposited hypereutectic Al-Si alloy (A390). An investigation concerning the evaluation of pitting corrosion resistance on the anodic oxide thin film with ions incorporated was carried out in NaCl solution using electrochemical measurements (i.e., potentiodynamic polarization and electrochemical impedance spectroscopy, EIS). The influence of Si phase morphology and size on the growth mechanism of an anodic oxide film was characterized by scanning electron microscopy (SEM) and X-ray diffraction (XRD). The results were then compared with those for its equivalent IM390 alloy (Al-17Si-4.5Cu-0.6Mg) produced through a conventional process ingot metallurgy, IM. The electrochemical findings indicate that sulfuric acid anodizing followed by a simple hot water sealing treatment was ineffective. In this manner, an intense attack was localized by pitting corrosion that occurred on the anodic oxide film in less than three days, as denoted by characteristic changes in the EIS spectra at the lowest frequencies. Improved results were achieved for Ce-Mo surface modification, which can provide better corrosion resistance on the aluminum alloys because no signs of pits were observed during the corrosion testing.

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Plasmacytoid dendritic cells (pDCs) are vital players in antiviral immune responses because of their high levels of IFN-α secretion. However, this attribute has also implicated them as critical factors behind the immunopathogenesis of inflammatory diseases, and no currently available therapy can efficiently inhibit pDCs' aberrant activation. Mesenchymal stromal cells (MSCs) possess stromal immunomodulatory functionality, regulating immune cell activation through several mechanisms, including the adenosinergic (CD39/CD73/adenosine) pathway. The IFN-γ preconditioning of bone marrow MSCs improves their inhibitory properties for therapy applications; however, isolating human gingival tissue-derived MSCs (hGMSCs) is more accessible. These cells have shown better immunomodulatory effects, yet the outcome of IFN-γ preconditioning and its impact on the adenosinergic pathway has not been evaluated. This study first validated the immunoregulatory properties of primary-cultured hGMSCs, and the results showed that IFN-γ preconditioning strengthens CD39/CD73 coexpression, adenosine production, and the regulatory properties of hGMSC, which were confirmed by describing for the first time their ability to reduce pDC activation and their IFN-α secretion and to increase the frequency of CD73+ pDC. In addition, when CD73's enzymatic activity was neutralized in hGMSCs, adenosine production and the IFN-γ preconditioning effect were restrained. This evidence might be applied to design hGMSCs- and adenosine-based immunotherapeutic strategies for treating inflammatory disorders that are associated with pDC overactivation.

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Sickle cell anemia has been classified as a noninfectious neglected tropical disease and, although not exclusively, affects African descendants more frequently. This study aimed to detect asymptomatic sickle cell hemoglobin carriers (HbAS) in marginalized and vulnerable populations during a public health screening in African descendants from Oaxaca, Mexico, and to validate an amplification refractory mutation system (ARMS)-PCR methodology to detect fetal-hemoglobin (HbF)-regulating genetic variants in BCL11A toward affordable routine association of single nucleotide variants (SNVs) with HbF concentrations. To this aim, hemoglobin variants were detected by acidic citrate agar and alkaline cellulose acetate electrophoreses. SNVs in the hemoglobin subunit beta gene (HBB) were identified by the ß-globin mutation detection assay (ß-GMDA) and ARMS-PCR, respectively, and validated by Sanger sequencing. The association between genotypes and HbF concentrations was evaluated using Spearman's correlation coefficient. The results obtained during a directed screening in 140 self-identified African descendants revealed 42 HbS-carriers (30%), of which 39 showed normal total hemoglobin concentrations (92.8%), only 3 presented anemia (7.2%), and 9 showed quantifiable HbF concentration (21.4%). As validated by Sanger sequencing, the designed ARMS-PCR efficiently detected homozygous and heterozygous variants in BCL11A. In a cohort of 42 heterozygous (HbAS) and 27 healthy (HbAA) individuals from the same population, only one SNV (rs766432) showed statistically significant association with increasing HbF concentration, and two new unrelated homozygous silent variants were identified. This study reveals the need to raise coverage of HbS screening in vulnerable populations and shows a feasible low-cost ARMS-PCR methodology to determine the presence of SNVs in quantitative trait loci affecting HbF.

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Background: Selumetinib is approved for the treatment of pediatric patients with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN) in multiple countries, including the USA (≥ 2 years). Until recently, individuals had to take selumetinib twice daily (BID) in a fasted state. This study evaluated the effect of a low-fat meal on selumetinib PK parameters and gastrointestinal (GI) tolerability in adolescent participants with NF1-PN. Methods: Eligible participants aged ≥ 12 to < 18 years took 25 mg/m2 selumetinib BID with a low-fat meal (T1) for 28 days, followed by a 7-day washout, and then administration in a fasted state (T2) for another 28 days. Primary objectives were to evaluate the effect of a low-fat meal on AUC0-12,ss and GI tolerability after multiple selumetinib doses in T1 versus T2. Key secondary objectives were additional PK parameters and adverse events (AEs). Results: At primary data cut-off, all 24 participants completed T1, and 23 participants completed T2. There were no significant differences in AUC0-12,ss between T1 and T2. In T1 and T2, 29.2% and 33.3% participants, respectively, reported ≥ 1 GI AE. No GI AEs Grade ≥ 3, or serious AEs, or GI AEs resulting in treatment interruptions, discontinuation, or dose reductions were reported in T1 and T2. Conclusions: Dosing selumetinib with a low-fat meal had no clinically relevant impact on selumetinib AUC0-12,ss nor GI tolerability in adolescents with NF1-PN. Trial registration ClinicalTrialsgov ID: NCT05101148.

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The title compound [systematic name: 1-(2-nitro-phen-yl)pyrrole-2,5-dione], C10H6N2O4, crystallizes in the monoclinic system (space group P21/n) with two mol-ecules in the asymmetric unit, which are linked by C-H⋯O hydrogen bonds. Hirshfeld surface analysis showed that the most significant contributions to the crystal packing are from H⋯O/O⋯H, H⋯C/C⋯H and H⋯H inter-actions, which contribute 54.7%, 15.2% and 15.6%, respectively. A DFT study was conducted using three different levels of theory [(B3LYP/6-311+G(d,p), wB97XD/Def2TZVPP and LC-wpbe/6-311(2 d,2p)] in order to determine the stability, structural and electronic properties of the title mol-ecule with a view to its potential applications and photochemical and copolymer properties.

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Development of effective vaccines for infectious diseases has been one of the most successful global health interventions in history. Though, while ideal subunit vaccines strongly rely on antigen and adjuvant(s) selection, the mode and time scale of exposure to the immune system has often been overlooked. Unfortunately, poor control over the delivery of many adjuvants, which play a key role in enhancing the quality and potency of immune responses, can limit their efficacy and cause off-target toxicities. There is a critical need for improved adjuvant delivery technologies to enhance their efficacy and boost vaccine performance. Nanoparticles have been shown to be ideal carriers for improving antigen delivery due to their shape and size, which mimic viral structures but have been generally less explored for adjuvant delivery. Here, we describe the design of self-assembled poly(ethylene glycol)-b-poly(lactic acid) nanoparticles decorated with CpG, a potent TLR9 agonist, to increase adjuvanticity in COVID-19 vaccines. By controlling the surface density of CpG, we show that intermediate valency is a key factor for TLR9 activation of immune cells. When delivered with the SARS-CoV-2 spike protein, CpG nanoparticle (CpG-NP) adjuvant greatly improves the magnitude and duration of antibody responses when compared to soluble CpG, and results in overall greater breadth of immunity against variants of concern. Moreover, encapsulation of CpG-NP into injectable polymeric-nanoparticle (PNP) hydrogels enhances the spatiotemporal control over codelivery of CpG-NP adjuvant and spike protein antigen such that a single immunization of hydrogel-based vaccines generates humoral responses comparable to those of a typical prime-boost regimen of soluble vaccines. These delivery technologies can potentially reduce the costs and burden of clinical vaccination, both of which are key elements in fighting a pandemic.

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Coping with dementia requires an integrated approach encompassing personal, health, research, and community domains. Here we describe "Walking the Talk for Dementia," an immersive initiative aimed at empowering people with dementia, enhancing dementia understanding, and inspiring collaborations. This initiative involved 300 participants from 25 nationalities, including people with dementia, care partners, clinicians, policymakers, researchers, and advocates for a 4-day, 40 km walk through the Camino de Santiago de Compostela, Spain. A 2-day symposium after the journey provided novel transdisciplinary and horizontal structures, deconstructing traditional hierarchies. The innovation of this initiative lies in its ability to merge a physical experience with knowledge exchange for diversifying individuals' understanding of dementia. It showcases the transformative potential of an immersive, embodied, and multi-experiential approach to address the complexities of dementia collaboratively. The initiative offers a scalable model to enhance understanding, decrease stigma, and promote more comprehensive and empathetic dementia care and research.

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INTRODUCTION: Randomized controlled trials (RCTs) are the cornerstone of systematic reviews and other evidence synthesis. RCT identification remains challenging because of limitations in their indexation in major databases and potential language bias. Scientific production in Latin American nursing is steadily increasing, but little is known about its design or main features. We aimed to identify the extent of evidence from RCTs in nursing conducted by Latin American research teams and evaluate their main characteristics, including potential risk of bias. DESIGN: Scoping review with risk of bias assessment. METHODS: We conducted a scoping review including a comprehensive electronic search in five relevant databases. We completed a descriptive data analysis and a risk of bias assessment of eligible studies using Cochrane's guidance. RESULTS: We identified 1784 references of which 47 were RCTs published in 40 journals. Twenty (42.6%) RCTs were published in journals in English. Chronic diseases were the most common health conditions studied (29.7%). Fifteen (31.9%) RCTs had a high risk of bias. Thirty (75%) journals were included in the Journal Citation Report (JCR) catalog and 5 (16.7%) were journals classified under nursing category. Twenty-one (52.5%) journals explicitly required CONSORT checklist recommendations for RCTs reporting. CONCLUSION: Publication of RCTs in nursing by Latin American authors has increased. Most journals where RCTs are published are in English and not specific to nursing. Searches in journals of other disciplines may be necessary to facilitate identification of RCTs in nursing. CONSORT statements need to be actively promoted to facilitate rigorous methodology and reporting of RCTs. CLINICAL RELEVANCE STATEMENT: This study highlights the need for an increased research focus on RCTs in nursing in Latin America, and the importance of enhancing the reporting quality of these studies to support evidence-based nursing practice.

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OBJECTIVE: To analyze the association of changes in social security (SS) continuity and mortality, using the Mexican Health and Aging Study (MHAS) in people aged 60 years and more. MATERIALS AND METHODS: Retrospective cohort. We analyzed the SS continuity condition -classified as stable, unstable with SS, unstable without SS, and without SS- and its relation with mortality; a probit regression model was utilized to obtain marginal effects, taking into consideration covariates related to mortality. RESULTS: Unstable continuity with and without SS and multimorbidity (two or more diseases) increased the probability of dying by 52.9% (p = 0.000, 95%CI: 0.508,0.551), 50.3% (p = 0.000, 95%CI: 0.474,0.531) and 13.3% (p = 0.000, 95%CI: 0.108,0.159), respectively. Meanwhile, being woman, at least one year of formal education, and marriage reduced it in 8.8% (p = 0.000, 95%CI: -0.106,-0.071), 7% (p = 0.000, 95%CI: -0.091,-0.050) and 7.8% (p = 0.000, 95%CI: -0.096,-0.061), respectively. CONCLUSION: Belonging to SS was associated with higher mortality, compared to other social health determinants, like education.

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The number of databases of natural products (NPs) has increased substantially. Latin America is extraordinarily rich in biodiversity, enabling the identification of novel NPs, which has encouraged both the development of databases and the implementation of those that are being created or are under development. In a collective effort from several Latin American countries, herein we introduce the first version of the Latin American Natural Products Database (LANaPDB), a public compound collection that gathers the chemical information of NPs contained in diverse databases from this geographical region. The current version of LANaPDB unifies the information from six countries and contains 12,959 chemical structures. The structural classification showed that the most abundant compounds are the terpenoids (63.2%), phenylpropanoids (18%) and alkaloids (11.8%). From the analysis of the distribution of properties of pharmaceutical interest, it was observed that many LANaPDB compounds satisfy some drug-like rules of thumb for physicochemical properties. The concept of the chemical multiverse was employed to generate multiple chemical spaces from two different fingerprints and two dimensionality reduction techniques. Comparing LANaPDB with FDA-approved drugs and the major open-access repository of NPs, COCONUT, it was concluded that the chemical space covered by LANaPDB completely overlaps with COCONUT and, in some regions, with FDA-approved drugs. LANaPDB will be updated, adding more compounds from each database, plus the addition of databases from other Latin American countries.

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Resumen: El estesioneuroblastoma es una neoplasia de las células del neuroepitelio olfatorio. Tiene una baja incidencia de 0.4 por cada millón de habitantes. Se caracteriza por síntomas como sinusitis, epistaxis, cefalea, discapacidad visual, obstrucción nasal, hiposmia y rinorrea. En este reporte se presenta el caso de un paciente masculino de 29 años con estesioneuroblastoma estadio Kadish C, quien fue programado para resección quirúrgica bajo anestesia total intravenosa con resultados satisfactorios durante el procedimiento quirúrgico.

Abstract: Esthesioneuroblastoma is a neoplasm of the olfactory neuroepithelium cells, it has a low incidence of 0.4 per million inhabitants. It is characterized by symptoms such as sinusitis, epistaxis, headache, visual impairment, nasal obstruction, hyposmia, and rhinorrhea. We present the case of a 29-year-old male patient with Kadish C stage esthesioneuroblastoma, who was scheduled for surgical resection under total intravenous anesthesia with satisfactory results during the surgical procedure.

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Introduction Benign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms in men. Holmium Laser Enucleation of the Prostate (HoLEP) has been recommended by international guidelines as an alternative to transurethral resection of the prostate (TURP). HoLEP's learning curve and the lack of adequate mentorship remains an obstacle for the worldwide adoption of this technique. Objective To report the first-year learning curve of a newly established mentorship program in young urologists without any previous HoLEP experience. Methods We report a cohort of patients with BPH, with prostate size ≥70 grams, treated with HoLEP, analyzed for perioperative data and complications, and short-term postoperative complications and functional outcomes, at three and six months after surgery. Results A total of 47 patients were managed with HoLEP. Mean total operative time was 149.8 ± 42.9 minutes. We experienced five (10.6%) intraoperative complications, including one intravesical resection of the prostate with bipolar energy, three conversions to TURP and one conversion to open prostatectomy. We experienced four postoperative complications, all of them Clavien-Dindo ≤2. Median International Prostate Symptom Score (IPSS) decrease at six months was -17 points from baseline. Mean post-void residual volume and prostate-specific antigen significantly decreased by the third postoperative month. Multiple linear regression showed that prostate size is directly related to increased surgical time during the early learning curve. Discussion Our experience adequately reflects the importance of HoLEP mentorship in young urologists seeking training in this technique. Both surgeons had perioperative and postoperative outcomes deemed satisfactory based on previously published learning curves. Conclusions HoLEP is a technically difficult procedure, however, adequate mentorship leads to satisfying short-term outcomes since the early stages of the learning curve in young urologists with no previous training on this technique.