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Purpose: Tissue inadequacy and operational challenges may limit lung cancer comprehensive biomarker testing. Here, we describe the initial implementation of a tailored tissue molecular journey at Oncoclínicas Precision Medicine Laboratory in Brazil, which includes fast-track (FT) non-next-generation sequencing (NGS) assays combined with a broad NGS panel., Methods: From 2021 to 2023, all nonsquamous lung cancer samples eligible for the patient support program "Lung Mapping Consortium" at Oncoclínicas & Co were evaluated using the FT panel (immunohistochemistry for PD-L1 and anaplastic lymphoma kinase [ALK], polymerase chain reaction for EGFR and BRAF , and fluorescence in situ hybridization for ROS1 ) plus a broad DNA and RNA sequencing panel of 180 genes (custom ARCHER panel)., Results: From 1,272 samples received by the laboratory, 3% had no tissue for any molecular testing, 20% was not eligible for broad NGS panel as per pathologist assessment (tumor purity and quantity), additional 12% did not reach presequencing analytical thresholds (nucleic acid quantity and/or quality), and 3% had postsequencing failure. Most frequent alterations were KRAS mutations (28.4%, KRAS G12C 9.7%), EGFR mutations (23.6%, exon20 insertions 2.9%), ALK fusions (6.4%), MET exon 14 skipping (4.4%), ERBB2 mutations (3.4%), ROS1 fusions (3.1%), and BRAF V600E (1.9%). In 35% of the samples, FT non-NGS tests were the only molecular diagnostics: EGFR mutations (14%), ALK fusions (4.4%), ROS1 fusions (1.8%), and BRAF V600E (0.7%). Overall, high PD-L1 expression (≥50%) was found in 12.3%., Conclusion: This study provides data on the molecular epidemiology of lung adenocarcinoma in Brazil, confirming high prevalence of EGFR mutations, ALK fusions, and MET exon 14 skipping alteration. Biomarker detection is largely affected by biospecimen collection and processing, with one third of the patients eligible for non-NGS testing only, which presents reduced coverage and sensitivity for actionable drivers.

Chitin-derived furans offer a sustainable alternative feedstock for nitrogen appended aromatic compounds. Herein, we address the challenge of using chitin-derived furans, 3-acetamido-5-acetylfuran (3A5AF) and 3-acetamido-5-furfural aldehyde (3A5F), to favour the formation of exo Diels-Alder adducts and 4-acetylaminophthalimides respectively, using a mechanochemical ball-milling technique. Mechanochemical activation is explored through the synthesis of 7-oxa-norbornene backbones with novel substitution pattern from 3A5AF in yields up to 77 % and improved exo:endo selectivity compared to solution-phase reactions. The synthesis of 4-acetylaminophthalimides from 3A5F in yields up to 79 % is also showcased from hydrazone derivatives., (© 2024 The Authors. ChemSusChem published by Wiley-VCH GmbH.)

Background: Premature loss of primary teeth presents a significant challenge in oral health, with conflicting views on using space maintainers., Aim: To assess mandibular arch space changes associated with premature lower primary molar (PM) loss with or without a space maintainer., Design: A randomized clinical trial with children (6-9 years old) with premature loss of a lower PM divided into two groups: control group (CG), without a space maintainer, and intervention group (IG), with a space maintainer. Dental casts were measured at baseline, 3 months, and 6 months. Linear distance; intercanine width and length; and arch width, length, and perimeter were measured. ANOVA and t-test were applied (p = .05)., Results: Twenty-six patients (mean: 7.3 years; standard deviation [SD]: 0.92) were included: 14 in CG and 12 in IG. CG had a greater space loss (-0.9 mm; SD: 0.45) than IG (-0.4 mm; SD: 0.61) at 3 months (p < .05). No difference between the groups was observed after 6 months (p = .610). CG decreases space at 6 months, especially with the first permanent molars without intercuspation (-2 mm; SD: 0.71; p = .007)., Conclusion: Premature lower PM loss resulted in reduced arch space loss after 6 months, regardless of a space maintainer use. CG showed more loss of space when the first permanent molars lacked intercuspal relationship., (© 2024 BSPD, IAPD and John Wiley & Sons Ltd.)

HbSC disease, a less severe form of sickle cell disease, affects the retina more frequently and patients have higher rates of proliferative retinopathy that can progress to vision loss. This study aimed to identify differences in the expression of endothelial cell-derived molecules associated with the pathophysiology of proliferative sickle cell retinopathy (PSCR). RNAseq was used to compare the gene expression profile of circulating endothelial colony-forming cells from patients with SC hemoglobinopathy and proliferative retinopathy (n = 5), versus SC patients without retinopathy (n = 3). Real-time polymerase chain reaction (qRT-PCR) was used to validate the RNAseq results. A total of 134 differentially expressed genes (DEGs) were found. DEGs were mainly associated with vasodilatation, type I interferon signaling, innate immunity and angiogenesis. Among the DEGs identified, we highlight the most up-regulated genes ROBO1 (log2FoldChange = 4.32, FDR = 1.35E-11) and SLC38A5 (log2FoldChange = 3.36 FDR = 1.59E-07). ROBO1 , an axon-guided receptor, promotes endothelial cell migration and contributes to the development of retinal angiogenesis and pathological ocular neovascularization. Endothelial SLC38A5, an amino acid (AA) transporter, regulates developmental and pathological retinal angiogenesis by controlling the uptake of AA nutrient, which may serve as metabolic fuel for the proliferation of endothelial cells (ECs) and consequent promotion of angiogenesis. Our data provide an important step towards elucidating the molecular pathophysiology of PSCR that may explain the differences in ocular manifestations between individuals with hemoglobinopathies and afford insights for new alternative strategies to inhibit pathological angiogenesis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 da Silva Costa, Ito, da Cruz, De Souza, Rios, Bertozzo, Camargo, Viturino, Lanaro, de Albuquerque, do Canto, Saad, Ospina-Prieto, Ozelo, Costa and de Melo.)

Per- and polyfluoroalkyl substances (PFAS) are widely used chemicals that exhibit exceptional chemical and thermal stability. However, their resistance to degradation has led to their widespread environmental contamination. PFAS also negatively affect the environment and other organisms, highlighting the need for effective remediation methods to mitigate their presence and prevent further contamination. Computational chemistry methods, such as Density Functional Theory (DFT) and Molecular Dynamics (MD) offer valuable tools for studying PFAS and simulating their interactions with other molecules. This review explores how computational chemistry methods contribute to understanding and tackling PFAS in the environment. PFAS have been extensively studied using DFT and MD, each method offering unique advantages and computational limitations. MD simulates large macromolecules systems however it lacks the ability model chemical reactions, while DFT provides molecular insights however at a high computational cost. The integration of DFT with MD shows promise in predicting PFAS behavior in different environments. This work summarizes reported studies on PFAS compounds, focusing on adsorption, destruction, and bioaccumulation, highlighting contributions of computational methods while discussing the need for continued research. The findings emphasize the importance of computational chemistry in addressing PFAS contamination, guiding risk assessments, and informing future research and innovations in this field., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ischemic stroke (IS) is one of the most impairing complications of sickle cell anemia (SCA), responsible for 20% of mortality in patients. Rheological alterations, adhesive properties of sickle reticulocytes, leukocyte adhesion, inflammation and endothelial dysfunction are related to the vasculopathy observed prior to ischemic events. The role of the vascular endothelium in this complex cascade of mechanisms is emphasized, as well as in the process of ischemia-induced repair and neovascularization. The aim of the present study was to perform a comparative transcriptomic analysis of endothelial colony-forming cells (ECFCs) from SCA patients with and without IS. Next, to gain further insights of the biological relevance of differentially expressed genes (DEGs), functional enrichment analysis, protein-protein interaction network (PPI) construction and in silico prediction of regulatory factors were performed. Among the 2469 DEGs, genes related to cell proliferation (AKT1, E2F1, CDCA5, EGFL7), migration (AKT1, HRAS), angiogenesis (AKT1, EGFL7) and defense response pathways (HRAS, IRF3, TGFB1), important endothelial cell molecular mechanisms in post ischemia repair were identified. Despite the severity of IS in SCA, widely accepted molecular targets are still lacking, especially related to stroke outcome. The comparative analysis of the gene expression profile of ECFCs from IS patients versus controls seems to indicate that there is a persistent angiogenic process even after a long time this complication has occurred. Thus, this is an original study which may lead to new insights into the molecular basis of SCA stroke and contribute to a better understanding of the role of endothelial cells in stroke recovery., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)