The Relevance of Pharmacokinetic Biomarkers in Response to Methadone Treatment: A Systematic Review.

: Methadone maintenance treatment (MMT) is widely used in opioid use disorder (OUD). Its efficacy is influenced by its metabolism, primarily mediated by Cytochrome P450 (CYP450) enzymes in the liver. Genetic polymorphisms in CYP450 genes and other factors, such as age, sex, and concomitant treatments, contribute to interindividual variability in methadone response.

CARTAR: a comprehensive web tool for identifying potential targets in chimeric antigen receptor therapies using TCGA and GTEx data.

Chimeric antigen receptor (CAR) therapy has emerged as a ground-breaking advancement in cancer treatment, harnessing the power of engineered human immune cells to target and eliminate cancer cells. The escalating interest and investment in CAR therapy in recent years emphasize its profound significance in clinical research, positioning it as a rapidly expanding frontier in the field of personalized cancer therapies. A crucial step in CAR therapy design is choosing the right target as it determines the therapy's effectiveness, safety and specificity against cancer cells, while sparing healthy tissues.

Stochastic Syncing in Sinusoidally Driven Atomic Orbital Memory.

Stochastically fluctuating multiwell systems are a promising route toward physical implementations of energy-based machine learning and neuromorphic hardware. One of the challenges is finding tunable material platforms that exhibit such multiwell behavior and understanding how complex dynamic input signals influence their stochastic response. One such platform is the recently discovered atomic Boltzmann machine, where each stochastic unit is represented by a binary orbital memory state of an individual atom.

Design, synthesis and validation of a new Crimped Head-Piece for DNA-Encoded libraries generation.

Codification of DNA Encoded Libraries (DELs) is critical for successful ligand identification of molecules that bind a protein of interest (POI). There are different encoding strategies that permit, for instance, the customization of a DEL for testing single or dual pharmacophores (single strand DNA) or for producing and screening large diversity libraries of small molecules (double strand DNA). Both approaches challenges, either from the synthetic and encoding point of view, or from the selection methodology to be utilized for the screening.

The function of wing bullae in mayflies (Insecta: Ephemeroptera) reveals new insights into the early evolution of Pterygota.

Background: Mayflies are basal winged insects of crucial importance for the understanding of the early evolution of Pterygota. Unlike all other insects, they have two successive winged stages, the subimago and the imago. Their forewings feature so-called bullae, which are desclerotized spots in the anterior main veins.

Effects of experimental warming on two tropical Andean aquatic insects.

Temperatures have increased around the globe, affecting many ecosystems, including high-elevation Andean streams where important aquatic insect species coexist. Depending on the magnitude of change, warming could lead to the mortality of sensitive species, and those tolerant to rising water temperatures may exhibit differences in growth rates and development. Taxon-specific optimal temperature ranges for growth determine how high or low temperatures alter an organism's body size.

Identification of Sodium Transients Through Na1.5 Channels as Regulators of Differentiation in Immortalized Dorsal Root Ganglia Neurons.

Neuronal differentiation is a complex process through which newborn neurons acquire the morphology of mature neurons and become excitable. We employed a combination of functional and transcriptomic approaches to deconvolute and identify key regulators of the differentiation process of a DRG neuron-derived cell line, and we focused our study on the Na 1.5 ion channel (encoded by ) as a channel involved in the acquisition of DRG neuronal features.

Katacine Is a New Ligand of CLEC-2 that Acts as a Platelet Agonist.

Background:  CLEC-2 is a platelet receptor with an important role in thromboinflammation but a minor role in hemostasis. Two endogenous ligands of CLEC-2 have been identified, the transmembrane protein podoplanin and iron-containing porphyrin hemin, which is formed following hemolysis from red blood cells. Other exogenous ligands such as rhodocytin have contributed to our understanding of the role of CLEC-2.

Mayfly taxonomy (Arthropoda: Hexapoda: Ephemeroptera) during the first two decades of the twenty-first century and the concentration of taxonomic publishing.

The twentieth anniversary of the first issue of Zootaxa (De Moraes Freire, 2001) provides an appropriate opportunity to reflect on some trends in global Ephemeroptera taxonomy publishing over the last two decades, with a focus on the description of new species and the outsized role of the journals Zootaxa and ZooKeys, in particular. Detailed reviews of world Ephemeroptera knowledge up to about 2000 were collected in a series of nine papers from a symposium on the subject, published together in the proceedings of the ninth International Conference on Ephemeroptera (Domínguez 2001). Domínguez Dos Santos (2014) provided updates and analysis for South America up to the year 2012.

Identification of Novel Regulators of Zalcitabine-Induced Neuropathic Pain.

Neuropathic pain is one of the foremost adverse effects that worsens quality of life for patients undergoing an antiretroviral treatment. Currently, there are no effective analgesics for relieving it; thus, there is an urgent need to develop novel treatments for neuropathic pain. Previously, we described and validated F11 cells as a model of DRG (dorsal root ganglia) neurons.

Normalization of DNA encoded library affinity selection results driven by high throughput sequencing and HPLC purification.

The output of an affinity selection screening results in a huge amount of valuable data that, after conducting the appropriate analysis, lead to the correct identification of the compounds enriched in the target of interest. The approach chosen to perform these analyses has become a key step in the development of a successful DNA Encoded Library platform. In this paper, we describe the combination of High Performance Liquid Chromatography purification during the library production with the Next Generation Sequencing analysis of the libraries to assess the yield of the chemical reactions prior to the affinity selection.

Description of a new species, nymphs of two known species and a new record of Miroculis/ Edmunds, 1963 (Ephemeroptera: Leptophlebiidae) from Brazil.

Miroculis is one of the most diversified Neotropical genera of Leptophlebiidae in South America with 26 species currently known. In this work we describe a new species of Miroculis based on imagos from Amazonas, and the unknown nymphs of Miroculis (Miroculis) caparaoensis and Miroculis (Ommaethus) misionensis, both associated with imagos. In addition, Miroculis (Ommaethus) misionensis is recorded for the first time from Brazil.

The PI3Kδ Inhibitor Idelalisib Diminishes Platelet Function and Shows Antithrombotic Potential.

Background: Clinical management of ischemic events and prevention of vascular disease is based on antiplatelet drugs. Given the relevance of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) as a candidate target in thrombosis, the main goal of the present study was to identify novel antiplatelet agents within the existing inhibitors blocking PI3K isoforms.

Methods: We performed a biological evaluation of the pharmacological activity of PI3K inhibitors in platelets.

Discovery of novel immunopharmacological ligands targeting the IL-17 inflammatory pathway.

Interleukin 17 (IL-17) is a proinflammatory cytokine that acts as an immune checkpoint for several autoimmune diseases. Therapeutic neutralizing antibodies that target this cytokine have demonstrated clinical efficacy in psoriasis. However, biologics have limitations such as their high cost and their lack of oral bioavailability.

Clinical predictors and explant lung pathology of acute exacerbation of idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is characterised by constant threat of acute exacerbation of IPF (AE-IPF). It would be significant to identify risk factors of AE-IPF. We sought to determine the prognostic value of lung transplantation candidacy testing for AE-IPF and describe explant pathology of recipients with and without AE-IPF before lung transplantation.

Author Correction: Identification and characterization of Cardiac Glycosides as senolytic compounds.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Etoposide as Salvage Therapy for Cytokine Storm Due to Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) has resulted in significant morbidity and mortality because of a lack of effective therapies. Therapeutic strategies under investigation target the overactive cytokine response with anti-cytokine or immunomodulators therapies. We present a unique case of severe cytokine storm resistant to multiple anti-cytokine therapies, but eventually responsive to etoposide.

Ecoregions, climate, topography, physicochemical, or a combination of all: Which criteria are the best to define river types based on abiotic variables and macroinvertebrates in neotropical rivers?

The baseline conditions for a particular river or stream type are essential to classify aquatic ecosystems based on physical and biological characteristics. In this study, we proposed a river typology for different ecoregions, climate and topography of northwestern Argentina using parameters, and combined key variables to establish reference conditions. A set of geographical, hydro-morphological, hydrological, geological (pedology and sedimentology) and physicochemical variables were measured from different rivers and analyzed with clustering and ordination techniques to develop a typology.

Flux-Based Assay for the Identification of Autophagy Modulators for Osteoarthritis.

Autophagy is a central mechanism to regulate homeostasis. Alterations of autophagy contribute to aging-related diseases. Phenotypic methods to identify regulators of autophagy could be used for the identification of novel therapeutics.

Ten years of the neonatal respiratory extracorporeal membrane oxygenation program in an Argentinian public hospital.

Introduction: Extracorporeal membrane oxygenation (ECMO) is a highly invasive rescue treatment for critically-ill patients. The objective of the study was to show the outcomes of patients treated with ECMO in the neonatal intensive care unit of Hospital de Pediatria Juan P. Garrahan in the first 10 years of the program, and to analyze the risk factors associated with mortality on ECMO.

A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction.

Food addiction is linked to obesity and eating disorders and is characterized by a loss of behavioral control and compulsive food intake. Here, using a food addiction mouse model, we report that the lack of cannabinoid type-1 receptor in dorsal telencephalic glutamatergic neurons prevents the development of food addiction-like behavior, which is associated with enhanced synaptic excitatory transmission in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc). In contrast, chemogenetic inhibition of neuronal activity in the mPFC-NAc pathway induces compulsive food seeking.

Beyond Tumor Suppression: Senescence in Cancer Stemness and Tumor Dormancy.

Here, we provide an overview of the importance of cellular fate in cancer as a group of diseases of abnormal cell growth. Tumor development and progression is a highly dynamic process, with several phases of evolution. The existing evidence about the origin and consequences of cancer cell fate specification (e.

A Comprehensive Tyrosine Phosphoproteomic Analysis Reveals Novel Components of the Platelet CLEC-2 Signaling Cascade.

C-type lectin-like receptor 2 (CLEC-2) plays a crucial role in different platelet-related physiological and pathological processes. It signals through a tyrosine kinase-mediated pathway that is highly dependent on the positive feedback exerted by the platelet-derived secondary mediators, adenosine diphosphate (ADP) and thromboxane A (TXA). Here, we aimed to analyze the tyrosine phosphoproteome of platelets activated with the CLEC-2 agonist rhodocytin to identify relevant phosphorylated tyrosine residues (p-Tyr) and proteins involved in platelet activation downstream of this receptor.