Unveiling the hidden interactome of CRBN molecular glues with chemoproteomics.

Targeted protein degradation and induced proximity refer to strategies that leverage the recruitment of proteins to facilitate their modification, regulation or degradation. As prospective design of glues remains challenging, unbiased discovery methods are needed to unveil hidden chemical targets. Here we establish a high throughput affinity purification mass spectrometry workflow in cell lysates for the unbiased identification of molecular glue targets.

Persistence, effectiveness, and tolerability of anti-calcitonin gene-related peptide monoclonal antibodies in patients with chronic migraine.

Objective: To evaluate, in patients with chronic migraine (CM) in real-world conditions, the persistence, effectiveness, and tolerability of erenumab, fremanezumab, and galcanezumab anti-calcitonin gene-related peptide (anti-CGRP) monoclonal antibodies (mAbs) and the persistence and effects of switching.

Background: Anti-CGRP mAbs represent a novel therapeutic approach to the management of CM; however, real-world data on persistence, effectiveness, and tolerability, especially after switching, are scarce.

Methods: This was a retrospective observational cohort study including all patients with CM treated with erenumab, fremanezumab, and/or galcanezumab in a tertiary hospital between January 2019 and December 2022.

Diagnostic and Therapeutic Approaches for Heart Failure in Long-Term Survivors of Childhood Cancer.

The improvement in survival rates in pediatric malignancies has led to an increase in the number of cancer survivors who are at risk of developing cardiotoxicity and heart failure. Cardiac dysfunction in these patients can occur asymptomatically, and the diagnosis in a symptomatic phase is associated with reduced treatment response and worse prognosis. For this reason, it is essential to establish protocols to follow up on these patients and identify those at risk of cardiotoxicity in order to start early and effective therapies.

Complete vs. incomplete percutaneous revascularization in patients with chronic total coronary artery occlusion.

Introduction: There is current controversy surrounding the benefits of percutaneous coronary intervention (PCI) of chronic total coronary occlusions (CTO). We aimed to evaluate the impact of complete percutaneous revascularization on major adverse cardiovascular events (MACE) in patients with CTO.

Methods: A retrospective observational study was conducted of consecutive patients referred for invasive coronary angiography at a single center between January 2018 and December 2019 and at least a CTO.

Correction: SARS-CoV-2 and endemic coronaviruses: Comparing symptom presentation and severity of symptomatic illness among Nicaraguan children.

[This corrects the article DOI: 10.1371/journal.pgph.

Targeted Degradation of CDK9 Potently Disrupts the MYC Transcriptional Network.

Unlabelled: Cyclin-dependent kinase 9 (CDK9) coordinates signaling events that regulate RNA polymerase II (Pol II) pause-release states. It is an important co-factor for transcription factors, such as MYC, that drive aberrant cell proliferation when their expression is deregulated. CDK9 modulation offers an approach for attenuating dysregulation in such transcriptional programs.

Evaluating Treatments for the Protection of Grapevine Pruning Wounds from Natural Infection by Trunk Disease Fungi.

Infection of grapevines by fungal pathogens causing grapevine trunk diseases (GTDs) primarily arises from annual pruning wounds made during the dormant season. While various studies have showcased the efficacy of products in shielding pruning wounds against GTD infections, most of these investigations hinge on artificial pathogen inoculations, which may not faithfully mirror real field conditions. This study aimed to evaluate and compare the efficacy of various liquid formulation fungicides (pyraclostrobin + boscalid) and paste treatments, as well as biological control agents (BCA: SC1, I-1237, and ICC012 + ICC080), for their potential to prevent natural infection of grapevine pruning wounds by trunk disease fungi in two field trials located in Samaniego (Northern Spain) and Madiran (Southern France) over three growing seasons.

Humoral Correlates of Protection Against Influenza A/H3N2 Virus Infection.

Background: Influenza virus remains a threat to human health, but gaps remain in our knowledge of the humoral correlates of protection against influenza virus A/H3N2, limiting our ability to generate effective, broadly protective vaccines. The role of antibodies against the hemagglutinin (HA) stalk, a highly conserved but immunologically subdominant region, has not been established for influenza virus A/H3N2.

Methods: Household transmission studies were conducted in Managua, Nicaragua, across 3 influenza seasons.

DrugMap: A quantitative pan-cancer analysis of cysteine ligandability.

Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors for a wide range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed "DrugMap," an atlas of cysteine ligandability compiled across 416 cancer cell lines.

Longitudinal analysis of post-acute chikungunya-associated arthralgia in children and adults: A prospective cohort study in Managua, Nicaragua (2014-2018).

Chikungunya can result in debilitating arthralgia, often presenting as acute, self-limited pain, but occasionally manifesting chronically. Little is known about differences in chikungunya-associated arthralgia comparing children to adults over time. To characterize long-term chikungunya-associated arthralgia, we recruited 770 patients (105 0-4 years old [y/o], 200 5-9 y/o, 307 10-15 y/o, and 158 16+ y/o) with symptomatic chikungunya virus infections in Managua, Nicaragua, during two consecutive chikungunya epidemics (2014-2015).

Exploration of bromodomain ligand-linker conjugation sites for efficient CBP/p300 heterobifunctional degrader activity.

Synthesis of proteolysis targeting chimeras (PROTACs) involves conjugation of an E3 ligase binding ligand to a ligand targeting a protein of interest via a rigid or flexible chemical linker. The choice of linker conjugation site on these ligands can be informed by structural analysis of ligand-target binding modes, the feasibility of synthetic procedures to access specific sites, and computational modeling of predicted ternary complex formations. Small molecules that target bromodomains - epigenetic readers of lysine acetylation - typically offer several potential options for linker conjugation sites.

Dengue severity by serotype and immune status in 19 years of pediatric clinical studies in Nicaragua.

Background: Dengue virus, a major global health threat, consists of four serotypes (DENV1-4) that cause a range of clinical manifestations from mild to severe and potentially fatal disease.

Methods: This study, based on 19 years of data from the Pediatric Dengue Cohort Study and Pediatric Dengue Hospital-based Study in Managua, Nicaragua, investigates the relationship of serotype and immune status with dengue severity. Dengue cases were confirmed by molecular, serological, and/or virological methods, and sudy participants 6 months to 17 years old were followed during their hospital stay or as ambulatory patients.

Very long-term follow-up after aortic stenting for coarctation of the aorta.

Introduction And Objectives: Stent implantation is the preferred treatment in older children and adults with aortic coarctation (CoA). We aimed to determine the incidence of very late events after CoA stenting.

Methods: We analyzed a cohort of CoA patients who underwent stent implantation at our center between 1993 and 2018.

Effects of boosting and waning in highly exposed populations on dengue epidemic dynamics.

Sequential infection with multiple dengue virus (DENV) serotypes is thought to induce enduring protection against dengue disease. However, long-term antibody waning has been observed after repeated DENV infection. Here, we provide evidence that highly immune Nicaraguan children and adults ( = 4478) experience boosting and waning of antibodies during and after major Zika and dengue epidemics.

DrugMap: A quantitative pan-cancer analysis of cysteine ligandability.

Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors of a wide-range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed , an atlas of cysteine ligandability compiled across 416 cancer cell lines.

Right Ventricular Function in Long-Term Survivors of Childhood Acute Lymphoblastic Leukemia: From the CTOXALL Study.

There are limited data regarding right ventricle (RV) impairment in long-term survivors of childhood acute lymphoblastic leukemia (CLS). The aim of this study was to assess RV function in these patients using echocardiographic conventional measurements and automated RV strain. Echocardiographic recordings of 90 CLS and 58 healthy siblings from the CTOXALL cohort were analyzed.

CTO and Bifurcation Lesions: An Expert Consensus From the European Bifurcation Club and EuroCTO Club.

Knowledge in the field of bifurcation lesions and chronic total occlusions (CTOs) has progressively improved over the past 20 years. Therefore, the European Bifurcation Club and the EuroCTO Club have decided to write a joint consensus statement to share general knowledge and practical approaches in this complex field. When percutaneously treating CTOs, bifurcation lesions with relevant side branches (SBs) are found in approximately one-third of cases (35% at the proximal cap, 38% at the distal cap, and 27% within the CTO body).

Spatial aggregation patterns in four mistletoe species: ecological and environmental determinants.

Plant spatial distribution is an important topic in ecology as it determines species coexistence and biodiversity dynamics. Usually, plants show clustered distributions in nature. Mistletoes are a good example of aggregated distributions, as they form dense aggregations due to several factors (availability of competent hosts, seed dispersal vectors, microclimate conditions).

Myocardial revascularization failure among patients requiring cardiac catheterization and secondary revascularization in contemporary clinical practice: Results of the REVASEC multicenter registry.

Background: Myocardial revascularization failure (MRF) and Secondary revascularization (SR) are contemporary interventional cardiology challenges.

Aim: To investigate the characteristics, management, and prognosis of patients with myocardial revascularization failure (MRF) and need for secondary revascularization (SR) in contemporary practice.

Methods: The REVASEC study is a prospective registry (NCT03349385), which recruited patients with prior revascularization referred for coronary angiography at 19 centers.