Transcription factor FOXD1 and miRNA-204-5p play a major role in B4GALNT2 downregulation in colon cancer.

The β1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) which synthesizes the histo-blood group antigen Sd is highly expressed by normal colon, but it is dramatically down-regulated in colorectal cancer (CRC). High B4GALNT2 expression in CRC tissues is a marker of longer survival. The molecular bases of B4GALNT2 inhibition in CRC are largely obscure.

Comparison of HDR-brachytherapy and tomotherapy for the treatment of non-melanoma skin cancers of the head and neck.

Purpose: This study aims to investigate and compare High Dose Rate Brachytherapy (HDR-BT) with Helical Tomotherapy (HT) treatment plans. The focus is on small target volumes near radiation-sensitive organs in the ocular region, to evaluate the advantages of these techniques in treating skin cancer.

Methods: This retrospective observational analysis included patients who underwent skin cancer HDR-BT Freiburg flap treatment between 2019 and 2023.

Design and Evaluation of Azaspirocycles as RNA binders.

This study presents efficient synthetic pathways for preparing novel azaspirocycles. These methodologies involve functionalizing key bicyclic hydrazines with a substituent on one of their bridgehead carbon atoms. The desired spirocyclic cores were successfully obtained through double reductive amination reactions, intramolecular cyclizations, and cleavages of the N-N bond.

The impact of SARS-CoV-2 (COVID-19) pandemic on educational and professional growth of young Italian epileptologists: a survey of the Young Epilepsy Section-Italian chapter.

Objectives: In March 2020, the World Health Organization declared the coronavirus-related disease SARS-CoV-2 infection pandemic. Italy was one of the most affected countries and managed the emergency also by a health care reorganization.

Methods: The Education and Career Development Task Force of the Young Epilepsy Section-Italy (YES-I) designed a survey to assess the impact of the pandemic on the training and work of young epileptologists (< 40 years).

Challenges in transitioning from adolescent to Adult Mental Health Services for young adults with ADHD in Italy: an observational study.

Aims: Ensuring a successful transition to Adult Mental Health Services (AMHS) is fundamental for attention deficit/hyperactivity disorder (ADHD) patients to prevent adverse scenarios in adults (e.g., psychiatric disorders, substance or alcohol abuse).

Is tumour sequencing effective for the identification of germline pathogenic variant carriers?

Introduction: Tumour /2 sequencing has progressively increased along with the expanding indications for poly(ADP-ribose) polymerase inhibitors. In our study, we investigated the feasibility and outcomes of a workflow for the identification of germline carriers based on tumour sequencing results.

Methods: Between April 2020 and December 2022, tumour testing results from 2020 patients were reviewed.

The French Medicinal Chemistry Society-SCT, an Historical Member of EFMC.

The French Society of Medicinal Chemistry or " Société de Chimie Thérapeutique " (SCT) was founded in 1966. Since its inception, its mission has been to promote knowledge in the main fields of pharmaceutical research and development, in particular the research and validation of biological targets of therapeutic interest, the screening, design and optimization of drug candidates, chemical biology, medicinal chemistry, pharmacokinetics, metabolism and toxicity. Since 1964, the Society has organized an annual international congress (RICT), and later thematic days for young researchers and workshops on specific topics.

The Use of Free Weight Squats in Sports: A Narrative Review-Squatting Movements, Adaptation, and Sports Performance: Physiological.

Stone, MH, Hornsby, G, Mizuguchi, S, Sato, K, Gahreman, D, Duca, M, Carroll, K, Ramsey, MW, Stone, ME, and Haff, GG. The use of free weight squats in sports: a narrative review-squatting movements, adaptation, and sports performance: physiological. J Strength Cond Res 38(8): 1494-1508, 2024-The squat and its variants can provide numerous benefits including positively affecting sports performance and injury prevention, injury severity reduction, and rehabilitation.

Introduction to the themed collection on 'Targeting RNA with small molecules'.

Guest Editors Ruth Brenk, Peng Wu and Maria Duca introduce the themed collection on 'Targeting RNA with small molecules'.

Educational needs and career development of young epileptologists in Italy.

Objective: The Education and Career Task Force of the Young Epilepsy Section-Italy focuses on educational and career development needs of young Italian epileptologists. Two surveys were developed (pre- and post COVID-19 pandemic) in order to identify the needs of members of the Lega Italiana Contro l'Epilessia under 40 years of age.

Methods: The first was distributed during the 42nd National Congress (Rome, June 5-7, 2019); the second during the 45th National Congress (Padova, June 8-10, 2022) and subsequently by e-mail until July 9, 2022.

Immunological characterization of a long-lasting response in a patient with metastatic triple-negative breast cancer treated with PD-1 and LAG-3 blockade.

In patients with advanced triple-negative breast cancer (TNBC), translational research efforts are needed to improve the clinical efficacy of immunotherapy with checkpoint inhibitors. Here, we report on the immunological characterization of an exceptional, long-lasting, tumor complete response in a patient with metastatic TNBC treated with dual PD-1 and LAG-3 blockade within the phase I/II study CLAG525X2101C (NCT02460224) The pre-treatment tumor biopsy revealed the presence of a CD3 and CD8 cell infiltrate, with few PD1 cells, rare CD4 cells, and an absence of both NK cells and LAG3 expression. Conversely, tumor cells exhibited positive staining for the three primary LAG-3 ligands (HLA-DR, FGL-1, and galectin-3), while being negative for PD-L1.

Small molecule approaches to targeting RNA.

The development of innovative methodologies to identify RNA binders has attracted enormous attention in chemical biology and drug discovery. Although antibiotics targeting bacterial ribosomal RNA have been on the market for decades, the renewed interest in RNA targeting reflects the need to better understand complex intracellular processes involving RNA. In this context, small molecules are privileged tools used to explore the biological functions of RNA and to validate RNAs as therapeutic targets, and they eventually are to become new drugs.

DAG1 haploinsufficiency is associated with sporadic and familial isolated or pauci-symptomatic hyperCKemia.

DAG1 encodes for dystroglycan, a key component of the dystrophin-glycoprotein complex (DGC) with a pivotal role in skeletal muscle function and maintenance. Biallelic loss-of-function DAG1 variants cause severe muscular dystrophy and muscle-eye-brain disease. A possible contribution of DAG1 deficiency to milder muscular phenotypes has been suggested.

Refining the electroclinical spectrum of NPRL3-related epilepsy: A novel multiplex family and literature review.

Objective: NPRL3-related epilepsy (NRE) is an emerging condition set within the wide GATOR-1 spectrum with a particularly heterogeneous and elusive phenotypic expression. Here, we delineated the genotype-phenotype spectrum of NRE, reporting an illustrative familial case and reviewing pertinent literature.

Methods: Through exome sequencing (ES), we investigated a 12-year-old girl with recurrent focal motor seizures during sleep, suggestive of sleep-related hypermotor epilepsy (SHE), and a family history of epilepsy in siblings.

Molecular Tumor Board as a Clinical Tool for Converting Molecular Data Into Real-World Patient Care.

Purpose: The investigation of multiple molecular targets with next-generation sequencing (NGS) has entered clinical practice in oncology, yielding to a paradigm shift from the histology-centric approach to the mutational model for personalized treatment. Accordingly, most of the drugs recently approved in oncology are coupled to specific biomarkers. One potential tool for implementing the mutational model of precision oncology in daily practice is represented by the Molecular Tumor Board (MTB), a multidisciplinary team whereby molecular pathologists, biologists, bioinformaticians, geneticists, medical oncologists, and pharmacists cooperate to generate, interpret, and match molecular data with personalized treatments.

Synthesis of Bleomycin-Inspired RNA Ligands Targeting the Biogenesis of Oncogenic miRNAs.

Noncoding RNAs (ncRNAs) play pivotal roles in the regulation of gene expression and represent a promising target for the development of new therapeutic approaches. Among these ncRNAs, microRNAs (miRNAs or miRs) are involved in the regulation of gene expression, and their dysregulation has been linked to several diseases such as cancers. Indeed, oncogenic miRNAs are overexpressed in cancer cells, thus promoting tumorigenesis and maintenance of cancer stem cells that are resistant to chemotherapy and often responsible for therapeutic failure.

Impact of gender inequality on the educational and career development of young epileptologists in Italy: A survey of the Young Epilepsy Section - Italian chapter.

Objective: The Young Epilepsy Section-Italian chapter (YES-I) is the Italian section of the International League Against Epilepsy (ILAE)-YES. It was founded in 2019 with the aim of increasing the involvement of young epileptologists within scientific associations and facilitating their educational training. The Education and Career Task Force designed a survey on the impact of gender inequality on the educational and professional growth of young epileptologists.

De-Novo Design of pre-miR-21 Maturation Inhibitors: Synthesis and Activity Assessment.

Targeting RNA with small molecules is a major challenge of current medicinal chemistry, and the identification and design of original scaffolds able to selectively interact with an RNA target remains difficult. Various approaches have been developed based on classical medicinal chemistry strategies (fragment-based drug design, dynamic combinatorial chemistry, HTS or DNA-encoded libraries) as well as on advanced structural biology and biochemistry methodologies (such as X-ray, cryo-EM, NMR, or SHAPE). Here, we report the de novo design, synthesis, and biological evaluation of RNA ligands by using a straightforward and sustainable chemistry combined with molecular docking and biochemical and biophysical studies that allowed us to identify a novel pharmacophore for RNA binding.

Moyamoya Vasculopathy in Neurofibromatosis Type 1 Pediatric Patients: The Role of Rare Variants of .

Neurofibromatosis type 1 (NF1) is a neurocutaneous disorder caused by mutations in gene, coding for neurofibromin 1. NF1 can be associated with Moyamoya disease (MMD), and this association, typical of paediatric patients, is referred to as Moyamoya syndrome (MMS). MMD is a cerebral arteriopathy characterized by the occlusion of intracranial arteries and collateral vessel formation, which increase the risk of ischemic and hemorrhagic events.

EFMC: Trends in Medicinal Chemistry and Chemical Biology.

Ground-breaking research in disease biology and continuous efforts in method development have uncovered a range of potential new drug targets. Increasingly, the drug discovery process is informed by technologies involving chemical probes as tools. Applications for chemical probes comprise target identification and assessment, as well as the qualification of small molecules as chemical starting points and drug candidates.

SARS-CoV-2 viral entry and replication is impaired in Cystic Fibrosis airways due to ACE2 downregulation.

As an inherited disorder characterized by severe pulmonary disease, cystic fibrosis could be considered a comorbidity for coronavirus disease 2019. Instead, current clinical evidence seems to be heading in the opposite direction. To clarify whether host factors expressed by the Cystic Fibrosis epithelia may influence coronavirus disease 2019 progression, here we describe the expression of SARS-CoV-2 receptors in primary airway epithelial cells.