Imagine, Discover, Inspire: Proceedings of the 4th International Conference of the Trisomy 21 Research Society.

Down syndrome (DS) or trisomy 21 (T21) is present in a significant number of children and adults around the world and is associated with cognitive and medical challenges. Through research, the T21 Research Society (T21RS), established in 2014, unites a worldwide community dedicated to understanding the impact of T21 on biological systems and improving the quality of life of people with DS across the lifespan. T21RS hosts an international conference every two years to support collaboration, dissemination, and information sharing for this goal.

Adaptive and Behavioral Profiles in Down Syndrome and Co-Occurring Autism Spectrum Disorder: A Case-Control Study.

Down syndrome (DS) is the most frequent genetic cause of intellectual disability (ID). Individuals with DS exhibit an elevated risk of other neurodevelopmental disorders, including autism spectrum disorder (ASD). The primary objective of this study was to explore the clinical characteristics of co-occurring ASD in children and adolescents with DS using a case-control approach.

Unveiling the Mechanism of Lurbinectedin's Action and Its Potential in Combination Therapies in Small Cell Lung Cancer.

Lurbinectedin is a selective inhibitor of oncogenic transcription approved for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. Preclinical data provide evidence for lurbinectedin exerting its actions in a unique manner that involves oncogenic transcription inhibition, DNA damage, reshaping of the tumor microenvironment, and inducing anticancer immunity. Understanding the mechanism of action (MoA) has facilitated the rational combination of lurbinectedin and anticancer therapies with complementary modes of action, in order to obtain synergistic effects that could potentially lead to improved efficacy.

Prospective memory in the developmental age: a systematic review to synthesize the evaluation tools and the main cognitive functions involved.

Prospective memory (PM) is the ability to remember and realize one's intentions in the future; therefore, it is crucial for the daily functioning of children and adolescents and their ability to become independent from caregivers. PM errors can have repercussions during childhood, such as influencing school performance and social relationships. The aim of this systematic review was to synthesize studies analysing PM in children and adolescents (age range: 0-16 years) following PRISMA guidelines.

Lipid droplets and small extracellular vesicles: More than two independent entities.

Despite increasing knowledge about small extracellular vesicle (sEV) composition and functions in cell-cell communication, the mechanism behind their biogenesis remains unclear. Here, we reveal for the first time that sEV biogenesis and release into the microenvironment are tightly connected with another important organelle, Lipid Droplets (LDs). The correlation was observed in several human cancer cell lines as well as patient-derived colorectal cancer stem cells (CR-CSCs).

The role of social motivation in sharing and fairness: insights from Williams syndrome.

Background: Sharing and fairness are important prosocial behaviors that help us navigate the social world. However, little is known about how and whether individuals with Williams Syndrome (WS) engage in these behaviors. The unique phenotype of individuals with WS, consisting of high social motivation and limited social cognition, can also offer insight into the role of social motivation in sharing and fairness when compared to typically developing (TD) individuals.

Characterizing thrombus adhesion strength on common cardiovascular device materials.

Thrombus formation in blood-contacting medical devices is a major concern in the medical device industry, limiting the clinical efficacy of these devices. Further, a locally formed clot within the device has the potential to detach from the surface, posing a risk of embolization. Clot embolization from blood-contacting cardiovascular devices can result in serious complications like acute ischemic stroke and myocardial infarction.

A hyper-viscoelastic uniaxial characterization of collagenous embolus analogs in acute ischemic stroke.

Purpose: Acute ischemic stroke is a leading cause of death and morbidity worldwide. Despite advances in medical technology, nearly 30% of strokes result in incomplete vessel recanalization. Recent studies have demonstrated that clot composition correlates with success rates of mechanical thrombectomy procedures.

Characterising repetitive behaviours in children and adolescents with Down syndrome.

Background: Individuals with intellectual disability, including people with Down syndrome (DS), often exhibit restricted and repetitive behaviours (RRBs). However, RRBs have not been deeply characterised in children and adolescents with DS.

Method: The study encompassed a cohort of 151 participants aged 4 to 18 years with DS.

Why do individuals with Williams syndrome or Down syndrome fail the Weather Prediction Task?

Williams syndrome (WS) and Down syndrome (DS) are two neurodevelopmental disorders with distinct genetic origins characterized by mild to moderate intellectual disability. Individuals with WS or DS exhibit impaired hippocampus-dependent place learning and enhanced striatum-dependent spatial response learning. Here, we used the Weather Prediction Task (WPT), which can be solved using hippocampus- or striatum-dependent learning strategies, to determine whether individuals with WS or DS exhibit similar profiles outside the spatial domain.

T-cell immunity against Severe Acute Respiratory Syndrome Coronavirus 2 proteins in patients with type 1 diabetes.

Aims: Individuals with type 1 diabetes (T1D) do not appear to have an elevated risk of severe Coronavirus Disease 19 (COVID-19). Pre-existing immune reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in unexposed individuals may serve as a protective factor. Hence, our study was designed to evaluate the existence of T cells with reactivity against SARS-CoV-2 antigens in unexposed patients with T1D.

New fracture patterns distal epiphysis femur in youth: Update of current classification.

Intro: Distal growth core fractures of the femur are the third most common fracture in patients older than 10 years. These fractures result from high-energy trauma and have a high risk of evolving into growth disorders. The classification most used to describe these types of fractures is that described by Salter and Harris.

Celiac disease in children and adolescents with Down syndrome: behavioural, adaptive and sleep profiles.

Background: Individuals with Down syndrome (DS) exhibit higher risk for celiac disease (CD) than general population. Although literature suggests CD could be associated with behavioural problems in both paediatric and adult age, such association has been poorly explored in children and adolescents DS. Therefore, the current study aimed to investigate differences in emotional/behavioural difficulties, adaptive skills and sleep problems between children with DS with and without CD.

The biological variation of serum 1,25-dihydroxyvitamin D and parathyroid hormone, and plasma fibroblast growth factor 23 in healthy individuals.

Background And Aims: Measuring 1,25-dihydroxyvitamin D (1,25(OH)D), parathyroid hormone 1-84 (PTH 1-84) and intact FGF23 (iFGF23) is crucial for diagnosing a variety of diseases affecting bone and mineral homeostasis. Biological variability (BV) data are important for defining analytical quality specifications (APS), the usefulness of reference intervals, and the significance of variations in serial measurements in the same subject. The aim of this study was to pioneer the provision of BV estimates for 1,25(OH)2D and to improve existing BV estimates for iFGF23 and PTH 1-84.

Transcranial Direct Current Stimulation in neurogenetic syndromes: new treatment perspectives for Down syndrome?

This perspective review aims to explore the potential neurobiological mechanisms involved in the application of transcranial Direct Current Stimulation (tDCS) for Down syndrome (DS), the leading cause of genetically-based intellectual disability. The neural mechanisms underlying tDCS interventions in genetic disorders, typically characterized by cognitive deficits, are grounded in the concept of brain plasticity. We initially present the neurobiological and functional effects elicited by tDCS applications in enhancing neuroplasticity and in regulating the excitatory/inhibitory balance, both associated with cognitive improvement in the general population.

Catatonia Induced by First-Time Use of Synthetic Cannabinoids: A Case Report.

We present the case of a 32-year-old woman who developed life-threatening catatonia in the setting of synthetic cannabis use. She was treated with high doses of lorazepam (up to 26 mg) and eventually transferred to receive electroconvulsive therapy (ECT). Synthetic cannabis poses a unique risk as it is widely available, difficult to regulate, and with adverse effects that are not well understood due to the presence of ever-changing chemical compounds.

Prostaglandin pathway activation in the diatom Skeletonema marinoi under grazer pressure.

Prostaglandins (Pgs) are eicosanoid lipid mediators detected in all vertebrates, in some marine invertebrates, macroalgae and in diatoms, a class of eukaryotic microalgae composing the phytoplankton. The enzymes involved in the Pgs pathway were found to be differentially expressed in two strains of the diatom Skeletonema marinoi, named FE7 and FE60, already known to produce different levels of oxylipins, a class of secondary metabolites involved in the defence of diatoms against copepod predation, with FE7 being higher producer than FE60. In the present study we investigated the response of genes involved in the production of oxylipins and Pgs, evaluating their expression after the exposure to the copepod Temora stylifera.

Emotional and behavioral features associated with subclinical hypothyroidism in children and adolescents with Down syndrome.

Background: Subclinical hypothyroidism (SH) is particularly frequent in individuals with Down syndrome (DS). Despite the amount of evidence suggesting SH is associated with psychopathological symptoms and sleep problems in general population, poor is known about the emotional and behavioral features associated with SH in children with DS.

Objective: The first aim of the current study was to investigate differences in emotional and behavioral profiles between a group of children with DS exhibiting co-occurring SH and a group of age and BMI-matched children with DS without co-occurring SH.

The spike-specific TCRβ repertoire shows distinct features in unvaccinated or vaccinated patients with SARS-CoV-2 infection.

Background: The evolving variants of SARS-CoV-2 may escape immunity from prior infections or vaccinations. It's vital to understand how immunity adapts to these changes. Both infection and mRNA vaccination induce T cells that target the Spike protein.

Diatom-Bacteria Interactions in the Marine Environment: Complexity, Heterogeneity, and Potential for Biotechnological Applications.

Diatom-bacteria interactions evolved during more than 200 million years of coexistence in the same environment. In this time frame, they established complex and heterogeneous cohorts and consortia, creating networks of multiple cell-to-cell mutualistic or antagonistic interactions for nutrient exchanges, communication, and defence. The most diffused type of interaction between diatoms and bacteria is based on a win-win relationship in which bacteria benefit from the organic matter and nutrients released by diatoms, while these last rely on bacteria for the supply of nutrients they are not able to produce, such as vitamins and nitrogen.

Analysis of Health-Related Quality of Life Reporting in Phase III RCTs of Advanced Genitourinary Tumors.

Background: As recommended in the European Society for Medical Oncology (ESMO) guidelines, assessment of health-related quality of life (HRQoL) should be a relevant endpoint in randomized controlled trials (RCTs) testing new anticancer therapies. However, previous publications by our group and others revealed a frequent underestimation and underreporting of HRQoL results in publication of RCTs in oncology. Herein, we systematically reviewed HRQoL reporting in RCTs testing new treatments in advanced prostate, kidney and urothelial cancers and published between 2010 and 2022.

Iron affects the sphere-forming ability of ovarian cancer cells in non-adherent culture conditions.

Detachment from the extracellular matrix (ECM) is the first step of the metastatic cascade. It is a regulated process involving interaction between tumor cells and tumor microenvironment (TME). Iron is a key micronutrient within the TME.