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.

Comprehensive histopathological analysis of gastric cancer in European and Latin America populations reveals differences in PDL1, HER2, p53 and MUC6 expression.

Introduction: Gastric cancer (GC) burden is currently evolving with regional differences associated with complex behavioural, environmental, and genetic risk factors. The LEGACy study is a Horizon 2020-funded multi-institutional research project conducted prospectively to provide comprehensive data on the tumour biological characteristics of gastroesophageal cancer from European and LATAM countries.

Material And Methods: Treatment-naïve advanced gastroesophageal adenocarcinoma patients were prospectively recruited in seven European and LATAM countries.

Biologically-targeted discovery-replication scan identifies G×G interaction in relation to risk of Barrett's esophagus and esophageal adenocarcinoma.

Inherited genetics represents an important contributor to risk of esophageal adenocarcinoma (EAC), and its precursor Barrett's esophagus (BE). Genome-wide association studies have identified ∼30 susceptibility variants for BE/EAC, yet genetic interactions remain unexamined. To address challenges in large-scale G×G scans, we combined knowledge-guided filtering and machine learning approaches, focusing on genes with (A) known/plausible links to BE/EAC pathogenesis (n=493) or (B) prior evidence of biological interactions (n=4,196).

ZAR1/2-Regulated Epigenetic Modifications are Essential for Age-Associated Oocyte Quality Maintenance and Zygotic Activation.

The developmental competence and epigenetic progression of oocytes gradually become dysregulated with increasing maternal age. However, the mechanisms underlying age-related epigenetic regulation in oocytes remain poorly understood. Zygote arrest proteins 1 and 2 (ZAR1/2) are two maternal factors with partially redundant roles in maintaining oocyte quality, mainly known by regulating mRNA stability.

A Novel RAGE Modulator Induces Soluble RAGE to Reduce BACE1 Expression in Alzheimer's Disease.

β-secretase (BACE1) is instrumental in amyloid-β (Aβ) production, with overexpression noted in Alzheimer's disease (AD) neuropathology. The interaction of Aβ with the receptor for advanced glycation endproducts (RAGE) facilitates cerebral uptake of Aβ and exacerbates its neurotoxicity and neuroinflammation, further augmenting BACE1 expression. Given the limitations of previous BACE1 inhibition efforts, the study explores reducing BACE1 expression to mitigate AD pathology.

High-Throughput Formation of Pre-Vascularized hiPSC-Derived Hepatobiliary Organoids on a Chip via Nonparenchymal Cell Grafting.

Liver organoids have been increasingly adopted as a critical in vitro model to study liver development and diseases. However, the pre-vascularization of liver organoids without affecting liver parenchymal specification remains a long-lasting challenge, which is essential for their application in regenerative medicine. Here, the large-scale formation of pre-vascularized human hepatobiliary organoids (vhHBOs) is presented without affecting liver epithelial specification via a novel strategy, namely nonparenchymal cell grafting (NCG).

The sarcoma ring trial: a case-based analysis of inter-center agreement across 21 German-speaking sarcoma centers.

Purpose: The management of soft tissue sarcoma (STS) at reference centers with specialized multidisciplinary tumor boards (MTB) improves patient survival. The German Cancer Society (DKG) certifies sarcoma centers in German-speaking countries, promoting high standards of care. This study investigated the variability in treatment recommendations for localized STS across different German-speaking tertiary sarcoma centers.

In-vitro and in-vivo assessment of biocompatibility and efficacy of ostrich eggshell membrane combined with platelet-rich plasma in Achilles tendon regeneration.

Tendon injuries present significant medical, social, and economic challenges globally. Despite advancements in tendon injury repair techniques, outcomes remain suboptimal due to inferior tissue quality and functionality. Tissue engineering offers a promising avenue for tendon regeneration, with biocompatible scaffolds playing a crucial role.

A word of caution in the functional monitoring of patients after rectal cancer surgery: a multicentre observational study.

Background: Patients with rectal cancer often experience adverse effects on urinary, sexual, and digestive functions. Despite recognised impacts and available treatments, they are not fully integrated into follow-up protocols, thereby hindering appropriate interventions. The aim of the study was to discern the activities conducted in our routine clinical practice outside of clinical trials.

Genetic landscape in undiagnosed patients with syndromic hearing loss revealed by whole exome sequencing and phenotype similarity search.

There are hundreds of rare syndromic diseases involving hearing loss, many of which are not targeted for clinical genetic testing. We systematically explored the genetic causes of undiagnosed syndromic hearing loss using a combination of whole exome sequencing (WES) and a phenotype similarity search system called PubCaseFinder. Fifty-five families with syndromic hearing loss of unknown cause were analyzed using WES after prescreening of several deafness genes depending on patient clinical features.

Data from the All of Us research program reinforces existence of activity inequality.

Large-scale and detailed analyses of activity in the United States (US) remain limited. In this work, we leveraged the comprehensive wearable, demographic, and survey data from the All of Us Research Program, the largest and most diverse population health study in the US to date, to apply and extend the previous global findings on activity inequality within the context of the US. We found that daily steps differed by sex at birth, age, body characteristics, geography, and built environment.

Ciliary muscle traction during accommodation is able to induce optic nerve head deformation.

Objectives: To use finite element (FE) modeling and in vivo optical coherence tomography (OCT) imaging to explore the effect of ciliary muscle traction on optic nerve head (ONH) deformation during accommodation.

Methods: We developed a FE model to mimic the ciliary muscle traction during accommodation, and varied the stiffness of the sclera, choroid, Bruch's membrane (BM), prelaminar neural tissue and lamina cribrosa (LC) to assess their effects on accommodation-induced ONH strains. To validate the FE model, OCT images of the right eyes' ONHs from 20 subjects (25 ± 1.

Harmonious ageing: a narrative review of music therapy in the biomedical literature.

Purpose: As the global population of older adults rises, the United Nations Decade of Healthy Ageing (2021-2030) advocates for disease prevention, management, and enhancing overall wellbeing in older adults. We reviewed the MEDLINE literature under the MeSH term "music therapy" (MT), for its role in promoting healthy ageing.

Methods: A systematic search of the MEDLINE biomedical database (Ovid) was conducted using "MT" and "Ageing" as keywords, retrieving relevant full-text studies in English.

A disintegrin and metallopeptidase domain (ADAM) 12, ADAM 17 mRNA and ADAM10 protein hold potential as biomarkers for detection of early gastric cancer.

No biomarker can effectively screen for early gastric cancer (EGC). Players in the A disintegrin and metalloproteinase (ADAM)-natural killer group 2 member D (NKG2D) receptor axis may have a role for that. As a proof-of-concept pilot study, the expression of ADAM8, ADAM9, ADAM10, ADAM12, ADAM17, and major histocompatibility complex (MHC) class I chain-related sequence A (MICA), a ligand for NKG2D, in gastric cancer was investigated in silico using The Cancer Genome Atlas (TCGA) database.

Prevalence of anhedonia in women with deep endometriosis.

Anhedonia, characterized by diminished motivation and pleasure sensitivity, is increasingly recognized as prevalent among patients with chronic pain. Deep Endometriosis (DE), the most severe endophenotype of the disease, is commonly presented with chronic pelvic pain. This cross-sectional study reports, for the first time, the prevalence of anhedonia in a sample comprised by 212 premenopausal women with suspected DE referred to a tertiary hospital.

Insulin signaling regulates R2 retrotransposon expression to orchestrate transgenerational rDNA copy number maintenance.

Preserving a large number of essential yet highly unstable ribosomal DNA (rDNA) repeats is critical for the germline to perpetuate the genome through generations. Spontaneous rDNA loss must be countered by rDNA copy number (CN) expansion. Germline rDNA CN expansion is best understood in Drosophila melanogaster, which relies on unequal sister chromatid exchange (USCE) initiated by DNA breaks at rDNA.

Unveiling nature's antidiabetic potential in Berberis orthobotrys seeds for alloxan-induced diabetic rats.

To illustrate the anti-diabetic properties of Berberis orthobotrys seeds was the aim of the current study. After a series of experiments, two doses of aqueous methanolic extract of the seeds were selected i.e.

Unsupervised self-organising map classification of Raman spectra from prostate cell lines uncovers substratified prostate cancer disease states.

Prostate cancer is a disease which poses an interesting clinical question: Should it be treated? Only a small subset of prostate cancers are aggressive and require removal and treatment to prevent metastatic spread. However, conventional diagnostics remain challenged to risk-stratify such patients; hence, new methods of approach to biomolecularly sub-classify the disease are needed. Here we use an unsupervised self-organising map approach to analyse live-cell Raman spectroscopy data obtained from prostate cell-lines; our aim is to exemplify this method to sub-stratify, at the single-cell-level, the cancer disease state using high-dimensional datasets with minimal preprocessing.

Effect of intramuscular treatment with different iron dextran dosages and non-inferiority study to gleptoferron.

Background: Prevention of iron deficiency in suckling piglets by intramuscular injection of a standardized amount of iron dextran or gleptoferron in the first days of life can lead to over- or underdosage with respective health risks. Currently, combined iron products containing an active substance against coccidia are also used on farms. When using a combination product targeting two diseases, an adjustment of the necessary amount of iron to prevent anaemia in the frame of a farm-specific treatment protocol is not possible.

Preclinical and clinical study on type 3 metabotropic glutamate receptors in Parkinson's disease.

Metabotropic glutamate (mGlu) receptors are candidate drug targets for therapeutic intervention in Parkinson's disease (PD). Here we focused on mGlu3, a receptor subtype involved in synaptic regulation and neuroinflammation. mGlu3 mice showed an enhanced nigro-striatal damage and microglial activation in response to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).

Uterus didelphys: the first case report on molecular profiling of endometrial tissue from both uterine cavities.

Background: A didelphic uterus represents a unique and infrequent congenital condition in which a woman possesses two distinct uteri, each with its own cervix. This anomaly arises due to partial or incomplete merging of the Müllerian ducts during the developmental stages in the womb. Accounting for uterine malformations, a didelphic uterus is a relatively rare condition, affecting approximately 0.

Current status and innovative developments of CAR-T-cell therapy for the treatment of breast cancer.

Breast cancer will overtake all other cancers in terms of diagnoses in 2024. Breast cancer counts highest among women in terms of cancer incidence and death rates. Innovative treatment approaches are desperately needed because treatment resistance brought on by current clinical drugs impedes therapeutic efficacy.

D-ribose-5-phosphate inactivates YAP and functions as a metabolic checkpoint.

Background: Targeting glucose uptake by glucose transporter (GLUT) inhibitors is a therapeutic opportunity, but efforts on GLUT inhibitors have not been successful in the clinic and the underlying mechanism remains unclear. We aim to identify the key metabolic changes responsible for cancer cell survival from glucose limitation and elucidate its mechanism.

Methods: The level of phosphorylated YAP was analyzed with Western blotting and Phos-tag immunoblotting.

Effect of porcine collagen matrix versus rotated pedicle palatal connective tissue flap on the soft-tissue closure after the immediate posterior implantation: study protocol for a randomised controlled trial.

Introduction: Soft-tissue defect is commonly seen in immediate maxillary posterior implantation because of tooth extraction wound and tension from bone graft. Bone graft materials exposure has a significant detrimental influence on bone augmentation. However, previous studies lack sufficient evidence to guide wound closure after immediate posterior implantation.

Influencing basic behavioral mechanisms of action while targeting daily walking in sedentary adults at risk for cardiovascular disease: randomised factorial design protocol.

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality worldwide, though it may be prevented by increasing physical activity (PA). When behaviour change techniques (BCTs) are bundled together, they increase PA, though which individual BCTs increase PA (and the behavioural mechanism of action (MoA) responsible for said increase) have not been studied. The aim of this study is to conduct a randomised factorial experiment to determine which of four BCTs significantly engage the proposed MoA-self-efficacy for PA-in adults at risk for CVD.