A Novel Large Duplication on the X Chromosome as a Cause of Familial Generalized Dystonia: A Case Report.

Chromosomal aberrations are rare but known causes of movement disorders, presenting with broad phenotypes in which dystonia may be predominant. During the investigation of such cases, chromosomal studies are not often considered as a first approach. In this article, the authors describe a family affected by a generalized form of dystonia, evolving from a focal phenotype, for which a new X chromosome large duplication was found to be the likely causative, therefore highlighting the role of such studies when facing complex movement disorders.

A comparative study of two data-driven modeling approaches to predict drug release from ER matrix tablets.

The pharmaceutical industry is striving to develop innovative and promising tools, increasingly embracing new data-driven approaches, to understand, improve and accelerate the drug product development process. While extended release (ER) oral formulations offer a number of advantages, including maintenance of therapeutic drug levels, a reduction in dosing frequency, and minimization of side effects, achieving consistent drug release profiles remains a significant challenge. As a critical attribute for drug absorption into systemic circulation, in vitro dissolution testing represents a time-consuming and complex method for the evaluation of such formulations.

Adaptation and validation of a tool for the quality assessment of genetic counseling in Brazil: perspectives from clinical geneticists.

In 2018, Portuguese researchers proposed the "Tool for Quality Assessment of Genetic Counseling," a 5-point Likert scale comprising 50 items across five dimensions, designed to assess genetic counseling from the professional's perspective. This descriptive, cross-sectional study aimed to adapt this tool to Brazilian Portuguese, validate it among Brazilian clinical geneticists, and conduct a preliminary assessment of the quality of genetic counseling in Brazil. The adaptation process involved expert-driven content validation and calculation of the Content Validity Index (CVI) to ensure equivalence between the original and adapted versions.

Quality of life and functional outcomes in patients with locally advanced rectal cancer receiving total neoadjuvant therapy versus concurrent chemoradiotherapy: An analysis of the XXX trial.

Objective: To explore differences in the effects of total neoadjuvant therapy (TNT) and preoperative concurrent chemoradiotherapy (CRT) on quality of life and functional outcomes in patients with locally advanced rectal cancer.

Methods: In the study, 591 patients with distal or middle-third, clinical primary tumor stage cT3-4 and/or regional lymph node-positive rectal cancer were randomly assigned (1:1) to receive short-term radiotherapy (25 Gy in five fractions) followed by 4 cycles of CAPOX (TNT group, n=297) or standard concurrent chemoradiotherapy (50 Gy in 25 fractions concurrently with oral capecitabine) (CRT group, n=294) before surgery. After a 6-year follow-up, the surviving patients were sent surveys, including the EORTC QLQ-C30, EORTC QLQ-CR29, and Wexner incontinence score questionnaires.

Tetraspanins CD63 and CD81 as potential prognostic biomarkers in breast cancer.

Exosome markers, CD63 and CD81, belong to the tetraspanin family and are expressed in solid tumors. It has been reported that these tetraspanin family members are prognostic factors in some cancers. However, the expression of CD63 and CD81 in pathological breast cancer specimens has not been reported.

Biological and environmental degradation of two-dimensional materials.

As the use of two-dimensional materials continues to grow, so too does the need to understand the environmental and biological impact of such materials. Degradation is a critical step in the life cycle of any material, but the majority of such knowledge is obtained from test tube and in vitro studies. Therefore, there remains a gap in understanding the degradability of two-dimensional materials in complex systems (in vivo) and in different ambient environments.

Fungi, immunosenescence and cancer.

Fungal microbes are a small but immunoreactive component of the human microbiome, which may influence cancer development, progression and therapeutic response. Immunosenescence is a process of immune dysfunction that occurs with aging, including lymphoid organ remodeling, contributing to alterations in the immune system in the elderly, which plays a critical role in many aspects of cancer. There is evidence for the interactions between fungi and immunosenescence in potentially regulating cancer progression and remodeling the tumor microenvironment (TME).

N88S seipin-related seipinopathy is a lipidopathy associated with loss of iron homeostasis.

Background: Seipin is a protein encoded by the BSCL2 gene in humans and SEI1 gene in yeast, forming an Endoplasmic Reticulum (ER)-bound homo-oligomer. This oligomer is crucial in targeting ER-lipid droplet (LD) contact sites, facilitating the delivery of triacylglycerol (TG) to nascent LDs. Mutations in BSCL2, particularly N88S and S90L, lead to seipinopathies, which correspond to a cohort of motor neuron diseases (MNDs) characterized by the accumulation of misfolded N88S seipin into inclusion bodies (IBs) and cellular dysfunctions.

Toward Resolving Heterogeneous Mixtures of Nanocarriers in Drug Delivery Systems through Light Scattering and Machine Learning.

Nanocarriers (NCs) have emerged as a revolutionary approach in targeted drug delivery, promising to enhance drug efficacy and reduce toxicity through precise targeting and controlled release mechanisms. Despite their potential, the clinical adoption of NCs is hindered by challenges in their physicochemical characterization, essential for ensuring drug safety, efficacy, and quality control. Traditional characterization methods, such as dynamic light scattering and nanoparticle tracking analysis, offer limited insights, primarily focusing on particle size and concentration, while techniques like high-performance liquid chromatography and mass spectrometry are hampered by extensive sample preparation, high costs, and potential sample degradation.

The effect of conditioned medium from human amniotic membrane-derived mesenchymal stem cells on thymus involution.

Aims: The development and selection of T cells occur within the thymus. This organ involutes throughout life, compromising the generation of T cells and, consequently, the efficacy of the immune system. Mesenchymal stem cells (MSC) have beneficial effects on the immune system.

A machine learning-based model to predict POD24 in follicular lymphoma: a study by the Chinese workshop on follicular lymphoma.

Background: Disease progression within 24 months (POD24) significantly impacts overall survival (OS) in patients with follicular lymphoma (FL). This study aimed to develop a robust predictive model, FLIPI-C, using a machine learning approach to identify FL patients at high risk of POD24.

Methods: A cohort of 1,938 FL patients (FL1-3a) from seventeen centers nationwide in China was randomly divided into training and internal validation sets (2:1 ratio).

Molecular properties of the RmlT wall teichoic acid rhamnosyltransferase that modulates virulence in Listeria monocytogenes.

Wall teichoic acids (WTAs) from the major Gram-positive foodborne pathogen Listeria monocytogenes are peptidoglycan-associated glycopolymers decorated by monosaccharides that, while not essential for bacterial growth, are required for bacterial virulence and resistance to antimicrobials. Here we report the structure and function of a bacterial WTAs rhamnosyltransferase, RmlT, strictly required for L. monocytogenes WTAs rhamnosylation.

Reconfigurable Amphiphilic DNA Nanotweezer for Targeted Delivery of Therapeutic Oligonucleotides.

Amphiphilic lipid oligonucleotide conjugates are powerful molecular-engineering materials that have been used for delivery of therapeutic oligonucleotides. However, conventional lipid oligonucleotide conjugates suffer from poor selectivity to target cells due to the nonspecific interaction between lipid tails and cell membranes. Herein, a reconfigurable DNA nanotweezer consisting of a c-Met aptamer and bischolesterol-modified antisense oligonucleotide was designed for c-Met-targeted delivery of therapeutic antisense oligonucleotides.

Hereditary Spastic Paraplegia Linked to Abnormal Splicing From an AIMP1 Missense Variant.

Hereditary spastic paraplegias (HSP) are a diverse group of neurodegenerative diseases characterized by lower limb spasticity and weakness. To date, over 80 genes have been associated with HSP, but many families remain without a molecular diagnosis. In this study, linkage analysis and whole-exome sequencing (WES) were performed to identify the causal gene in a HSP family with autosomal recessive inheritance.

ZYG-12/Hook's dual role as a dynein adaptor for early endosomes and nuclei is regulated by alternative splicing of its cargo binding domain.

The microtubule motor cytoplasmic dynein-1 transports and positions various organelles, but the molecular basis of this functional diversity is not fully understood. Cargo adaptors of the Hook protein family recruit dynein to early endosomes (EE) in fungi and human cells by forming the FTS-Hook-FHIP (FHF) complex. By contrast, the Hook homolog ZYG-12 recruits dynein to the nuclear envelope (NE) in the meiotic gonad and mitotic early embryo by forming a Linker of Nucleoskeleton and Cytoskeleton (LINC) complex.

Capilliposide A alleviates DSS-induced colitis by regulating the intestinal flora and its metabolites of origin.

Ulcerative colitis is a chronic idiopathic inflammatory disease that impacts the mucous membrane of the colon. Lately, the incidence and prevalence of UC has been increasing globally. However, there are significant side effects of existing drugs for UC intervention.

A multicenter, randomized, parallel-controlled clinical trial protocol to evaluate the safety and efficacy of irreversible electroporation compared with radiofrequency ablation for the treatment of small hepatocellular carcinoma.

Background: At present, the main clinical application of local ablation therapy, such as radiofrequency ablation (RFA), is to heat the tissue to a certain temperature. However, high temperature will cause thermal damage. Irreversible electroporation (IRE) is a novel minimally invasive local ablation technology for tumors.

cGAS-like receptors drive a systemic STING-dependent host response in Drosophila.

cGAS-like receptor (cGLR)-stimulator of interferon genes (STING) recently emerged as an important pathway controlling viral infections in invertebrates. However, its exact contribution at the organismal level remains uncharacterized. Here, we use STING::GFP knockin reporter Drosophila flies to document activation of the pathway in vivo.

Reorganization of lateral habenula neuronal connectivity underlies pain-related impairment in spatial memory encoding.

Dysfunctional hyperactivity of the lateral habenula nucleus (LHb) has emerged as a critical marker for pain-related mood impairments. Acting as a central hub, the LHb filters and disseminates pertinent information to other brain structures during learning. However, it is not well understood how intra-LHb activity is altered during cognitive demand under neuropathic pain conditions.

A comprehensive study of common and rare genetic variants in spermatogenesis-related loci identifies new risk factors for idiopathic severe spermatogenic failure.

Study Question: Can genome-wide genotyping data be analysed using a hypothesis-driven approach to enhance the understanding of the genetic basis of severe spermatogenic failure (SPGF) in male infertility?

Summary Answer: Our findings revealed a significant association between SPGF and the gene and identified three novel genes (, , and ) along with 32 potentially pathogenic rare variants in 30 genes that contribute to this condition.

What Is Known Already: SPGF is a major cause of male infertility, often with an unknown aetiology. SPGF can be due to either multifactorial causes, including both common genetic variants in multiple genes and environmental factors, or highly damaging rare variants.

Prognostic Factors in Postoperative Brain Metastases Derive From Non-small Cell Lung Cancer: A Retrospective Analysis.

Background: Brain metastases are crucial in cancer progression, requiring focused efforts on the screening, early detection, and treatment. However, accurate forecasting the postoperative prognosis of patients with non-small cell lung cancer brain metastasis remains a challenge. This retrospective study aims to discern the factors that influence the prognosis of such patients.

Regional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3.

Introduction: Knowledge about the distribution and frequency of the respective haplotypes on the wildtype and mutant allele is highly relevant in the context of future gene therapy clinical studies in Spinocerebellar Ataxia Type 3, the most common autosomal dominantly inherited ataxia. Single nucleotide polymorphisms associated to the disease-causing gene, ATXN3, have been determined. We wanted to investigate the frequency and regional distribution of two intragenic single nucleotide polymorphisms (SNPs) in a large European SCA3 cohort and their relation to the clinical phenotype.

Injury-induced KIF4A neural expression and its role in Schwann cell proliferation suggest a dual function for this kinesin in neural regeneration.

Contrary to the adult central nervous system, the peripheral nervous system has an intrinsic ability to regenerate that relies on the expression of regeneration-associated genes, such as some kinesin family members. Kinesins contribute to nerve regeneration through the transport of specific cargo, such as proteins and membrane components, from the cell body towards the axon periphery. We show here that KIF4A, associated with neurodevelopmental disorders and previously believed to be only expressed during development, is also expressed in the adult vertebrate nervous system and up-regulated in injured peripheral nervous system cells.