Rewiring cancer: 3D genome determinants of cancer hallmarks.

In modern cancer biology, Hanahan and Weinberg's classic depiction of the Hallmarks of Cancer serves as a heuristic for understanding malignant phenotypes [1]. Genetic determinants of these phenotypes promote cancer induction and progression, and these mutations drive current approaches to understanding and treating cancer. Meanwhile, for over a century, pathologists have noted that profound alterations of nuclear structure accompany transformation, integrating these changes into diagnostic classifications (Figure 1).

The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Protocol for assessing and visualizing cell microaggregate formation in whole blood by imaging flow cytometry.

Blood cell aggregates are clinically useful biomarkers in a number of medical disorders. This protocol provides accurate and quantitative analysis of cell aggregates using a small volume of whole blood and imaging flow cytometry. We describe steps for sample collection, staining, and measurement.

The contribution of cognitive disengagement syndrome symptoms to depressive symptoms among pediatric brain tumor survivors.

Objective: Pediatric brain tumor survivors (PBTS) are at risk for neurocognitive late effects that can resemble symptoms of cognitive disengagement syndrome (CDS). In the current study, we compared the CDS symptoms of PBTS to those of healthy comparison classmates (CC) and examined whether CDS might explain group differences in depressive symptoms. We also explored whether CDS symptoms were associated with engagement-based coping strategies and stress responses, thereby testing one mechanism by which CDS could lead to affective difficulties.

A-kinase anchor protein 12 promotes oligodendrogenesis and cognitive recovery in carbon monoxide therapy for traumatic brain injury.

Therapeutic drug development for central nervous system injuries, such as traumatic brain injury (TBI), presents significant challenges. TBI results in primary mechanical damage followed by secondary injury, leading to cognitive dysfunction and memory loss. Our recent study demonstrated the potential of carbon monoxide-releasing molecules (CORMs) to improve TBI recovery by enhancing neurogenesis.

'It is scary to pause treatment': perspectives on HIV cure-related research and analytical treatment interruptions from women diagnosed during acute HIV in Durban, South Africa.

Background: HIV remains a major challenge in KwaZulu-Natal, South Africa, particularly for young women who face disproportionate risks and barriers to prevention and treatment. Most HIV cure trials, however, occur in high-income countries.

Objective: To examine the perspectives of young women diagnosed with acute HIV in a longitudinal study, focusing on their perceptions on ATI-inclusive HIV cure trials and the barriers and facilitators to participation.

Use of the Adaptive Behaviour Dementia Questionnaire in a Down Syndrome Specialty Clinic.

Objective: To study the use of a dementia screening tool in our clinic cohort of adults with Down syndrome.

Study Design: A retrospective chart review of patients with Down syndrome was conducted to follow the use of the Adaptive Behaviour Dementia Questionnaire (ABDQ) in a dementia screening protocol. The ABDQ results for patients aged 40 years and older at a Down syndrome specialty clinic program were assessed.

Viral Transcript and Tumor Immune Microenvironment-Based Transcriptomic Profiling of HPV-Associated Head and Neck Squamous Cell Carcinoma Identifies Subtypes Associated with Prognosis.

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HPV-positive HNSCC) has distinct biological characteristics from HPV-negative HNSCC. Using an AI-based analytical platform on meta cohorts, we profiled expression patterns of viral transcripts and HPV viral genome integration, and classified the tumor microenvironment (TME). Unsupervised clustering analysis revealed five distinct and novel TME subtypes across patients (immune-enriched, highly immune and B-cell enriched, fibrotic, immune-desert, and immune-enriched luminal).

The Application of Resolvin D1-Loaded Gelatin Methacrylate in a Rat Periodontitis Model.

To evaluate the drug release, cytocompatibility with periodontal ligament cells (PDLCs), and therapeutic efficacy of GelMA hydrogel loaded with resolvin D1 (RvD1) in treating rat periodontal inflammation and alveolar bone damage. An RvD1 complexed with GelMA was prepared, and its release kinetics and compatibility with PDLCs were assessed. Rats with induced periodontitis were treated weekly with topical applications of vehicle, GelMA, RvD1, or RvD1 complexed with GelMA for four weeks.

Associations of Maternal Prenatal Zinc Consumption with Infant Brain Tissue Organization and Neurodevelopmental Outcomes.

Background/objectives: While studies in rat pups suggest that early zinc exposure is critical for optimal brain structure and function, associations of prenatal zinc intake with measures of brain development in infants are unknown. This study aimed to assess the associations of maternal zinc intake during pregnancy with MRI measures of brain tissue microstructure and neurodevelopmental outcomes, as well as to determine whether MRI measures of the brain mediated the relationship between maternal zinc intake and neurodevelopmental indices.

Methods: Forty-one adolescent mothers were recruited for a longitudinal study during pregnancy.

Adherence to the Mediterranean Diet and the Risk of Head and Neck Cancer: A Systematic Review and Meta-Analysis of Case-Control Studies.

Background/objectives: Head and neck cancer (HNC) is the seventh most common cancer worldwide, with rising incidence rates and significant mortality. While tobacco use, alcohol consumption, and viral infections are established risk factors, the role of dietary patterns, particularly adherence to the Mediterranean diet (MD), in HNC prevention has gained increasing attention. The aim of the current systematic review and meta-analysis is to investigate the association between adherence to the MD and the risk of HNC.

Magnesium Depletion Score and Mortality in Individuals with Metabolic Dysfunction Associated Steatotic Liver Disease over a Median Follow-Up of 26 Years.

Unlabelled: Metabolic dysfunction associated steatotic liver disease (MASLD) has been associated with increased risks of all-cause and cardiovascular disease (CVD) mortality. Identification of modifiable risk factors that may contribute to higher risks of mortality could facilitate targeted and intensive intervention strategies in this population. This study aims to examine whether the magnesium depletion score (MDS) is associated with all-cause and CVD mortality among individuals with MASLD or metabolic and alcohol associated liver disease (MetALD).

Non-Celiac Gluten/Wheat Sensitivity-State of the Art: A Five-Year Narrative Review.

Non-celiac gluten/wheat sensitivity (NCGWS) is a syndrome for which pathogenesis and management remain debated. It is described as a condition characterized by gastrointestinal and extra-intestinal symptoms rapidly occurring after gluten ingestion in subjects who have had celiac disease or wheat allergy excluded. To date, the diagnosis of NCGWS is challenging as no universally recognized biomarkers have been yet identified, nor has a predisposing genetic profile been described.

Utilization Trends of Glucose-Lowering Medications Among Adult Kidney Transplant Recipients with Type 2 Diabetes in the United States.

To date, there are limited studies describing the use of glucose-lowering medications (GLMs) in adult kidney transplant recipients (KTRs), and the uptake of sodium glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP1RAs). Thus, we aimed to evaluate the use of GLMs, including SGLT2i and GLP1RA, among adult KTRs with type 2 diabetes (T2D). This is an ecologic study of adult KTR with T2D.

Advancing Insights into Pediatric Macular Diseases: A Comprehensive Review.

Pediatric macular disorders are a diverse group of inherited retinal diseases characterized by central vision loss due to dysfunction and degeneration of the macula, the region of the retina responsible for high-acuity vision. Common disorders in this category include Stargardt disease, Best vitelliform macular dystrophy, and X-linked retinoschisis. These conditions often manifest during childhood or adolescence, with symptoms such as progressive central vision loss, photophobia, and difficulty with fine visual tasks.

Restoration of Genuine Sensation and Proprioception of Individual Fingers Following Transradial Amputation with Targeted Sensory Reinnervation as a Mechanoneural Interface.

: Tactile gnosis derives from the interplay between the hand's tactile input and the memory systems of the brain. It is the prerequisite for complex hand functions. Impaired sensation leads to profound disability.

Medical Digital Twin: A Review on Technical Principles and Clinical Applications.

The usage of digital twins (DTs) is growing across a wide range of businesses. The health sector is one area where DT use has recently increased. Ultimately, the concept of digital health twins holds the potential to enhance human existence by transforming disease prevention, health preservation, diagnosis, treatment, and management.

Prescription of Strong Opioids in Chronic Non-Cancer Pain in the Province of Valladolid (Spain).

Chronic non-cancer pain (CNCP) is one of the leading causes of disability. The use of strong opioids (SOs) in the management of CNCP is increasing, although evidence supporting their use remains limited. Primary care (PC) plays a key role in this context.

Associations of Voice Metrics with Postural Function in Parkinson's Disease.

Background: This study aimed to explore the potential associations between voice metrics of patients with PD and their motor symptoms.

Methods: Motor and vocal data including the Unified Parkinson's Disease Rating Scale part III (UPDRS-III), Harmonic-Noise Ratio (HNR), jitter, shimmer, and smoothed cepstral peak prominence (CPPS) were analyzed through exploratory correlations followed by univariate linear regression analyses. We employed these four voice metrics as independent variables and the total and sub-scores of the UPDRS-III as dependent variables.

Cross-Species Epitope Sequence Analysis for Discovery of Existing Antibodies Useful for Phospho-Specific Protein Detection in Model Species.

Signaling pathways play key roles in many important biological processes, such as cell division, differentiation, and migration. Phosphorylation site-specific antibodies specifically target proteins phosphorylated on a given tyrosine, threonine, or serine residue. The use of phospho-specific antibodies facilitates the analysis of signaling pathway regulation and activity.

Comprehensive Analysis of the Proteome of Wild-Type and 5Δ Cells in Response to Bisphenol A (BPA) Exposure.

Bisphenol A, an endocrine-disrupting compound, is widely used in the industrial production of plastic products. Despite increasing concerns about its harmful effects on human health, animals, and the environment, the use of BPA has been banned only in infant products, and its effects on cellular processes are not fully understood. To investigate the impact of BPA on eukaryotic cells, we analyzed the proteome changes of wild-type and -deleted strains exposed to different doses of BPA using sample multiplexing-based proteomics.

Missing Regulation Between Genetic Association and Transcriptional Abundance for Hypercholesterolemia Genes.

Low-density lipoprotein cholesterol (LDL-C) is a well-established risk factor for cardiovascular disease, and it plays a causal role in the development of atherosclerosis. Genome-wide association studies (GWASs) have successfully identified hundreds of genetic variants associated with LDL-C. Most of these risk loci fall in non-coding regions of the genome, and it is unclear how these non-coding variants affect circulating lipid levels.

Chromosome 4 Duplication Associated with Strabismus Leads to Gene Expression Changes in iPSC-Derived Cortical Neurons.

Background/objectives: Strabismus is the most common ocular disorder of childhood. Three rare, recurrent genetic duplications have been associated with both esotropia and exotropia, but the mechanisms by which they contribute to strabismus are unknown. This work aims to investigate the mechanisms of the smallest of the three, a 23 kb duplication on chromosome 4 (hg38|4:25,554,985-25,578,843).