Disease modelling

Research into aging has grown substantially with the creation of molecular biomarkers of biological age that can be used to determine age acceleration. Concurrently, nuclear magnetic resonance (NMR) assessment of biomarkers of inflammation and metabolism provides researchers with new ways to examine intermediate risk factors for chronic disease. We used data from a cardiac catheterization cohort to examine associations between biomarkers of cardiometabolic health and accelerated aging assessed using both gene expression (Transcriptomic Age) and DNA methylation (Hannum Age, GrimAge, Horvath Age, and Phenotypic Age)...

Self-supervised learning (SSL) has emerged as a powerful technique for improving the efficiency and effectiveness of deep learning models. Contrastive methods are a prominent family of SSL that extract similar representations of two augmented views of an image while pushing away others in the representation space as negatives. However, the state-of-the-art contrastive methods require large batch sizes and augmentations designed for natural images that are impractical for 3D medical images. To address these limitations, we propose a new longitudinal SSL method, 3DTINC, based on non-contrastive learning...

Functional magnetic resonance imaging (fMRI) is a commonly used technique to measure neural activation. Its application has been particularly important in identifying underlying neurodegenerative conditions such as Parkinson's, Alzheimer's, and Autism. Recent analysis of fMRI data models the brain as a graph and extracts features by graph neural networks (GNNs). However, the unique characteristics of fMRI data require a special design of GNN. Tailoring GNN to generate effective and domain-explainable features remains challenging...

In neurodegenerative disorders, neuronal firing patterns and oscillatory activity are remarkably altered in specific brain regions, which can serve as valuable biomarkers for the identification of deep brain regions. The subthalamic nucleus (STN) has been the primary target for DBS in patients with Parkinson's disease (PD). In this study, changes in the spike firing patterns and spectral power of local field potentials (LFPs) in the pre-STN (zona incerta, ZI) and post-STN (cerebral peduncle, cp) regions were investigated in PD rats, providing crucial evidence for the functional localization of the STN...

Generating radiology reports automatically reduces the workload of radiologists and helps the diagnoses of specific diseases. Many existing methods take this task as modality transfer process. However, since the key information related to disease accounts for a small proportion in both image and report, it is hard for the model to learn the latent relation between the radiology image and its report, thus failing to generate fluent and accurate radiology reports. To tackle this problem, we propose a memory-based cross-modal semantic alignment model (MCSAM) following an encoder-decoder paradigm...

PURPOSE OF REVIEW: This article reviews recent advances in ultrasound elastography in diagnosing and evaluating the normal nongravid uterus and the infertile uterus in the gynecologic patient. RECENT FINDINGS: Focusing on the most recent primary literature, studies have demonstrated new findings among a breadth of gynecologic clinical settings. Studies in the nongravid uterus have found that menopausal status, age, and menstrual phase have not been associated with changes in uterine tissue stiffness...

BACKGROUND: The severity of chronic histopathologic lesions on kidney biopsy is independently associated with higher risk of progressive chronic kidney disease (CKD). Because kidney biopsies are invasive, identification of blood markers that report on underlying kidney histopathology has the potential to enhance CKD care. METHODS: We examined the association between 6592 plasma protein levels measured by aptamers and the severity of interstitial fibrosis and tubular atrophy (IFTA), glomerulosclerosis, arteriolar sclerosis, and arterial sclerosis among 434 participants of the Boston Kidney Biopsy Cohort...

BACKGROUND: The transcription factor Grainyhead-like 2 (GRHL2) plays a crucial role in maintaining the epithelial barrier properties of the renal collecting duct and is essential for osmoregulation. We noticed a reduction in GRHL2 expression in cysts derived from the collecting ducts in kidneys affected by Autosomal Dominant Polycystic Kidney Disease (ADPKD). However, the specific role of GRHL2 in cystic kidney disease remains unknown. METHODS: The functional role of the transcription factor Grhl2 in the context of cystic kidney disease was examined through analysis of its expression pattern in patient samples with ADPKD and generating a transgenic cystic kidney disease (TCKD) mouse model by overexpressing the human proto-oncogene c-MYC in kidney collecting ducts...

AIM: Myostatin is a myokine involved in muscle mass regulation. The associations between circulating myostatin levels and clinical characteristics in patients with acute liver failure (ALF) and late-onset hepatic failure (LOHF) are unclear. METHODS: In this retrospective study, 51 patients with ALF or LOHF were included. Serum myostatin was measured using an enzyme-linked immunosorbent assay. RESULTS: Myostatin levels were significantly lower in patients with ALF and LOHF than in controls (ALF/LOHF: 2522 pg/mL, controls: 3853 pg/mL, p = 0...

PURPOSE: To evaluate the effect and mechanism of 1,25(OH)2 D3 on pancreatic stellate cells (PSCs) in type 2 diabetes mellitus (T2DM). METHODS: A mouse model of T2DM was successfully established by high-fat diet (HFD) /streptozotocin (STZ) and administered 1,25(OH)2 D3 for 3 weeks. Fasting blood glucose (FBG), glycated hemoglobin A1c (GHbA1c), insulin (INS) and glucose tolerance were measured. Histopathology changes and fibrosis of pancreas were examined by hematoxylin and eosin staining and Masson staining...

Acute coronary artery blockage leads to acute myocardial infarction (AMI). Cardiomyocytes are terminally differentiated cells that rarely divide. Treatments preventing cardiomyocyte loss during AMI have a high therapeutic benefit. Accumulating evidence shows that microRNAs (miRNAs) may play an essential role in cardiovascular diseases. This study aims to explore the biological function and underlying regulatory molecular mechanism of miR-322-5p on myocardial infarction (MI). This study's miR-322-5p is downregulated in MI-injured hearts according to integrative bioinformatics and experimental analyses...

OBJECTIVE: Navigating obstacles involves adjusting walking patterns, particularly when stepping over them. This task may be particularly challenging for people with Parkinson disease (PD) for several reasons. This review aims to compare the spatiotemporal gait parameters of people with and without PD while stepping over obstacles. LITERATURE SURVEY: A systematic literature search was conducted in six databases (PubMed, Scopus, Web of Science, EBSCO, Embase, and SciELO) from inception to September 2023...

OBJECTIVE: To investigate the production of leucine-rich α-2-glycoprotein-1 (LRG1) in periodontitis patients and its effectiveness as a new diagnostic marker for periodontitis. SUBJECTS AND METHODS: In vitro experiments were conducted to analyze LRG1 mRNA expression in human gingival epithelial cells and fibroblasts via quantitative real-time PCR. In vivo experiments were conducted to analyze LRG1 localization in periodontitis patients. The correlation between the serum LRG1 levels and alveolar bone resorption in the mouse periodontitis model was also investigated...

AIM: To compare the adherence to gluten-free diet between children with serology-based and biopsy-proven coeliac disease. METHODS: Medical records were retrospectively reviewed in 257 Swedish children diagnosed with coeliac disease between 2012 and 2019 at a tertiary hospital. Adherence to a gluten-free diet was systematically assessed by trained dietitians at follow-up. Mixed models were used to analyse the dietary adherence by mode of diagnosis (serology-based vs...

We consider the problem of targeted mass screening of heterogeneous populations under limited testing capacity. Mass screening is an essential tool that arises in various settings, e.g., ensuring a safe supply of blood, reducing prevalence of sexually transmitted diseases, and mitigating the spread of infectious disease outbreaks. The goal of mass screening is to classify whole population groups as positive or negative for an infectious disease as efficiently and accurately as possible. Under limited testing capacity, it is not possible to screen the entire population and hence administrators must reserve testing and target those among the population that are most in need or most susceptible...

Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. 4R-cembranoid (4R) is a natural compound that inhibits hippocampal pro-inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild-type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle...

AIMS: Atrial fibrillation (AF) is the most common arrhythmia. Heart failure (HF) is a disease caused by heart dysfunction. The prevalence of AF and HF were progressively increasing over time. The co-existence of AF and HF presents a significant therapeutic challenge. In order to provide new ideas for the diagnosis of AF and HF, it is necessary to carry out biomarker related studies. METHODS AND RESULTS: The training set and validation set data of AF and HF patient samples were downloaded from the GEO database, 'limma' was used to compare the differences in gene expression levels between the disease group and the normal group to screen for differentially expressed genes (DEGs)...

Sjögren's disease (SjD), characterized by circulating autoantibodies and exocrine gland inflammation, is typically diagnosed in women over 50 years of age. However, the contribution of age to SjD pathogenesis is unclear. C57BL/6 female mice at different ages were studied to investigate how aging influences the dynamics of salivary gland inflammation. Salivary glands were characterized for immune cell infiltration, inflammatory gene expression, and saliva production. At 8 months, gene expression of several chemokines involved in immune cell trafficking was significantly elevated...

AIM: Aberrant expression of ATPase sarcoplasmic/endoplasmic retic Ca2+  transporting 2 (ATP2A2) has attracted attention for its pathophysiologic role in pulmonary hypertension (PH). Several miRNAs, including miR-210-5p, have also been reported to be pathogenic factors in PH, but their exact mechanisms remain unknown. This study aimed to elucidate the potential mechanisms of miR-210-5p and ATP2A2 in MCT-induced PH. METHODS: Eighteen Sprague-Dawley rats were randomly divided into two groups-monoclonal (MCT) group and control group-and then administered MCT (60 mg/kg) and saline, respectively...

PURPOSE OF REVIEW: More than a century since its discovery, the pathogenesis of Chagas heart disease (CHD) remains incompletely understood. The role of derangements in the autonomic control of the heart in triggering malignant arrhythmia before the appearance of contractile ventricular impairment was reviewed. RECENT FINDINGS: Although previous investigations had demonstrated the anatomical and functional consequences of parasympathetic dysautonomia upon the heart rate control, only recently, coronary microvascular disturbances and sympathetic denervation at the ventricular level have been reported in patients and experimental models of CHD, exploring with nuclear medicine methods their impact on the progression of myocardial dysfunction and cardiac arrhythmias...