Features Of Disease Research Articles

Features of systemic autoimmune disease associated with anti-Ku antibodies (descriptions of two clinical cases)

Anti-Ku antibodies are a special type of myositis-associated antibodies that are characteristic of patients with the overlap syndrome of systemic scleroderma and immune-inflammatory myopathy, as well as occurring in other autoimmune diseases. Patients with these antibodies have their own clinical and laboratory features of the disease and can be identified as a separate anti-Ku syndrome.For the first time in the domestic literature, descriptions of two clinical cases of the development of a cross syndrome associated with anti-Ku antibodies are presented. The features of the course of the disease and the response to various options for immunosuppressive therapy were analyzed.

The contribution of white matter changes to clinical phenotype in progressive supranuclear palsy.

White matter hyperintensities (WMH) are considered magnetic brain imaging (MRI) biomarkers of cerebral small vessel disease but their clinical role in neurodegenerative-related disorders is poorly understood. This study describes the distribution of WMH on brain MRI in Progressive Supranuclear Palsy (PSP) in comparison with Parkinson's disease (PD) and explores their possible impact on disease's features. Sixty PSP and 33 PD patients were included. Motor symptoms, cardiovascular risk factors and the age-related white matter changes (ARWMC) score was computed to rate WMH for both groups. Pearson's correlation and linear or logistic regression analysis were used to check for relationships between ARWMC and PSP clinical scores. The mean (standard deviation) ARWMC total score in the PSP cohort was 4.66 (3.25). Any degree of WMH was present in 68% of PSP (ARWMC +). Compared to ARWMC-, ARWMC + did not have greater disease severity or more cardiovascular risk factors. WMH were frequently localized in fronto-parietal lobes and were mild in severity. Linear regression analysis showed that ARWMC total score was related to the PSP-rating scale, irrespective of age, disease duration and the Charlson modified comorbidity index. Logistic regression analysis confirmed that ARWMC total score was related to the use of wheelchair, irrespective of above-mentioned covariates. Vascular risk factors as well as severity and distribution of WMH did not have an impact on the PSP phenotype. No differences were found with PD patients. Our results suggest that WMH in PSP might be markers of neurodegenerative-related pathology rather than being simple expression of atherosclerotic cerebrovascular changes.

Clinical characteristics of double negative atypical inflammatory demyelinating disease: A prospective study.

This study aimed to investigate the clinical characteristics and predictors of relapse in double negative atypical inflammatory demyelinating disease (IDD) and to explore potential antigenic targets by tissue-based assays (TBA) using rat brain indirect immunofluorescence. We compared the clinical, laboratory, and MRI data of double negative atypical IDD with other IDD patients. Serum samples were collected for TBA. The predictors of relapse were examined over a minimum of 24 months follow-up. In our cohort of 98 patients with double negative atypical IDD, there was no significant female predominance (58.2%, 57/98). The lesions primarily affected the spinal cord and brain stem, with fewer cases of involvement in the area postrema (5.1%, 5/98) and longitudinally extensive transverse myelitis (43.9%, 43/98). A total of 62.5% (50/80) patients tested positive for anti-astrocyte antibodies based on rat brain TBA. Over a median duration of 39.5 months, 80 patients completed the entire follow-up, and 47.5% (38/80) patients exhibited monophasic course. A total of 36% (18/50) patients positively for anti-astrocyte antibodies had a monophasic course, which is significantly lower than patients negatively for anti-astrocyte antibodies (66.7%, 20/30) (p = 0.008). The presence of anti-astrocyte antibodies (hazard ratio (HR), 2.243; 95% CI, 1.087-4.627; p = 0.029) and ≥4 cerebrum lesions at first attack (HR, 2.494; 95% CI, 1.224-5.078; p = 0.012) were risk factors for disease relapse, while maintenance immunotherapy during remission (HR, 0.361; 95% CI, 0.150-0.869; p = 0.023) was protective factor. Double negative atypical IDD are unique demyelinating diseases with a high relapse rate. Maintenance immunotherapy is helpful to the prevention of relapse, particularly in patients with anti-astrocyte antibodies or ≥4 cerebrum lesions at first attack.

Pathological features of connective tissue disease-associated interstitial lung disease in transbronchial cryobiopsies.

Transbronchial cryobiopsies are increasingly used for the diagnosis of interstitial lung disease (ILD), but there is a lack of published information on the features of specific ILD in cryobiopsies. Here we attempt to provide pathological guidelines for separating usual interstitial pneumonia (UIP) of idiopathic pulmonary fibrosis (IPF), fibrotic hypersensitivity pneumonitis (FHP) and connective tissue disease-associated ILD (CTD-ILD) in cryobiopsies. We examined 120 cryobiopsies from patients with multidisciplinary discussion (MDD)-established CTD-ILD and compared them to a prior series of 121 biopsies from patients with MDD-established IPF or FHP. A non-specific interstitial pneumonia (NSIP) pattern alone was seen in 36 of 120 (30%) CTD-ILD, three of 83 (3.6%) FHP and two of 38 (5.2%) IPF cases, statistically favouring a diagnosis of CTD-ILD. The combination of NSIP + OP was present in 29 of 120 (24%) CTD-ILD, two of 83 (2.4%) FHP and none of 38 (0%) IPF cases, favouring a diagnosis of CTD-ILD. A UIP pattern, defined as fibroblast foci plus any of patchy old fibrosis/fibrosis with architectural distortion/honeycombing, was identified in 28 of 120 (23%) CTD-ILD, 45 of 83 (54%) FHP and 27 of 38 (71%) IPF cases and supported a diagnosis of FHP or IPF. The number of lymphoid aggregates/mm2 and fibroblast foci/mm2 was not different in IPF, CTD-ILD or FHP cases with a UIP pattern. Interstitial giant cells supported a diagnosis of FHP or CTD-ILD over IPF, but were infrequent. In the correct clinical/radiological context the pathological findings of NSIP, and particularly NSIP plus OP, favour a diagnosis of CTD-ILD in a cryobiopsy, but CTD-ILD with a UIP pattern, FHP with a UIP pattern and IPF generally cannot be distinguished.

Improved Mathematical Models of Parkinson's Disease with Hopf Bifurcation and Huntington's Disease with Chaos.

Using delay differential equations to study mathematical models of Parkinson's disease and Huntington's disease is important to show how important it is for synchronization between basal ganglia loops to work together. We used the delay circuit RLC (resistor, inductor, capacitor) model to show how the direct pathway and the indirect pathway in the basal ganglia excite and inhibit the motor cortex, respectively. A term has been added to the mathematical model without time delay in the case of the hyperdirect pathway. It is proposed to add a non-linear term to adjust the synchronization. We studied Hopf bifurcation conditions for the proposed models. The desynchronization of response times between the direct pathway and the indirect pathway leads to different symptoms of Parkinson's disease. Tremor appears when the response time in the indirect pathway increases at rest. The simulation confirmed that tremor occurs and the motor cortex is in an inhibited state. The direct pathway can increase the time delay in the dopaminergic pathway, which significantly increases the activity of the motor cortex. The hyperdirect pathway regulates the activity of the motor cortex. The simulation showed bradykinesia occurs when we switch from one movement to another that is less exciting for the motor cortex. A decrease of GABA in the striatum or delayed excitation of the substantia nigra from the subthalamus may be a major cause of Parkinson's disease. An increase in the response time delay in one of the pathways results in the chaotic movement characteristic of Huntington's disease.

Human Orthohantavirus disease prevalence and genotype distribution in the U.S., 2008–2020: a retrospective observational study

In the United States (U.S.), hantavirus pulmonary syndrome (HPS) and non-HPS hantavirus infection are nationally notifiable diseases. Criteria for identifying human cases are based on clinical symptoms (HPS or non-HPS) and acute diagnostic results (IgM+, rising IgG+ titers, RT-PCR+, or immunohistochemistry (IHC)+). Here we provide an overview of diagnostic testing and summarize human Hantavirus disease occurrence and genotype distribution in the U.S. from 2008 to2020. Epidemiological data from the national hantavirus registry was merged with laboratory diagnostic testing results performed at the CDC. Residual hantavirus-positive specimens were sequenced, and the available epidemiological and genetic data sets were linked to conduct a genomic epidemiological study of hantavirus disease in the U.S. From 1993 to 2020, 833 human hantavirus cases have been identified, and from 2008 to 2020, 335 human cases have occurred. Among New World (NW) hantavirus cases detected at the CDC diagnostic laboratory (representing 29.2% of total cases), most (85.0%) were detected during acute disease, however, some convalescent cases were detected in states not traditionally associated with hantavirus infections (Connecticut, Missouri, New Jersey, Pennsylvania, Tennessee, and Vermont). From 1993 to 2020, 94.9% (745/785) of U.S. hantaviruses cases were detected west of the Mississippi with 45.7% (359/785) in the Four Corners region of the U.S. From 2008 to 2020, 67.7% of NW hantavirus cases were detected between the months of March and August. Sequencing of RT-PCR-positive cases demonstrates a geographic separation of Orthohantavirus sinnombreense species [Sin Nombre virus (SNV), New York virus, and Monongahela virus]; however, there is a large gap in viral sequence data from the Northwestern and Central U.S. Finally, these data indicate that commercial IgM assays are not concordant with CDC-developed assays, and that "concordant positive" (i.e., commercial IgM+ and CDC IgM+ results) specimens exhibit clinical characteristics of hantavirus disease. Hantaviral disease is broadly distributed in the contiguous U.S, viral variants are localised to specific geographic regions, and hantaviral disease infrequently detected in most Southeastern states. Discordant results between two diagnostic detection methods highlight the need for an improved standardised testing plan in the U.S. Hantavirus surveillance and detection will continue to improve with clearly defined, systematic reporting methods, as well as explicit guidelines for clinical characterization and diagnostic criteria. This work was funded by core funds provided to the Viral Special Pathogens Branch at CDC.

Identification of endoplasmic reticulum stress-associated genes and subtypes for predicting risk signature and depicting immune features in inflammatory bowel disease

Endoplasmic reticulum stress (ERS) becomes a significant factor in inflammatory bowel disease (IBD), like Crohn’s disease (CD) and ulcerative colitis (UC). Our research was aimed at identifying molecular markers to enhance our understanding of ERS and inflammation in IBD, recognizing risk factors and high-risk groups at the molecular level, and developing a predictive model on the grounds of based on ERS-associated genes.This research adopted the least absolute shrinkage and selection operator (LASSO) regression and logistic regression to build a predictive model, and categorized IBD patients into high- and low-risk groups, and then identified four gene clusters. Our key findings included a significant increase in drug target gene expression in high-risk groups, notable discrepancies in immune levels, and functions between high-risk and low-risk groups. Notably, the TAP1 gene emerged as a strong predictor with the highest diagnostic value (area under the curve [AUC]=0.941). TAP1 encodes proteins required for antigenic peptide transfer across the endoplasmic reticulum (ER) membrane, and its potential as a diagnostic marker and therapeutic target is reflected by its overexpression in IBD tissues.Our study established a new ERS-associated gene model which could forecast the risk, immunological status, and treatment efficacy of patients with IBD. These findings suggest potential targets for personalized therapy and highlight the significance of ERS in the etiology and therapy of IBD. Future studies should explore the therapeutic potential of targeting TAP1 and other ERS-related genes for IBD management.

Dysphagia in primary progressive aphasia: Clinical predictors and neuroanatomical basis.

Dysphagia is an important feature of neurodegenerative diseases and potentially life-threatening in primary progressive aphasia (PPA) but remains poorly characterized in these syndromes. We hypothesized that dysphagia would be more prevalent in nonfluent/agrammatic variant (nfv)PPA than other PPA syndromes, predicted by accompanying motor features, and associated with atrophy affecting regions implicated in swallowing control. In a retrospective case-control study at our tertiary referral centre, we recruited 56 patients with PPA (21 nfvPPA, 22 semantic variant [sv]PPA, 13 logopenic variant [lv]PPA). Using a pro forma based on caregiver surveys and clinical records, we documented dysphagia (present/absent) and associated, potentially predictive clinical, cognitive, and behavioural features. These were used to train a machine learning model. Patients' brain magnetic resonance imaging scans were assessed using voxel-based morphometry and region-of-interest analyses comparing differential atrophy profiles associated with dysphagia presence/absence. Dysphagia was significantly more prevalent in nfvPPA (43% vs. 5% svPPA and no lvPPA). The machine learning model revealed a hierarchy of features predicting dysphagia in the nfvPPA group, with excellent classification accuracy (90.5%, 95% confidence interval = 77.9-100); the strongest predictor was orofacial apraxia, followed by older age, parkinsonism, more severe behavioural disturbance, and more severe cognitive impairment. Significant grey matter atrophy correlates of dysphagia in nfvPPA were identified in left middle frontal, right superior frontal, and right supramarginal gyri and right caudate. Dysphagia is a common feature of nfvPPA, linked to underlying corticosubcortical network dysfunction. Clinicians should anticipate this symptom particularly in the context of other motor features and more severe disease.

Factors Associated with Mortality in Patients with Coronavirus Disease (COVID-19) in Babol, North of Iran.

The spectrum of the clinical features of coronavirus disease 2019 (COVID-19) spans from asymptomatic or mild disease to severe respiratory failure, while different factors are related to its mortality rate. This research aimed to determine the clinical and laboratory characteristics and the associated factors of mortality in patients with COVID-19. Data were collected from hospitalized patients (May to June 2020), and COVID-19 was confirmed in patients by real-time polymerase chain reaction (PCR). The patient group was classified into survivor and deceased groups. The chi-square and the independent t-test with Statistical Package for the Social Sciences (SPSS) software program, version 18, were used for analysis. Mean age, hemoglobin, serum C-reactive protein (CRP), alkaline phosphatase (ALP), white blood cells, and level of procalcitonin in non-survivors were significantly higher than in survivors. Serum tumour necrosis factor-alpha (TNF-a) had a significant relationship with Ddimer (p = 0.0006). The risk of mortality in patients with serum CRP ≥ 100 mg/dl was significantly higher than those with CRP < 100 mg/dl (odds ratio (OR) = 4.8 (95% CI, 1.33-12.44, p = 0.01). COVID-19 has different clinical features and can be an asymptomatic, mild, or severe disease. Thus, findings about the disease and the consequent outcomes differ in patients. Further studies are needed to evaluate the clinical features and consequences of COVID-19 infection.

A Review of the Common Neurodegenerative Disorders: Current Therapeutic Approaches and the Potential Role of Bioactive Peptides.

Neurodegenerative disorders, which include Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), represent a significant and growing global health challenge. Current therapies predominantly focus on symptom management rather than altering disease progression. In this review, we discuss the major therapeutic strategies in practice for these disorders, highlighting their limitations. For AD, the mainstay treatments are cholinesterase inhibitors and N-methyl-D-aspartate (NMDA) receptor antagonists. For PD, dopamine replacement therapies, including levodopa, are commonly used. HD is managed primarily with symptomatic treatments, and reusable extends survival in ALS. However, none of these therapies halts or substantially slows the neurodegenerative process. In contrast, this review highlights emerging research into bioactive peptides as potential therapeutic agents. These naturally occurring or synthetically designed molecules can interact with specific cellular targets, potentially modulating disease processes. Preclinical studies suggest that bioactive peptides may mitigate oxidative stress, inflammation, and protein misfolding, which are common pathological features in neurodegenerative diseases. Clinical trials using bioactive peptides for neurodegeneration are limited but show promising initial results. For instance, hemiacetal, a γ-secretase inhibitor peptide, has shown potential in AD by reducing amyloid-beta production, though its development was discontinued due to side effects. Despite these advancements, many challenges remain, including identifying optimal peptides, confirming their mechanisms of action, and overcoming obstacles related to their delivery to the brain. Future research should prioritize the discovery and development of novel bioactive peptides and improve our understanding of their pharmacokinetics and pharmacodynamics. Ultimately, this approach may lead to more effective therapies for neurodegenerative disorders, moving beyond symptom management to potentially modify the course of these devastating diseases.

Microglia either promote or restrain TRAIL-mediated excitotoxicity caused by Aβ1-42 oligomers.

Alzheimer's disease (AD) features progressive neurodegeneration and microglial activation that results in dementia and cognitive decline. The release of soluble amyloid (Aβ) oligomers into the extracellular space is an early feature of AD pathology. This can promote excitotoxicity and microglial activation. Microglia can adopt several activation states with various functional outcomes. Protective microglial activation states have been identified in response to Aβ plaque pathology in vivo. However, the role of microglia and immune mediators in neurotoxicity induced by soluble Aβ oligomers is unclear. Further, there remains a need to identify druggable molecular targets that promote protective microglial states to slow or prevent the progression of AD. Hippocampal entorhinal brain slice culture (HEBSC) was employed to study mechanisms of Aβ1-42 oligomer-induced neurotoxicity as well as the role of microglia. The roles of glutamate hyperexcitation and immune signaling in Aβ-induced neurotoxicity were assessed using MK801 and neutralizing antibodies to the TNF-related apoptosis-inducing ligand (TRAIL) respectively. Microglial activation state was manipulated using Gi-hM4di designer receptor exclusively activated by designer drugs (DREADDs), microglial depletion with the colony-stimulating factor 1 receptor (CSF1R) antagonist PLX3397, and microglial repopulation (PLX3397 withdrawal). Proteomic changes were assessed by LC-MS/MS in microglia isolated from control, repopulated, or Aβ-treated HEBSCs. Neurotoxicity induced by soluble Aβ1-42 oligomers involves glutamatergic hyperexcitation caused by the proinflammatory mediator and death receptor ligand TRAIL. Microglia were found to have the ability to both promote and restrain Aβ-induced toxicity. Induction of microglial Gi-signaling with hM4di to prevent pro-inflammatory activation blunted Aβ neurotoxicity, while microglial depletion with CSF1R antagonism worsened neurotoxicity caused by Aβ as well as TRAIL. HEBSCs with repopulated microglia, however, showed a near complete resistance to Aβ-induced neurotoxicity. Comparison of microglial proteomes revealed that repopulated microglia have a baseline anti-inflammatory and trophic phenotype with a predicted pathway activation that is nearly opposite that of Aβ-exposed microglia. mTORC2 and IRF7 were identified as potential targets for intervention. Microglia are key mediators of both protection and neurodegeneration in response to Aβ. Polarizing microglia toward a protective state could be used as a preventative strategy against Aβ-induced neurotoxicity.

Enhancing Panax notoginseng Leaf Disease Classification with Inception-SSNet and Image Generation via Improved Diffusion Model

The rapid and accurate classification of Panax notoginseng leaf diseases is vital for timely disease control and reducing economic losses. Recently, image classification algorithms have shown great promise for plant disease diagnosis, but dataset quantity and quality are crucial. Moreover, classifying P. notoginseng leaf diseases faces severe challenges, including the small features of anthrax and the strong similarity between round spot and melasma diseases. In order to address these problems, we have proposed an ECA-based diffusion model and Inception-SSNet for the classification of the six major P. notoginseng leaf diseases, namely gray mold, powdery mildew, virus infection, anthrax, melasma, and round spot. Specifically, we propose an image generation scheme, in which the lightweight attention mechanism, ECA, is used to capture the dependencies between channels for improving the dataset quantity and quality. To extract disease features more accurately, we developed an Inception-SSNet hybrid model with skip connection, attention feature fusion, and self-calibrated convolutional. These innovative methods enable the model to make better use of local and global information, especially when dealing with diseases with similar features and small targets. The experimental results show that our proposed ECA-based diffusion model FID reaches 42.73, compared with the baseline model, which improved by 74.71%. Further, we tested the classification model using the data set of P. notoginseng leaf disease generation, and the accuracy of 11 mainstream classification models was improved. Our proposed Inception-SSNet classification model achieves an accuracy of 97.04% on the non-generated dataset, which is an improvement of 0.11% compared with the baseline model. On the generated dataset, the accuracy reached 99.44%, which is an improvement of 1.02% compared to the baseline model. This study provides an effective solution for the monitoring of Panax notoginseng diseases.

Inflammatory Bowel Disease in Children

Background: Pediatric inflammatory bowel disease (IBD) is an idiopathic inflammatory disease in the digestive system with chronic onset, which often presents with unique and atypical phenotypes. This study aimed to dissect the important features of inflammatory bowel disease in children Discussion: The two types of inflammatory bowel disease (IBD) are ulcerative colitis (UC) and Crohn’s disease (CD). In children, IBD may exhibit classic symptoms such as weight loss, abdominal pain, and bloody diarrhea. However, many patient present with atypical symptoms such as isolated poor growth, anemia, or other extraintestinal manifestations. Early diagnosis of IBD in children is crucial as delayed diagnosis may lead to serious complications like bowel narrowing or abnormal connections, and stunted growth. The recommended initial evaluations in a pediatric patient with suspected IBD are complete blood test, stool examination, endoscopy and imaging. Furthermore, the aims of IBD treatment in children are to improve quality of life, relieve symptoms, promote normal growth, and prevent complications, all while minimizing medication side effects. Conclusion: Early diagnosis and treatment are essential in managing pediatric IBD. Additionally, addressing the disease's impact on bone health, growth, development, and psychosocial well-being is also crucial to achieve comprehensive management.

Integration of Diffusion Transformer and Knowledge Graph for Efficient Cucumber Disease Detection in Agriculture

In this study, a deep learning method combining knowledge graph and diffusion Transformer has been proposed for cucumber disease detection. By incorporating the diffusion attention mechanism and diffusion loss function, the research aims to enhance the model’s ability to recognize complex agricultural disease features and to address the issue of sample imbalance efficiently. Experimental results demonstrate that the proposed method outperforms existing deep learning models in cucumber disease detection tasks. Specifically, the method achieved a precision of 93%, a recall of 89%, an accuracy of 92%, and a mean average precision (mAP) of 91%, with a frame rate of 57 frames per second (FPS). Additionally, the study successfully implemented model lightweighting, enabling effective operation on mobile devices, which supports rapid on-site diagnosis of cucumber diseases. The research not only optimizes the performance of cucumber disease detection, but also opens new possibilities for the application of deep learning in the field of agricultural disease detection.

Gut bacterial type III secretion systems aggravate colitis in mice and serve as biomarkers of Crohn's Disease

Mesenteric adipose tissue (mAT) hyperplasia, known as creeping fat, is a pathologic characteristic of Crohn's disease (CD). In our previously reported cohort, we observed that Achromobacter pulmonis was the most abundant and prevalent bacteria cultivated from creeping fat. A whole genomic sequencing and identification of T3SS orthologs of mAT-derived A. pulmonis were used. A functional type III secretion system (T3SS) mediated the pathogenic potential of A. pulmonis invitro and in mouse colitis model. Furthermore, a T3SS Finder pipeline was introduced to evaluate gut bacterial T3SS orthologs in the feces of CD patients, ulcerative colitis and colorectal cancer patients. Here, we reveal that mAT-derived A. pulmonis possesses a functional T3SS, aggravates colitis in mice via T3SS, and exhibits T3SS-dependent cytotoxicity via a caspase-independent mechanism in macrophages and epithelial cells, which demonstrated the pathogenic potential of the T3SS-harboring A. pulmonis. Metagenomic analyses demonstrate an increased abundance of Achromobacter in the fecal of Crohn's disease patients compared to healthy controls. A comprehensive comparison of total microbial vT3SS abundance in various intestine diseases demonstrated that the specific enrichment of vT3SS genes was shown in fecal samples of CD, neither ulcerative colitis nor colorectal cancer patients, and ten T3SS gene-based biomarkers for CD were discovered and validated in a newly recruited CD cohort. Furthermore, treatment with exclusive enteral nutrition (EEN), an intervention that improves CD patient symptomatology, was found associated with a significant reduction in the prevalence of T3SS genes in fecal samples. These findings highlight the pathogenic significance of T3SSs in the context of CD and identify specific T3SS genes that could potentially function as biomarkers for diagnosing and monitoring the clinical status of CD patients. This work is supported by the National Key Research and Development Program of China (2020YFA0907800), the China Postdoctoral Science Foundation (2023M744089), the National Natural Science Foundation of China (32000096), the Shenzhen Science and Technology Programs (KQTD20200820145822023, RCIC20231211085944057, and ZDSYS20220606100803007), National Key Clinical Discipline, Guangdong Provincial Clinical Research Center for Digestive Diseases (2020B1111170004), Qingfeng Scientific Research Fund of the China Crohn's & Colitis Foundation (CCCF) (CCCF-QF-2022B71-1), and the Sixth Affiliated Hospital, Sun Yat-sen University Clinical Research 1010 Program 1010CG(2023)-08. These funding provided well support for this research work, which involved data collection, analysis, interpretation, patient recruitment and so on.

TriFusion enables accurate prediction of miRNA-disease association by a tri-channel fusion neural network.

The identification of miRNA-disease associations is crucial for early disease prevention and treatment. However, it is still a computational challenge to accurately predict such associations due to improper information encoding. Previous methods characterize miRNA-disease associations only from single levels, causing the loss of multi-level association information. In this study, we propose TriFusion, a powerful and interpretable deep learning framework for miRNA-disease association prediction. It develops a tri-channel architecture to encode the association features of miRNAs and diseases from different levels and designs a feature fusion encoder to smoothly fuse these features. After training and testing, TriFusion outperforms other leading methods and offers strong interpretability through its learned representations. Furthermore, TriFusion is applied to three high-risk sexually associated cancers (ovarian, breast, and prostate cancers) and exhibits remarkable ability in the identification of miRNAs associated with the three diseases.

Unraveling the Structure and Dynamics of Ac-PHF6-NH2 Tau Segment Oligomers.

The aggregation of the proteins tau and amyloid-β is a salient feature of Alzheimer's disease, the most common form of neurodegenerative disorders. Upon aggregation, proteins transition from their soluble, monomeric, and functional state into insoluble, fibrillar deposits through a complex process involving a variety of intermediate species of different morphologies, including monomers, toxic oligomers, and insoluble fibrils. To control and direct peptide aggregation, a complete characterization of all species present and an understanding of the molecular processes along the aggregation pathway are essential. However, this is extremely challenging due to the transient nature of oligomers and the complexity of the reaction networks. Therefore, we have employed a combined approach that allows us to probe the structure and kinetics of oligomeric species, following them over time as they form fibrillar structures. Targeting the tau protein peptide segment Ac-PHF6-NH2, which is crucial for the aggregation of the full protein, soft nano-electrospray ionization combined with ion mobility mass spectrometry has been employed to study the kinetics of heparin-induced intact oligomer formation. The oligomers are identified and characterized using high-resolution ion mobility mass spectrometry, demonstrating that the addition of heparin does not alter the structure of the oligomeric species. The kinetics of fibril formation is monitored through a Thioflavin T fluorescence assay. Global fitting of the kinetic data indicates that secondary nucleation plays a key role in the aggregation of the Ac-PHF6-NH2 tau segment, while the primary nucleation rate is greatly accelerated by heparin.

Shared and distinct cortical morphometric alterations in five neuropsychiatric symptoms of Parkinson's disease.

Neuropsychiatric symptoms (including anxiety, depression, apathy, impulse-compulsive behaviors and hallucinations) are among the most common non-motor features of Parkinson's disease. Whether these symptoms should be considered as a direct consequence of the pathophysiologic mechanisms of Parkinson's disease is controversial. Morphometric similarity network analysis and epicenter mapping approach were performed on T1-weighted images of 505 patients with Parkinson's disease and 167 age- and sex-matched healthy participants from Parkinson's Progression Markers Initiative database to reveal the commonalities and specificities of distinct neuropsychiatric symptoms. Abnormal cortical co-alteration pattern in patients with neuropsychiatric symptoms was in somatomotor, vision and frontoparietal regions, with epicenters in somatomotor regions. Apathy, impulse-compulsive behaviors and hallucinations shares structural abnormalities in somatomotor and vision regions, with epicenters in somatomotor regions. In contrast, the cortical abnormalities and epicenters of anxiety and depression were prominent in the default mode network regions. By embedding each symptom within their co-alteration space, we observed a cluster composed of apathy, impulse-compulsive behaviors and hallucinations, while anxiety and depression remained separate. Our findings indicate different structural mechanisms underlie the occurrence and progression of different neuropsychiatric symptoms. Based upon these results, we propose that apathy, impulse-compulsive behaviors and hallucinations are directly related to damage of motor circuit, while anxiety and depression may be the combination effects of primary pathophysiology of Parkinson's disease and psychosocial causes.

Telomere biology disorders: from dyskeratosis congenita and beyond.

Defective telomerase function or telomere maintenance causes genomic instability. Alterations in telomere length and/or attrition are the primary features of rare diseases known as telomere biology disorders or telomeropathies. Recent advances in the molecular basis of these disorders and cutting-edge methods assessing telomere length have increased our understanding of this topic. Multiorgan manifestations and different phenotypes have been reported even in carriers within the same family. In this context, apart from dyskeratosis congenita, disorders formerly considered idiopathic (i.e. pulmonary fibrosis, liver cirrhosis) frequently correlate with underlying defective telomere maintenance mechanisms. Moreover, these patients are prone to developing specific cancer types and exhibit exceptional sensitivity and toxicity in standard chemotherapy regimens. The current review describes the diverse spectrum of clinical manifestations of telomere biology disorders in pediatric and adult patients, their correlation with pathogenic variants, and considerations during their management to increase awareness and improve a multidisciplinary approach.

Ultra-Wide-Field Fluorescein Angiographic Features Influencing Visual Prognosis in Coats' Disease.

To investigate the retinal vascular abnormalities in both affected and fellow eyes of presumed unilateral Coats' disease patients using ultra-wide-field fluorescein angiography (UWF-FA) and their association with visual prognosis. A retrospective review of 30 patients diagnosed with presumed unilateral Coats' disease, evaluated with UWF-FA from March 2003 to May 2024 in a tertiary referral hospital. Clinical features and multimodal imaging findings were evaluated and factors related to final visual outcomes were analyzed. All 30 patients were diagnosed with presumed unilateral Coats' disease at presentation, comprising 36.7% childhood-onset and 63.3% adult-onset patients. Retinal vascular telangiectasia was observed in 51.7% of fellow eyes. The extent of telangiectasia and exudate in the affected eyes did not significantly correlate with extent of telangiectasia in the fellow eyes. In the more affected eyes, the childhood-onset group had a significantly greater extent of capillary drop-out compared to the adult-onset group (5.0 vs 2.8 clock hours, p = 0.023). In the fellow eyes, telangiectasia tended to be more frequent in the childhood-onset group (63.6% vs. 44.4%), without significance (p = 0.160). In the multivariable regression analysis, the final best-corrected visual acuity (BCVA) in the more affected eye was significantly associated with initial BCVA. The mean extent of telangiectasia in the temporal and nasal quadrants and the initial BCVA of the more affected eyes were identified as prognostic factors for final moderate to severe visual loss (Snellen BCVA < 20/66) (OR = 12.8, p = 0.043; OR = 11.8, p = 0.024, respectively). About half of presumed unilateral Coats' disease cases exhibited features of bilateral disease. Visual prognosis is associated with the peripheral retinal telangiectasia in the temporal and nasal quadrants as well as initial BCVA in the affected eyes while it is not associated with retinal vascular abnormalities in the fellow eyes.