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NSPLformer: exploration of non-stationary progressively learning model for time series prediction
Interventions to improve cognitive performance in chronic kidney disease: A scoping review
Rationale & objective Cognitive impairment is commonly associated with chronic kidney disease (CKD. A number of intervention approaches have the potential to improve cognitive performance in CKD. Our objective was to characterize interventions studied to improve cognitive performance for adults with CKD across all categories of severity, including kidney failure. Study design Scoping review following JBI methodology. Setting and study populations Adults (≥18 years) with CKD or kidney failure. Selection criteria for studies We searched 5 electronic databases for studies published up to April 5, 2024. Eligible sources were primary research studies that investigated any intervention targeting cognition in adults (≥18 years) with CKD or kidney failure. Full-text article screening was performed in duplicate. Data extraction Characteristics of interventions, populations studied, and outcomes investigated. Analytical approach Descriptive statistics and narrative syntheses. Results Seventy-one studies were included. Over half (n = 37, 52%) were conducted within the past five years, and most studies (n = 47, 66%) targeted people on maintenance hemodialysis therapy. Just over one-third of studies investigated pharmacological interventions, with much of the pharmacological or medical research focusing on anemia management or dialysis adequacy. Although recent research has expanded in focus, many other purported mechanisms of cognitive dysfunction in CKD remain understudied in interventional research. Exercise training (n = 14) was the most common nonpharmacological approach studied, but few studies have explored other promising nonpharmacological approaches such as cognitive rehabilitation interventions. Limitations Abstract screening not performed in duplicate; non-English studies excluded. Conclusion Research into cognitive interventions for people with kidney disease has primarily focused on the hemodialysis population and investigated erythropoietin stimulating agents, frequent or prolonged dialysis, and exercise, although there has been recent growth of research activity into other interventions. Future research should aim to address a broader range of purported pathophysiological mechanisms of cognitive impairment in CKD, investigate interventions for predialysis and peritoneal dialysis patients, and explore the impacts of established cognitive rehabilitation approaches.
Spatial transcriptomics reveals human cortical layer and area specification
Abstract The human cerebral cortex is composed of six layers and dozens of areas that are molecularly and structurally distinct1–4. Although single-cell transcriptomic studies have advanced the molecular characterization of human cortical development, a substantial gap exists owing to the loss of spatial context during cell dissociation5–8. Here we used multiplexed error-robust fluorescence in situ hybridization (MERFISH)9, augmented with deep-learning-based nucleus segmentation, to examine the molecular, cellular and cytoarchitectural development of the human fetal cortex with spatially resolved single-cell resolution. Our extensive spatial atlas, encompassing more than 18 million single cells, spans eight cortical areas across seven developmental time points. We uncovered the early establishment of the six-layer structure, identifiable by the laminar distribution of excitatory neuron subtypes, 3 months before the emergence of cytoarchitectural layers. Notably, we discovered two distinct modes of cortical areal specification during mid-gestation: (1) a continuous, gradual transition observed across most cortical areas along the anterior–posterior axis and (2) a discrete, abrupt boundary specifically identified between the primary (V1) and secondary (V2) visual cortices as early as gestational week 20. This sharp binary transition in V1–V2 neuronal subtypes challenges the notion that mid-gestation cortical arealization involves only gradient-like transitions6,10. Furthermore, integrating single-nucleus RNA sequencing with MERFISH revealed an early upregulation of synaptogenesis in V1-specific layer 4 neurons. Collectively, our findings underscore the crucial role of spatial relationships in determining the molecular specification of cortical layers and areas. This study establishes a spatially resolved single-cell analysis paradigm and paves the way for the construction of a comprehensive developmental atlas of the human brain.
Investigating the correlation between IDO1/PD-L1 expression or co-expression and EGFR/KRAS gene mutations in advanced NSCLC
Ghrelin improves small intestinal barrier damage in sepsis by promoting miR-143/ATG2B-mediated autophagy
Intestinal barrier damage is crucial for the development of sepsis. Ghrelin (GHS) can restore intestinal barrier function. However, the mechanisms of GHS on intestinal barrier damage in sepsis remain unclear. We aimed to explore the mechanisms of GHS against intestinal barrier damage in sepsis. Septic models were established by cecal ligation and puncture surgery for rats and lipopolysaccharides exposure for IEC-6 cells. Furthermore, these septic models were overexpressed miR-143 and treated with GHS. In vivo, small intestinal pathological injury and D-lactic acid level were detected. Tight junction protein (Claudin-1, Occludin and ZO-1) expressions and autophagosome number were evaluated. In vitro, cell viability, autolysosome number, and relationship between miR-143 and ATG2B were determined. miR-143, ATG2B and autophagy-related protein (Beclin-1, p62 and LC3I/LC3II) levels were evaluated in rats and cells. GHS mitigated small intestinal pathological injury and decreased D-lactic acid level for septic rats. Additionally, GHS elevated tight junction protein expressions, ATG2B, Beclin-1 and LC3I/LC3II levels, and autophagosome number, but reduced miR-143 and p62 levels for septic rats. However, miR-143 overexpression presented the opposite results. Consistently, cellular experiments found that GHS increased cell viability, autolysosome number, and presented similar results for miR-143, ATG2B and autophagy-related protein levels for lipopolysaccharides-exposed cells. Additionally, ATG2B directly targeted miR-143 in IEC-6 cells. Both animal and cellular experiments found the effects of GHS on sepsis-induced small intestinal barrier damage were reversed by miR-143 overexpression. GHS may improve small intestinal barrier damage in sepsis through miR-143/ATG2B-mediated autophagy, indicating miR-143/ATG2B was an underlying therapeutic target for sepsis.
Neuronal transfer of mitochondria to tumour cells promotes cancer spread
Green supply chain strategy considering participant fairness concern and uncertainty of research and development
AI-Assisted identification of sex-specific patterns in diabetic retinopathy using retinal fundus images
Diabetic retinopathy (DR) is a microvascular complication of diabetes that can lead to blindness if left untreated. Regular monitoring is crucial for detecting early signs of referable DR, and the progression to moderate to severe non-proliferative DR, proliferative DR (PDR), and macular edema (ME), the most common cause of vision loss in DR. Currently, aside from considerations during pregnancy, sex is not factored into DR diagnosis, management or treatment. Here we examine whether DR manifests differently in male and female patients, using a dataset of retinal images and leveraging convolutional neural networks (CNN) integrated with explainable artificial intelligence (AI) techniques. To minimize confounding variables, we curated 2,967 fundus images from a larger dataset of DR patients acquired from EyePACS, matching male and female groups for age, ethnicity, severity of DR, and hemoglobin A1C levels. Next, we fine-tuned two pre-trained VGG16 models—one trained on the ImageNet dataset and another on a sex classification task using healthy fundus images—achieving AUC scores of 0.72 and 0.75, respectively, both significantly above chance level. To uncover how these models distinguish between male and female retinas, we used the Guided Grad-CAM technique to generate saliency maps, highlighting critical retinal regions for correct classification. Saliency maps showed CNNs focused on different retinal regions by sex: the macula in females, and the optic disc and peripheral vasculature along the arcades in males. This pattern differed noticeably from the saliency maps generated by CNNs trained on healthy eyes. These findings raise the hypothesis that DR may manifest differently by sex, with women potentially at higher risk for developing ME, as opposed to men who may be at greater risk for PDR.
Giardia duodenalis stabilizes HIF-1α and induces glycolytic alterations in intestinal epithelial cells
Environmental politics is doomed to fail — unless we tell better stories
ITGAV as a promising diagnostic, immunological, and prognostic biomarker in pan-cancer
Abstract Integrin αV (ITGAV) plays a key role in cell adhesion, migration, and immune regulation, and is implicated in tumor progression. However, its comprehensive expression profile and functional relevance across different cancers remain poorly understood. We conducted an integrative pan-cancer analysis of ITGAV using data from TCGA, GTEx, CCLE, and other public databases. Expression, diagnostic value (via ROC analysis), and prognostic significance (via Cox and Kaplan–Meier analyses of OS, DSS, PFS, and DFS) were assessed. We further explored ITGAV’s correlation with immune cell infiltration and immune-related genes, its predictive role in immunotherapy response based on immunophenoscore (IPS), and its drug-binding potential through molecular docking. (1) ITGAV was significantly overexpressed in multiple cancer types including LIHC, COAD, and STAD. (2) ROC analysis confirmed its strong diagnostic value, particularly in HNSC, UCEC, and ESCA. (3) High ITGAV expression was associated with poorer survival outcomes in most cancers, while a protective role was observed in KIRC. (4) ITGAV expression was positively correlated with immune cell infiltration and co-expressed with immune-activating and immunosuppressive genes. (5) The expression level of ITGAV correlates with the IPS score, suggesting its predictive value for the benefit of immunotherapy. (6) Molecular docking identified strong binding affinities between ITGAV and six candidate compounds, including gemcitabine and pioglitazone. Our findings demonstrate that ITGAV is a promising biomarker for diagnosis, prognosis, and immunotherapy prediction across cancers. Its immunological associations and druggability highlight its potential as a candidate therapeutic target.
Machine learning derived development and validation of extracellular matrix related signature for predicting prognosis in adolescents and young adults glioma
Abstract The mortality rates have been increasing for glioma in adolescents and young adults (AYAs, aged 15–39 years). However, current biomarkers for clinical assessment in AYAs glioma are limited, prompting the urgent need for identifying ideal prognostic signature. Extracellular matrix is involved in the development of tumors, while their prognostic significance in AYAs glioma remains unclear. By an integrated machine learning workflow and circuit training and validation procedure, we developed a machine learning-derived prognostic signature (MLDPS) based on 1,026 extracellular matrix-related genes and 3 AYAs glioma cohorts. MLDPS exhibited robust and consistent predictive performance in overall survival and could serve as an independent prognostic factor for AYAs glioma. Simultaneously, MLDPS outperformed previous 89 published prognostic signatures and traditional clinical characteristics, confirming the robust predictive capability. Besides, MLDPS had the potential to stratify prognosis in patients with other cancer types. In addition, the tumor microenvironment between high and low MLDPS groups displayed different patterns while more tumor-infiltrating immune cells were observed in high MLDPS group. Additionally, patients in low MLDPS group had significantly prolonged survival when received immunotherapy in cancers including glioblastoma, urothelial carcinoma and melanoma. Overall, our study proposes a promising signature, which can be utilized for clinicians to evaluate prognosis and might provide individualized clinical management for AYAs glioma.