The state-of-art polyurethane nanoparticles for drug delivery applications.

Nowadays, polyurethanes (PUs) stand out as a promising option for drug delivery owing to their versatile properties. PUs have garnered significant attention in the biomedical sector and are extensively employed in diverse forms, including bulk devices, coatings, particles, and micelles. PUs are crucial in delivering various therapeutic agents such as antibiotics, anti-cancer medications, dermal treatments, and intravaginal rings. Effective drug release management is essential to ensure the intended therapeutic impact of PUs. Commercially available PU-based drug delivery products exemplify the adaptability of PUs in drug delivery, enabling researchers to tailor the polymer properties for specific drug release patterns. This review primarily focuses on the preparation of PU nanoparticles and their physiochemical properties for drug delivery applications, emphasizing how the formation of PUs affects the efficiency of drug delivery systems. Additionally, cutting-edge applications in drug delivery using PU nanoparticle systems, micelles, targeted, activatable, and fluorescence imaging-guided drug delivery applications are explored. Finally, the role of artificial intelligence and machine learning in drug design and delivery is discussed. The review concludes by addressing the challenges and providing perspectives on the future of PUs in drug delivery, aiming to inspire the design of more innovative solutions in this field.

Comprehension of metaphors in patients with mild cognitive impairment: Evidence from behavioral and ERP data.

The ability of metaphor comprehension reflects the cognitive status of elders. This study explored the ability of Chinese aMCI patients to access metaphorical meaning based on linguistic models of metaphor processing. ERPs were recorded from 30 aMCI patients and 30 control participants when judging the meaningfulness of literal sentences, conventional metaphors, novel metaphors, and anomalous expressions. The lower accuracy of the aMCI group revealed an impairment in metaphoric comprehension ability, but this difference was not reflected in ERPs data. In all participants, anomalous endings to sentences evoked the most negative N400 amplitude, whereas conventional metaphors evoked the smallest N400 amplitude. The LPC amplitude might be masked by a metaphor rebound effect when processing novel metaphors, which was consistent with the Graded Salience Model that novel metaphors needed further semantic integration. The results suggest that the aMCI patients may suffer an impairment in metaphorical meaning recognition, which the declined working memory may cause.

Older adults' refusal speech act in cognitive assessment: A multimodal pragmatic perspective.

This paper explores how older adults with different cognitive abilities perform the refusal speech act in the cognitive assessment in the setting of memory clinics. The refusal speech act and its corresponding illocutionary force produced by nine Chinese older adults in the Montreal Cognitive Assessment-Basic was annotated and analyzed from a multimodal perspective. Overall, regardless of the older adults' cognitive ability, the most common discursive device to refuse is the demonstration of their inability to carry out or continue the cognitive task. Individuals with lower cognitive ability were found to perform the refusal illocutionary force (hereafter RIF) with higher frequency and degree. Additionally, under the pragmatic compensation mechanism, which is influenced by cognitive ability, multiple expression devices (including prosodic features and non-verbal acts) interact dynamically and synergistically to help older adults carry out the refusal behavior and to unfold older adults' intentional state and emotion as well. The findings indicate that both the degree and the frequency of performing the refusal speech act in the cognitive assessment are related to the cognitive ability of older adults.

Comparative analysis of sensitivity and specificity of computer-aided cognitive test in screening mild cognitive impairment patients and test of reliability and validity.

OBJECTIVES: To evaluate the reliability and validity of the computer-aided cognitive test (CACT). METHODS: 219 Subjects of Tongji Hospital's Brain Health cohort (115 cases of Mild Cognitive Impairment (MCI) patients and 104 cases of normal controls) were enrolled, of which 24 cases received a retest after 2 weeks. Finally, the reliability and validity of the scale were tested and analyzed. RESULTS: (1) Reliability: (a) the internal consistency reliability of the total score of the scale was 0.645; (b) the retest reliability correlation coefficient of the total score of the scale was 0.900; (c) the Guttman Split-Half coefficient was 0.631; (2) Validity: (a) construct validity analysis showed that the correlation coefficient between each section score was between 0.036 and 0.408, and the correlation coefficient between each section score and the total score was between 0.468 and 0.781; (b) criterion validity analysis showed that the correlation coefficient between the total score of CACT and that of the Mini Mental State Examination (MMSE) was 0.733, and the coefficient between the total score of CACT and that of the basic version of the Montreal Cognitive Assessment (MoCA) was 0.763; (c) the area under the ROC curve of the CACT to distinguish between MCI patients and controls was 0.920, with an optimal diagnostic threshold of 20, a sensitivity of 88.5%, and a specificity of 80.9%. CONCLUSION: The CACT is little influenced by education level. It has good reliability and validity, which can be used for early clinical screening of cognitive dysfunction.

Research on nonstroke dementia screening and cognitive function prediction model for older people based on brain atrophy characteristics.

BACKGROUND: Brain atrophy is an important feature in dementia and is meaningful to explore a brain atrophy model to predict dementia. Using machine learning algorithm to establish a dementia model and cognitive function model based on brain atrophy characteristics is unstoppable. METHOD: We acquired 157 dementia and 156 normal old people.s clinical information and MRI data, which contains 44 brain atrophy features, including visual scale assessment of brain atrophy and multiple linear measurement indexes and brain atrophy index. Five machine learning models were used to establish prediction models for dementia, general cognition, and subcognitive domains. RESULTS: The extreme Gradient Boosting (XGBoost) model had the best effect in predicting dementia, with a sensitivity of 0.645, a specificity of 0.839, and the area under curve (AUC) of 0.784. In this model, the important brain atrophy features for predicting dementia were temporal horn ratio, cella media index, suprasellar cistern ratio, and the thickness of the corpus callosum genu. CONCLUSION: For nonstroke elderly people, the machine learning model based on clinical head MRI brain atrophy features had good predictive value for dementia, general cognitive impairment, immediate memory impairment, word fluency disorder, executive dysfunction, and visualspatial disorder.

Incompleteness features in the descriptive discourse of Chinese elders with and without Alzheimer's disease.

Alzheimer's disease (AD) can manifest itself with prominent language dysfunction. Incompleteness in discourse refers to the lack of indispensable sentence-constructing elements that hinder communication fluency and accuracy. The current study investigates how the pattern of incompleteness is associated with the descriptive discourse produced by elders without AD and those with different stages of AD. The Chinese discourse samples were collected from the picture description of 40 elders with mild probable AD (Mini-Mental State Examination (MMSE) 21-26, Montreal Cognitive Assessment Scale-Basic (MoCA-B) 15-19), 40 elders with moderate probable AD (MMSE 11-20, MoCA-B 10-14), and 40 controls (MMSE 26-29, MoCA-B 24-29). The total production of incomplete sentences and six incompleteness features were examined. The Mild AD, Moderate AD, and Control groups differed in the total output of the incomplete sentence. Group differences also emerged in four incompleteness features: missing subject, missing predicate, missing object, and missing functional word. The Moderate AD group differed from the Mild AD group with respect to most significant features, while Mild AD and Control groups were very similar. The results suggested that AD impairs the sentence construction ability of Chinese elders, especially at the later stage. These statistically significant differences between the groups might provide some references when diagnosing the risk and possibility of cognitive impairment of Chinese elders, facilitating the design of clinical evaluation or screening for probable AD.

Neural Mechanism of Repeated Transcranial Magnetic Stimulation to Enhance Visual Working Memory in Elderly Individuals With Subjective Cognitive Decline.

Visual working memory (VWM), the core process inherent to many advanced cognitive processes, deteriorates with age. Elderly individuals usually experience defects in the processing of VWM. The dorsolateral prefrontal cortex is a key structure for the top-down control of working memory processes. Many studies have shown that repeated transcranial magnetic stimulation (rTMS) improves VWM by modulating the excitability of neurons in the target cortical region, though the underlying neural mechanism has not been clarified. Therefore, this study sought to assess the characteristics of brain memory function post-rTMS targeting the left dorsolateral prefrontal cortex. The study stimulated the left dorsolateral prefrontal cortex in elderly individuals by performing a high-frequency rTMS protocol and evaluated behavioral performance using cognitive tasks and a VWM task. Based on the simultaneously recorded electroencephalogram signals, event-related potential and event-related spectral perturbation analysis techniques were used to investigate the variation characteristics of event-related potential components' (N2PC and CDA) amplitudes and neural oscillations in elderly individuals to elucidate the effect of high-frequency rTMS. The results found that rTMS enhanced VWM performance and significantly improved attention and executive function in elderly individuals with subjective cognitive decline. We therefore speculate that rTMS enhances VWM by increasing the N2PC and CDA amplitude, alongside increasing ß oscillation activity. This would improve the attention and allocation of resources in elderly individuals such as to improve an individual's VWM.

Clinical characteristics of perivascular space and brain CT perfusion in stroke-free patients with intracranial and extracranial atherosclerosis of different extents.

BACKGROUND: This study aimed to investigate the clinical characteristics of perivascular space (PVS) and cerebral blood flow (CBF) in stroke-free patients with intracranial and extracranial atherosclerosis of different extents. METHODS: Two hundred and twenty-two patients received carotid artery ultrasonography, magnetic resonance imaging (MRI), cranial computed tomography angiography (CTA) and computed tomography perfusion (CTP). PVS was scored. The extents of intracranial and extracranial arteriosclerosis were evaluated based on the scores of intracranial and extracranial arteriosclerosis. CTP was done to determine the CBF in the region of interest (ROI). The risk factors of vascular disease were assessed in patients with and without PVS. The relationship between PVS and CBF was evaluated among patients with different scores of intracranial and extracranial atherosclerosis. RESULTS: The incidences of intracranial atherosclerosis and extracranial carotid plaque were higher in PVS patients. Subjects with intracranial and/or extracranial arteriosclerosis also had a higher incidence of PVS as compared to controls. The score of intracranial and/or extracranial arteriosclerosis was positively related to the score of basal ganglia PVS. Patients with intracranial and/or extracranial arteriosclerosis had lower CBF as compared to controls. The CBF was negatively associated with the intracranial and/or extracranial arteriosclerosis and the PVS score. CONCLUSIONS: The incidence of PVS in patients with intracranial and extracranial arteriosclerosis is higher than in patients without arteriosclerosis. The extent of intracranial and extracranial atherosclerosis is related to PVS, especially the basal ganglia PVS. The decreased CBF may be associated with the occurrence of PVS.

Analysis of correlation between cerebral perfusion and KIM score of white matter lesions in patients with Alzheimer's disease.

PURPOSE: This study aimed to characterize white matter lesions (WMLs) and regional cerebral perfusion, and evaluate their correlations with cognitive deficits in Alzheimer's disease (AD) patients. PATIENT AND METHODS: One hundred and twenty-eight patients with AD (AD group) and 75 subjects without AD (control group) were recruited. The medical information was collected from each subject. Montreal cognitive assessment (MoCA) was employed for the assessment of cognition. Cranial MRI was performed, and the KIM scoring system was used to evaluate the white matter hyperintensity. The CT perfusion (CTP) imaging was employed to assess the whole cerebral perfusion, and the region of interest (ROI) was selected to determine the blood perfusion at different parts. RESULTS: The education level and MoCA score in AD group were significantly lower than in control group (P<0.001). The KIM score of juxtaventricular WML (JVWMLs) was significantly different between two groups (P<0.05) and AD group showed a higher incidence of severe JVWML and periventricular WML (PVWMLs); in AD group, the total KIM score and KIM scores of JVWMLs, PVWMLs and deep WML (DWMLs) showed negative relationships with the MoCA score (P<0.001). As compared to control group, the blood perfusion of either whole brain or different parts in the AD group reduced significantly (P<0.05). In the AD group, there was a negative correlations of blood perfusion at JVWM and PVWM with corresponding KIM scores (P<0.05 or 0.01). In the AD group, the blood perfusions of the whole brain, JVWMLs, PVWMLs and deep WML were negatively related to MoCA score (P<0.05). CONCLUSION: In conclusion, the cognitive deficits in the AD patients are associated with the degree of WMLs, especially the JVWML, PVWML and DWML as well as with the reduced perfusion of JVWM, PVWM and deep WM.

Discovery of Aberrant Alteration of Genome in Colorectal Cancer by Exome Sequencing.

BACKGROUND: This study analyzed multiple parameters including somatic single nucleotide variations (SNVs), Insertion/Deletions, significantly mutated genes (SMGs), copy number variations and frequently altered pathways aims to discover novel aberrances in the tumorigenesis of colorectal cancer (CRC). MATERIALS AND METHODS: Exome sequencing was performed on an Illumina platform to identify novel potential somatic variances in 34 paired tumor and adjacent normal tissues from 17 CRC patients. Results were compared with databases (dbSNP138, 1000 genomes SNP, Hapmap, Catalogue of Somatic Mutation of Cancer and ESP6500) and analyzed. MuSic software was used to identify SMGs. RESULTS: In total, 1,637 somatic SNVs in 17 analyzed tumors were identified. Only 7 SNVs were shared by more than 1 tumor, suggesting that over 99% of the analyzed SNVs were independent events. Mutation of KRAS p. G12D and ZNF717 p. L39V were the most common SNVs. Moreover, 10 SMGs namely KRAS, TP53, SMAD4, ZNF717, FBXW7, APC, ZNF493, CDR1, the Armadillo repeat containing 4 (ARMC4) and sulfate-modifying factor 2 (SUMF2) were found. Among those, ZNF717, ZNF493, CDR1, ARMC4 and SUMF2 were novel frequent genes in CRC. For copy number variations analysis, gains in 10q25.3, 1p31.1, 1q44, 10q23.33, 11p15.4 and 20q13.33, and loss of 3q21.3 and 3q29 were frequent aberrations identified in our results. CONCLUSIONS: We frequently found novel genes ZNF717, ZNF493, CDR1, ARMC4 and SUMF2 and gains in 10q25.3, which may be functional mutation in CRC. The high-frequency private events such as SNVs confirm the highly heterogeneous mutations found in CRCs. The mutated genes sites in different patients may vary significantly, which may also be more challenging for clinical treatment.