A region-specific modulation of sleep slow waves on interictal epilepsy markers in focal epilepsy.

OBJECTIVE: Sleep strongly activates interictal epileptic activity through an unclear mechanism. We investigated how scalp sleep slow waves (SSWs), whose positive and negative half-waves reflect the fluctuation of neuronal excitability between the up and down states, respectively, modulate interictal epileptic events in focal epilepsy. METHODS: Simultaneous polysomnography was performed in 45 patients with drug-resistant focal epilepsy during intracranial electroencephalographic recording. Scalp SSWs and intracranial spikes and ripples (80-250 Hz) were detected; ripples were classified as type I (co-occurring with spikes) or type II (occurring alone). The Hilbert transform was used to analyze the distributions of spikes and ripples in the phases of SSWs. RESULTS: Thirty patients with discrete seizure-onset zone (SOZ) and discernable sleep architecture were included. Intracranial spikes and ripples accumulated around the negative peaks of SSWs and increased with SSW amplitude. Phase analysis revealed that spikes and both ripple subtypes in SOZ were similarly facilitated by SSWs exclusively during down state. In exclusively irritative zones outside SOZ (EIZ), SSWs facilitated spikes and type I ripples across a wider range of phases and to a greater extent than those in SOZ. The type II and type I ripples in EIZ were modulated by SSWs in different patterns. Ripples in normal zones decreased specifically during the up-to-down transition and then increased after the negative peak of SSW, with a characteristically high post-/pre-negative peak ratio. SIGNIFICANCE: SSWs modulate interictal events in an amplitude-dependent and region-specific pattern. Pathological ripples and spikes were facilitated predominantly during the cortical down state. Coupling analysis of SSWs could improve the discrimination of pathological and physiological ripples and facilitate seizure localization.

The Value of the Cardiac Magnetic Resonance Intravoxel Incoherent Motion Technique in Evaluating Microcirculatory Dysfunction in Hypertrophic Cardiomyopathy.

Objective: To evaluate the value of the cardiac magnetic resonance intravoxel incoherent motion (IVIM) technique in microcirculatory dysfunction in patients with hypertrophic cardiomyopathy (HCM). Methods: The medical records of 19 patients with HCM in our hospital from January 2020 to May 2021 were collected retrospectively, and 23 healthy people with a similar age and gender distribution to the patients with HCM were included as controls. All the included subjects underwent clinical assessment and cardiac magnetic resonance imaging. The original IVIM images were analysed, and the imaging parameters of each segment were measured. The HCM group was divided into non-hypertrophic myocardium and hypertrophic myocardium groups. The differences in imaging parameters between the normal and HCM groups were compared. A Spearman correlation analysis was used to explore the correlation between end-diastolic thickness (EDTH) and each IVIM parameter. Results: The D∗ and f values in the HCM group were lower than those in the normal group (p < 0.0001 and p = 0.004, respectively). The f, D, D∗, and EDTH values of the hypertrophic segment, non-hypertrophic segment, and normal groups were statistically significant (p < 0.05). The difference in D∗ values among the mild, moderate, severe, and very severe HCM groups was statistically significant (p < 0.05). There was a statistically significant difference in EDTH among the mild, moderate, severe, and very severe groups (p < 0.001). There were significant differences in the values of D, D∗, and f between the non-delayed enhancement group and the delayed enhancement group (p < 0.05). The EDTH values of 304 segments in the HCM group were negatively correlated with f (r = -0.219, p = 0.028) and D∗ values (r = -0.310, p < 0.001). Conclusion: The use of IVIM technology can achieve a non-invasive early quantitative assessment of microvascular disease in HCM without the injection of a contrast agent and provide a reference for the early diagnosis of and intervention in myocardial ischemia in patients with HCM.

A rare case report of primary Sjögren's syndrome with clinical characteristics similar to those of CLIPPERS.

BACKGROUND: Primary Sjögren's syndrome (pSS) is an autoimmune inflammatory disease characterized by dryness of the eyes, mouth and other mucous membranes. Patients with pSS can also present with extraglandular manifestations, such as pulmonary, kidney and nervous system involvement. Central nervous system (CNS) manifestations have rarely been described in pSS. CASE PRESENTATION: A 33-year-old man was admitted with a one-month history of dizziness, speech disturbance, and walking instability. His brain enhanced magnetic resonance imaging (MRI) showed symmetrical, enhanced "salt-and-pepper-like" speckled lesions in the brainstem, basal ganglia, and subcortical regions, and his diagnosis was considered possible chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Further examination revealed that anti-SSA antibody was positive, and the Schirmer test and labial salivary gland histopathology were abnormal, which supported the diagnosis of pSS. CONCLUSION: pSS is a chronic systemic autoimmune disease that involves neurological complications. This case suggests that CNS lesions of pSS can present with clinical and MRI findings similar to those of CLIPPERS.

The Role of the Three-Dimensional Edge-Enhancing Gradient Echo Sequence at 3T MRI in the Detection of Focal Cortical Dysplasia: A Technical Case Report and Literature Review.

INTRODUCTION: Focal cortical dysplasia (FCD) is a most common cause of intractable focal epilepsy in children. Surgery is considered as a radical option for such patients with the prerequisite of lesion detection. Magnetic resonance imaging (MRI) plays a significant role in detection of FCDs in epilepsy patients; however, the detection of FCDs even in epilepsy dedicated MRI sequence shows relatively low positive rate. Last year, Middlebrooks et al introduced the novel three-dimensional Edge-Enhancing Gradient Echo (3D-EDGE) MRI sequence and using this sequence successfully identified five cases of FCDs which indicates its potential role in those epilepsy patients who may have FCDs. CASE PRESENTATION: We present a 14-year-old, right-handed, male patient who has suffered from drug-resistant epilepsy over the past 3 years. It was unable to localize the lesion of the seizure, even using the series of epilepsy dedicated MRI sequences. Inspired by the previous report, the lesion of the seizure was successfully targeted by 3D-EDGE sequence. Combined with intraoperative navigation and precisely removed the lesion. He was uneventfully recovered with no signs of cerebral dysfunction and no seizure recurrence 8 months after surgery. CONCLUSION: The 3D-EDGE sequences show a higher sensitivity for FCD detection in epilepsy patients compared with a series of epilepsy-dedicated MRI protocols. We confirmed that the study by Middlebrooks et al is of great clinical value. If the findings on routine MRI sequences or even epilepsy-dedicated MRI sequences were reported as negative, however, the semiology, video-electroencephalography, and fluorodeoxyglucose-positron emission tomography results suggest a local abnormality, and the results are concordant with each other, a 3D-EDGE sequence may be a good option.

Focal cortical dysplasia links to sleep-related epilepsy in symptomatic focal epilepsy.

OBJECTIVE: In sleep-related epilepsy (SRE), epileptic seizures predominantly occur during sleep, but the clinical characteristics of SRE remain elusive. We aimed to identify the clinical features associated with the occurrence of SRE in a large cohort of symptomatic focal epilepsy. METHODS: We retrospectively included patients with four etiologies, including focal cortical dysplasia (FCD), low-grade tumors (LGT), temporal lobe epilepsy with hippocampal sclerosis (TLE-HS), and encephalomalacia. SRE was defined as more than 70% of seizures occurring during sleep according to the seizure diary. The correlation between SRE and other clinical variables, such as etiology of epilepsy, pharmacoresistance, seizure frequency, history of bilateral tonic-clonic seizures, and seizure localization was analyzed. RESULTS: A total of 376 patients were included. Among them 95 (25.3%) were classified as SRE and the other 281(74.7%) as non-SRE. The incidence of SRE was 53.5% in the FCD group, which was significantly higher than the other three groups (LGT: 19.0%; TLE-HS: 9.9%; encephalomalacia: 16.7%; P < 0.001). The etiology of FCD (p < 0.001) was significantly associated with SRE (OR: 9.71, 95% CI: 3.35-28.14) as an independent risk factor. In addition, small lesion size (p = 0.009) of FCD further increased the risk of SRE (OR: 3.18, 95% CI: 1.33-7.62) in the FCD group. SIGNIFICANCE: Our data highlight that FCD markedly increased the risk of sleep-related epilepsy independently of seizure localization. A small lesion of FCD further increased the risk of sleep-related epilepsy by 2.18 times in the FCD group.

Clinical characteristics and chest computed tomography findings related to the infectivity of pulmonary tuberculosis.

AIM: This study mainly evaluates the clinical characteristics and chest chest computed tomography (CT) findings of AFB-positive and AFB-negative pulmonary tuberculosis (PTB) patients to explore the relationship between AFB-positive and clinico-radiological findings. METHODS: A retrospective analysis of 224 hospitalized tuberculosis patients from 2018 to 2020 was undertaken. According to the AFB smear results, they were divided into AFB-positive pulmonary tuberculosis (positive by Ziehl-Neelsen staining) and AFB-negative pulmonary tuberculosis and patients' CT results and laboratory test results were analyzed. RESULTS: A total of 224 PTB patients were enrolled. AFB-positive (n = 94, 42%) and AFB-negative (n = 130, 58%). AFB-positive patients had more consolidation (77.7% vs. 53.8%, p < 0.01), cavity (55.3% vs. 34.6%, p < 0.01), calcification (38.3% vs. 20%, p < 0.01), bronchiectasis (7.5% vs. 1.5%, p < 0.05), bronchiarctia (6.4% vs. 0.8%, p < 0.05), and right upper lobe involvement (57.5% vs. 33.1%, p < 0.01), left upper lobe involvement (46.8% vs. 33.1%, p < 0.05) and lymphadenopathy (58.5% vs. 37.7%, p < 0.01). CONCLUSION: The study found that when pulmonary tuberculosis patients have consolidation, cavity, upper lobe involvement and lymphadenopathy on chest CT images, they may have a higher risk of AFB-positive tuberculosis.

Cystatin C promotes tau protein phosphorylation and causes microtubule instability by inhibiting intracellular turnover of GSK3ß in neurons.

In Alzheimer's disease (AD) tau protein hyperphosphorylation causes neurofibrillary tangle formation, microtubule instability and neurodegeneration. Determining the mechanism of tau hyperphosphorylation will provide a better understanding of AD pathology. Cystatin C (CysC) is a risk factor for late-onset AD and its level is upregulated in the brains of AD patients. The role of CysC is AD pathogenesis is not known. In this study, we found that CysC level is upregulated in 3xTg-AD mouse brain. We demonstrate that CysC does not affect cellular Aß production. However, when overexpressed in neuron (NGF-differentiated PC12 cells), CysC inhibits turnover of GSK3ß, promotes GSK3ß-catalyzed tau phosphorylation at Ser396/404 and causes microtubule instability. Our data provide a novel insight into the role of CysC in AD pathogenesis.

Inhibition of Early Growth Response 1 in the Hippocampus Alleviates Neuropathology and Improves Cognition in an Alzheimer Model with Plaques and Tangles.

A sporadic form of Alzheimer disease (AD) and vascular dementia share many risk factors, and their pathogenic mechanisms are suggested to be related. Transcription factor early growth response 1 (Egr-1) regulates various vascular pathologies and is up-regulated in both AD brains and AD mouse models; however, its role in AD pathogenesis is unclear. Herein, we report that silencing of Egr-1 in the hippocampus by shRNA reduces tau phosphorylation, lowers amyloid-ß (Aß) pathology, and improves cognition in the 3xTg-AD mouse model. Egr-1 silencing does not affect levels of cyclin-dependent protein kinase 5 (Cdk5), glycogen synthase kinase 3ß, protein phosphatase 1, or protein phosphatase 2A, but reduces p35 subunit of Cdk5. Egr-1 silencing also reduces levels of ß-secretase 1 (BACE-1) and BACE-1-cleaved amyloid precursor protein (APP) metabolites (secreted APPß, C99, Aß40, and Aß42) but has no effect on presenilin 1 and presenilin 2. In hippocampal primary neurons, Egr-1 binds to BACE-1 and p35 promoters, enhances tau phosphorylation, activates Cdk5 and BACE-1, and accelerates amyloidogenic APP processing. Blocking Cdk5 action blocks Egr-1-induced tau phosphorylation but has no effect on BACE-1 activation and amyloidogenic APP processing. Blocking BACE-1 action, on the other hand, blocks Egr-1-induced amyloidogenic APP processing but does not affect tau phosphorylation. Egr-1 regulates tau phosphorylation and Aß synthesis in the brain by respectively controlling activities of Cdk5 and BACE-1, suggesting that Egr-1 is a potential therapeutic candidate for the treatment of AD.

Early Growth Response 1 (Egr-1) Is a Transcriptional Activator of ß-Secretase 1 (BACE-1) in the Brain.

Accumulation of amyloid-ß peptide (Aß) in the brain is regarded as central to Alzheimer's disease (AD) pathogenesis. Aß is generated by a sequential cleavage of amyloid precursor protein (APP) by ß-secretase 1 (BACE-1) followed by γ-secretase. BACE-1 cleavage of APP is the committed step in Aß synthesis. Understanding the mechanism by which BACE-1 is activated leading to Aß synthesis in the brain can provide better understanding of AD pathology and help to develop novel therapies. In this study, we found that the levels of Aß and BACE-1 are significantly reduced in the brains of mice lacking transcription factor early growth response 1 (Egr-1) when compared with the WT. We demonstrate that in COS-7 cells, Egr-1 binds to the BACE-1 promoter and activates BACE-1 transcription. In rat hippocampal primary neurons, overexpression of Egr-1 induces BACE-1 expression, activates BACE-1, promotes amyloidogenic APP processing, and enhances Aß synthesis. In mouse hippocampal primary neurons, knockdown of BACE-1 almost completely blocks Egr-1-induced amyloidogenic APP processing and Aß synthesis. Our data indicate that Egr-1 promotes Aß synthesis via transcriptional activation of BACE-1 and suggest that Egr-1 plays role in activation of BACE-1 and acceleration of Aß synthesis in AD brain. Egr-1 is a potential therapeutic target for AD.

Amyloid ß peptide promotes lysosomal degradation of clusterin via sortilin in hippocampal primary neurons.

Progressive accumulation of amyloid-ß peptide (Aß) in the brain is implicated as the central event in the development of Alzheimer's disease (AD). It is thought that extracellular Aß triggers toxic signals leading to neurodegeneration. The events downstream of Aß however are not entirely clear. Clusterin (Apo J) is one of the major risk factors for sporadic form of AD. Clusterin binds to Aß and prevents Aß aggregation. In addition, clusterin promotes Aß degradation and accelerates Aß clearance from the brain. Clusterin thus protects neurons from Aß and loss of clusterin level in the brain is implicated as promoting AD pathology. In this study, we found that the level of clusterin protein but not mRNA is reduced in the brains of 3xTg-AD mice. When rat hippocampal primary neurons were treated with Aß1-42, level of clusterin protein but not mRNA was downregulated. Aß1-42-induced downregulation of clusterin was blocked by lysosome inhibitors bafilomycin A1 and ammonium chloride. In neurons, Aß1-42 induced expression of sortilin, a lysosomal sorting protein that targets proteins to lysosome for degradation. In BE(2) M17 human neuroblastoma cells, clusterin bound to sortilin and when sortilin expression was silenced, Aß1-42-induced clusterin downregulation was almost completely blocked. Our data demonstrate that in neurons, Aß1-42 promotes lysosomal degradation of clusterin by inducing expression of sortilin and provide a novel mechanism by which Aß promotes AD pathogenesis.

Early Growth Response 1 (Egr-1) Regulates N-Methyl-d-aspartate Receptor (NMDAR)-dependent Transcription of PSD-95 and α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor (AMPAR) Trafficking in Hippocampal Primary Neurons.

The N-methyl-d-aspartate receptor (NMDAR) controls synaptic plasticity and memory function and is one of the major inducers of transcription factor Egr-1 in the hippocampus. However, how Egr-1 mediates the NMDAR signal in neurons has remained unclear. Here, we show that the hippocampus of mice lacking Egr-1 displays electrophysiology properties and ultrastructure that are similar to mice overexpressing PSD-95, a major scaffolding protein of postsynaptic density involved in synapse formation, synaptic plasticity, and synaptic targeting of AMPA receptors (AMPARs), which mediate the vast majority of excitatory transmission in the CNS. We demonstrate that Egr-1 is a transcription repressor of the PSD-95 gene and is recruited to the PSD-95 promoter in response to NMDAR activation. Knockdown of Egr-1 in rat hippocampal primary neurons blocks NMDAR-induced PSD-95 down-regulation and AMPAR endocytosis. Likewise, overexpression of Egr-1 in rat hippocampal primary neurons causes reduction in PSD-95 protein level and promotes AMPAR endocytosis. Our data indicate that Egr-1 is involved in NMDAR-mediated PSD-95 down-regulation and AMPAR endocytosis, a process important in the expression of long term depression.

Utility of MRI Diffusion Tensor Imaging in Carpal Tunnel Syndrome: A Meta-Analysis.

BACKGROUND After successful utilization of diffusion tensor imaging (DTI) in detecting brain pathologies, it is now being examined for use in the detection of peripheral neuropathies. The aim of this meta-analysis was to evaluate the diagnostic potentials of DTI in carpal tunnel syndrome (CTS). MATERIAL AND METHODS The literature search was performed in multiple electronic databases using a keyword search and final selection of the studies was based on predetermined inclusion and exclusion criteria. We performed a meta-analyses of mean differences in fractional anisotropy (FA) and apparent diffusion coefficient (ADC) between CTS patient and healthy subjects. Publication bias detection was done with Begg's test and sensitivity analyses were performed to explore the source/s of higher heterogeneity and the authenticity of results. RESULTS FA was significantly lower in CTS patients in comparison with healthy subjects (mean and the difference [95% confidence interval] was -0.06 [-0.10, -0.02] (p=0.003). The ADC was significantly higher in CTS patients (mean difference [95% CI] was 0.10 [0.02, 0.18], p=0.02). Overall sensitivity of FA-based diagnosis was 82.82%, with 77.83% specificity. CONCLUSIONS DTI can be a valuable tool in diagnosing CTS.

High expression of transcriptional factor HoxB9 predicts poor prognosis in patients with lung adenocarcinoma.

AIMS: HoxB9, as a Hox family member, is known to play important roles in embryonic development. Recent studies showed that HoxB9 is engaged in cancer progression. However, the role of Hoxb9 in lung adenocarcinoma is unknown. The purpose of this study is to investigate the expression and prognostic value of HoxB9 in patients with lung adenocarcinoma. METHODS AND RESULTS: The localization and expression of HoxB9 in lung adenocarcinoma were examined by immunohistochemistry. The correlation between HoxB9 expression levels with patient survival was assessed by Kaplan-Meier analysis. The epithelial-mesenchymal transition (EMT) markers and migratory ability were evaluated in HoxB9 up- and down-regulated H1299 lung adenocarcinoma cells. HoxB9 was found to be localized predominantly in the cell nuclei and expressed in 21.3% of lung adenocarcinomas. A significant increase in HoxB9 intensity in the high stage of lung adenocarcinoma was observed (P < 0.01). Increased expression of HoxB9 was related to T classification, more lymph node metastasis and a shorter patient overall survival (P < 0.05). However, the expression level of HoxB9 was not correlated with age and gender. Functionally, HoxB9 up-regulated EMT-related molecules and promoted cell migration in H1299 cells. CONCLUSION: High expression of HoxB9 is a prognostic marker for lung adenocarcinoma patients.

Kindlin 2 forms a transcriptional complex with ß-catenin and TCF4 to enhance Wnt signalling.

Kindlin 2, as a focal adhesion protein, controls integrin activation. However, the association of Kindlin 2 with cancer-related signalling pathways is unknown. Here we identified a new direct interaction between Kindlin 2 and the active ß-catenin. Importantly, Kindlin 2 forms a tripartite complex with ß-catenin and TCF4. Mechanistically, Kindlin 2 selectively strengthens the occupancy of ß-catenin on the Wnt target gene Axin2 and enhances Axin2 gene expression. Functionally, the ß-catenin-Axin2-Snail cascade is required for Kindlin 2-induced tumour cell invasion. Our data indicate that Kindlin 2 is a new regulator of Wnt signalling, providing a mechanistic insight into the role of Kindlin 2 in cancer progression.

Rapid detection of the irinotecan-related UGT1A1 & 5-fluorouracil related DPYD polymorphism by asymmetric polymerase chain reaction melting curve analysis.

BACKGROUND: Determination of DPYD and UGT1A1 polymorphisms prior to 5-fluorouracil and irinotecan therapy is crucial for avoiding severe adverse drug effects. Hence, there is a pressing need for accurate and reliable genotyping methods for the most common DPYD and UGT1A1 polymorphisms. In this study, we introduce a novel polymerase chain reaction (PCR) melting curve analysis method for discriminating DPYD c.1236G > A, c.1679 T > G, c.2846A > T, IVS14 + 1G > A and UGT1A1*1, *28, *6 (G71R) genotypes. METHODS: Following protocol optimization, this technique was employed to genotype 28 patients, recruited between March 2023 and October 2023, at the First Affiliated Hospital of Xiamen University. These patients included 20 with UGT1A1 *1/*1, 8 with UGT1A1 *1/*28, 4 with UGT1A1 *28/*28, 22 with UGT1A1*6 G/G, 6 with UGT1A1*6 G/A, 4 with UGT1A1*6 A/A, 27 with DPYD(c.1236) G/G, 3 with DPYD(c.1236) G/A, 2 with DPYD(c.1236) A/A, 27 with DPYD(c.1679) T/T, 2 with DPYD(c.1679) T/G, 3 with DPYD(c.1679) G/G, 28 with DPYD(c.2846A/T) A/A, 2 with DPYD(c.2846A/T) A/T, 2 with DPYD(c.2846A/T) T/T, 28 with DPYD(c.IVS14 + 1) G/G, 2 with DPYD(c.IVS14 + 1) G/G, and 2 with DPYD(c.IVS14 + 1) G/G, as well as 3 plasmid standards. Method accuracy was assessed by comparing results with those from Sanger sequencing or Multiplex quantitative PCR(qPCR). Intra- and inter-run precision of melting temperatures (Tms) were calculated to evaluate reliability, and sensitivity was assessed through limit of detection examination. RESULTS: The new method accurately identified all genotypes and exhibited higher accuracy than Multiplex qPCR. Intra- and inter-run coefficients of variation for Tms were both ≤1.97 %, with standard deviations ≤0.95 °C. The limit of detection was 0.09 ng/µL of input genomic DNA. CONCLUSION: Our developed PCR melting curve analysis offers accurate, reliable, rapid, simple, and cost-effective detection of DPYD and UGT1A1 polymorphisms. Its application can be easily extended to clinical laboratories equipped with a fluorescent PCR platform.

MR-based radiomics predictive modelling of EGFR mutation and HER2 overexpression in metastatic brain adenocarcinoma: a two-centre study.

OBJECTIVES: Magnetic resonance (MR)-based radiomics features of brain metastases are utilised to predict epidermal growth factor receptor (EGFR) mutation and human epidermal growth factor receptor 2 (HER2) overexpression in adenocarcinoma, with the aim to identify the most predictive MR sequence. METHODS: A retrospective inclusion of 268 individuals with brain metastases from adenocarcinoma across two institutions was conducted. Utilising T1-weighted imaging (T1 contrast-enhanced [T1-CE]) and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequences, 1,409 radiomics features were extracted. These sequences were randomly divided into training and test sets at a 7:3 ratio. The selection of relevant features was done using the least absolute shrinkage selection operator, and the training cohort's support vector classifier model was employed to generate the predictive model. The performance of the radiomics features was evaluated using a separate test set. RESULTS: For contrast-enhanced T1-CE cohorts, the radiomics features based on 19 selected characteristics exhibited excellent discrimination. No significant differences in age, sex, and time to metastasis were observed between the groups with EGFR mutations or HER2 + and those with wild-type EGFR or HER2 (p > 0.05). Radiomics feature analysis for T1-CE revealed an area under the curve (AUC) of 0.98, classification accuracy of 0.93, sensitivity of 0.92, and specificity of 0.93 in the training cohort. In the test set, the AUC was 0.82. The 19 radiomics features for the T2-FLAIR sequence showed AUCs of 0.86 in the training set and 0.70 in the test set. CONCLUSIONS: This study developed a T1-CE signature that could serve as a non-invasive adjunctive tool to determine the presence of EGFR mutations and HER2 + status in adenocarcinoma, aiding in the direction of treatment plans. CLINICAL RELEVANCE STATEMENT: We propose radiomics features based on T1-CE brain MR sequences that are both evidence-based and non-invasive. These can be employed to guide clinical treatment planning in patients with brain metastases from adenocarcinoma.

Role of long non-coding RNA TCONS_02443383 in regulating cell adhesion and peroxisome proliferator-activated receptor (PPAR) signaling genes in atherosclerosis: A New Zealand white rabbit model study.

OBJECTIVE: In this study, we performed RNA sequencing (RNA-seq) on the abdominal aorta tissue of New Zealand rabbits and investigated the potential association of lncRNA TCONS_02443383 with the development of AS through bioinformatics analysis of the sequencing data. The obtained results were further validated using quantitative real-time polymerase chain reaction (qRT-PCR). METHOD: We induced an AS model in New Zealand rabbits by causing balloon injury to the abdominal aorta vascular wall and administering a high-fat diet. We then upregulated the expression level of the lncRNA TCONS_02443383 by injecting lentiviral plasmids through the ear vein. RNA sequencing (RNA-seq) was performed on the abdominal aorta tissues. We conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway and Gene Ontology (GO) analyses. RESULT: The overexpression of the lncRNA TCONS_02443383 led to an upregulation of peroxisome proliferator-activated receptor (PPAR) signaling pathways as well as genes related to cell adhesion. CONCLUSION: The overexpression of the lncRNA TCONS_02443383 can inhibit the occurrence and development of AS by upregulating peroxisome proliferator-activated receptor (PPAR) signaling pathways and genes related to cell adhesion.

Calibrating ultrasonic sensor measurements of crop canopy heights: a case study of maize and wheat.

Canopy height serves as an important dynamic indicator of crop growth in the decision-making process of field management. Compared with other commonly used canopy height measurement techniques, ultrasonic sensors are inexpensive and can be exposed in fields for long periods of time to obtain easy-to-process data. However, the acoustic wave characteristics and crop canopy structure affect the measurement accuracy. To improve the ultrasonic sensor measurement accuracy, a four-year (2018-2021) field experiment was conducted on maize and wheat, and a measurement platform was developed. A series of single-factor experiments were conducted to investigate the significant factors affecting measurements, including the observation angle (0-60°), observation height (0.5-2.5 m), observation period (8:00-18:00), platform moving speed with respect to the crop (0-2.0 m min-1), planting density (0.2-1 time of standard planting density), and growth stage (maize from three-leaf to harvest period and wheat from regreening to maturity period). The results indicated that both the observation angle and planting density significantly affected the results of ultrasonic measurements (p-value< 0.05), whereas the effects of other factors on measurement accuracy were negligible (p-value > 0.05). Moreover, a double-input factor calibration model was constructed to assess canopy height under different years by utilizing the normalized difference vegetation index and ultrasonic measurements. The model was developed by employing the least-squares method, and ultrasonic measurement accuracy was significantly improved when integrating the measured value of canopy heights and the normalized difference vegetation index (NDVI). The maize measurement accuracy had a root mean squared error (RMSE) ranging from 81.4 mm to 93.6 mm, while the wheat measurement accuracy had an RMSE from 37.1 mm to 47.2 mm. The research results effectively combine stable and low-cost commercial sensors with ground-based agricultural machinery platforms, enabling efficient and non-destructive acquisition of crop height information.

A novel score for early prediction of urinary tract infection risk in patients with acute ischemic stroke: a nomogram-based retrospective cohort study.

This study aimed to construct and externally validate a user-friendly nomogram-based scoring model for predicting the risk of urinary tract infections (UTIs) in patients with acute ischemic stroke (AIS). A retrospective real-world cohort study was conducted on 1748 consecutive hospitalized patients with AIS. Out of these patients, a total of 1132 participants were ultimately included in the final analysis, with 817 used for model construction and 315 utilized for external validation. Multivariate regression analysis was applied to develop the model. The discriminative capacity, calibration ability, and clinical effectiveness of the model were evaluated. The overall incidence of UTIs was 8.13% (92/1132), with Escherichia coli being the most prevalent causative pathogen in patients with AIS. After multivariable analysis, advanced age, female gender, National Institute of Health Stroke Scale (NIHSS) score ≥ 5, and use of urinary catheters were identified as independent risk factors for UTIs. A nomogram-based SUNA model was constructed using these four factors (Area under the receiver operating characteristic curve (AUC) = 0.810), which showed good discrimination (AUC = 0.788), calibration, and clinical utility in the external validation cohort. Based on four simple and readily available factors, we derived and externally validated a novel and user-friendly nomogram-based scoring model (SUNA score) to predict the risk of UTIs in patients with AIS. The model has a good predictive value and provides valuable information for timely intervention in patients with AIS to reduce the occurrence of UTIs.

Multiparametric MRI-Based Interpretable Radiomics Machine Learning Model Differentiates Medulloblastoma and Ependymoma in Children: A Two-Center Study.

RATIONALE AND OBJECTIVES: Medulloblastoma (MB) and Ependymoma (EM) in children, share similarities in age group, tumor location, and clinical presentation. Distinguishing between them through clinical diagnosis is challenging. This study aims to explore the effectiveness of using radiomics and machine learning on multiparametric magnetic resonance imaging (MRI) to differentiate between MB and EM and validate its diagnostic ability with an external set. MATERIALS AND METHODS: Axial T2 weighted image (T2WI) and contrast-enhanced T1weighted image (CE-T1WI) MRI sequences of 135 patients from two centers were collected as train/test sets. Volume of interest (VOI) was manually delineated by an experienced neuroradiologist, supervised by a senior. Feature selection analysis and the least absolute shrinkage and selection operator (LASSO) algorithm identified valuable features, and Shapley additive explanations (SHAP) evaluated their significance. Five machine-learning classifiers-extreme gradient boosting (XGBoost), Bernoulli naive Bayes (Bernoulli NB), Logistic Regression (LR), support vector machine (SVM), linear support vector machine (Linear SVC) classifiers were built based on T2WI (T2 model), CE-T1WI (T1 model), and T1 + T2WI (T1 + T2 model). A human expert diagnosis was developed and corrected by senior radiologists. External validation was performed at Sun Yat-Sen University Cancer Center. RESULTS: 31 valuable features were extracted from T2WI and CE-T1WI. XGBoost demonstrated the highest performance with an area under the curve (AUC) of 0.92 on the test set and maintained an AUC of 0.80 during external validation. For the T1 model, XGBoost achieved the highest AUC of 0.85 on the test set and the highest accuracy of 0.71 on the external validation set. In the T2 model, XGBoost achieved the highest AUC of 0.86 on the test set and the highest accuracy of 0.82 on the external validation set. The human expert diagnosis had an AUC of 0.66 on the test set and 0.69 on the external validation set. The integrated T1 + T2 model achieved an AUC of 0.92 on the test set, 0.80 on the external validation set, achieved the best performance. Overall, XGBoost consistently outperformed in different classification models. CONCLUSION: The combination of radiomics and machine learning on multiparametric MRI effectively distinguishes between MB and EM in childhood, surpassing human expert diagnosis in training and testing sets.