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BACKGROUND: Dysfunction of the glymphatic system in the brain in different stages of altered glucose metabolism and its influencing factors are not well characterized. AIM: To investigate the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states, the present study employed diffusion tensor imaging along the perivascular space (DTI-ALPS) index. METHODS: Sample size was calculated using the pwr package in R software. This cross-sectional study enrolled 22 patients with normal glucose metabolism (NGM), 20 patients with prediabetes, and 22 patients with type 2 diabetes mellitus (T2DM). A 3.0T magnetic resonance imaging was used to evaluate the function of the glymphatic system. The mini-mental state examination (MMSE) was used to assess general cognitive function. The DTI-ALPS index of bilateral basal ganglia and the mean DTI-ALPS index was calculated. Further, the correlation between DTI-ALPS and clinical features was assessed. RESULTS: The left-side, right-side, and mean DTI-ALPS index in the T2DM group were significantly lower than that in the NGM group. The right-side DTI-ALPS and mean DTI-ALPS index in the T2DM group were significantly lower than those in the prediabetes group. DTI-ALPS index lateralization was not observed. The MMSE score in the T2DM group was significantly lower than that in the NGM and prediabetes group. After controlling for sex, the left-side DTI-ALPS and mean DTI-ALPS index in the prediabetes group were positively correlated with 2-hour postprandial blood glucose level; the left-side DTI-ALPS index was negatively correlated with total cholesterol and low-density lipoprotein level. The right-side DTI-ALPS and mean DTI-ALPS index were negatively correlated with the glycosylated hemoglobin level and waist-to-hip ratio in the prediabetes group. The left-side, right-side, and mean DTI-ALPS index in the T2DM group were positively correlated with height. The left-side and mean DTI-ALPS index in the T2DM group were negatively correlated with high-density lipoprotein levels. CONCLUSION: Cerebral glymphatic system dysfunction may mainly occur in the T2DM stage. Various clinical variables were found to affect the DTI-ALPS index in different glucose metabolism states. This study enhances our understanding of the pathophysiology of diabetic brain damage and provides some potential biological evidence for its early diagnosis.
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BACKGROUND: Carbamoyl phosphate synthetase 1 (CPS1) deficiency (OMIM 237300), an autosomal recessive rare and severe urea cycle disorder, is associated with hyperammonemia and high mortality. METHODS: Herein we present 12 genetic variants identified in seven clinically well-characterized Chinese patients with CPS1 deficiency who were admitted to the Children's Medical Center of Peking University First Hospital from September 2014 to August 2023. RESULTS: Seven patients (two male and five female patients including two sisters) experienced symptoms onset between 2 days and 13 years of age, and they were diagnosed with CPS1 deficiency between 2 months and 20 years. Peak blood ammonia levels ranged from 160 to 1,000 µmol/L. Three patients showed early-onset CPS1 deficiency, with only one surviving after treatment with sodium phenylbutyrate, N-carbamoyl-L-glutamate, and liver transplantation at 4 months, showing a favorable outcome. The remaining four patients had late-onset CPS1 deficiency, presenting with mental retardation, psychiatric symptoms, and self-selected low-protein diets. Among the 12 CPS1 variants identified in these patients, 10 were novel, with all patients exhibiting compound heterozygosity for CPS1 mutant alleles. Seven variants (c.149T > C, c.616 A > T, c.1145 C > T, c.1294G > A, c.3029 C > T, c.3503 A > T, and c.3793 C > T) resulted in single amino acid substitutions. Three frameshift variations (c.2493del, c.3067dup, and c.3241del) were identified, leading to enzyme truncation. One mutation (c.3506_3508del) caused an in-frame single amino acid deletion, while another (c.2895 + 2T > C) resulted in aberrant splicing. CONCLUSIONS: Except for two known variants, all other variants were identified as novel. No hotspot variants were observed among the patients. Our data contribute to expanding the mutation spectrum of CPS1.
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Carbamoil-Fosfato Sintase (Amônia) , Doença da Deficiência da Carbamoil-Fosfato Sintase I , Humanos , Feminino , Masculino , Doença da Deficiência da Carbamoil-Fosfato Sintase I/genética , Carbamoil-Fosfato Sintase (Amônia)/genética , Lactente , Criança , Pré-Escolar , Adolescente , Recém-Nascido , China , Mutação , Adulto Jovem , Povo Asiático/genética , População do Leste AsiáticoRESUMO
BACKGROUND: The relationship between frailty and neoplasms has attracted increasing attention from researchers in recent years. This study aims to identify current research hotspots and status in this field through bibliometric and visualization analysis. METHODS: Literature on the relationship between frailty and neoplasms, meeting the inclusion criteria, was collected from the Core Collection. Bibliometric analysis and visualization were performed using WoS, VOSviewer, and CiteSpace. RESULTS: Our study included 7410 documents on frailty and neoplasms, authored by 43,605 researchers from 9478 institutions across 115 countries, and published in 2067 journals. The USA emerged as the most productive and influential country in this field, with 3059 publications and 89,319 citations. The University of Texas MD Anderson Cancer Center and Mayo Clinic were recognized as the most productive institution and the institution with the highest citation count, respectively. The Journal of Geriatric Oncology was the leading publisher. Kirsten K Ness and James L Kirkland were identified as the most productive and most cited authors, respectively. Cluster analysis identified five key areas: body condition and nutrition, quality of life, frailty, mortality and care, and the elderly and frailty. CONCLUSION: The relationship between frailty and neoplasms remains a contentious and frequently discussed topic. Our findings indicate that research primarily focuses on cancer, the elderly, clinical trials, adverse health outcomes, frailty assessment, and nutrition.
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Bibliometria , Fragilidade , Neoplasias , Humanos , Qualidade de Vida , Idoso , Análise por Conglomerados , Pesquisa Biomédica/estatística & dados numéricosRESUMO
Brain metastases challenge cancer treatments with poor prognoses, despite ongoing advancements. Immunotherapy effectively alleviates advanced cancer, exhibiting immense potential to revolutionize brain metastasis management. To identify research priorities that optimize immunotherapies for brain metastases, 2164 related publications were analyzed. Scientometric visualization via R software, VOSviewer, and CiteSpace showed the interrelationships among literature, institutions, authors, and topic areas of focus. The publication rate and citations have grown exponentially over the past decade, with the US, China, and Germany as the major contributors. The University of Texas MD Anderson Cancer Center ranked highest in publications, while Memorial Sloan Kettering Cancer Center was most cited. Clusters of keywords revealed six hotspots: 'Immunology', 'Check Point Inhibitors', 'Lung Cancer', 'Immunotherapy', 'Melanoma', 'Breast Cancer', and 'Microenvironment'. Melanoma, the most studied primary tumor with brain metastases offers promising immunotherapy advancements with generalizability and adaptability to other cancers. Our results outline the holistic overview of immunotherapy research for brain metastases, which pinpoints the forefront in the field, and directs researchers toward critical inquiries for enhanced mechanistic insight and improved clinical outcomes. Moreover, governmental and funding agencies will benefit from assigning financial resources to entities and regions with the greatest potential for combating brain metastases through immunotherapy.
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BACKGROUND AND AIMS: To investigate the clinical features, ALDH5A1 gene variations, treatment, and prognosis of patients with succinic semialdehyde dehydrogenase (SSADH) deficiency. MATERIALS AND METHODS: This retrospective study evaluated the findings in 13 Chinese patients with SSADH deficiency admitted to the Pediatric Department of Peking University First Hospital from September 2013 to September 2023. RESULTS: Thirteen patients (seven male and six female patients; two sibling sisters) had the symptoms aged from 1 month to 1 year. Their urine 4-hydroxybutyrate acid levels were elevated and were accompanied by mildly increased serum lactate levels. Brain magnetic resonance imaging (MRI) showed symmetric abnormal signals in both sides of the globus pallidus and other areas. All 13 patients had psychomotor retardation, with seven showing epileptic seizures. Among the 18 variants of the ALDH5A1 gene identified in these 13 patients, six were previously reported, while 12 were novel variants. Among the 12 novel variants, three (c.85_116del, c.206_222dup, c.762C > G) were pathogenic variants; five (c.427delA, c.515G > A, c.637C > T, c.755G > T, c.1274T > C) were likely pathogenic; and the remaining four (c.454G > C, c.479C > T, c.1480G > A, c.1501G > C) were variants of uncertain significance. The patients received drugs such as L-carnitine, vigabatrin, and taurine, along with symptomatic treatment. Their urine 4-hydroxybutyric acid levels showed variable degrees of reduction. CONCLUSIONS: A cohort of 13 cases with early-onset SSADH deficiency was analyzed. Onset of symptoms occurred from 1 month to 1 year of age. Twelve novel variants of the ALDH5A1 gene were identified.
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Erros Inatos do Metabolismo dos Aminoácidos , Succinato-Semialdeído Desidrogenase , Humanos , Succinato-Semialdeído Desidrogenase/deficiência , Succinato-Semialdeído Desidrogenase/genética , Feminino , Masculino , Erros Inatos do Metabolismo dos Aminoácidos/genética , Lactente , Estudos Retrospectivos , Povo Asiático/genética , Mutação , China , Pré-Escolar , Deficiências do Desenvolvimento/genética , Imageamento por Ressonância Magnética , População do Leste AsiáticoRESUMO
BACKGROUND: To evaluate the neurological alterations induced by Omicron infection, to compare brain changes in chronic insomnia with those in exacerbated chronic insomnia in Omicron patients, and to examine individuals without insomnia alongside those with new-onset insomnia. METHODS: In this study, a total of 135 participants were recruited between January 11 and May 4, 2023, including 26 patients with chronic insomnia without exacerbation, 24 patients with chronic insomnia with exacerbation, 40 patients with no sleep disorder, and 30 patients with new-onset insomnia after infection with Omicron (a total of 120 participants with different sleep statuses after infection), as well as 15 healthy controls who were never infected with Omicron. Neuropsychiatric data, clinical symptoms, and multimodal magnetic resonance imaging data were collected. The gray matter thickness and T1, T2, proton density, and perivascular space values were analyzed. Associations between changes in multimodal magnetic resonance imaging findings and neuropsychiatric data were evaluated with correlation analyses. RESULTS: Compared with healthy controls, gray matter thickness changes were similar in the patients who have and do not have a history of chronic insomnia groups after infection, including an increase in cortical thickness near the parietal lobe and a reduction in cortical thickness in the frontal, occipital, and medial brain regions. Analyses showed a reduced gray matter thickness in patients with chronic insomnia compared with those with an aggravation of chronic insomnia post-Omicron infection, and a reduction was found in the right medial orbitofrontal region (mean [SD], 2.38 [0.17] vs. 2.67 [0.29] mm; P < 0.001). In the subgroups of Omicron patients experiencing sleep deterioration, patients with a history of chronic insomnia whose insomnia symptoms worsened after infection displayed heightened medial orbitofrontal cortical thickness and increased proton density values in various brain regions. Conversely, patients with good sleep quality who experienced a new onset of insomnia after infection exhibited reduced cortical thickness in pericalcarine regions and decreased proton density values. In new-onset insomnia patients post-Omicron infection, the thickness in the right pericalcarine was negatively correlated with the Self-rating Anxiety Scale (r = - 0.538, P = 0.002, PFDR = 0.004) and Self-rating Depression Scale (r = - 0.406, P = 0.026, PFDR = 0.026) scores. CONCLUSIONS: These findings help us understand the pathophysiological mechanisms involved when Omicron invades the nervous system and induces various forms of insomnia after infection. In the future, we will continue to pay attention to the dynamic changes in the brain related to insomnia caused by Omicron infection.
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COVID-19 , Imageamento por Ressonância Magnética , Distúrbios do Início e da Manutenção do Sono , Humanos , COVID-19/complicações , COVID-19/diagnóstico por imagem , COVID-19/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Distúrbios do Início e da Manutenção do Sono/diagnóstico por imagem , Qualidade do Sono , SARS-CoV-2 , Neuroimagem/métodos , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Imagem Multimodal/métodos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , IdosoRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0297015.].
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Background: Reliable predictors for rehabilitation outcomes in patients with congenital sensorineural hearing loss (CSNHL) after cochlear implantation (CI) are lacking. The purchase of this study was to develop a nomogram based on clinical characteristics and neuroimaging features to predict the outcome in children with CSNHL after CI. Methods: Children with CSNHL prior to CI surgery and children with normal hearing were enrolled into the study. Clinical data, high resolution computed tomography (HRCT) for ototemporal bone, conventional brain MRI for structural analysis and brain resting-state fMRI (rs-fMRI) for the power spectrum assessment were assessed. A nomogram combining both clinical and imaging data was constructed using multivariate logistic regression analysis. Model performance was evaluated and validated using bootstrap resampling. Results: The final cohort consisted of 72 children with CSNHL (41 children with poor outcome and 31 children with good outcome) and 32 healthy controls. The white matter lesion from structural assessment and six power spectrum parameters from rs-fMRI, including Power4, Power13, Power14, Power19, Power23 and Power25 were used to build the nomogram. The area under the receiver operating characteristic (ROC) curve of the nomogram obtained using the bootstrapping method was 0.812 (95 % CI = 0.772-0.836). The calibration curve showed no statistical difference between the predicted value and the actual value, indicating a robust performance of the nomogram. The clinical decision analysis curve showed a high clinical value of this model. Conclusions: The nomogram constructed with clinical data, and neuroimaging features encompassing ototemporal bone measurements, white matter lesion values from structural brain MRI and power spectrum data from rs-fMRI showed a robust performance in predicting outcome of hearing rehabilitation in children with CSNHL after CI.
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OBJECTIVE: The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage. Lipopolysaccharide (LPS) has been widely used to induce inflammation in animal models. Therefore, this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium, as well as the potential underlying molecular mechanisms involved. METHODS: In vivo, an animal model was established by intraperitoneal injection of 300 µg/ kg LPS in rats on gestational day 21. Hematoxylin-eosin (H&E) staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle. Enzyme-linked immunosorbent assay (ELISA) was used to detect inflammatory cytokines. Immunohistochemistry, tissue fluorescence, and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4 (TLR4) and the nuclear factor kappa-B (NF-κB) signaling pathway. In vitro, human uterine smooth muscle cells (HUtSMCs) were exposed to 2 µg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation. RESULTS: In this study, LPS induced uterine myometrial dysfunction in rats, leading to a disorganized arrangement, a significant increase in collagen fiber deposition, and widespread infiltration of inflammatory cells. In both in vivo animal models and in vitro HUtSMCs, LPS elevated IL-6, IL-1ß, and TNF-α levels while concurrently suppressing the expression of connexin 43 (Cx43) and oxytocin receptor (OXTR). Mechanistically, the LPS-treated group exhibited TLR4 activation, and the phosphorylation levels of p65 and IκBα were notably increased. CONCLUSION: LPS triggered the TLR4/NF-κB signaling pathway, inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.
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Inflamação , Lipopolissacarídeos , Miométrio , NF-kappa B , Transdução de Sinais , Receptor 4 Toll-Like , Feminino , Animais , Miométrio/patologia , Miométrio/metabolismo , Ratos , Receptor 4 Toll-Like/metabolismo , Receptor 4 Toll-Like/genética , Inflamação/patologia , Inflamação/metabolismo , Inflamação/induzido quimicamente , NF-kappa B/metabolismo , Humanos , Gravidez , Ratos Sprague-Dawley , Citocinas/metabolismo , Contração Uterina/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Modelos Animais de Doenças , Útero/patologia , Útero/metabolismoRESUMO
Potassium-ion hybrid capacitors (PIHCs) represent a burgeoning class of electrochemical energy storage devices characterized by their remarkable energy and power densities. Utilizing amorphous carbon derived from sustainable biomass presents an economical and environmentally friendly option for anode material in high-rate potassium-ion storage applications. Nevertheless, the potassium-ion storage capacity of most biomass-derived carbon materials remains modest. Addressing this challenge, nitrogen doping engineering and the design of distinctive nanostructures emerge as effective strategies for enhancing the electrochemical performance of amorphous carbon anodes. Developing highly nitrogen-doped nanocarbon materials is a challenging task because most lignocellulosic biomasses lack nitrogen functional groups. In this work, we propose a general strategy for directly carbonizing supermolecule-mediated lignin organic molecular aggregate (OMA) to prepare highly nitrogen-doped biomass-derived nanocarbon. We obtained lignin-derived, highly nitrogen-doped turbine-like carbon (LNTC). Featuring a three-dimensional turbine-like structure composed of amorphous, thin carbon nanosheets, LNTC demonstrated a capacity of 377 mAh g-1 when used as the anode for PIHCs. This work also provides a new synthesis method for preparing highly nitrogen-doped nanocarbon materials derived from biomass.
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BACKGROUND: With the continuous development of deep learning algorithms in the field of medical images, models for medical image processing based on convolutional neural networks have made great progress. Since medical images of rectal tumors are characterized by specific morphological features and complex edges that differ from natural images, achieving good segmentation results often requires a higher level of enrichment through the utilization of semantic features. PURPOSE: The efficiency of feature extraction and utilization has been improved to some extent through enhanced hardware arithmetic and deeper networks in most models. However, problems still exist with detail loss and difficulty in feature extraction, arising from the extraction of high-level semantic features in deep networks. METHODS: In this work, a novel medical image segmentation model has been proposed for Magnetic Resonance Imaging (MRI) image segmentation of rectal tumors. The model constructs a backbone architecture based on the idea of jump-connected feature fusion and solves the problems of detail feature loss and low segmentation accuracy using three novel modules: Multi-scale Feature Retention (MFR), Multi-branch Cross-channel Attention (MCA), and Coordinate Attention (CA). RESULTS: Compared with existing methods, our proposed model is able to segment the tumor region more effectively, achieving 97.4% and 94.9% in Dice and mIoU metrics, respectively, exhibiting excellent segmentation performance and computational speed. CONCLUSIONS: Our proposed model has improved the accuracy of both lesion region and tumor edge segmentation. In particular, the determination of the lesion region can help doctors identify the tumor location in clinical diagnosis, and the accurate segmentation of the tumor edge can assist doctors in judging the necessity and feasibility of surgery.
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Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Neoplasias Retais , Neoplasias Retais/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Humanos , Aprendizado ProfundoRESUMO
Mechanical bruise is one of the most crucial factors affecting the quality of pears, which has a huge influence on postharvest transportation, storage, and sale of pears. To rapidly detect early bruises of pears across different bruise types, hyperspectral imaging technology coupled with transfer learning methods was performed in this study. Two transfer learning methods, that is, transfer component analysis (TCA) and manifold embedded distribution alignment (MEDA), were applied for two tasks (impact bruise â crush bruise, crush bruise â impact bruise). Supporting vector machine (SVM) was set as a baseline to conduct analysis and comparison of the transferability of the models. The result showed that, for task 1 (impact bruise â crush bruise), MEDA and TCA-SVM model achieved a classification accuracy of 93.33% and 91.11% in target domain, individually. For task 2 (crush bruise âimpact bruise), MEDA and TCA-SVM model achieved an accuracy of 88.89% and 85.19% in target domain, respectively. Both the two models improved the accuracy compared with SVM models (84.44% for task 1; 77.04% for task 2). Overall, the results indicated that transfer learning approaches could perform pear bruise detection across different bruise types. Hyperspectral imaging in combination with transfer learning methods is a promising possibility for the efficient and cost-saving field detection of fruit bruises among different bruise types. PRACTICAL APPLICATION: The production and export of pears are faced with problems of mechanical damage due to vibration, collision, impact, and other factors, which cause chemical changes in color, odor, and taste. Sometimes the bruise was too slight to be ignored which would infect with other fruits in the future. In this study, we used hyperspectral imaging combined with transfer learning method could detect these slight bruises caused by different factors. Distinguishing different types of damage can provide a reference for quick judgment of the process causing damage and take prompt measures to reduce economic losses.
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Frutas , Imageamento Hiperespectral , Pyrus , Máquina de Vetores de Suporte , Pyrus/química , Imageamento Hiperespectral/métodos , ContusõesRESUMO
Objective: The purpose of this study is to analyze the distribution characteristics of atherosclerotic lesions and the risk factors of recurrence in patients with ischemic stroke. Methods: A total of 505 patients diagnosed with ischemic stroke from October 2016 to October 2022 were included. Divide 505 patients with ischemic stroke into old stroke group and new stroke group. Patients without old cerebral infarction were included in the first ischemic stroke group (first group), while patients with old cerebral infarction were included in the recurrent ischemic stroke group (recurrence group).Carotid artery color Doppler ultrasonography and transcranial Doppler ultrasonography were performed on all patients. Results: We compared the distribution and risk factors of atherosclerotic lesions between the first and recurrent groups (378 cases) (127 cases). Mild, moderate, and severe stenosis of the middle cerebral artery (MCA) and occlusion of the intracranial vertebral artery (VA) were the most common in both groups. Intracranial artery stenosis is significantly higher than extracranial artery stenosis, and the anterior circulation artery is more affected than the posterior circulation artery. In the initial and recurrent groups, the proportion of patients with intracranial artery stenosis was significantly higher than that of patients with extracranial artery stenosis (43.4% vs. 22.5% and 53.4% vs. 22.5%), and the number of patients with anterior circulation stenosis was higher than that of other groups. Compared with the first group, the recurrence group had a higher incidence of hypertension, dyslipidemia, and insufficient physical exercise. There is a significant difference in the levels of triglycerides (TG) and platelets (PLT) between the two groups in biochemical indicators. In the first group, infarction was most common in 284 cases (75.1%) of the frontal lobe, followed by 232 cases (61.4%) of the basal ganglia, and 147 cases (38.9%) of the parietal lobe. In the recurrence group, the proportion of frontal lobe infarction [284 (74.0%)], basal ganglia infarction [232 (70.1%)], and parietal lobe infarction [147 (37.0%)] was the highest. It can be observed that the recurrence group had a higher incidence of basal ganglia infarction (70.1% vs. 61.4%), but a lower incidence of occipital lobe infarction (0.8% vs. 4.2%). Conclusions: Our study found no significant difference in the distribution of intracranial and extracranial atherosclerotic lesions between first-ever and recurrent ischemic stroke patients in China. Notably, hypertension, years of dyslipidemia, insufficient physical exercise, elevated triglyceride (TG) levels, and increased platelet (PLT) counts were identified as significant risk factors for stroke recurrence. These findings may have implications for the management and prevention of recurrent ischemic strokes in clinical practice.
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OBJECTIVES: To evaluate the performance of multiparametric neurite orientation dispersion and density imaging (NODDI) radiomics in distinguishing between glioblastoma (Gb) and solitary brain metastasis (SBM). MATERIALS AND METHODS: In this retrospective study, NODDI images were curated from 109 patients with Gb (n = 57) or SBM (n = 52). Automatically segmented multiple volumes of interest (VOIs) encompassed the main tumor regions, including necrosis, solid tumor, and peritumoral edema. Radiomics features were extracted for each main tumor region, using three NODDI parameter maps. Radiomics models were developed based on these three NODDI parameter maps and their amalgamation to differentiate between Gb and SBM. Additionally, radiomics models were constructed based on morphological magnetic resonance imaging (MRI) and diffusion imaging (diffusion-weighted imaging [DWI]; diffusion tensor imaging [DTI]) for performance comparison. RESULTS: The validation dataset results revealed that the performance of a single NODDI parameter map model was inferior to that of the combined NODDI model. In the necrotic regions, the combined NODDI radiomics model exhibited less than ideal discriminative capabilities (area under the receiver operating characteristic curve [AUC] = 0.701). For peritumoral edema regions, the combined NODDI radiomics model achieved a moderate level of discrimination (AUC = 0.820). Within the solid tumor regions, the combined NODDI radiomics model demonstrated superior performance (AUC = 0.904), surpassing the models of other VOIs. The comparison results demonstrated that the NODDI model was better than the DWI and DTI models, while those of the morphological MRI and NODDI models were similar. CONCLUSION: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM. CLINICAL RELEVANCE STATEMENT: The NODDI radiomics model showed promising performance for preoperative discrimination between Gb and SBM, and radiomics features can be incorporated into the multidimensional phenotypic features that describe tumor heterogeneity. KEY POINTS: ⢠The neurite orientation dispersion and density imaging (NODDI) radiomics model showed promising performance for preoperative discrimination between glioblastoma and solitary brain metastasis. ⢠Compared with other tumor volumes of interest, the NODDI radiomics model based on solid tumor regions performed best in distinguishing the two types of tumors. ⢠The performance of the single-parameter NODDI model was inferior to that of the combined-parameter NODDI model.
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BACKGROUND: Prusogliptin is a potent and selective DPP-4 inhibitor. In different animal models, Prusogliptin showed potential efficacy in the treatment of type 2 diabetes. However, the knowledge of its pharmacokinetics and safety in patients with liver dysfunction is limited. OBJECTIVES: The present study evaluated the pharmacokinetics and safety of Prusogliptin in subjects with mild or moderate hepatic impairment compared with healthy subjects. METHODS: According to the liver function of the subjects, we divided them into a mild liver dysfunction group, a moderate liver dysfunction group and a normal liver function group. All subjects in three groups received a single oral dose of Prusogliptin 100-mg tablets. Pharmacokinetics and safety index collection was carried out before and after taking the drug. Plasma pharmacokinetics of Prusogliptin were evaluated, and geometric least- -squares mean (GLSM) and associated 90% confidence intervals for insufficient groups versus the control group were calculated for plasma exposures. RESULTS: After a single oral administration of 100 mg of Prusogliptin tablets, the exposure level of Prusogliptin in subjects with mild liver dysfunction was slightly higher than that in healthy subjects. The exposure level of Prusogliptin was significantly increased in subjects with moderate liver dysfunction. There were no adverse events in this study. CONCLUSION: The exposure level of Prusogliptin in subjects with liver dysfunction was higher than that in healthy subjects. No participant was observed of adverse events. Prusogliptin tablets were safe and well tolerated in Chinese subjects with mild to moderate liver dysfunction and normal liver function.
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Comprimidos , Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Insuficiência Hepática/metabolismo , Inibidores da Dipeptidil Peptidase IV/farmacocinética , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Uracila/análogos & derivados , Uracila/farmacocinética , Uracila/efeitos adversos , Uracila/administração & dosagem , Uracila/uso terapêutico , Hipoglicemiantes/farmacocinética , Hipoglicemiantes/efeitos adversos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Piperidinas/farmacocinética , Piperidinas/efeitos adversos , Piperidinas/administração & dosagem , Piperidinas/uso terapêutico , Adulto Jovem , Administração Oral , Fígado/metabolismo , Fígado/efeitos dos fármacos , PiperazinasRESUMO
Gene expression is highly impacted by the environment and can be reflective of past events that affected developmental processes. It is therefore expected that gene expression can serve as a signal of a current or future phenotypic traits. In this paper we identify sets of genes, which we call Prognostic Transcriptomic Biomarkers (PTBs), that can predict firmness in Malus domestica (apple) fruits. In apples, all individuals of a cultivar are clones, and differences in fruit quality are due to the environment. The apples transcriptome responds to these differences in environment, which makes PTBs an attractive predictor of future fruit quality. PTBs have the potential to enhance supply chain efficiency, reduce crop loss, and provide higher and more consistent quality for consumers. However, several questions must be addressed. In this paper we answer the question of which of two common modeling approaches, Random Forest or ElasticNet, outperforms the other. We answer if PTBs with few genes are efficient at predicting traits. This is important because we need few genes to perform qPCR, and we answer the question if qPCR is a cost-effective assay as input for PTBs modeled using high-throughput RNA-seq. To do this, we conducted a pilot study using fruit texture in the 'Gala' variety of apples across several postharvest storage regiments. Fruit texture in 'Gala' apples is highly controllable by post-harvest treatments and is therefore a good candidate to explore the use of PTBs. We find that the RandomForest model is more consistent than an ElasticNet model and is predictive of firmness (r2 = 0.78) with as few as 15 genes. We also show that qPCR is reasonably consistent with RNA-seq in a follow up experiment. Results are promising for PTBs, yet more work is needed to ensure that PTBs are robust across various environmental conditions and storage treatments.
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Malus , Humanos , Malus/genética , Frutas/genética , Transcriptoma , Projetos Piloto , Perfilação da Expressão GênicaRESUMO
OBJECTIVE: To investigate the feasibility and diagnostic efficacy of a 3D multiecho Dixon (qDixon) research application for simultaneously quantifying the liver iron concentration (LIC) and steatosis in thalassemia patients. MATERIALS AND METHODS: This prospective study enrolled participants with thalassemia who underwent 3 T MRI of the liver for the evaluation of hepatic iron overload. The imaging protocol including qDixon and conventional T2* mapping based on 2D multiecho gradient echo (ME GRE) sequences respectively. Regions of interest (ROIs) were drawn in the liver on the qDixon maps to obtain R2* and proton density fat fraction (PDFF). The reference R2* value was measured and calculated on conventional T2* mapping using the CMRtools software. Correlation analysis, Linear regression analysis, and Bland-Altman analysis were performed. RESULTS: 84 patients were finally included in this study. The median R2*-ME-GRE was 366.97 (1/s), range [206.68 (1/s), 522.20 (1/s)]. 8 patients had normal hepatic iron deposition, 16 had Insignificant, 42 had mild, 18 had moderate. The median of R2*-qDixon was 376.88 (1/s) [219.33 (1/s), 491.75 (1/s)]. A strong correlation was found between the liver R2*-qDixon and the R2*-ME-GRE (r = 0.959, P < 0.001). The median value of PDFF was 1.76% (1.10%, 2.95%). 8 patients had mild fatty liver, and 1 had severe fatty liver. CONCLUSION: MR qDixon research sequence can rapidly and accurately quantify liver iron overload, that highly consistent with the measured via conventional GRE sequence, and it can also simultaneously detect hepatic steatosis, this has great potential for clinical evaluation of thalassemia patients.
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Fígado Gorduroso , Imageamento Tridimensional , Sobrecarga de Ferro , Fígado , Imageamento por Ressonância Magnética , Talassemia , Humanos , Sobrecarga de Ferro/diagnóstico por imagem , Sobrecarga de Ferro/complicações , Feminino , Masculino , Talassemia/diagnóstico por imagem , Talassemia/complicações , Imageamento por Ressonância Magnética/métodos , Adulto , Fígado/diagnóstico por imagem , Fígado/metabolismo , Estudos Prospectivos , Fígado Gorduroso/diagnóstico por imagem , Fígado Gorduroso/complicações , Imageamento Tridimensional/métodos , Adolescente , Adulto Jovem , Ferro/metabolismo , Ferro/análise , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Criança , Interpretação de Imagem Assistida por Computador/métodosRESUMO
INTRODUCTION: Gestational diabetes mellitus (GDM) is a prevalent pregnancy complication featuring impaired insulin sensitivity. MiR-155-5p is associated with various metabolic diseases. However, its specific role in GDM remains unclear. CCAAT enhancer binding protein beta (CEBPB), a critical role in regulating glucolipid metabolism, has been identified as a potential target of miR-155-5p. This study aims to investigate the impact of miR-155-5p and CEBPB on insulin sensitivity of trophoblasts in GDM. METHODS: Placental tissues were obtained from GDM and normal pregnant women; miR-155-5p expression was then evaluated by RTâqPCR and CEBPB expression by western blot and immunohistochemical staining. To investigate the impact of miR-155-5p on insulin sensitivity and CEBPB expression, HTR-8/SVneo cells were transfected with either miR-155-5p mimic or inhibitor under basal and insulin-stimulated conditions. Cellular glucose uptake consumption was quantified using a glucose assay kit. Furthermore, the targeting relationship between miR-155-5p and CEBPB was validated using a dual luciferase reporter assay. RESULTS: Reduced miR-155-5p expression and elevated CEBPB expression were observed in GDM placentas and high glucose treated HTR8/SVneo cells. The overexpression of miR-155-5p significantly enhanced insulin signaling and glucose uptake in trophoblasts. Conversely, inhibiting miR-155-5p induced the opposite effects. Additionally, CEBPB was directly targeted and negatively regulated by miR-155-5p in HTR8/SVneo cells. Silencing CEBPB effectively restored the inhibitory effect of miR-155-5p downregulation on insulin sensitivity in trophoblasts. DISCUSSION: These findings suggest that miR-155-5p could enhance insulin sensitivity in trophoblasts by targeting CEBPB, highlighting the potential of miR-155-5p as a therapeutic target for improving the intrauterine hyperglycemic environment in GDM.
Assuntos
Diabetes Gestacional , Resistência à Insulina , MicroRNAs , Humanos , Feminino , Gravidez , Diabetes Gestacional/metabolismo , Placenta/metabolismo , MicroRNAs/metabolismo , Proteína beta Intensificadora de Ligação a CCAAT/genética , Proteína beta Intensificadora de Ligação a CCAAT/metabolismo , Trofoblastos/metabolismo , Glucose/metabolismo , Insulina/metabolismo , Proliferação de CélulasRESUMO
BACKGROUND: Rheumatoid Arthritis Magnetic Resonance Imaging Score (RAMRIS) is usually used for the semi-quantitative evaluation of joint changes in Rheumatoid Arthritis (RA). However, this method cannot evaluate early changes in bone marrow edema (BME). OBJECTIVE: To determine whether T1 mapping of wrist BME predicts early treatment response in RA. METHODS: This study prospectively enrolled 48 RA patients administered oral anti-rheumatic drugs. MRI of the most severely affected wrist was performed before and after 4 (48 patients) and 8 weeks of treatment (38 patients). Mean T1 values of BME in the lunate, triangular, and capitate bones; RAMRIS for each wrist; Erythrocyte-Sedimentation Rate (ESR); and 28-joint Disease Activity Score (DAS28)-ESR score were analyzed. Patients were divided into responders (4 weeks, 30 patients; 8 weeks, 32 patients) and non-responders (4 weeks, 18 patients; 8 weeks, 6 patients), according to EULAR response criteria. Receiver operating characteristic (ROC) curves were used to evaluate the efficacy of T1 values. RESULTS: ESR and DAS28-ESR were not correlated with T1 value and RAMRIS at each examination (P > 0.05). Changes in T1 value and DAS28-ESR relative to the baseline were moderately positively correlated with each other at 4 and 8 weeks (r = 0.555 and 0.527, respectively; P < 0.05). At 4 weeks, the change and rate of change in T1 value significantly differed between responders and non-responders (-85.63 vs. -19.92 ms; -12.89% vs. -2.81%; P < 0.05). The optimal threshold of the rate of change in T1 value at 4 weeks for predicting treatment response was -5.32% (area under the ROC curve, 0.833; sensitivity, 0.900; specificity, 0.667). CONCLUSION: T1 mapping provides a new imaging method for monitoring RA lesions; changes in wrist BME T1 values reflect early treatment response.
Assuntos
Artrite Reumatoide , Sinovite , Humanos , Sinovite/diagnóstico , Sinovite/patologia , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/tratamento farmacológico , Imageamento por Ressonância Magnética/métodos , Articulação do Punho/diagnóstico por imagem , Articulação do Punho/patologia , Edema/diagnóstico , Edema/patologia , Espectroscopia de Ressonância MagnéticaRESUMO
Cultivated pear consists of several Pyrus species with Pyrus communis (European pear) representing a large fraction of worldwide production. As a relatively recently domesticated crop and perennial tree, pear can benefit from genome-assisted breeding. Additionally, comparative genomics within Rosaceae promises greater understanding of evolution within this economically important family. Here, we generate a fully phased chromosome-scale genome assembly of P. communis 'd'Anjou.' Using PacBio HiFi and Dovetail Omni-C reads, the genome is resolved into the expected 17 chromosomes, with each haplotype totaling nearly 540 Megabases and a contig N50 of nearly 14â Mb. Both haplotypes are highly syntenic to each other and to the Malus domestica 'Honeycrisp' apple genome. Nearly 45,000 genes were annotated in each haplotype, over 90% of which have direct RNA-seq expression evidence. We detect signatures of the known whole-genome duplication shared between apple and pear, and we estimate 57% of d'Anjou genes are retained in duplicate derived from this event. This genome highlights the value of generating phased diploid assemblies for recovering the full allelic complement in highly heterozygous crop species.