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Estrogens play a significant role in endocrinology and oncology. Although separation methods coupled with mass spectrometry (MS) have emerged as a powerful tool for studying estrogens, imaging the spatial distributions of estrogens is crucial but remains challenging due to its low endogenous concentration and poor ionization efficiency. Charge-generation derivatization, such as N-alkylpyridinium quaternization and S-methyl thioetherification, represents a method wherein neutral molecules involving analytes and derivatization reagents undergo chemical reactions to establish permanent charges directly onto the analytes to improve detection sensitivity. Here, we developed a novel derivatization reagent, thianthrene (TT), which enabled oxidization to radical cations ([TT]â¢+) using an electrochemical method and completed the online charge-generation derivatization of estrogens on a mass spectrometry imaging platform. In this strategy, [TT]â¢+ can efficiently and selectively derivatize estrogens via an electrophilic aromatic substitution reaction. Results indicated that derivatization with [TT]â¢+ can significantly enhance imaging sensitivity (3 orders of magnitude), enabling the visualization of estrogen and its metabolites in ovarian and breast tissues. Furthermore, a higher mass intensity of these estrogens was captured in breast para-cancerous tissues than in cancerous tissues, which might provide estrogens spatial dimension information for further research on the initiation and progression of breast cancer.
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Alternanthera philoxeroides is a perennial herbaceous plant used as a forage crop (Wang et al. 2005) and is known to have medicinal properties. One of notable active components is flavonoids, which have been found to exhibit anti-Hepatitis B Virus activity (Li et al. 2016). In 2021, a leaf spot on A. philoxeroides was observed in the science and education experimental park of Hebei Agricultural University (38°49'38â³ N, 115°26'39â³ E). Initial symptoms included leaf tissue water loss, chloro-sis and elliptical lesions scattered across the leaf margin with further development leading to ellipse-shaped disease spots and leaf wilting (Fig. 1A). In the field, 50 plants of A. philoxeroides were randomly selected to investigate and quantify dis-ease. Incidence of leaf disease was approximately 25%, and the infected leaves ex-hibited an average affected area of about 20%. In order to identify the pathogen, three diseased plants were randomly selected from different areas. Stems and leaves of diseased plants were cut into pieces (2 to 3 mm × 5 mm) and disinfested with 1% sodium hypochlorite for 1 minute. After rinsing with sterile water three times, each lesion sample was isolated and purified on PDA at 25°C. Eventually, all samples pro-duced morphologically consistent colonies of pure strains. From the 9 isolates ob-tained, ZLQ-1 was selected as a representative isolate for further study. Colonies were initially white, turning gray from the centre, then gray-brown with cottony aerial hyphae, and finally growing black, stiff, round or irregular sclerotia (0.6 to 4.0 mm × 1.1 to 4.2 mm, n=50) (Fig1. B, C). ZLQ-1 exhibited branched conidia with en-larged apical cells. The conidia of this isolate were unicellular, ovoid or ellipsoid in shape, with dimensions ranging from 5.8 to 16.9 µm × 6.3 to 11.2 µm (n=50) (Fig. 1D). These morphological characteristics were consistent with Botrytis cinerea (Ellis, 1971). The genes of internal transcribed spacer (ITS), heat shock protein (HSP60), DNA-dependent RNA polymerase subunit II (RPB2), and glyceraldehyde-3-phosphate dehydrogenase (G3PDH) were amplified with specific primers ITS1/ITS4, HSP60-F/HSP60-R, RPB2-F/RPB2-R and G3PDH-F/G3PDH-R (Aktaruzzaman et al., 2022). Sequences were deposited into GenBank with accession numbers ON479490 for ITS, ON572246 for G3PDH, ON572248 for HSP60, ON572247 for RPB2. BLASTn analysis showed that the ITS sequence shared 99.62% similarity to B. cinerea (CP009808), and the sequences of the other three nuclear protein-encoding genes (G3PDH, HSP60, and RPB2) showed at least 99.9% identity with the genome of B. ci-nerea (B05.10) (Staats et al. 2005). We have inoculated 10 healthy A. philoxeroides leaves with a suspension of 1x105 spores/mL, and used sterile water treatment as control (Aktaruzzaman et al., 2022). Each leaf was inoculated with 10 µL spore sus-pension. After 7 days in a controlled incubation environment (25â, 40%RH), the plants inoculated with conidial suspensions displayed lesions covered in a gray-white mycelial layer, resembling those observed in the field (Fig. 1E-G). In con-trast, the plants inoculated with sterile water remained unaffected. Morphological and PCR analysis confirmed that the pathogen responsible for the observed symp-toms was B. cinerea. Koch's postulates were fulfilled as the same pathogen was con-sistently re-isolated from the inoculated leaves and confirmed to be B. cinerea through morphological and molecular methods. This is the first reported case of B. cinerea causing gray mold on A. philoxeroides in China. It is important to monitor and prevent B. cinerea infection during cultivation to ensure the production of healthy Chinese medicine and feed.
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Stem End Rot (SER) is a devastating post-harvest disease of mango fruits causing severe losses during storage. In 22 July 2023, 31 out of 50 intact mangoes (cv. Sensation) collected from five orchards in Huaping county (26°37'N 101°15') showed typical symptoms of SER after stored for 9 d in room temperature (24-28â). Initially, small dark brown to black spots appeared around the fruit peduncle, which rapidly expanded through the pulp tissues. The symptomatic mangoes were surface disinfected by 3% NaClO for 30 s after soaking in 75% alcohol for 3 min, and cleaned by sterile water for 3 times. Tissues were cut from the edge of lesions, dried by sterile filter paper, transferred to PDA and cultured at 28 â for 5 d (Tovar-Pedraza et al., 2020). The single-spore isolation method was used to obtain pure culture. Thirty eight isolates presented four distinct kind of morphology on PDA medium. Among them, 11 isolates with same morphology were significantly distinct from common pathogens of SER. The colonies were white and pale yellow on reverse side. Mycelia grew fast and reached the edge of 90 mm Petri dish after cultured for 5d. Pycnidia were black and scattered on the mycelial mats after 15-20 d. Conidia were fusoid, straight to slightly curved, four septa, and brown. Pigmented median cells doliiform, 14.97 - 18.62(16.11 ±0.89)×5.61- 7.28 (6.61±0.51) µm. Apical cell hyaline, subcylindrical; 1-3 tubular transparent apical appendages 12.27 - 16.68 (13.65±3.78)×1.14 - 1.99 (1.59±0.36) µm. Basal cell conical with a truncate base, hyaline, and 1-2 tubulose basal appendages with 2.85 - 7.97 (5.18±1.88)×0.99 - 1.85 (1.38±0.29) µm (n=50). These fungi were described as Pestalotiopsis kenyana. based on morphological characters (Maharachchikumbura et al., 2014) which were different from isolates characterized as other common SER pathogens (Botryosphaeria, Neofusicoccum). Based on morphology, HPSX-4 was selected for further identification. ITS region, tef1-α, ß-tub of HPSX-4 were amplified and sequenced (Xun et al., 2023). The sequences were deposited in GenBank (ITS:OR889126, tef1-α:OR913431, ß-tub: OR913432). The ITS, tef1-α, ß-tub sequence of HPSX-4 showed 100% (525/525)ï¼99.59% (241/242), and 100% (742/742) identity to the P. kenyana CBS442.67 sequences (ITS: NR147549ï¼tef1-α: KM199502, ß-tub: KM199395), respectively. HPSX-4 clustered with P. kenyana CBS 442.67 (type strain) based on maximum likelihood method by MEGA 7.0.21(Minh et al., 2013). Pathogenicity test was performed on 12 healthy mangoes (cv. Golek) by placing mycelial plugs around the peduncle and the middle of the fruit by pin-prick method according to Feng et al.(2023). Sterile PDA were used as control (three mangoes). Every inoculated fruit was incubated at 28°C, 95% ± 3% humidity with three replicates for each treatment. The experiment was repeated three times. Typical symptoms of SER were observed. There were no symptoms in the control group. The strain was reisolated and identified as P. kenyana with the method mentioned above which fulfilled Koch's postulates. This is the first report of P. kenyana causing SER disease on Mangifera indica L.. This study expands our understanding of the pathogen range of mango SER which conducive to prevent and control the SER caused by P. kenyana.
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In the realm of biological research, the invention of super-resolution microscopy (SRM) has enabled the visualization of ultrafine sub-cellular structures and their functions in live cells at the nano-scale level, beyond the diffraction limit, which has opened up a new window for advanced biomedical studies to unravel the complex unknown details of physiological disorders at the sub-cellular level with unprecedented resolution and clarity. However, most of the SRM techniques are highly reliant on the personalized special photophysical features of the fluorophores. In recent times, there has been an unprecedented surge in the development of robust new fluorophore systems with personalized features for various super-resolution imaging techniques. To date, xanthene, cyanine, oxazine and BODIPY cores have been authoritatively utilized as the basic fluorophore units in most of the small-molecule-based organic fluorescent probe designing strategies for SRM owing to their excellent photophysical characteristics and easy synthetic acquiescence. Since the future of next-generation SRM studies will be decided by the availability of advanced fluorescent probes and these four fluorescent building blocks will play an important role in progressive new fluorophore design, there is an urgent need to review the recent advancements in designing fluorophores for different SRM methods based on these fluorescent dye cores. This review article not only includes a comprehensive discussion about the recent developments in designing fluorescent probes for various SRM techniques based on these four important fluorophore building blocks with special emphasis on their effective integration into live cell super-resolution bio-imaging applications but also critically evaluates the background of each of the fluorescent dye cores to highlight their merits and demerits towards developing newer fluorescent probes for SRM.
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Liquid chromatography-mass spectrometry (LC-MS) is widely used in the detection of pesticide residues. However, the detection sensitivity of low-polarity pesticides by commonly used electrospray ionization may be severely suppressed, which greatly affects the limit of detection and repeatability. Herein, a plasma-excited nebulizer gas-assisted electrospray ionization (PENG-ESI) device has been developed. By introducing the discharge plasma formed by Tesla coil into the electrospray nebulizer gas channel, the sensitivity of low-polarity pesticides was significantly increased while maintaining sensitivity to polar pesticides. Under the optimized conditions, the limit of detection for S-bioallethrin was achieved at the level of 100 pg/g with good linearity (R2 > 0.99) and precision (RSD ≤ 4.61%). The matrix effect of a series of spiked matrix samples is less than 13.1%. Finally, different pyrethroid pesticide residues were successfully analyzed without separation, highlighting that the technology has potential application prospects in food quality control, environmental monitoring, and other fields.
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Background Cerebral blood volume (CBV) maps derived from dynamic susceptibility contrast-enhanced (DSC) MRI are useful but not commonly available in clinical scenarios. Purpose To test image-to-image translation techniques for generating CBV maps from standard MRI sequences of brain tumors using the bookend technique DSC MRI as ground-truth references. Materials and Methods A total of 756 MRI examinations, including quantitative CBV maps produced from bookend DSC MRI, were included in this retrospective study. Two algorithms, the feature-consistency generative adversarial network (GAN) and three-dimensional encoder-decoder network with only mean absolute error loss, were trained to synthesize CBV maps. The performance of the two algorithms was evaluated quantitatively using the structural similarity index (SSIM) and qualitatively by two neuroradiologists using a four-point Likert scale. The clinical value of combining synthetic CBV maps and standard MRI scans of brain tumors was assessed in several clinical scenarios (tumor grading, prognosis prediction, differential diagnosis) using multicenter data sets (four external and one internal). Differences in diagnostic and predictive accuracy were tested using the z test. Results The three-dimensional encoder-decoder network with T1-weighted images, contrast-enhanced T1-weighted images, and apparent diffusion coefficient maps as the input achieved the highest synthetic performance (SSIM, 86.29% ± 4.30). The mean qualitative score of the synthesized CBV maps by neuroradiologists was 2.63. Combining synthetic CBV with standard MRI improved the accuracy of grading gliomas (standard MRI scans area under the receiver operating characteristic curve [AUC], 0.707; standard MRI scans with CBV maps AUC, 0.857; z = 15.17; P < .001), prediction of prognosis in gliomas (standard MRI scans AUC, 0.654; standard MRI scans with CBV maps AUC, 0.793; z = 9.62; P < .001), and differential diagnosis between tumor recurrence and treatment response in gliomas (standard MRI scans AUC, 0.778; standard MRI scans with CBV maps AUC, 0.853; z = 4.86; P < .001) and brain metastases (standard MRI scans AUC, 0.749; standard MRI scans with CBV maps AUC, 0.857; z = 6.13; P < .001). Conclusion GAN image-to-image translation techniques produced accurate synthetic CBV maps from standard MRI scans, which could be used for improving the clinical evaluation of brain tumors. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Branstetter in this issue.
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Neoplasias Encefálicas , Glioma , Humanos , Volume Sanguíneo Cerebral , Estudos Retrospectivos , Recidiva Local de Neoplasia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/patologiaRESUMO
BACKGROUND: Water exchange across blood-brain barrier (BBB) (WEXBBB ) is an emerging biomarker of BBB dysfunction with potential applications in many brain diseases. Several MRI methods have been proposed to measure WEXBBB , but evidence remains scarce whether different methods can produce comparable WEXBBB . PURPOSE: To explore whether dynamic contrast-enhanced (DCE)-MRI and vascular water exchange imaging (VEXI) could produce comparable WEXBBB in high-grade glioma (HGG) patients. STUDY TYPE: Prospective cross-sectional. SUBJECTS: 13 HGG patients (58.4 ± 9.4 years, 9 females, 4 WHO III and 9 WHO IV). FIELD STRENGTH/SEQUENCE: A 3 T, spoiled gradient-recalled-echo DCE-MRI and VEXI containing two pulsed-gradient spin-echo blocks separated by a mixing block. ASSESSMENTS: The enhanced tumor and contralateral normal-appearing white matter (cNAWM) volume-of-interests (VOIs) were drew by two neuroradiologists. And whole-brain NAWM and normal-appearing gray matter (NAGM) without tumor-affected regions were segmented by automated segmentation algorithm in FSL. STATISTICAL TESTS: Student's t-test was used to evaluate parameters difference between cNAWM and tumor, NAGM and NAWM, respectively. The correlation between vascular water efflux rate constant (kbo ) from DCE-MRI and apparent exchange rate across BBB (AXRBBB ) from VEXI was evaluated by Pearson correlation. P < 0.05 was considered statistically significant. RESULTS: Compared with cNAWM, both kbo and AXRBBB were significantly reduced in tumor (kbo = 3.50 ± 1.18 sec-1 vs. 1.03 ± 0.75 sec-1 ; AXRBBB = 3.54 ± 1.11 sec-1 vs. 1.94 ± 1.04 sec-1 ). Both kbo and AXRBBB showed significantly higher values in NAWM than NAGM (kbo = 3.50 ± 0.59 sec-1 vs. 2.10 ± 0.56 sec-1 ; AXRBBB = 3.35 ± 0.77 sec-1 vs. 2.07 ± 0.52 sec-1 ). The VOI-averaged kbo and AXRBBB were also linearly correlated in tumor, NAWM, and NAGM (r = 0.59). DATA CONCLUSION: DCE-MRI and VEXI showed comparable and correlated WEXBBB in HGG patients, suggesting that the consistence and reliability of these two MRI methods in measuring WEXBBB . EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 1.
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Neoplasias Encefálicas , Glioma , Feminino , Humanos , Barreira Hematoencefálica/diagnóstico por imagem , Barreira Hematoencefálica/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Reprodutibilidade dos Testes , Estudos Transversais , Estudos Prospectivos , Imageamento por Ressonância Magnética/métodos , Glioma/diagnóstico por imagem , Glioma/patologia , Meios de ContrasteRESUMO
BACKGROUND: We aimed to develop a nomogram that can be combined with point-of-care gastric ultrasound and utilised to predict postoperative nausea and vomiting (PONV) in adult patients after emergency surgery. METHODS: Imaging and clinical data of 236 adult patients undergoing emergency surgery in a university hospital between April 2022 and February 2023 were prospectively collected. Patients were divided into a training cohort (n = 177) and a verification cohort (n = 59) in a ratio of 3:1, according to a random number table. After univariate analysis and multivariate logistic regression analysis of the training cohort, independent risk factors for PONV were screened to develop the nomogram model. The receiver operating characteristic curve, calibration curve, decision curve analysis (DCA) and clinical impact curve (CIC) were used to evaluate the prediction efficiency, accuracy, and clinical practicability of the model. RESULTS: Univariate analysis and multivariate logistic regression analysis showed that female sex, history of PONV, history of migraine and gastric cross-sectional area were independent risk factors for PONV. These four independent risk factors were utilised to construct the nomogram model, which achieved significant concordance indices of 0.832 (95% confidence interval [CI], 0.771-0.893) and 0.827 (95% CI, 0.722-0.932) for predicting PONV in the training and validation cohorts, respectively. The nomogram also had well-fitted calibration curves. DCA and CIC indicated that the nomogram had great clinical practicability. CONCLUSIONS: This study demonstrated the prediction efficacy, differentiation, and clinical practicability of a nomogram for predicting PONV. This nomogram may serve as an intuitive and visual guide for rapid risk assessment in patients with PONV before emergency surgery.
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Nomogramas , Náusea e Vômito Pós-Operatórios , Adulto , Humanos , Feminino , Náusea e Vômito Pós-Operatórios/epidemiologia , Sistemas Automatizados de Assistência Junto ao Leito , Ultrassonografia , EstômagoRESUMO
OBJECTIVES: To assess the efficacy and safety of ultrasound-guided percutaneous ablation (US-PA) for adrenal metastases (AMs) using a meta-analysis. METHODS: A systematic search of PubMed, Cochrane, Web of Science, and Embase electronic databases was performed to identify studies on US-PA for AM. Seven studies published between January 2000 and August 2022 were analyzed, which resulted in a sample size of 140 patients. Both random effects and common effects meta-analysis models were used to analyze the following efficacy and safety outcomes: the first and secondary technical success rate, 1-year overall survival rates, 1-year local tumor control rate, incidence rate of intraoperative hypertensive crises, and major complications. The subgroup analysis was performed to explore the origin of heterogeneity. RESULTS: Among 140 patients from 7 studies included in this meta-analysis: 51 (36.43%) underwent radiofrequency ablation (RFA), and 89 (63.57%) underwent microwave ablation (MWA). Pooled data analysis revealed that the first and secondary technical success rates were 85% (95% confidence interval [CI], 73-96) and 99% (95% CI, 96-100), the 1-year overall survival rate was 83% (95% CI, 71-93), the 1-year local tumor control rate was 83% (95% CI, 75-90), and the incidence rate of intraoperative hypertensive crises was 14% (95% CI, 8-20). The overall rate of major complications was 3.6%. In the subgroup analysis, lower heterogeneity was indicated to be associated with mean tumor size and ablation type. CONCLUSIONS: This meta-analysis showed that US-PA can be both effective and safe for AM in terms of overall survival, technical success rate, and local control for AM.
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Neoplasias das Glândulas Suprarrenais , Ablação por Cateter , Neoplasias Hepáticas , Ablação por Radiofrequência , Humanos , Neoplasias Hepáticas/cirurgia , Resultado do Tratamento , Ablação por Radiofrequência/métodos , Neoplasias das Glândulas Suprarrenais/diagnóstico por imagem , Neoplasias das Glândulas Suprarrenais/cirurgia , Ablação por Cateter/métodos , Ultrassonografia de IntervençãoRESUMO
BACKGROUND: Studies have suggested that many down-regulated miRNAs identified in the brain tissue or serum of Alzheimer's disease (AD) patients were involved in the formation of senile plaques and neurofibrillary tangles. Specifically, our previous study revealed that microRNA-22-3p (miR-22-3p) was significantly down-regulated in AD patients. However, the molecular mechanism underlying the down-regulation of miR-22-3p has not been comprehensively investigated. METHODS: The ameliorating effect of miR-22-3p on apoptosis of the Aß-treated HT22 cells was detected by TUNEL staining, flow cytometry, and western blotting. The cognition of mice with stereotaxic injection of agomir or antagomir of miR-22-3p was assessed by Morris water maze test. Pathological changes in the mouse hippocampus were analyzed using hematoxylin and eosin (HE) staining, Nissl staining, and immunohistochemistry. Proteomics analysis was performed to identify the targets of miR-22-3p, which were further validated using dual-luciferase reporter analysis and western blotting analysis. RESULTS: The miR-22-3p played an important role in ameliorating apoptosis in the Aß-treated HT22 cells. Increased levels of miR-22-3p in the mouse hippocampus improved the cognition in mice. Although the miR-22-3p did not cause the decrease of neuronal loss in the hippocampus, it reduced the Aß deposition. Proteomics analysis revealed Sox9 protein as the target of miR-22-3p, which was verified by the luciferase reporter experiments. CONCLUSION: Our study showed that miR-22-3p could improve apoptosis and reduce Aß deposition by acting on Sox9 through the NF-κB signaling pathway to improve the cognition in AD mice. We concluded that miR-22-3p ameliorated AD by targeting Sox9 through the NF-κB signaling pathway in the hippocampus.
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Doença de Alzheimer , Hipocampo , MicroRNAs , NF-kappa B , Fatores de Transcrição SOX9 , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Animais , Hipocampo/metabolismo , Hipocampo/patologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismo , Transdução de SinaisRESUMO
Adenoviruses are highly prevalent pathogens responsible for a wide range of clinical diseases, including respiratory tract infection, acute gastroenteritis, and conjunctivitis. However, adenovirus infection is rarely associated with central nervous system involvement. Here, we report a fatal viral sepsis and encephalitis in a child caused by a human adenovirus type 7 infection. We detected human adenovirus type 7 in the patient's nasopharyngeal swab, blood, and cerebrospinal fluid. Our findings indicate clinicians should be aware of the possible central nervous system involvement in adenovirus infection.
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Infecções por Adenoviridae , Infecções por Adenovirus Humanos , Adenovírus Humanos , Encefalite , Infecções por Adenoviridae/complicações , Infecções por Adenoviridae/diagnóstico , Infecções por Adenovirus Humanos/complicações , Infecções por Adenovirus Humanos/diagnóstico , Adenovírus Humanos/genética , Criança , Humanos , ViremiaRESUMO
BACKGROUND: Rhinovirus is a common viral aetiology of upper respiratory infection and is mostly associated with common cold or flu-like illness. Although rhinovirus has been recognized as a pathogen for lower respiratory infections in severe cases credited to advances in molecular detection, central nervous system involvement and multiorgan dysfunction are extremely rare. CASE PRESENTATION: A previously healthy 10-year-old girl developed fever, sore throat and conjunctive injection after contact with an upper respiratory infection patient, followed by seizures, haematuria, and severe diarrhoea. She experienced viral sepsis and multiorgan dysfunction after admission. Cerebral computed tomography showed significant diffuse encephaledema. Cerebrospinal fluid analysis showed significantly elevated protein levels. After her consciousness disturbance improved, she still took a long time to recover from haematuria and diarrhoea. We identified a rarely reported rhinovirus A45 in her oropharyngeal and anal swabs by metagenomic next-generation sequencing, and bacterial culture of blood specimens yielded negative results. CONCLUSIONS: This case presents a patient with severe rhinovirus infection, which was very likely responsible for her central nervous system symptoms and viral sepsis.
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Enterovirus , Infecções por Picornaviridae , Infecções Respiratórias , Sistema Nervoso Central , Criança , Diarreia , Feminino , Hematúria/complicações , Humanos , Masculino , Infecções por Picornaviridae/complicações , Infecções por Picornaviridae/diagnóstico , Rhinovirus , ViremiaRESUMO
OBJECTIVES: To develop and validate a multimodality MRI-based radiomics approach to predicting the posttreatment response of lung cancer brain metastases (LCBM) to gamma knife radiosurgery (GKRS). METHODS: We retrospectively analyzed 213 lesions from 137 patients with LCBM who received GKRS between January 2017 and November 2020. The data were divided into a primary cohort (102 patients with 173 lesions) and an independent validation cohort (35 patients with 40 lesions) according to the time of treatment. Benefit result was defined using pretreatment and 3-month follow-up MRI images based on the Response Assessment in Neuro-Oncology Brain Metastases criteria. Valuable radiomics features were extracted from pretreatment multimodality MRI images using random forests. Prediction performance among the radiomics features of tumor core (RFTC) and radiomics features of peritumoral edema (RFPE) together was evaluated separately. Then, the random forest radiomics score and nomogram were developed through the primary cohort and evaluated through an independent validation cohort. Prediction performance was evaluated by ROC curve, calibration curve, and decision curve. RESULTS: Gender (p = 0.018), histological subtype (p = 0.009), epidermal growth factor receptor mutation (p = 0.034), and targeted drug treatment (p = 0.021) were significantly associated with posttreatment response. Adding RFPE to RFTC showed improved prediction performance than RFTC alone in primary cohort (AUC = 0.848 versus AUC = 0.750; p < 0.001). Finally, the radiomics nomogram had an AUC of 0.930, a C-index of 0.930 (specificity of 83.1%, sensitivity of 87.3%) in primary cohort, and an AUC of 0.852, a C-index of 0.848 (specificity of 84.2%, sensitivity of 76.2%) in validation cohort. CONCLUSIONS: Multimodality MRI-based radiomics models can predict the posttreatment response of LCBM to GKRS. KEY POINTS: ⢠Among the selected radiomics features, texture features basically contributed the dominant force in prediction tasks (80%), especially gray-level co-occurrence matrix features (40%). ⢠Adding RFPE to RFTC showed improved prediction performance than RFTC alone in primary cohort (AUC = 0.848 versus AUC = 0.750; p < 0.001). ⢠The multimodality MRI-based radiomics nomogram showed high accuracy for distinguishing the posttreatment response of LCBM to GKRS (AUC = 0.930, in primary cohort; AUC = 0.852, in validation cohort).
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Neoplasias Encefálicas , Neoplasias Pulmonares , Radiocirurgia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/radioterapia , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/genética , Imageamento por Ressonância Magnética/métodos , Nomogramas , Estudos RetrospectivosRESUMO
γ-glutamyl transpeptidase (GGT) is a kind of cell-surface enzyme that is overexpressed in many cancer cells. It is of great significance to develop an ideal tool for the diagnosis of GGT-rich cancer cells. Here, we reported a simple-structured but effective imaging probe for the detection of GGT activity. In the presence of GGT, the γ-glutamyl linkage could be cleaved specifically to produce amino-substituted product, resulting in significant fluorescence enhancement at 578 nm. Moreover, we successfully employed the probe to monitor GGT activity in HepG2 cells. We envisaged that such a simple but effective imaging tool could improve the practical applications for bioimaging.
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Corantes Fluorescentes , gama-Glutamiltransferase , Fluorescência , Células Hep G2 , Humanos , ÁguaRESUMO
MOTIVATION: The multimodal data fusion analysis becomes another important field for brain disease detection and increasing researches concentrate on using neural network algorithms to solve a range of problems. However, most current neural network optimizing strategies focus on internal nodes or hidden layer numbers, while ignoring the advantages of external optimization. Additionally, in the multimodal data fusion analysis of brain science, the problems of small sample size and high-dimensional data are often encountered due to the difficulty of data collection and the specialization of brain science data, which may result in the lower generalization performance of neural network. RESULTS: We propose a genetically evolved random neural network cluster (GERNNC) model. Specifically, the fusion characteristics are first constructed to be taken as the input and the best type of neural network is selected as the base classifier to form the initial random neural network cluster. Second, the cluster is adaptively genetically evolved. Based on the GERNNC model, we further construct a multi-tasking framework for the classification of patients with brain disease and the extraction of significant characteristics. In a study of genetic data and functional magnetic resonance imaging data from the Alzheimer's Disease Neuroimaging Initiative, the framework exhibits great classification performance and strong morbigenous factor detection ability. This work demonstrates that how to effectively detect pathogenic components of the brain disease on the high-dimensional medical data and small samples. AVAILABILITY AND IMPLEMENTATION: The Matlab code is available at https://github.com/lizi1234560/GERNNC.git.
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Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/genética , Encéfalo , Disfunção Cognitiva/genética , Humanos , Imageamento por Ressonância Magnética , Redes Neurais de ComputaçãoRESUMO
Quantitative physiological parameters can be obtained from nonlinear pharmacokinetic models, such as the extended Tofts (eTofts) model, applied to dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). However, the computation of such nonlinear models is time consuming. The aim of this study was to develop a convolutional neural network (CNN) for accelerating the computation of fitting eTofts model without sacrificing agreement with conventional nonlinear-least-square (NLLS) fitting. This was a retrospective study, which included 13 patients with brain glioma for training (75%) and validation (25%), and 11 patients (three glioma, four brain metastases, and four lymphoma) for testing. CAIPIRINHA-Dixon-TWIST DCE-MRI and double flip angle T1 map acquired at 3 T were used. A CNN with both local pathway and global pathway modules was designed to estimate the eTofts model parameters, the volume transfer constant (Ktrans ), blood volume fraction (vp ), and volume fraction of extracellular extravascular space (ve ), from DCE-MRI data of tumor and normal-appearing voxels. The CNN was trained on mixed dataset consisting of synthetic and patient data. The CNN result and computation speed were compared with NLLS fitting. The robustness to noise variations and generalization to brain metastases and lymphoma data were also evaluated. Statistical tests used were Student's t test on mean absolute error, concordance correlation coefficient (CCC), and normalized root mean squared error. Including global pathway modules in the CNN and training the network with mixed data significantly (p < 0.05) improved the CNN performance. Compared with NLLS fitting, CNN yields an average CCC greater than 0.986 for Ktrans , greater than 0.965 for vp , and greater than 0.948 for ve . The CNN accelerated computation speed approximately 2000 times compared to NLLS, showed robustness to noise (signal-to-noise ratio >34.42 dB), and had no significant (p > 0.21) difference applied to brain metastases and lymphoma data. In conclusion, the proposed CNN to estimate eTofts parameters showed comparable result as NLLS fitting while significantly reducing the computation time. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 1.
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Meios de Contraste , Imageamento por Ressonância Magnética , Humanos , Análise dos Mínimos Quadrados , Redes Neurais de Computação , Estudos RetrospectivosRESUMO
Invasive pneumococcal disease (IPD) is associated with significant morbidity and mortality. However, limited studies have reported clinical features of IPD cases among Chinese children. This study aimed to evaluate clinical characteristics as well as serotype distribution of hospitalized IPD children in Beijing, China. Children with confirmed IPD were retrospectively recruited from January 2014 to December 2019. Clinical data were gathered from medical records, and serotypes of Streptococcus pneumoniae isolates were detected. Clinical differences between deaths and survivors were also compared, and risk factors associated with death were determined. Of sixty-eight children diagnosed with IPD, 58 (85.3%) were < 5 years. 19F was the predominant serotype (23, 33.8%), followed by 19A (14, 20.6%), 14 (12, 17.6%), 23F (5, 7.4%), and non-vaccine serotype (NVT) 15A (3, 4.4%). The coverage rate of 13-valent pneumococcal conjugate vaccine (PCV) was 92.6% (63). After introduction of PCV-13, there was a significant increase of IPD due to NVTs (p = 0.047). Sixteen (23.5%) children died, and diagnoses of 11 (68.8%) were meningitis. Risk factors for death were < 2 years (odds ratio [OR] [95% confidence interval {CI}]: 6.64 [1.14-32.10]; p = 0.019), altered mental status (OR [95%CI]: 10.10 [2.11-48.31]; p = 0.004), and septic shock (OR [95%CI]: 6.61 [1.11-39.50]; p = 0.038). This study revealed that the case fatality rate of hospitalized IPD children was high in this hospital. Fatal cases were more likely to be children < 2 years, presented with changed mental status and septic shock. Notably, we found that NVTs increased after PCV13 availability in China.
Assuntos
Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/epidemiologia , Sorogrupo , Streptococcus pneumoniae/classificação , Pequim/epidemiologia , Criança , Pré-Escolar , Coinfecção/epidemiologia , Coinfecção/microbiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Masculino , Infecções Pneumocócicas/microbiologia , Infecções Pneumocócicas/mortalidade , Vacinas Pneumocócicas/administração & dosagem , Estudos Retrospectivos , Fatores de Risco , Streptococcus pneumoniae/patogenicidade , Vacinação/estatística & dados numéricosRESUMO
Type 2 diabetes mellitus (T2DM) is one of the most common chronic diseases among the elderly people. The T2DM increases the risk of cardio-cerebrovascular disease (CCD), and the main pathological change of the CCD is atherosclerosis (AS). Meanwhile, the carbonic anhydrases (CAs) are involved in the formation and progression of plaques in AS. However, the exact physiological mechanism of carbonic anhydrase III (CAIII) has not been clear yet, and there are also no correlation study between CAIII protein and T2DM with CCD. The 8-week old diabetic mice (db/db-/- mice) and wild-type mice (wt mice) were feed by a normal diet till 32 weeks, and detected the carotid artery vascular opening angle using the method of biomechanics; The changes of cerebral cortex and myocardium were watched by the ultrastructure, and the autophagy were observed by electron microscope; The tissue structure, inflammation and cell injury were observed by Hematoxylin and eosin (HE) staining; The apoptosis of cells were observed by TUNEL staining; The protein levels of CAIII, IL-17, p53 were detected by immunohistochemical and Western Blot, and the Beclin-1, LC3, NF-κB were detected by Western Blot. All statistical analysis is performed using PRISM software. Compared with wt mice, db/db-/- mice' carotid artery open angle increased significantly. Electron microscope results indicated that autophagy in db/db-/- mice cerebral cortex and heart tissue decreased and intracellular organelle ultrastructure were damaged. HE staining indicated that, db/db-/- mice' cerebral cortex and heart tissue stained lighter, inflammatory cells infiltration, cell edema were obvious, myocardial fibers were disorder, and myocardial cells showed different degrees of degeneration. Compared with wt mice, TUNEL staining showed that there was obviously increase in db/db-/- mice cortex and heart tissue cell apoptosis. The results of immunohistochemistry and Western Blot indicated that CAIII, Beclin-1 and LC3II/I expression levels conspicuously decreased in cortex and heart tissue of db/db-/- mice, and the expression level of IL-17, NF-κB and p53 obviously increased. The carotid artery' vascular stiffness was increased and which was probably related with formation of AS in diabetic mice. And the autophagy participated in the occurrence and development of diabetic CCD. CAIII protein might somehow be involved in the regulation of autophagy probably through affecting cell apoptosis and inflammation, but the underlying mechanism remains to be further studied.
Assuntos
Anidrase Carbônica III , Transtornos Cerebrovasculares , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Autofagia , CamundongosRESUMO
BACKGROUND: The shutter-speed model dynamic contrast-enhanced (SSM-DCE) MRI pharmacokinetic analysis adds a metabolic dimension to DCE-MRI. This is of particular interest in cancers, since abnormal metabolic activity might happen. PURPOSE: To develop a DCE-MRI SSM analysis framework for glioblastoma multiforme (GBM) cases considering the heterogeneous tissue found in GBM. STUDY TYPE: Prospective. SUBJECTS: Ten GBM patients. FIELD STRENGTH/SEQUENCE: 3T MRI with DCE-MRI. ASSESSMENTS: The corrected Akaike information criterion (AICc ) was used to automatically separate DCE-MRI data into proper SSM versions based on the contrast agent (CA) extravasation in each pixel. The supra-intensive parameters, including the vascular water efflux rate constant (kbo ), the cellular efflux rate constant (kio ), and the CA vascular efflux rate constant (kpe ), together with intravascular and extravascular-extracellular water mole fractions (pb and po , respectively) were determined. Further error analyses were also performed to eliminate unreliable estimations on kio and kbo . STATISTICAL TESTS: Student's t-test. RESULTS: For tumor pixels of all subjects, 88% show lower AICc with SSM than with the Tofts model. Compared to normal-appearing white matter (NAWM), tumor tissue showed significantly larger pb (0.045 vs. 0.011, P < 0.001) and higher kpe (3.0 × 10-2 s-1 vs. 6.1 × 10-4 s-1 , P < 0.001). In the contrast, significant kbo reduction was observed from NAWM to GBM tumor tissue (2.8 s-1 vs. 1.0 s-1 , P < 0.001). In addition, kbo is four orders and two orders of magnitude greater than kpe in the NAWM and GBM tumor, respectively. These results indicate that CA and water molecule have different transmembrane pathways. The mean tumor kio of all subjects was 0.57 s-1 . DATA CONCLUSION: We demonstrate the feasibility of applying SSM models in GBM cases. Within the proposed SSM analysis framework, kio and kbo could be estimated, which might be useful biomarkers for GBM diagnosis and survival prediction in future. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY: Stage 1 J. Magn. Reson. Imaging 2020;52:850-863.
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Glioblastoma , Meios de Contraste , Glioblastoma/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Estudos ProspectivosRESUMO
OBJECTIVES: This study aimed to investigate the feasibility of segmentation-independent volume rendering (SI-VR) in visualising the root entry zone (REZ), and to explore the influence on the management of vascular compression syndromes (VCSs). METHODS: Two hundred and twenty patients with VCSs were recruited in this prospective study from July 2015 to May 2019. SI-VR was reconstructed based on inverted 3D fast spin echo T2WI. They were assigned to the experimental group and control group randomly. Patients in the experimental group would accept extra evaluation based on SI-VR before microvascular decompression. Image quality and diagnostic accuracy between SI-VR and 3D fast spin echo T2WI in the experimental group were compared by Mann-Whitney U test and chi-square test, separately. Interobserver agreement was performed with intraclass correlation coefficient. Postsurgical outcomes and complications between two groups were compared by chi-square test. RESULTS: SI-VR had a better interobserver agreement (0.82 vs 0.68) and diagnostic accuracy (95.5% vs 83.6%, p = 0.004) than that of 3D fast spin echo T2WI. Especially, significantly improved diagnostic accuracy was reached in detecting the multi-vascular branches compression (100% vs 15.4%, p < 0.001). There were fewer complications (7.1% vs 26.8%, p = 0.004) and less operation time (20.7 min vs 14.5 min, p = 0.007) but no significant difference of pain relief (p = 0.19) in the experimental group than in the control group. CONCLUSIONS: The SI-VR method is feasible for the precise demonstration of the anatomy structure along the REZ, with high reliability and reproducibility. Unbiased pre-surgical visualisation could reduce redundant explorations and post-surgical complications in patients who undergo microvascular decompression. KEY POINTS: ⢠Visualisation of the root entry zone by the segmentation-independent volume rendering is in accordance with the landscape by the neuro-endoscopy. ⢠Segmentation-independent volume rendering has an advantage over 3D fast spin echo T2WI in the visualisation of multi-vascular branches compression. ⢠Presurgical 3D visualisation of the neurovascular compression at the root entry zone leads to less postsurgical complications from the decrease of redundant exploration.