Impact of COVID-19 Nonpharmaceutical Interventions on Respiratory Syncytial Virus Infections in Hospitalized Children.

BACKGROUND: Nonpharmaceutical interventions (NPIs) targeted at SARS-CoV-2 have remarkably affected the circulation of other respiratory pathogens, including respiratory syncytial virus (RSV). This study aimed to assess the changes in epidemiological and clinical characteristics of RSV infections in hospitalized children before and during the pandemic in Suzhou, China. METHODS: We prospectively enrolled children aged < 18 years who were hospitalized in Soochow University Affiliated Children's Hospital with acute lower respiratory infection (ALRIs) from January 2018 to July 2022. Changes in epidemiological and clinical characteristics of RSV infections were analyzed. RESULTS: Compared with the same period in 2018-2019, the difference in the overall positive rate of RSV was not statistically significant in 2020, while it increased significantly in 2021 (11.8% [662/5621] vs. 20.8% [356/1711], p < 0.001) and 2022 (9.0% [308/3406] vs. 18.9% [129/684], p < 0.001). Specifically, the positive rates declined considerably from October to December 2020 but sharply increased during the summer of 2021. Compared to prepandemic period, RSV infections were more frequently observed in older children during the pandemic. RSV-positive children exhibited milder clinical characteristics during the COVID-19 pandemic, including decreased proportion of patients with hospital stay ≥ 11 days (10.3% vs. 6.7%, p < 0.05), less requirement for oxygen therapy (13.7% vs. 6.9%, p < 0.001), and fewer cases of polypnea (12.2% vs. 9.7%, p < 0.05) and wheeze (50.1% vs. 42.9%, p < 0.001). CONCLUSIONS: The implementation of multilayered NPIs targeted at COVID-19 has affected the activity of RSV. Ongoing monitoring of RSV is warranted as the changing RSV epidemiology can provide valuable insights for future healthcare system planning.

Interpretable Inference and Classification of Tissue Types in Histological Colorectal Cancer Slides Based on Ensembles Adaptive Boosting Prototype Tree.

Digital pathology images are treated as the "gold standard" for the diagnosis of colorectal lesions, especially colon cancer. Real-time, objective and accurate inspection results will assist clinicians to choose symptomatic treatment in a timely manner, which is of great significance in clinical medicine. However, Manual methods suffers from long inspection cycle and serious reliance on subjective interpretation. It is also a challenging task for existing computer-aided diagnosis methods to obtain models that are both accurate and interpretable. Models that exhibit high accuracy are always more complex and opaque, while interpretable models may lack the necessary accuracy. Therefore, the framework of ensemble adaptive boosting prototype tree is proposed to predict the colorectal pathology images and provide interpretable inference by visualizing the decision-making process in each base learner. The results showed that the proposed method could effectively address the "accuracy-interpretability trade-off" issue by ensemble of m adaptive boosting neural prototype trees. The superior performance of the framework provides a novel paradigm for interpretable inference and high-precision prediction of pathology image patches in computational pathology.

Interpretable classification of pathology whole-slide images using attention based context-aware graph convolutional neural network.

BACKGROUND AND OBJECTIVE: Whole slide image (WSI) classification and lesion localization within giga-pixel slide are challenging tasks in computational pathology that requires context-aware representations of histological features to adequately infer nidus. The existing weakly supervised learning methods mainly treat different locations in the slide as independent regions and cannot learn potential nonlinear interactions between instances based on i.i.d assumption, resulting in the model unable to effectively utilize context-ware information to predict the labels of WSIs and locate the region of interest (ROI). METHODS: Here, we propose an interpretable classification model named bidirectional Attention-based Multiple Instance Learning Graph Convolutional Network (ABMIL-GCN), which hierarchically aggregates context-aware features of instances into a global representation in a topology fashion to predict the slide labels and localize the region of lymph node metastasis in WSIs. RESULTS: We verified the superiority of this method on the Camelyon16 dataset, and the results show that the average predicted ACC and AUC of the proposed model after flooding optimization can reach 90.89% and 0.9149, respectively. The average accuracy and ACC score are improved by more than 7% and 4% compared with the existing state-of-the-art algorithms. CONCLUSIONS: The results demonstrate that context-aware GCN outperforms existing weakly supervised learning methods by introducing spatial correlations between the neighbor image patches, which also addresses the 'accuracy-interpretability trade-off' problem. The framework provides a novel paradigm for the clinical application of computer-aided diagnosis and intelligent systems.

Precoded and pre-equalized multi-band FBMC transmission enabled by radio-frequency DACs and the undersampling technique.

In this Letter, we use radio-frequency digital-to-analog converters (DACs) operating in different frequency response modes to generate a high spectral-efficiency multi-band (MB) filter bank multicarrier (FBMC) signal. In the receiver, the undersampling technique is employed to realize down-conversions. No electrical mixers are required. Besides, discrete Fourier transform and orthogonal circulant matrix transform precoding techniques combined with channel-independent digital pre-equalization are enabled to enhance transmission performance. Both numerical simulations and offline experiments are performed. The relevant results show that the MB-FBMC without a cyclic prefix (CP) is robust against inter-symbol interference induced by the band-pass filtering. By using precoding and pre-equalization techniques, the bit error rate can be improved by more than one order of magnitude. In contrast, an additional 12.5% CP overhead is required for the MB orthogonal frequency division multiplexing system to achieve such an improvement.

TNFα Triggers an Augmented Inflammatory Response in Brain Neurons from Dahl Salt-Sensitive Rats Compared with Normal Sprague Dawley Rats.

Tumor Necrosis Factor (TNF)-α is a proinflammatory cytokine (PIC) and has been implicated in a variety of illness including cardiovascular disease. The current study investigated the inflammatory response trigged by TNFα in both cultured brain neurons and the hypothalamic paraventricular nucleus (PVN), a key cardiovascular relevant brain area, of the Sprague Dawley (SD) rats. Our results demonstrated that TNFα treatment induces a dose- and time-dependent increase in mRNA expression of PICs including Interleukin (IL)-1ß and Interleukin-6 (IL6); chemokines including C-C Motif Chemokine Ligand 5 (CCL5) and C-C Motif Chemokine Ligand 12 (CCL12), inducible nitric oxide synthase (iNOS), as well as transcription factor NF-kB in cultured brain neurons from neonatal SD rats. Consistent with this finding, immunostaining shows that TNFα treatment increases immunoreactivity of IL1ß, CCL5, iNOS and stimulates activation or expression of NF-kB, in both cultured brain neurons and the PVN of adult SD rats. We further compared mRNA expression of the aforementioned genes in basal level as well as in response to TNFα challenge between SD rats and Dahl Salt-sensitive (Dahl-S) rats, an animal model of salt-sensitive hypertension. Dahl-S brain neurons presented higher baseline levels as well as greater response to TNFα challenge in mRNA expression of CCL5, iNOS and IL1ß. Furthermore, central administration of TNFα caused significant higher response in CCL12 in the PVN of Dahl-S rats. The increased inflammatory response to TNFα in Dahl-S rats may be indicative of an underlying mechanism for enhanced pressor reactivity to salt intake in the Dahl-S rat model.

Acetate Mediates Alcohol Excitotoxicity in Dopaminergic-like PC12 Cells.

Neuronal excitotoxicity is the major cause of alcohol-related brain damage, yet the underlying mechanism remains poorly understood. Using dopaminergic-like PC12 cells, we evaluated the effect of N-methyl-d-aspartate receptors (NMDAR) on acetate-induced changes in PC12 cells: cell death, cytosolic calcium, and expression levels of the pro-inflammatory cytokine tumor necrosis factor alpha (TNFα). Treatment of PC12 cells with increasing concentrations of acetate for 4 h caused a dose-dependent increase in the percentage of cells staining positive for cell death using propidium iodide (PI) exclusion and cytosolic reactive oxygen species (ROS) using cell ROX detection analyzed via flow cytometry. The EC50 value for acetate was calculated and found to be 4.40 mM for PI and 1.81 mM for ROS. Ethanol up to 100 mM had no apparent changes in the percent of cells staining positive for PI or ROS. Acetate (6 mM) treatment caused an increase in cytosolic calcium measured in real-time with Fluo-4AM, which was abolished by coapplication with the NMDAR blocker memantine (10 µM). Furthermore, cells treated with acetate (6 mM) for 4 h had increased expression levels of TNFα relative to control, which was abolished by coapplication of memantine (10 µM). Co-application of acetate (6 mM) and memantine had no apparent reduction in acetate-induced cell death. These findings suggest that acetate is capable of increasing cytosolic calcium concentrations and expression levels of the pro-inflammatory cytokine TNFα through an NMDAR-dependent mechanism. Cell death from acetate was not reduced through NMDAR blockade, suggesting alternative pathways independent of NMDAR activation for excitotoxicity.

Determination of Cadmium in Shrimp and Shell Fish Samples by Coprecipitation Enrichment with Mn(â ¡)-5-Br-PADAP Flame Atomic Absorption Spectrometry.

A separation/preconcentration procedure with coprecipitation has been proposed for the flame atomic absorption spectrometric (FAAS) determination of cadmium at trace level in food and environmental samples. Manganese(Ⅱ) was used as a carrier which chelated with 2-(5-bromo-2-pyridylazo)-5-diethylaminophenol to detect the content of trace cadmium in shrimp and shell fish samples with flame atomic absorption spectrometry for the first time. The precipitate could be easily dissolved with concentrated nitric acid. The optimum coprecipitation of this new method including the amount of reagent, amount of manganese(Ⅱ), the pH, and the standing time of the precipitate had been confirmed for the quantitative recoveries of the analytes. The effect of matrix ions and the interference of co-existing ions were also evaluated. Under the experimental conditions established by the optimization step, the system of Mn(Ⅱ)-5-Br-PADAP was able to overcome the matrix interference which showed the effect of separation and enrichment well. The linear range of cadmium content was determined to be 0.1～1.0 mg·L-1. The sensitivity and the relative standard deviation(RSD) were found 0.147(mg·L-1)-1, 0.73%, respectively. The optimum procedure allows the determination of cadmium with limit of detection of 4.27 µg·L-1. The complexity of preprocessing was determined by the complexity of food samples. So the differences of cadmium content in the samples between the direct determination with atomic absorption spectrometry and the measurement after coprecipitation were examined, which providedevidences for the superiority of the system again. Cadmium in shell fish and shrimp samples were 1.85 mg·kg-1 and 1.74 mg·kg-1, which in line with international standards of the Codex Alimentarius Commission(CAC). The credibility of the method was evaluated by standard additional method and recovery experiments. The standard addition recoveries of sample and RSDs of the method were in the range of 99.9%～100.3% and 0.15%～0.83%. The results of recovery experiment showed that the presented coprecipitation procedure had good repetition, high accuracy. In addition, with the method, we could draw conclusions that the experiments were simple and rapid. The developed method described in the literature was successfully applied for the determination of trace cadmium in shrimp and shell fish samples with satisfactory results.

Activation of the (pro)renin receptor in the paraventricular nucleus increases sympathetic outflow in anesthetized rats.

Previous studies have indicated that hyperactivity of brain prorenin receptors (PRR) is implicated in neurogenic hypertension. However, the role of brain PRR in regulating arterial blood pressure (ABP) is not well understood. Here, we test the hypothesis that PRR activation in the hypothalamic paraventricular nucleus (PVN) contributes to increased sympathetic nerve activity (SNA). In anaesthetized adult Sprague-Dawley (SD) rats, bilateral PVN microinjection of human prorenin (2 pmol/side) significantly increased splanchnic SNA (SSNA; 71 ± 15%, n = 7). Preinjection of either prorenin handle region peptide, the PRR binding blocker (PRRB), or tiron (2 nmol/side), the scavenger of reactive oxygen species (ROS), significantly attenuated the increase in SSNA (PRRB: 32 ± 5% vs. control, n = 6; tiron: 8 ± 10% vs. control, n = 5; P < 0.05) evoked by prorenin injection. We further investigated the effects of PRR activation on ROS production as well as downstream gene expression using cultured hypothalamus neurons from newborn SD rats. Incubation of brain neurons with human prorenin (100 nM) dramatically enhanced ROS production and induced a time-dependent increase in mRNA levels of inducible nitric oxide synthase (iNOS), NAPDH oxidase 2 subunit cybb, and FOS-like antigen 1 (fosl1), a marker for neuronal activation and a component of transcription factor activator protein-1 (AP-1). The maximum mRNA increase in these genes occurred 6 h following incubation (iNOS: 201-fold; cybb: 2 -fold; Ffosl1: 11-fold). The increases in iNOS and cybb mRNA were not attenuated by the AT1 receptor antagonist losartan but abolished by the AP-1 blocker curcumin. Our results suggest that PVN PRR activation induces sympathoexcitation possibly through stimulation of an ANG II-independent, ROS-AP-1-iNOS signaling pathway.

Intra-carotid hyperosmotic stimulation increases Fos staining in forebrain organum vasculosum laminae terminalis neurones that project to the hypothalamic paraventricular nucleus.

Body fluid hyperosmolality has long been known to elicit homeostatic responses that range from drinking to inhibition of salt appetite to release of neurohypohyseal hormones (i.e. vasopressin and oxytocin). More recently, it has been recognized that hyperosmolality is capable of also provoking a significant increase of sympathetic nerve activity (SNA). It has been reported that neurones in the forebrain organum vasculosum laminae terminalis (OVLT) and hypothalamic paraventricular nucleus (PVN) each contribute significantly to this response. Here we sought to determine if sympathoexcitatory levels of hyperosmolality activate specifically those OVLT neurones that form a monosynaptic pathway to the PVN. First, we established in anaesthetized rats that graded concentrations of hypertonic NaCl (1.5 and 3.0 osmol kg(-1)) elicit graded increases of renal SNA (RSNA) when infused at a rate of 0.1 ml min(-1) through an internal carotid artery (ICA) - the major vascular supply of the forebrain. Next, infusions were performed in conscious rats in which OVLT neurones projecting to the PVN (OVLT-PVN) were retrogradely labelled with cholera toxin subunit B (CTB). Immunostaining of the immediate early gene product Fos and CTB was performed to quantify osmotic activation of OVLT-PVN neurones. ICA infusions of hypertonic NaCl and mannitol each significantly (P < 0.01-0.001) increased the number of Fos immunoreactive (Fos-ir) neuronal nuclei in the dorsal cap (DC) and lateral margins (LM) of OVLT. In the LM, infusions of 1.5 and 3.0 osmol kg(-1) NaCl produced similar increases in the number of Fos-ir neurones. In the DC, these infusions produced graded increases in Fos expression. Among OVLT neurones with axons projecting directly to the PVN (i.e. CTB-ir), graded hypertonic NaCl infusions again produced graded increases in Fos expression and this was observed in both the DC and LM. Although the DC and LM contained a similar number of OVLT-PVN neurones, the proportion of such neurones that expressed Fos-ir in responses to ICA hypertonic NaCl infusions was greater in the DC (P < 0.001). These findings support the conclusion that PVN-projecting neurones in the DC and LM of OVLT could participate in behavioural, neuroendocrine, and sympathetic nervous system responses to body fluid hyperosmolality.