Impact of the COVID-19 pandemic on the demographic and disease burden of pediatric malignant solid tumors in China: a single-center, cross-sectional study.

Background: With the development of the novel coronavirus disease 2019 (COVID-19), China implemented measures in an attempt to control the infection rate. We conducted a single-center, cross-sectional study to ascertain the impact of the COVID-19 pandemic on the equitable availability of medical resources for children diagnosed with malignant solid tumors in China. Methods: Data on the demographics, clinical characteristics, and medical expenses of 876 patients diagnosed with neuroblastoma, rhabdomyosarcoma (RMS), Wilms tumor, hepatoblastoma (HB), Ewing sarcoma (ES), and central nervous system (CNS) tumors from 2019 to 2021, during the COVID-19 pandemic, were retrospectively collected from the National Center for Children's Health. The Pearson χ2 test and Mann-Whitney test were performed to analyze the differences among variables. Results: Except for the regional origin of children with tumors during the epidemic, no significant differences were found in the demographic or clinical characteristics of patients at initial diagnosis. The number of patients from northern China and northeastern China who attended Beijing Children's Hospital (BCH) increased after the outbreak of COVID-19 (P=0.001). There was no significant alteration observed in the frequency of hospitalizations per individual per annum (P=0.641) or the mean expense incurred per individual per hospitalization (P=0.361). In addition, the medical insurance coverage rate of real-time settlement increased year by year. Conclusions: After the COVID-19 outbreak, the origin of patients with solid tumor who visited BCH was concentrated in the northern region of China. COVID-19 had no impact on the other demographic factors, clinical characteristics, or economic burden of patients with pediatric malignant solid tumors.

Photosensitized 1,2-Difunctionalization of Alkenes to Access ß-Amino Sulfonamides.

A metal-free photosensitized 1,2-imino-sulfamoylation of olefins by employing a tailor-made sulfamoyl carbamate as the difunctionalization reagent has been established. This protocol exhibits versatility across a broad substrate scope, including aryl and aliphatic alkenes, leading to the synthesis of diverse ß-imino sulfonamides in moderate to good yields. This method is characterized by its metal-free reaction system, mild reaction conditions, excellent regioselectivity, and high atom economy, serving as a promising platform for the preparation of ß-amino sulfonamide-containing molecules, particularly in the context of drug discovery.

Exploring the extensin gene family: an updated genome-wide survey in plants and algae.

Extensins (EXTs), a class of hydroxyproline-rich glycoprotein with multiple Ser-Pro3-5 motifs, are known to play roles in cell wall reinforcement and environmental responses. EXTs with repetitive Tyr-X-Tyr (YXY) motifs for crosslinking are referred as crosslinking EXTs. Our comprehensive study spanned 194 algal and plant species, categorizing EXTs into seven subfamilies: classical extensins (EXT I and II), arabinogalactan-protein extensins (AGP-EXTs), proline-rich extensin-like receptor kinases (PERKs), leucine-rich repeat extensins (LRX I and II), formin homology (FH) domain-containing extensins (FH-EXTs), proline-rich, arabinogalactan proteins, conserved cysteines (PAC) domain-containing extensins (PAC I and II), and eight-cysteine motif (8CM)-containing extensins (8CM-EXTs). In the examined dataset, EXTs were detected ubiquitously in plants but infrequently in algae, except for one Coccomyxa and four Chlamydomonadales species. No crosslinking EXTs were found in Poales or certain Zingiberales species. Notably, the previously uncharacterized EXT II, PAC II, and liverwort-specific 8CM-EXTs were found to be crosslinking EXTs. EXT II, featuring repetitive YY motifs instead of the conventional YXY motif, was exclusively identified in Solanaceae. Furthermore, tandem genes encoding distinctive 8CM-EXTs specifically expressed in the germinating spores of Marchantia polymorpha. This updated classification of EXT types allows us to propose a plausible evolutionary history of EXT genes during the course of plant evolution.

Comprehensive Genomic and Transcriptomic Analysis of Sclerosing Pneumocytoma.

Sclerosing pneumocytoma is a rare and distinct lung neoplasm whose histogenesis and molecular alterations are the subject of ongoing research. Our recent study revealed that AKT1 internal tandem duplications (ITD), point mutations, and short indels were present in almost all tested sclerosing pneumocytomas, suggesting that AKT1 mutations are a major driving oncogenic event in this tumor. Although the pathogenic role of AKT1 point mutations is well established, the significance of AKT1 ITD in oncogenesis remains largely unexplored. We conducted comprehensive genomic and transcriptomic analyses of sclerosing pneumocytoma to address this knowledge gap. RNA-sequencing data from 23 tumors and whole-exome sequencing data from 44 tumors were used to obtain insights into their genetic and transcriptomic profiles. Our analysis revealed a high degree of genetic and transcriptomic similarity between tumors carrying AKT1 ITD and those with AKT1 point mutations. Mutational signature analysis revealed COSMIC signatures 1 and 5 as the prevailing signatures of sclerosing pneumocytoma, associated with the spontaneous deamination of 5-methylcytosine and an unknown etiology, respectively. RNA-sequencing data analysis revealed that the sclerosing pneumocytoma gene expression profile is characterized by activation of the PI3K/AKT/mTOR pathway, which exhibits significant similarity between tumors harboring AKT1 ITD and those with AKT1 point mutations. Notably, an upregulation of SOX9, a transcription factor known for its involvement in fetal lung development, was observed in sclerosing pneumocytoma. Specifically, SOX9 expression was prominent in the round cell component, whereas it was relatively lower in the surface cell component of the tumor. To the best of our knowledge, this is the first comprehensive investigation of the genomic and transcriptomic characteristics of sclerosing pneumocytoma. Results of the present study provide insights into the molecular attributes of sclerosing pneumocytoma and a basis for future studies of this enigmatic tumor.

Chronic mild stress leads to anxiety-like behavior and decreased p70 S6K1 activity in the hippocampus of male mice.

Major affective disorders are highly prevalent, however, current treatments are limited in their effectiveness due to a lack of understanding of underlying molecular mechanisms. Recent studies have shown that reduced activity of p70 S6 kinase 1 (S6K1), a downstream target of the mechanistic target of rapamycin complex 1 (mTORC1), is linked to anxiety-like behavior in both humans and rodents. The purpose of this study was to investigate the relationship between S6K1 and anxiety-like behavior following chronic mild stress (CMS) and drug-induced inhibition of S6K1. Following CMS, anxiety-like behavior was evaluated using an open field (OF) and elevated plus maze (EPM) in adult male C57/Bl6 mice. After behavior analysis, samples of the hippocampus were harvested for quantification of S6K1, S6 ribosomal protein, glycogen synthase kinase-3 ß (GSK3ß), and beta tubulin via western blot. Our results demonstrate that CMS mice exhibit anxiety-like behavior in the OF and EPM and reduced activity of S6K1 in the hippocampus (HPC). We measured phosphorylation levels of GSK3ß and found that GSK3ß phosphorylation was also reduced following CMS compared to control mice. Furthermore, pharmacological inhibition of S6K1 with PF-4708671 in male mice was sufficient to produce anxiety-like behavior in the OF and EPM. These results further support the significant role of S6K1 in the pathogenesis of anxiety and affective disorders.

Dual-Pulse Repeated Frequency Waveform Design of Time-Division Integrated Sensing and Communication Based on a 5G New Radio Communication System.

With the development of 5G communication systems, it is a hot topic to embed integrated sensing and communication (ISAC) based on the existing 5G base station by sharing the hardware and the same frequency spectrum. In this paper, we propose a dual pulse repeated frequency (dual-PRF) waveform design of time-division ISAC (TD-ISAC) based on a 5G new radio (NR) communication system using downlink communication slots. We choose time-division mode to design waveform to avoid the interference between sensing and communication. Embedding sensing functions in a 5G NR system, we design a dual-PRF sensing slot to satisfy the constraints of common channel and uplink communication. Considering two uplink modes, namely flexible and fixed, we design two dual-PRF waveforms and illustrate the sensing theory performance of the designed waveform by the ambiguity function. Then, we exploit the designed waveform to the vehicle parameter estimation. To verify that the designed waveform has good adaptability to different signal processing methods, we realize the parameter estimation by two types of methods: the discrete Fourier transformation-based method and the compressed sensing-based method. At last, we verify the effectiveness of the designed waveform system by simulation experiments and real traffic scenarios.

Photoredox-Catalyzed Selective α-Scission of PR3-OH Radicals to Access Hydroalkylation of Alkenes.

Photoinduced generation of phosphoranyl radicals offers a versatile strategy to access a variety of synthetically valuable radicals. A long-standing challenge remains in the regulation of phosphoranyl radical to undergo α-scission pathway, although the ß-scission mode has been intensively studied. We herein developed an unprecedented protocol for selective α-scission of the P(OH)R3 radical intermediate under photocatalytic conditions. This efficient P-C bond cleavage via α-scission of the P(OH)R3 radicals has been successfully utilized in the alkylation/fluoroalkylation of alkenes.

Visible-Light-Induced, Catalyst-Free Monofluoromethyl Sulfonylation of Alkenes with Iodine(III) Reagent and DABSO.

A visible-light-induced radical relay strategy to access heterocycles bearing a monofluoromethylsufonyl moiety is reported, with PhI(OCOCH2F)2 as the CH2F radical precursor and DABSO as the SO2 source. A range of oxindoles, containing a CH2FSO2CH2- group at the C3 position, were synthesized from N-arylacrylamides in up to 97% yields. The protocol features catalyst-free photochemical tandem, mild reaction conditions, broad functional group compatibility, and good to excellent yields.

Insights into Grape Ripe Rot: A Focus on the Colletotrichum gloeosporioides Species Complex and Its Management Strategies.

Grape ripe rot, which is predominantly caused by the Colletotrichum species, presents a growing threat to global grape cultivation. This threat is amplified by the increasing populations of the Colletotrichum species in response to warmer climates. In this review, we investigate the wide-ranging spectrum of grape ripe rot, specifically highlighting the role and characteristics of the C. gloeosporioides species complex (CGSC). We incorporate this understanding as we explore the diverse symptoms that lead to infected grapevines, their intricate life cycle and epidemiology, and the escalating prevalence of C. viniferum in Asia and globally. Furthermore, we delve into numerous disease management strategies, both conventional and emerging, such as prevention and mitigation measures. These strategies include the examination of host resistances, beneficial cultivation practices, sanitation measures, microbiome health maintenance, fungicide choice and resistance, as well as integrated management approaches. This review seeks to enhance our understanding of this globally significant disease, aspiring to assist in the development and improvement of effective prevention and control strategies.

Inner-Frame Time Division Multiplexing Waveform Design of Integrated Sensing and Communication in 5G NR System.

The design of an integrated sensing and communication (ISAC) waveform compatible with the 5G new radio (NR) system is crucial in enabling ISAC by utilizing the hardware of existing base stations (BSs). In this paper, we design an inner-frame time division multiplexed sensing waveform in the frame structure of 5G NR to achieve ISAC. The designed waveform is computed by the simulated annealing algorithm on an optimization cost function of a constrained combination of the peak-to-sidelobe ratio (PSLR) and the integrated sidelobe ratio (ISLR) of the velocity ambiguity function. Specifically, the constraints are the 5G communication protocol and 5G NR frame structure. In addition, we conducted corresponding signal detection and estimation methods to illustrate the performance of the sensing waveform. Both theoretical analysis and simulation experiments show that the designed waveform can effectively achieve target detection and parameter estimation under low sensing cost conditions.

Translational practice of fluorescence in situ hybridisation to identify neuroblastic tumours with TERT rearrangements.

Recently, telomerase reverse transcriptase (TERT) gene rearrangements have been identified in neuroblastoma (NB), the typical pathological type of neuroblastic tumours (NTs); however, the prevalence of TERT rearrangements in other types of NT remains unknown. This study aimed to develop a practical method for detecting TERT defects and to evaluate the clinical relevance of TERT rearrangements as a biomarker for NT prognosis. A TERT break-apart probe for fluorescence in situ hybridisation (FISH) was designed, optimised, and applied to assess the genomic status of TERT in Chinese children with NTs at the Beijing Children's Hospital from 2016 to 2019. Clinical, histological, and genetic characteristics of TERT-rearranged NTs were further addressed. Genomic TERT rearrangements could be effectively detected by FISH and were mutually exclusive with MYCN amplification. TERT rearrangements were identified in 6.0% (38/633) of NTs overall, but 12.4% (31/250) in high-risk patients. TERT rearrangements identified a subtype of aggressive NTs with the characteristics of Stage 3/4, high-risk category, over 18 months old, and presenting all histological subtypes of NB and ganglioneuroblastoma nodular. Moreover, TERT rearrangements were significantly associated with elevated TERT expression levels and decreased survival chances. Multivariable analysis confirmed that it was an independent prognostic marker for NTs. FISH is an easily applicable method for evaluating TERT defects, which define a subgroup of NTs with unfavourable prognosis. TERT rearrangements would contribute to characterising NT molecular signatures in clinical practice.

N-Chlorosulfonyl carbamate-enabled, photoinduced amidation of quinoxalin-2(1H)-ones.

Reported herein is the design and development of a new photo-induced amidation protocol with the readily available N-chlorosulfonyl carbamate as an effective amidyl-radical precursor, which could be readily prepared from commercial low-cost chlorosulfonyl isocyanate (CSI) and alcohol feedstocks. The synthetic potency of this developed protocol was well demonstrated by direct amidation of various quinoxalin-2(1H)-ones. The protocol could be further streamlined by implementing a one-pot/two-step/three-component process of CSI, alcohol, and quinoxalin-2(1H)-one, with significantly improved reaction efficiency. This methodology offers an intriguing opportunity for rapid expansion of nitrogen-containing molecular complexity, thus inspiring comprehensive exploration of a new reaction mode of CSI reagent.

Epidemiological characteristics of paediatric burn patients in China from 2016 to 2019: a retrospective study.

BACKGROUND: Epidemiological characteristics of paediatric burn can help to protect children from burn injuries. Most of the previous studies have been conducted on small scale and single centre in China. This study analysed the epidemiological characteristics of paediatric burn using a large-scale and multicentre database from 23 children's hospitals in China to increase child protection against burn injuries, improve the quality of care and reduce hospitalisation costs. METHODS: Excerpted information from medical records of 6741 paediatric burn cases was extracted from the Futang Research Center of Pediatric Development database from 2016 to 2019. The epidemiological characteristics of patients, including gender, age, cause of burn injuries, complication, the timing of hospitalisation (season and month) and hospitalisation length and cost, were collected. RESULTS: Male gender (63.23%), aged 1-2 years (69.95%), and hydrothermal scald (80.57%) were significantly dominant among cases. Furthermore, complications were significantly different among groups with different age of patients. Pneumonia was the most common complication (21%). Meanwhile, most paediatric burn occurred in spring (26.73%), and hospitalisation length and cost significantly depended on the cause of the burn injuries and surgical intervention. CONCLUSIONS: This large-scale epidemiological study of paediatric burn in China revealed that boys aged 1-2 years with higher activity and lack of self-awareness are more likely to suffer from burn injuries by hydrothermal scald. In addition, complications, especially pneumonia, need attention and early prevention in paediatric burn.

BPTF in bone marrow provides a potential progression biomarker regulated by TFAP4 through the PI3K/AKT pathway in neuroblastoma.

BACKGROUND: Neuroblastoma (NB) is the most common extracranial malignant solid tumor in children, which is highly prone to bone marrow (BM) metastasis. BM can monitor early signs of mild disease and metastasis. Existing biomarkers are insufficient for the diagnosis and treatment of NB. Bromodomain PHD finger transcription factor (BPTF) is an important subunit of the chromatin-remodeling complex that is closely associated with tumors. Here, we evaluated whether BPTF in BM plays an important role in predicting NB progression, and explore the molecular mechanism of BPTF in NB. METHODS: The clinical relevance of the BPTF was predicted in the GEO (GSE62564) and TARGET database. The biological function of BPTF in NB was investigated by constructing cell lines and employing BPTF inhibitor AU1. Western blot was used to determine the changes of BPTF, TFAP4, PI3K/AKT signaling and Epithelial-mesenchymal transition (EMT) related markers. A total of 109 children with newly diagnosed NB in Beijing Children's Hospital from January 2018 to March 2021 were included in this study. RT-PCR was used to measure the BPTF and TFAP4 expression in BM. The cut-off level was set at the median value of BPTF expression levels. RESULTS: Databases suggested that BPTF expression was higher in NB and was significantly associated with stage and grade. Proliferation and migration of NB cells were slowed down when BPTF was silenced. Mechanistically, TFAP4 could positively regulate BPTF and promotes EMT process through activating the PI3K/AKT signaling pathway. Moreover, detection of the newly diagnosed BM specimens showed that BPTF expression was significantly higher in high-risk group, stage IV group and BM metastasis group. Children with high BPTF at initial diagnosis were considered to have high risk for disease progression and recurrence. BPTF is an independent risk factor for predicting NB progression. CONCLUSIONS: A novel and convenient BPTF-targeted humoral detection that can prompt minimal residual and predict NB progression in the early stages of the disease were identified. BPTF inhibitor AU1 is expected to become a new targeted drug for NB therapy. It's also reveal previously unknown mechanisms of BPTF in NB cell proliferation and metastasis through TFAP4 and PI3K/AKT pathways.

Spinal Dural Arterio-Venous Fistula: A Vital Differential Diagnosis to Consider for Myelopathy.

Introduction: Spinal dural arterio-venous fistula (SDAVF) is a rare and underdiagnosed cause of myelopathy which can result in a devastating neurological outcome if not properly managed. Case description: We report a case of SDAVF in a middle-aged man with gradual progressively deteriorating myelopathy and associated symptoms. This was first managed as demyelinating disease but was refractory to steroid therapy. Vigilant review of his spinal magnetic resonance imaging (MRI) scans showed dilated perimedullary veins, suspicious for SDAVF. The diagnosis was confirmed with catheter angiography. Neurological symptoms resolved after surgical treatment. Discussion: SDAVF can closely mimic demyelinating conditions such as transverse myelitis or multiple sclerosis. MRI finding of dilated perimedullary veins can be subtle and masked in the late stage, posing a diagnostic challenge for physicians. It is potentially curable after timely treatment. Conclusion: Clinicians should maintain a high level of suspicion for SDAVF and actively review all available radiological imaging for clues, particularly when there is a lack of response to treatment for other causes of myelopathy. LEARNING POINTS: Spinal dural arterio-venous fistula (SDAVF) can have clinical and radiological features similar to those of demyelinating disease, often causing a diagnostic dilemma for physicians. Neurological sequalae can be devastating if left untreated.Clinicians should be aware of this rare yet important differential diagnosis for myelopathy and its classic MRI findings (spinal cord oedema and dilated perimedullary veins).The gold standard for diagnosis is catheter spinal angiography. Treatment options include endovascular embolization and surgical ligation of the fistula.

TAF1D promotes proliferation by transcriptionally activating G2/M phase-related genes in MYCN-amplified neuroblastoma.

High-risk neuroblastoma (HR-NB) is an aggressive childhood cancer that responds poorly to currently available therapies and is associated with only about a 50% 5-year survival rate. MYCN amplification is a critical driver of these aggressive tumors, but so far there have not been any approved treatments to effectively treat HR-NB by targeting MYCN or its downstream effectors. Thus, the identification of novel molecular targets and therapeutic strategies to treat children diagnosed with HR-NB represents an urgent unmet medical need. Here, we conducted a targeted siRNA screening and identified TATA box-binding protein-associated factor RNA polymerase I subunit D, TAF1D, as a critical regulator of the cell cycle and proliferation in HR-NB cells. Analysis of three independent primary NB cohorts determined that high TAF1D expression correlated with MYCN-amplified, high-risk disease and poor clinical outcomes. TAF1D knockdown more robustly inhibited cell proliferation in MYCN-amplified NB cells compared with MYCN-non-amplified NB cells, as well as suppressed colony formation and inhibited tumor growth in a xenograft mouse model of MYCN-amplified NB. RNA-seq analysis revealed that TAF1D knockdown downregulates the expression of genes associated with the G2/M transition, including the master cell-cycle regulator, cell-cycle-dependent kinase 1 (CDK1), resulting in cell-cycle arrest at G2/M. Our findings demonstrate that TAF1D is a key oncogenic regulator of MYCN-amplified HR-NB and suggest that therapeutic targeting of TAF1D may be a viable strategy to treat HR-NB patients by blocking cell-cycle progression and the proliferation of tumor cells.

The impact of metformin on survival in diabetes patients with operable colorectal cancer: A nationwide retrospective cohort study.

OBJECTIVE: To investigate the impact of metformin on survival of diabetic patients following surgery for colorectal cancer (CRC). METHODS: This was a retrospective cohort study. From Taiwan's population-based National Health Insurance Research Database (NHIRD) we identified 12,512 patients with CRC and type II diabetes who underwent curative surgery between 2000 and 2012. Of these, 6222 patients were included in a matched cohort. Using Cox regression models with time-dependent covariates we examined the impact of metformin on survival. RESULTS: Average duration of follow-up was 49 and 54 months for metformin users and non-users, respectively. Cox proportional hazard model showed that metformin was associated with 5-year overall survival benefit (Hazard ratio, 0.23 [95% CI, 0.20-0.26]) and inverse association with risk of liver metastasis (Hazard ratio, 0.79 [95% CI, 0.68-0.93]). CONCLUSIONS: Metformin was associated with a survival benefit in diabetic patients with CRC following surgery, and an inverse association with risk of liver metastases suggesting a potential anti-tumorigenic effect.

Immunogenicity of a spike protein subunit-based COVID-19 vaccine with broad protection against various SARS-CoV-2 variants in animal studies.

SARS-CoV-2 pandemic has profound impacts on human life and global economy since the outbreak in 2019. With the new variants continue to emerge with greater immune escaping capability, the protectivity of the available vaccines is compromised. Therefore, development a vaccine that is capable of inducing immunity against variants including omicron strains is in urgent need. In this study, we developed a protein-based vaccine BCVax that is consisted of antigen delta strain spike protein and QS21-based adjuvant AB801 in nanoparticle immune stimulation complex format (AB801-ISCOM). Results from animal studies showed that high level of anti-S protein IgG was induced after two doses of BCVax and the IgG was capable of neutralizing multiple variants of pseudovirus including omicron BA.1 or BA.2 strains. In addition, strong Th1 response was stimulated after BCVax immunization. Furthermore, BCvax with AB801-ISCOM as the adjuvant showed significant stronger immunity compared with the vaccine using aluminum hydroxide plus CpG 1018 as the adjuvant. BCVax was also evaluated as a booster after two prior vaccinations, the IgG titers and pseudovirus neutralization activities against BA.2 or BA.4/BA.5 were further enhanced suggesting BCVax is a promising candidate as booster. Taken together, the pre-clinical data warrant BCVax for further development in clinic.

Clinical analysis of eye movement-based data in the medical diagnosis of amblyopia.

Amblyopia is an abnormal visual processing-induced developmental disorder of the central nervous system that affects static and dynamic vision, as well as binocular visual function. Currently, changes in static vision in one eye are the gold standard for amblyopia diagnosis. However, there have been few comprehensive analyses of changes in dynamic vision, especially eye movement, among children with amblyopia. Here, we proposed an optimization scheme involving a video eye tracker combined with an "artificial eye" for comprehensive examination of eye movement in children with amblyopia; we sought to improve the diagnostic criteria for amblyopia and provide theoretical support for practical treatment. The resulting eye movement data were used to construct a deep learning approach for diagnostic and predictive applications. Through efforts to manage the uncooperativeness of children with strabismus who could not complete the eye movement assessment, this study quantitatively and objectively assessed the clinical implications of eye movement characteristics in children with amblyopia. Our results indicated that an amblyopic eye is always in a state of adjustment, and thus is not "lazy." Additionally, we found that the eye movement parameters of amblyopic eyes and eyes with normal vision are significantly different. Finally, we identified eye movement parameters that can be used to supplement and optimize the diagnostic criteria for amblyopia, providing a diagnostic basis for evaluation of binocular visual function.